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manisnesan/test_flashrank_bm25_scifact.ipynb

Created August 24, 2024 20:25
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Evaluation notebook on scifact dataset using bm25 and flashrank along with examples of ranx and reranker library
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test_flashrank_bm25_scifact.ipynb
{
"cells": [
{
"cell_type": "code",
"execution_count": 28,
"metadata": {},
"outputs": [
{
"name": "stderr",
"output_type": "stream",
"text": [
"huggingface/tokenizers: The current process just got forked, after parallelism has already been used. Disabling parallelism to avoid deadlocks...\n",
"To disable this warning, you can either:\n",
"\t- Avoid using `tokenizers` before the fork if possible\n",
"\t- Explicitly set the environment variable TOKENIZERS_PARALLELISM=(true | false)\n"
]
}
],
"source": [
"!export TOKENIZERS_PARALLELISM=false"
]
},
{
"cell_type": "code",
"execution_count": 1,
"metadata": {},
"outputs": [],
"source": [
"# %pip install fastcore -q"
]
},
{
"cell_type": "code",
"execution_count": 2,
"metadata": {},
"outputs": [],
"source": [
"from rich import inspect as rinspect\n",
"from fastcore.all import *"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"## BM25s for top 100 docs"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "5dbe5c3afe4e42b4b155fe2c6eb13afb",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"name": "stderr",
"output_type": "stream",
"text": [
"DEBUG:bm25s:Building index from IDs objects\n"
]
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "73343836f065491888bcfa441ac334b8",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Count Tokens: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "c05b853ee1404528801b2fb33c080dd6",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Compute Scores: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "eaee8c9935bc4ef1ac7197bca35d12ff",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "5854435798924c4ab8fd6d2da948a508",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Retrieve: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"import bm25s\n",
"\n",
"# Create your corpus here\n",
"corpus = [\n",
" \"a cat is a feline and likes to purr\",\n",
" \"a dog is the human's best friend and loves to play\",\n",
" \"a bird is a beautiful animal that can fly\",\n",
" \"a fish is a creature that lives in water and swims\",\n",
"]\n",
"\n",
"# Create the BM25 model and index the corpus\n",
"retriever = bm25s.BM25(corpus=corpus)\n",
"retriever.index(bm25s.tokenize(corpus))\n",
"\n",
"# Query the corpus and get top-k results\n",
"query = \"does the fish purr like a cat?\"\n",
"results, scores = retriever.retrieve(bm25s.tokenize(query), k=2)\n",
"\n",
"# Let's see what we got!\n",
"doc, score = results[0, 0], scores[0, 0]"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"(array([['a cat is a feline and likes to purr',\n",
" 'a fish is a creature that lives in water and swims']],\n",
" dtype='<U50'),\n",
" array([[1.0584376 , 0.48158914]], dtype=float32))"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"results, scores"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"name": "stdout",
"output_type": "stream",
"text": [
"Rank 1 (score: 1.06): a cat is a feline and likes to purr\n",
"Rank 2 (score: 0.48): a fish is a creature that lives in water and swims\n"
]
}
],
"source": [
"for i in range(len(results[0])):\n",
" doc, score = results[0][i], scores[0][i]\n",
" print(f\"Rank {i+1} (score: {score:.2f}): {doc}\")"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"HuggingFace Integration: BM25S is tightly integrated with Huggingface Hub, allowing you to easily save to, and load from the hub"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Ensure you can login to huggingface hub using the CLI `huggingface-cli login`"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "5dbc53d836c9451bbe7739a191a1e3ac",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"name": "stderr",
"output_type": "stream",
"text": [
"DEBUG:bm25s:Building index from IDs objects\n"
]
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "7ea4ed53f8bd4fd7a4a874b130b4ee4c",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Count Tokens: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "18f50234ac6f46789d158c7779db3cb7",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Compute Scores: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"ename": "HfHubHTTPError",
"evalue": " (Request ID: Root=1-66ca0291-4cafe089383ea6347c6e2237;a6711ddd-8d89-4d45-9846-fff40b2b7903)\n\n403 Forbidden: You don't have the rights to create a model under the namespace \"msivanes\".\nCannot access content at: https://huggingface.co/api/repos/create.\nIf you are trying to create or update content, make sure you have a token with the `write` role.",
"output_type": "error",
"traceback": [
"\u001b[0;31m---------------------------------------------------------------------------\u001b[0m\n",
"\u001b[0;31mHTTPError\u001b[0m Traceback (most recent call last)\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/huggingface_hub/utils/_errors.py:304\u001b[0m, in \u001b[0;36mhf_raise_for_status\u001b[0;34m(response, endpoint_name)\u001b[0m\n",
"\u001b[1;32m 303\u001b[0m \u001b[38;5;28;01mtry\u001b[39;00m:\n",
"\u001b[0;32m--> 304\u001b[0m \u001b[43mresponse\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mraise_for_status\u001b[49m\u001b[43m(\u001b[49m\u001b[43m)\u001b[49m\n",
"\u001b[1;32m 305\u001b[0m \u001b[38;5;28;01mexcept\u001b[39;00m HTTPError \u001b[38;5;28;01mas\u001b[39;00m e:\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/requests/models.py:1024\u001b[0m, in \u001b[0;36mResponse.raise_for_status\u001b[0;34m(self)\u001b[0m\n",
"\u001b[1;32m 1023\u001b[0m \u001b[38;5;28;01mif\u001b[39;00m http_error_msg:\n",
"\u001b[0;32m-> 1024\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m HTTPError(http_error_msg, response\u001b[38;5;241m=\u001b[39m\u001b[38;5;28mself\u001b[39m)\n",
"\n",
"\u001b[0;31mHTTPError\u001b[0m: 403 Client Error: Forbidden for url: https://huggingface.co/api/repos/create\n",
"\n",
"The above exception was the direct cause of the following exception:\n",
"\n",
"\u001b[0;31mHfHubHTTPError\u001b[0m Traceback (most recent call last)\n",
"Cell \u001b[0;32mIn[38], line 17\u001b[0m\n",
"\u001b[1;32m 15\u001b[0m \u001b[38;5;66;03m# Set your username and token\u001b[39;00m\n",
"\u001b[1;32m 16\u001b[0m user \u001b[38;5;241m=\u001b[39m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mmsivanes\u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[0;32m---> 17\u001b[0m \u001b[43mretriever\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43msave_to_hub\u001b[49m\u001b[43m(\u001b[49m\u001b[38;5;124;43mf\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[38;5;132;43;01m{\u001b[39;49;00m\u001b[43muser\u001b[49m\u001b[38;5;132;43;01m}\u001b[39;49;00m\u001b[38;5;124;43m/bm25s-animals\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[43m)\u001b[49m\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/bm25s/hf.py:277\u001b[0m, in \u001b[0;36mBM25HF.save_to_hub\u001b[0;34m(self, repo_id, token, local_dir, corpus, private, commit_message, overwrite_local, include_readme, allow_pickle, **kwargs)\u001b[0m\n",
"\u001b[1;32m 233\u001b[0m \u001b[38;5;250m\u001b[39m\u001b[38;5;124;03m\"\"\"\u001b[39;00m\n",
"\u001b[1;32m 234\u001b[0m \u001b[38;5;124;03mThis function saves the BM25 model to the Hugging Face Hub.\u001b[39;00m\n",
"\u001b[1;32m 235\u001b[0m \n",
"\u001b[0;32m (...)\u001b[0m\n",
"\u001b[1;32m 274\u001b[0m \u001b[38;5;124;03m Additional keyword arguments to pass to `HfApi.upload_folder` call.\u001b[39;00m\n",
"\u001b[1;32m 275\u001b[0m \u001b[38;5;124;03m\"\"\"\u001b[39;00m\n",
"\u001b[1;32m 276\u001b[0m api \u001b[38;5;241m=\u001b[39m HfApi(token\u001b[38;5;241m=\u001b[39mtoken)\n",
"\u001b[0;32m--> 277\u001b[0m repo_url \u001b[38;5;241m=\u001b[39m \u001b[43mapi\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mcreate_repo\u001b[49m\u001b[43m(\u001b[49m\n",
"\u001b[1;32m 278\u001b[0m \u001b[43m \u001b[49m\u001b[43mrepo_id\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mrepo_id\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 279\u001b[0m \u001b[43m \u001b[49m\u001b[43mtoken\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mapi\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mtoken\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 280\u001b[0m \u001b[43m \u001b[49m\u001b[43mprivate\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mprivate\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 281\u001b[0m \u001b[43m \u001b[49m\u001b[43mrepo_type\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[38;5;124;43mmodel\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 282\u001b[0m \u001b[43m \u001b[49m\u001b[43mexist_ok\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43;01mTrue\u001b[39;49;00m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 283\u001b[0m \u001b[43m\u001b[49m\u001b[43m)\u001b[49m\n",
"\u001b[1;32m 284\u001b[0m repo_id \u001b[38;5;241m=\u001b[39m repo_url\u001b[38;5;241m.\u001b[39mrepo_id\n",
"\u001b[1;32m 286\u001b[0m username, repo_name \u001b[38;5;241m=\u001b[39m repo_id\u001b[38;5;241m.\u001b[39msplit(\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124m/\u001b[39m\u001b[38;5;124m\"\u001b[39m, \u001b[38;5;241m1\u001b[39m)\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/huggingface_hub/utils/_validators.py:114\u001b[0m, in \u001b[0;36mvalidate_hf_hub_args.<locals>._inner_fn\u001b[0;34m(*args, **kwargs)\u001b[0m\n",
"\u001b[1;32m 111\u001b[0m \u001b[38;5;28;01mif\u001b[39;00m check_use_auth_token:\n",
"\u001b[1;32m 112\u001b[0m kwargs \u001b[38;5;241m=\u001b[39m smoothly_deprecate_use_auth_token(fn_name\u001b[38;5;241m=\u001b[39mfn\u001b[38;5;241m.\u001b[39m\u001b[38;5;18m__name__\u001b[39m, has_token\u001b[38;5;241m=\u001b[39mhas_token, kwargs\u001b[38;5;241m=\u001b[39mkwargs)\n",
"\u001b[0;32m--> 114\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m \u001b[43mfn\u001b[49m\u001b[43m(\u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43margs\u001b[49m\u001b[43m,\u001b[49m\u001b[43m \u001b[49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[38;5;241;43m*\u001b[39;49m\u001b[43mkwargs\u001b[49m\u001b[43m)\u001b[49m\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/huggingface_hub/hf_api.py:3376\u001b[0m, in \u001b[0;36mHfApi.create_repo\u001b[0;34m(self, repo_id, token, private, repo_type, exist_ok, resource_group_id, space_sdk, space_hardware, space_storage, space_sleep_time, space_secrets, space_variables)\u001b[0m\n",
"\u001b[1;32m 3374\u001b[0m \u001b[38;5;28;01mreturn\u001b[39;00m RepoUrl(\u001b[38;5;124mf\u001b[39m\u001b[38;5;124m\"\u001b[39m\u001b[38;5;132;01m{\u001b[39;00m\u001b[38;5;28mself\u001b[39m\u001b[38;5;241m.\u001b[39mendpoint\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m/\u001b[39m\u001b[38;5;132;01m{\u001b[39;00mrepo_type\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m/\u001b[39m\u001b[38;5;132;01m{\u001b[39;00mrepo_id\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m\"\u001b[39m)\n",
"\u001b[1;32m 3375\u001b[0m \u001b[38;5;28;01mexcept\u001b[39;00m HfHubHTTPError:\n",
"\u001b[0;32m-> 3376\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m err\n",
"\u001b[1;32m 3377\u001b[0m \u001b[38;5;28;01melse\u001b[39;00m:\n",
"\u001b[1;32m 3378\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/huggingface_hub/hf_api.py:3363\u001b[0m, in \u001b[0;36mHfApi.create_repo\u001b[0;34m(self, repo_id, token, private, repo_type, exist_ok, resource_group_id, space_sdk, space_hardware, space_storage, space_sleep_time, space_secrets, space_variables)\u001b[0m\n",
"\u001b[1;32m 3360\u001b[0m \u001b[38;5;28;01mbreak\u001b[39;00m\n",
"\u001b[1;32m 3362\u001b[0m \u001b[38;5;28;01mtry\u001b[39;00m:\n",
"\u001b[0;32m-> 3363\u001b[0m \u001b[43mhf_raise_for_status\u001b[49m\u001b[43m(\u001b[49m\u001b[43mr\u001b[49m\u001b[43m)\u001b[49m\n",
"\u001b[1;32m 3364\u001b[0m \u001b[38;5;28;01mexcept\u001b[39;00m HTTPError \u001b[38;5;28;01mas\u001b[39;00m err:\n",
"\u001b[1;32m 3365\u001b[0m \u001b[38;5;28;01mif\u001b[39;00m exist_ok \u001b[38;5;129;01mand\u001b[39;00m err\u001b[38;5;241m.\u001b[39mresponse\u001b[38;5;241m.\u001b[39mstatus_code \u001b[38;5;241m==\u001b[39m \u001b[38;5;241m409\u001b[39m:\n",
"\u001b[1;32m 3366\u001b[0m \u001b[38;5;66;03m# Repo already exists and `exist_ok=True`\u001b[39;00m\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/huggingface_hub/utils/_errors.py:367\u001b[0m, in \u001b[0;36mhf_raise_for_status\u001b[0;34m(response, endpoint_name)\u001b[0m\n",
"\u001b[1;32m 360\u001b[0m \u001b[38;5;28;01melif\u001b[39;00m response\u001b[38;5;241m.\u001b[39mstatus_code \u001b[38;5;241m==\u001b[39m \u001b[38;5;241m403\u001b[39m:\n",
"\u001b[1;32m 361\u001b[0m message \u001b[38;5;241m=\u001b[39m (\n",
"\u001b[1;32m 362\u001b[0m \u001b[38;5;124mf\u001b[39m\u001b[38;5;124m\"\u001b[39m\u001b[38;5;130;01m\\n\u001b[39;00m\u001b[38;5;130;01m\\n\u001b[39;00m\u001b[38;5;132;01m{\u001b[39;00mresponse\u001b[38;5;241m.\u001b[39mstatus_code\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m Forbidden: \u001b[39m\u001b[38;5;132;01m{\u001b[39;00merror_message\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m.\u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[1;32m 363\u001b[0m \u001b[38;5;241m+\u001b[39m \u001b[38;5;124mf\u001b[39m\u001b[38;5;124m\"\u001b[39m\u001b[38;5;130;01m\\n\u001b[39;00m\u001b[38;5;124mCannot access content at: \u001b[39m\u001b[38;5;132;01m{\u001b[39;00mresponse\u001b[38;5;241m.\u001b[39murl\u001b[38;5;132;01m}\u001b[39;00m\u001b[38;5;124m.\u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[1;32m 364\u001b[0m \u001b[38;5;241m+\u001b[39m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;130;01m\\n\u001b[39;00m\u001b[38;5;124mIf you are trying to create or update content, \u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[1;32m 365\u001b[0m \u001b[38;5;241m+\u001b[39m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mmake sure you have a token with the `write` role.\u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[1;32m 366\u001b[0m )\n",
"\u001b[0;32m--> 367\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m HfHubHTTPError(message, response\u001b[38;5;241m=\u001b[39mresponse) \u001b[38;5;28;01mfrom\u001b[39;00m \u001b[38;5;21;01me\u001b[39;00m\n",
"\u001b[1;32m 369\u001b[0m \u001b[38;5;66;03m# Convert `HTTPError` into a `HfHubHTTPError` to display request information\u001b[39;00m\n",
"\u001b[1;32m 370\u001b[0m \u001b[38;5;66;03m# as well (request id and/or server error message)\u001b[39;00m\n",
"\u001b[1;32m 371\u001b[0m \u001b[38;5;28;01mraise\u001b[39;00m HfHubHTTPError(\u001b[38;5;28mstr\u001b[39m(e), response\u001b[38;5;241m=\u001b[39mresponse) \u001b[38;5;28;01mfrom\u001b[39;00m \u001b[38;5;21;01me\u001b[39;00m\n",
"\n",
"\u001b[0;31mHfHubHTTPError\u001b[0m: (Request ID: Root=1-66ca0291-4cafe089383ea6347c6e2237;a6711ddd-8d89-4d45-9846-fff40b2b7903)\n",
"\n",
"403 Forbidden: You don't have the rights to create a model under the namespace \"msivanes\".\n",
"Cannot access content at: https://huggingface.co/api/repos/create.\n",
"If you are trying to create or update content, make sure you have a token with the `write` role."
]
}
],
"source": [
"import bm25s\n",
"from bm25s.hf import BM25HF\n",
"\n",
"# Create your corpus here\n",
"corpus = [\n",
" \"a cat is a feline and likes to purr\",\n",
" \"a dog is the human's best friend and loves to play\",\n",
" \"a bird is a beautiful animal that can fly\",\n",
" \"a fish is a creature that lives in water and swims\",\n",
"]\n",
"\n",
"retriever = BM25HF(corpus=corpus)\n",
"retriever.index(bm25s.tokenize(corpus))\n",
"\n",
"# Set your username and token\n",
"user = \"msivanes\"\n",
"retriever.save_to_hub(f\"{user}/bm25s-animals\")\n"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Faced the error \n",
"```\n",
"403 Forbidden: You don't have the rights to create a model under the namespace \"msivanes\".\n",
"Cannot access content at: https://huggingface.co/api/repos/create.\n",
"If you are trying to create or update content, make sure you have a token with the `write` role.\n",
"```\n",
"\n",
"Went to HuggingFace Hub Access Tokens Settings and update the write permissions."
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "7b70f60b546948faa14fb386f9099c3d",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"name": "stderr",
"output_type": "stream",
"text": [
"DEBUG:bm25s:Building index from IDs objects\n"
]
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "66da0011a78f4368b4729cde0cf24182",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Count Tokens: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "7e0a149614d4451ab3da33ced33d7563",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Compute Scores: 0%| | 0/4 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "f45a114c50f6462baabc011b48e80c1c",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Finding newlines for mmindex: 0%| | 0.00/264 [00:00<?, ?B/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"ename": "ValueError",
"evalue": "unexpected '{' in field name",
"output_type": "error",
"traceback": [
"\u001b[0;31m---------------------------------------------------------------------------\u001b[0m\n",
"\u001b[0;31mValueError\u001b[0m Traceback (most recent call last)\n",
"Cell \u001b[0;32mIn[39], line 17\u001b[0m\n",
"\u001b[1;32m 15\u001b[0m \u001b[38;5;66;03m# Set your username and token\u001b[39;00m\n",
"\u001b[1;32m 16\u001b[0m user \u001b[38;5;241m=\u001b[39m \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mmsivanes\u001b[39m\u001b[38;5;124m\"\u001b[39m\n",
"\u001b[0;32m---> 17\u001b[0m \u001b[43mretriever\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43msave_to_hub\u001b[49m\u001b[43m(\u001b[49m\u001b[38;5;124;43mf\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[38;5;132;43;01m{\u001b[39;49;00m\u001b[43muser\u001b[49m\u001b[38;5;132;43;01m}\u001b[39;49;00m\u001b[38;5;124;43m/bm25s-animals\u001b[39;49m\u001b[38;5;124;43m\"\u001b[39;49m\u001b[43m)\u001b[49m\n",
"\n",
"File \u001b[0;32m~/miniconda3/envs/rerankers/lib/python3.11/site-packages/bm25s/hf.py:303\u001b[0m, in \u001b[0;36mBM25HF.save_to_hub\u001b[0;34m(self, repo_id, token, local_dir, corpus, private, commit_message, overwrite_local, include_readme, allow_pickle, **kwargs)\u001b[0m\n",
"\u001b[1;32m 300\u001b[0m num_tokens \u001b[38;5;241m=\u001b[39m \u001b[38;5;28mself\u001b[39m\u001b[38;5;241m.\u001b[39mscores[\u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mdata\u001b[39m\u001b[38;5;124m\"\u001b[39m]\u001b[38;5;241m.\u001b[39mshape[\u001b[38;5;241m0\u001b[39m]\n",
"\u001b[1;32m 301\u001b[0m avg_tokens_per_doc \u001b[38;5;241m=\u001b[39m \u001b[38;5;28mround\u001b[39m(num_tokens \u001b[38;5;241m/\u001b[39m num_docs, \u001b[38;5;241m2\u001b[39m)\n",
"\u001b[0;32m--> 303\u001b[0m results \u001b[38;5;241m=\u001b[39m \u001b[43mREADME_TEMPLATE\u001b[49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mformat\u001b[49m\u001b[43m(\u001b[49m\n",
"\u001b[1;32m 304\u001b[0m \u001b[43m \u001b[49m\u001b[43musername\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43musername\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 305\u001b[0m \u001b[43m \u001b[49m\u001b[43mversion\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43m__version__\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 306\u001b[0m \u001b[43m \u001b[49m\u001b[43mrepo_name\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mrepo_name\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 307\u001b[0m \u001b[43m \u001b[49m\u001b[43mnum_docs\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mnum_docs\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 308\u001b[0m \u001b[43m \u001b[49m\u001b[43mnum_tokens\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mnum_tokens\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 309\u001b[0m \u001b[43m \u001b[49m\u001b[43mavg_tokens_per_doc\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[43mavg_tokens_per_doc\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 310\u001b[0m \u001b[43m \u001b[49m\u001b[43mk1\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mk1\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 311\u001b[0m \u001b[43m \u001b[49m\u001b[43mb\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mb\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 312\u001b[0m \u001b[43m \u001b[49m\u001b[43mdelta\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mdelta\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 313\u001b[0m \u001b[43m \u001b[49m\u001b[43mmethod\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43mmethod\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 314\u001b[0m \u001b[43m \u001b[49m\u001b[43midf_method\u001b[49m\u001b[38;5;241;43m=\u001b[39;49m\u001b[38;5;28;43mself\u001b[39;49m\u001b[38;5;241;43m.\u001b[39;49m\u001b[43midf_method\u001b[49m\u001b[43m,\u001b[49m\n",
"\u001b[1;32m 315\u001b[0m \u001b[43m\u001b[49m\u001b[43m)\u001b[49m\n",
"\u001b[1;32m 317\u001b[0m \u001b[38;5;28;01mwith\u001b[39;00m \u001b[38;5;28mopen\u001b[39m(os\u001b[38;5;241m.\u001b[39mpath\u001b[38;5;241m.\u001b[39mjoin(save_dir, \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mREADME.md\u001b[39m\u001b[38;5;124m\"\u001b[39m), \u001b[38;5;124m\"\u001b[39m\u001b[38;5;124mw\u001b[39m\u001b[38;5;124m\"\u001b[39m) \u001b[38;5;28;01mas\u001b[39;00m f:\n",
"\u001b[1;32m 318\u001b[0m f\u001b[38;5;241m.\u001b[39mwrite(results)\n",
"\n",
"\u001b[0;31mValueError\u001b[0m: unexpected '{' in field name"
]
}
],
"source": [
"import bm25s\n",
"from bm25s.hf import BM25HF\n",
"\n",
"# Create your corpus here\n",
"corpus = [\n",
" \"a cat is a feline and likes to purr\",\n",
" \"a dog is the human's best friend and loves to play\",\n",
" \"a bird is a beautiful animal that can fly\",\n",
" \"a fish is a creature that lives in water and swims\",\n",
"]\n",
"\n",
"retriever = BM25HF(corpus=corpus)\n",
"retriever.index(bm25s.tokenize(corpus))\n",
"\n",
"# Set your username and token\n",
"user = \"msivanes\"\n",
"retriever.save_to_hub(f\"{user}/bm25s-animals\")\n"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"[TODO] This seems to be an issue with the Hub Integration. This is not important."
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"## Rerankers - FlashRank"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Install the rerankers and explore the overview"
]
},
{
"cell_type": "code",
"execution_count": 3,
"metadata": {},
"outputs": [],
"source": [
"# %pip install \"rerankers[flashrank]\" # FlashRank rerankers (ONNX-optimised, very fast on CPU)\n"
]
},
{
"cell_type": "code",
"execution_count": 4,
"metadata": {},
"outputs": [
{
"name": "stderr",
"output_type": "stream",
"text": [
"INFO:flashrank.Ranker:Downloading ms-marco-MiniLM-L-12-v2...\n"
]
},
{
"name": "stdout",
"output_type": "stream",
"text": [
"Torch not installed...\n",
"Loading default flashrank model for language en\n",
"Default Model: ms-marco-MiniLM-L-12-v2\n",
"Loading FlashRankRanker model ms-marco-MiniLM-L-12-v2\n",
"Loading model FlashRank model ms-marco-MiniLM-L-12-v2...\n"
]
},
{
"name": "stderr",
"output_type": "stream",
"text": [
"ms-marco-MiniLM-L-12-v2.zip: 100%|██████████| 21.6M/21.6M [00:00<00:00, 44.7MiB/s]\n"
]
}
],
"source": [
"from rerankers import Reranker\n",
"ranker = Reranker('flashrank')"
]
},
{
"cell_type": "code",
"execution_count": 5,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"<rerankers.models.flashrank_ranker.FlashRankRanker at 0x7fec84499d50>"
]
},
"execution_count": 5,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"ranker"
]
},
{
"cell_type": "code",
"execution_count": 6,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"RankedResults(results=[Result(document=Document(text='I hate you', doc_id=0, metadata={}), score=0.21780753135681152, rank=1), Result(document=Document(text='I really like you', doc_id=1, metadata={}), score=0.0441853404045105, rank=2)], query='I love you', has_scores=True)"
]
},
"execution_count": 6,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"results = ranker.rank(query=\"I love you\", docs=[\"I hate you\", \"I really like you\"], doc_ids=[0,1])\n",
"results"
]
},
{
"cell_type": "code",
"execution_count": 7,
"metadata": {},
"outputs": [],
"source": [
"results = ranker.rank(query=\"I love you\", docs=[\"I hate you\", \"I really like you\"], doc_ids=[0,1], metadata=[{'source': 'twitter'}, {'source': 'reddit'}])\n"
]
},
{
"cell_type": "code",
"execution_count": 8,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"RankedResults(results=[Result(document=Document(text='I hate you', doc_id=0, metadata={'source': 'twitter'}), score=0.21780753135681152, rank=1), Result(document=Document(text='I really like you', doc_id=1, metadata={'source': 'reddit'}), score=0.0441853404045105, rank=2)], query='I love you', has_scores=True)"
]
},
"execution_count": 8,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"results"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Now use the tests module containing the Consistency tests to check the reranker's consistency.\n",
"- scifact dataset - [test_colbert](https://github.com/AnswerDotAI/rerankers/blob/main/tests/consistency_notebooks/test_colbert.ipynb)"
]
},
{
"cell_type": "code",
"execution_count": 9,
"metadata": {},
"outputs": [],
"source": [
"from ranx import Qrels, Run\n"
]
},
{
"cell_type": "code",
"execution_count": 10,
"metadata": {},
"outputs": [
{
"data": {
"text/html": [
"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭───────────────────────── </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">class</span><span style=\"color: #000000; text-decoration-color: #000000\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">'ranx.data_structures.qrels.Qrels'</span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080\"> ──────────────────────────╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #00ffff; text-decoration-color: #00ffff; font-style: italic\">class </span><span style=\"color: #800000; text-decoration-color: #800000; font-weight: bold\">Qrels</span><span style=\"font-weight: bold\">(</span>qrels: Dict<span style=\"font-weight: bold\">[</span>str, Dict<span style=\"font-weight: bold\">[</span>str, int<span style=\"font-weight: bold\">]]</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span>, name: str = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span><span style=\"font-weight: bold\">)</span>: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">`Qrels`, or _query relevance judgments_, stores the ground truth for conducting evaluations.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">The preferred way for creating a `Qrels` instance is converting Python dictionary as follows:</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">```python</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">qrels_dict = </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"q_1\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_1\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"q_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_3\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_5\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">3</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">qrels = </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Qrels</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">qrels_dict, </span><span style=\"color: #808000; text-decoration-color: #808000\">name</span><span style=\"color: #008080; text-decoration-color: #008080\">=</span><span style=\"color: #008000; text-decoration-color: #008000\">\"MSMARCO\"</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">qrels = </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Qrels</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">()</span><span style=\"color: #008080; text-decoration-color: #008080\"> # Creates an empty Qrels with no name</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">```</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">size</span> = <span style=\"font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">property</span><span style=\"color: #000000; text-decoration-color: #000000\"> object at </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0x7fec31180cc0</span><span style=\"font-weight: bold\">&gt;</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">╰───────────────────────────────────────────────────────────────────────────────────────────────╯</span>\n",
"</pre>\n"
],
"text/plain": [
"\u001b[34m╭─\u001b[0m\u001b[34m────────────────────────\u001b[0m\u001b[34m \u001b[0m\u001b[1;34m<\u001b[0m\u001b[1;95mclass\u001b[0m\u001b[39m \u001b[0m\u001b[32m'ranx.data_structures.qrels.Qrels'\u001b[0m\u001b[1;34m>\u001b[0m\u001b[34m \u001b[0m\u001b[34m─────────────────────────\u001b[0m\u001b[34m─╮\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;96mclass \u001b[0m\u001b[1;31mQrels\u001b[0m\u001b[1m(\u001b[0mqrels: Dict\u001b[1m[\u001b[0mstr, Dict\u001b[1m[\u001b[0mstr, int\u001b[1m]\u001b[0m\u001b[1m]\u001b[0m = \u001b[3;35mNone\u001b[0m, name: str = \u001b[3;35mNone\u001b[0m\u001b[1m)\u001b[0m: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m`Qrels`, or _query relevance judgments_, stores the ground truth for conducting evaluations.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mThe preferred way for creating a `Qrels` instance is converting Python dictionary as follows:\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m```python\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mqrels_dict = \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"q_1\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_1\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m1\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m2\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[1;36m}\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"q_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_3\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m2\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m1\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_5\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m3\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[1;36m}\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[1;36m}\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mqrels = \u001b[0m\u001b[1;35mQrels\u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mqrels_dict, \u001b[0m\u001b[33mname\u001b[0m\u001b[36m=\u001b[0m\u001b[32m\"MSMARCO\"\u001b[0m\u001b[1;36m)\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mqrels = \u001b[0m\u001b[1;35mQrels\u001b[0m\u001b[1;36m(\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m # Creates an empty Qrels with no name\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m```\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;33msize\u001b[0m = \u001b[1m<\u001b[0m\u001b[1;95mproperty\u001b[0m\u001b[39m object at \u001b[0m\u001b[1;36m0x7fec31180cc0\u001b[0m\u001b[1m>\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m╰───────────────────────────────────────────────────────────────────────────────────────────────╯\u001b[0m\n"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"rinspect(Qrels, help=True)"
]
},
{
"cell_type": "code",
"execution_count": 11,
"metadata": {},
"outputs": [
{
"data": {
"text/html": [
"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭─────────────────────────── </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">class</span><span style=\"color: #000000; text-decoration-color: #000000\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">'ranx.data_structures.run.Run'</span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080\"> ────────────────────────────╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #00ffff; text-decoration-color: #00ffff; font-style: italic\">class </span><span style=\"color: #800000; text-decoration-color: #800000; font-weight: bold\">Run</span><span style=\"font-weight: bold\">(</span>run: Dict<span style=\"font-weight: bold\">[</span>str, Dict<span style=\"font-weight: bold\">[</span>str, float<span style=\"font-weight: bold\">]]</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span>, name: str = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span><span style=\"font-weight: bold\">)</span>: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">`Run` stores the relevance scores estimated by the model under evaluation.</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">&lt;</span><span style=\"color: #000000; text-decoration-color: #000000\">\\br</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">&gt;</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">The preferred way for creating a `Run` instance is converting a Python dictionary as follows:</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">```python</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">run_dict = </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"q_1\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_1\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1.5</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2.6</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"q_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_3\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2.8</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_2\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1.2</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">\"d_5\"</span><span style=\"color: #008080; text-decoration-color: #008080\">: </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">3.1</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span><span style=\"color: #008080; text-decoration-color: #008080\">,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">run = </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Run</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">run_dict, </span><span style=\"color: #808000; text-decoration-color: #808000\">name</span><span style=\"color: #008080; text-decoration-color: #008080\">=</span><span style=\"color: #008000; text-decoration-color: #008000\">\"bm25\"</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">run = </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Run</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">()</span><span style=\"color: #008080; text-decoration-color: #008080\"> # Creates an empty Run with no name</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">```</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">size</span> = <span style=\"font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">property</span><span style=\"color: #000000; text-decoration-color: #000000\"> object at </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0x7fec311ff420</span><span style=\"font-weight: bold\">&gt;</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">╰───────────────────────────────────────────────────────────────────────────────────────────────╯</span>\n",
"</pre>\n"
],
"text/plain": [
"\u001b[34m╭─\u001b[0m\u001b[34m──────────────────────────\u001b[0m\u001b[34m \u001b[0m\u001b[1;34m<\u001b[0m\u001b[1;95mclass\u001b[0m\u001b[39m \u001b[0m\u001b[32m'ranx.data_structures.run.Run'\u001b[0m\u001b[1;34m>\u001b[0m\u001b[34m \u001b[0m\u001b[34m───────────────────────────\u001b[0m\u001b[34m─╮\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;96mclass \u001b[0m\u001b[1;31mRun\u001b[0m\u001b[1m(\u001b[0mrun: Dict\u001b[1m[\u001b[0mstr, Dict\u001b[1m[\u001b[0mstr, float\u001b[1m]\u001b[0m\u001b[1m]\u001b[0m = \u001b[3;35mNone\u001b[0m, name: str = \u001b[3;35mNone\u001b[0m\u001b[1m)\u001b[0m: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m`Run` stores the relevance scores estimated by the model under evaluation.\u001b[0m\u001b[1;36m<\u001b[0m\u001b[39m\\br\u001b[0m\u001b[1;36m>\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mThe preferred way for creating a `Run` instance is converting a Python dictionary as follows:\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m```python\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mrun_dict = \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"q_1\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_1\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m1.5\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m2.6\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[1;36m}\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"q_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m{\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_3\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m2.8\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_2\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m1.2\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[32m\"d_5\"\u001b[0m\u001b[36m: \u001b[0m\u001b[1;36m3.1\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m \u001b[0m\u001b[1;36m}\u001b[0m\u001b[36m,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[1;36m}\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mrun = \u001b[0m\u001b[1;35mRun\u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mrun_dict, \u001b[0m\u001b[33mname\u001b[0m\u001b[36m=\u001b[0m\u001b[32m\"bm25\"\u001b[0m\u001b[1;36m)\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mrun = \u001b[0m\u001b[1;35mRun\u001b[0m\u001b[1;36m(\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m # Creates an empty Run with no name\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m```\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;33msize\u001b[0m = \u001b[1m<\u001b[0m\u001b[1;95mproperty\u001b[0m\u001b[39m object at \u001b[0m\u001b[1;36m0x7fec311ff420\u001b[0m\u001b[1m>\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m╰───────────────────────────────────────────────────────────────────────────────────────────────╯\u001b[0m\n"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"rinspect(Run, help=True)"
]
},
{
"cell_type": "code",
"execution_count": 12,
"metadata": {},
"outputs": [
{
"data": {
"text/html": [
"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭────────────────────────────── </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">function</span><span style=\"color: #000000; text-decoration-color: #000000\"> Qrels.from_ir_datasets at </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0x7fec3117bec0</span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080\"> ──────────────────────────────╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #00ffff; text-decoration-color: #00ffff; font-style: italic\">def </span><span style=\"color: #800000; text-decoration-color: #800000; font-weight: bold\">Qrels.from_ir_datasets</span><span style=\"font-weight: bold\">(</span>dataset_id: str<span style=\"font-weight: bold\">)</span>: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">Convert `ir-datasets` qrels into ranx.Qrels. It automatically downloads data if missing.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">Args:</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> dataset_id </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">str</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span><span style=\"color: #008080; text-decoration-color: #008080\">: ID of the detaset in `ir-datasets`. `ir-datasets` catalog is available here: </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #0000ff; text-decoration-color: #0000ff; text-decoration: underline\">https://ir-datasets.com/index.html.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">Returns:</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> Qrels: ranx.Qrels</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">37</span><span style=\"font-style: italic\"> attribute(s) not shown.</span> Run <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">inspect</span><span style=\"font-weight: bold\">(</span>inspect<span style=\"font-weight: bold\">)</span> for options. <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯</span>\n",
"</pre>\n"
],
"text/plain": [
"\u001b[34m╭─\u001b[0m\u001b[34m─────────────────────────────\u001b[0m\u001b[34m \u001b[0m\u001b[1;34m<\u001b[0m\u001b[1;95mfunction\u001b[0m\u001b[39m Qrels.from_ir_datasets at \u001b[0m\u001b[1;36m0x7fec3117bec0\u001b[0m\u001b[1;34m>\u001b[0m\u001b[34m \u001b[0m\u001b[34m─────────────────────────────\u001b[0m\u001b[34m─╮\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;96mdef \u001b[0m\u001b[1;31mQrels.from_ir_datasets\u001b[0m\u001b[1m(\u001b[0mdataset_id: str\u001b[1m)\u001b[0m: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mConvert `ir-datasets` qrels into ranx.Qrels. It automatically downloads data if missing.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mArgs:\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m dataset_id \u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mstr\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m: ID of the detaset in `ir-datasets`. `ir-datasets` catalog is available here: \u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[4;94mhttps://ir-datasets.com/index.html.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mReturns:\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m Qrels: ranx.Qrels\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[1;36m37\u001b[0m\u001b[3m attribute(s) not shown.\u001b[0m Run \u001b[1;35minspect\u001b[0m\u001b[1m(\u001b[0minspect\u001b[1m)\u001b[0m for options. \u001b[34m│\u001b[0m\n",
"\u001b[34m╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯\u001b[0m\n"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"rinspect(Qrels.from_ir_datasets, help=True)"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Load the scifact test dataset mentioned here https://ir-datasets.com/beir.html#beir/scifact/test "
]
},
{
"cell_type": "code",
"execution_count": 13,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
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1}, 1202: {3475317: 1}, 1204: {31141365: 1}, 1207: {18909530: 1}, 1213: {14407673: 1}, 1216: {24142891: 1}, 1221: {19736671: 1}, 1225: {9650982: 1}, 1226: {13777138: 1}, 1232: {13905670: 1}, 124: {4883040: 1}, 1241: {4427392: 1}, 1245: {7662395: 1}, 1259: {24341590: 1}, 1262: {44172171: 1}, 1266: {37480103: 1}, 127: {21598000: 1}, 1270: {13900610: 1}, 1271: {13768432: 1}, 1272: {17081238: 1}, 1273: {11041152: 1}, 1274: {12428814: 1, 27731651: 1, 4406819: 1}, 1278: {11335781: 1}, 1279: {11335781: 1}, 128: {8290953: 1}, 1280: {4387784: 1}, 1281: {4387784: 1}, 1282: {23649163: 1}, 129: {27768226: 1}, 1290: {4687948: 1}, 1292: {56893404: 1}, 1298: {11718220: 1}, 13: {1606628: 1}, 130: {27768226: 1}, 1303: {12631697: 1}, 1316: {27910499: 1}, 1319: {16284655: 1}, 132: {7975937: 1}, 1320: {16284655: 1}, 133: {38485364: 1, 6969753: 1, 17934082: 1, 16280642: 1, 12640810: 1}, 1332: {5304891: 1}, 1335: {27910499: 1}, 1336: {27910499: 1}, 1337: {20231138: 1}, 1339: {15482274: 1}, 1344: {9559146: 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14241418: 1, 14819804: 1}, 279: {14376683: 1}, 294: {10874408: 1}, 295: {20310709: 1}, 298: {39381118: 1}, 3: {14717500: 1}, 300: {3553087: 1}, 303: {4388470: 1}, 312: {6173523: 1}, 314: {4347374: 1}, 324: {2014909: 1}, 327: {17997584: 1}, 338: {23349986: 1}, 343: {7873737: 1, 5884524: 1}, 350: {16927286: 1}, 354: {8774475: 1}, 36: {5152028: 1, 11705328: 1}, 362: {38587347: 1}, 380: {19005293: 1}, 384: {13770184: 1}, 385: {9955779: 1, 9767444: 1}, 386: {16495649: 1}, 388: {1148122: 1}, 399: {791050: 1}, 410: {14924526: 1}, 411: {14924526: 1}, 415: {6309659: 1}, 42: {18174210: 1}, 421: {11172205: 1}, 431: {28937856: 1}, 436: {14637235: 1}, 437: {18399038: 1}, 439: {4423559: 1}, 440: {4423559: 1}, 443: {10165258: 1}, 452: {12804937: 1, 464511: 1}, 475: {18678095: 1}, 478: {14767844: 1}, 48: {13734012: 1}, 49: {5953485: 1}, 491: {56893404: 1}, 5: {13734012: 1}, 50: {12580014: 1}, 501: {17930286: 1}, 502: {13071728: 1}, 507: {30774694: 1}, 508: {13980338: 1}, 51: {45638119: 1}, 513: {13230773: 1}, 514: {16256507: 1}, 516: {29564505: 1}, 517: {15663829: 1}, 521: {34873974: 1}, 525: {13639330: 1}, 527: {3863543: 1}, 528: {5476778: 1}, 53: {45638119: 1}, 532: {12991445: 1}, 533: {12991445: 1}, 535: {39368721: 1}, 536: {16056514: 1}, 539: {13282296: 1}, 54: {49556906: 1}, 540: {11886686: 1, 25007443: 1}, 544: {24221369: 1}, 549: {9433958: 1}, 551: {33499189: 1}, 552: {1471041: 1}, 554: {1049501: 1}, 56: {4709641: 1}, 560: {40096222: 1}, 569: {23460562: 1}, 57: {4709641: 1}, 575: {10300888: 1}, 577: {5289038: 1}, 578: {8764879: 1}, 587: {16999023: 1}, 589: {10984005: 1}, 593: {19675911: 1}, 597: {12779444: 1, 36355784: 1, 25742130: 1}, 598: {25742130: 1}, 613: {9638032: 1}, 619: {20888849: 1, 2565138: 1}, 623: {17000834: 1}, 628: {24512064: 1}, 636: {24294572: 1}, 637: {25649714: 1}, 641: {5912283: 1, 31554917: 1}, 644: {13619127: 1}, 649: {12789595: 1}, 659: {1215116: 1}, 660: {1215116: 1}, 674: {2095573: 1}, 684: {4942718: 1}, 690: {18750453: 1}, 691: {10991183: 1}, 692: {24088502: 1}, 693: {24088502: 1}, 70: {5956380: 1, 4414547: 1}, 700: {4350400: 1}, 702: {4350400: 1}, 715: {18421962: 1}, 716: {18421962: 1}, 718: {17587795: 1}, 72: {6076903: 1}, 721: {1834762: 1}, 723: {5531479: 1}, 727: {7521113: 1}, 728: {7521113: 1, 36444198: 1}, 729: {26851674: 1}, 742: {32159283: 1}, 743: {32159283: 1}, 744: {8460275: 1}, 75: {4387784: 1}, 756: {2831620: 1}, 759: {1805641: 1}, 768: {6421792: 1}, 770: {15476777: 1}, 775: {32275758: 1}, 781: {24338780: 1}, 783: {40632104: 1}, 784: {2356950: 1}, 785: {12471115: 1}, 793: {8551160: 1}, 800: {22543403: 1}, 805: {22180793: 1}, 808: {36606083: 1}, 811: {19799455: 1}, 814: {33387953: 1}, 820: {8646760: 1}, 821: {8646760: 1}, 823: {15319019: 1}, 830: {1897324: 1}, 831: {1897324: 1}, 832: {30303335: 1}, 834: {5483793: 1}, 837: {15928989: 1}, 839: {1469751: 1}, 845: {17741440: 1}, 847: {16787954: 1}, 852: {13843341: 1}, 859: {1982286: 1}, 870: {195689316: 1}, 873: {1180972: 1, 19307912: 1, 27393799: 1, 29025270: 1, 3315558: 1}, 879: {8426046: 1}, 880: {8426046: 1}, 882: {14803797: 1}, 887: {18855191: 1}, 903: {10648422: 1}, 904: {7370282: 1}, 907: {6923961: 1}, 911: {11254556: 1}, 913: {3203590: 1}, 914: {3203590: 1}, 921: {1642727: 1}, 922: {17077004: 1}, 936: {5483793: 1}, 94: {1215116: 1}, 956: {12956194: 1}, 957: {123859: 1}, 960: {8780599: 1}, 967: {2119889: 1, 8997410: 1}, 971: {46695481: 1, 27873158: 1, 28617573: 1, 9764256: 1}, 975: {5304891: 1}, 982: {2988714: 1}, 985: {6828370: 1}, 99: {18810195: 1}, 993: {16472469: 1}})"
]
},
"execution_count": 13,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"Qrels.from_ir_datasets(dataset_id='beir/scifact/test')"
]
},
{
"cell_type": "code",
"execution_count": 14,
"metadata": {},
"outputs": [],
"source": [
"qrels: Qrels = Qrels.from_ir_datasets(dataset_id='beir/scifact/test')"
]
},
{
"cell_type": "code",
"execution_count": 194,
"metadata": {},
"outputs": [],
"source": [
"# rinspect(qrels, all=True)"
]
},
{
"cell_type": "code",
"execution_count": 16,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
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3315558: 1}, 879: {8426046: 1}, 880: {8426046: 1}, 882: {14803797: 1}, 887: {18855191: 1}, 903: {10648422: 1}, 904: {7370282: 1}, 907: {6923961: 1}, 911: {11254556: 1}, 913: {3203590: 1}, 914: {3203590: 1}, 921: {1642727: 1}, 922: {17077004: 1}, 936: {5483793: 1}, 94: {1215116: 1}, 956: {12956194: 1}, 957: {123859: 1}, 960: {8780599: 1}, 967: {2119889: 1, 8997410: 1}, 971: {46695481: 1, 27873158: 1, 28617573: 1, 9764256: 1}, 975: {5304891: 1}, 982: {2988714: 1}, 985: {6828370: 1}, 99: {18810195: 1}, 993: {16472469: 1}})"
]
},
"execution_count": 16,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"qrels"
]
},
{
"cell_type": "code",
"execution_count": 193,
"metadata": {},
"outputs": [],
"source": [
"# rinspect(qrels)"
]
},
{
"cell_type": "code",
"execution_count": 18,
"metadata": {},
"outputs": [],
"source": [
"from rerankers import Reranker"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"[srsly](https://pypi.org/project/srsly/)\n",
"- package bundles some of the best Python serialization libraries into one standalone package, with a high-level API that makes it easy to write code that's correct across platforms and Pythons. \n",
"- This allows us to provide all the serialization utilities we need in a single binary wheel. \n",
"- Currently supports JSON, JSONL, MessagePack, Pickle and YAML.\n"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Download the datasets using ir_datasets export command"
]
},
{
"cell_type": "code",
"execution_count": 31,
"metadata": {},
"outputs": [
{
"name": "stderr",
"output_type": "stream",
"text": [
"huggingface/tokenizers: The current process just got forked, after parallelism has already been used. Disabling parallelism to avoid deadlocks...\n",
"To disable this warning, you can either:\n",
"\t- Avoid using `tokenizers` before the fork if possible\n",
"\t- Explicitly set the environment variable TOKENIZERS_PARALLELISM=(true | false)\n",
"huggingface/tokenizers: The current process just got forked, after parallelism has already been used. Disabling parallelism to avoid deadlocks...\n",
"To disable this warning, you can either:\n",
"\t- Avoid using `tokenizers` before the fork if possible\n",
"\t- Explicitly set the environment variable TOKENIZERS_PARALLELISM=(true | false)\n"
]
}
],
"source": [
"!ir_datasets export beir/scifact/test queries --format jsonl > ./data/scifact/queries.jsonl\n",
"!ir_datasets export beir/scifact/test docs --format jsonl > ./data/scifact/corpus.jsonl"
]
},
{
"cell_type": "code",
"execution_count": 32,
"metadata": {},
"outputs": [],
"source": [
"corpus_fname = './data/scifact/corpus.jsonl'\n",
"queries_fname = './data/scifact/queries.jsonl'"
]
},
{
"cell_type": "code",
"execution_count": 33,
"metadata": {},
"outputs": [],
"source": [
"assert Path(corpus_fname).exists()\n",
"assert Path(queries_fname).exists()"
]
},
{
"cell_type": "code",
"execution_count": 40,
"metadata": {},
"outputs": [],
"source": [
"import srsly \n",
"corpus = [x for x in srsly.read_jsonl('./data/scifact/corpus.jsonl')]\n",
"queries = [x for x in srsly.read_jsonl('./data/scifact/queries.jsonl')]\n",
"queries = [{'_id': x['query_id'], 'text': x['text']} for x in queries]\n",
"\n",
"# preprocess the corpus\n",
"# rename the key doc_id to _id\n",
"proc_corpus = [{'_id': x['doc_id'], 'title': x['title'], 'text': x['text'], 'metadata': {}} for x in corpus]"
]
},
{
"cell_type": "code",
"execution_count": 131,
"metadata": {},
"outputs": [],
"source": [
"corpus_map = {x['_id']: f\"{x['title']} {x['text']}\" for x in proc_corpus}"
]
},
{
"cell_type": "code",
"execution_count": 132,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"('4983',\n",
" 'Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.')"
]
},
"execution_count": 132,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"next(corpus_map.items().__iter__())"
]
},
{
"cell_type": "code",
"execution_count": 133,
"metadata": {},
"outputs": [],
"source": [
"corpus_texts = list(corpus_map.values())\n",
"corpus_ids = [x for x in list(corpus_map.keys())]"
]
},
{
"cell_type": "code",
"execution_count": 134,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"(['Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.',\n",
" 'Induction of myelodysplasia by myeloid-derived suppressor cells. Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.'],\n",
" ['4983', '5836'])"
]
},
"execution_count": 134,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"corpus_texts[:2], corpus_ids[:2]"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"### Get top-k (100) results for scifact test dataset queries using BM25-lucene index"
]
},
{
"cell_type": "code",
"execution_count": 135,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "8652cfec18e6416e87e63432a53d7e66",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/5183 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"name": "stderr",
"output_type": "stream",
"text": [
"DEBUG:bm25s:Building index from IDs objects\n"
]
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "02bdcb28e0d84bdda0bd19d5edebb841",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Count Tokens: 0%| | 0/5183 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "2b7ac6c820ff4fd8a3ceda39daa07893",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Compute Scores: 0%| | 0/5183 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"# Create and index the BM25 model\n",
"retriever = BM25HF(corpus=corpus_texts)\n",
"retriever.index(bm25s.tokenize(corpus_texts))"
]
},
{
"cell_type": "code",
"execution_count": 189,
"metadata": {},
"outputs": [],
"source": [
"from rerankers.results import Result\n",
"from rerankers.documents import Document"
]
},
{
"cell_type": "code",
"execution_count": 192,
"metadata": {},
"outputs": [],
"source": [
"# rinspect(Document, help=True)"
]
},
{
"cell_type": "code",
"execution_count": 190,
"metadata": {},
"outputs": [
{
"name": "stdout",
"output_type": "stream",
"text": [
"text='4983' doc_id='Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging. Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.' metadata=None\n",
"text='5836' doc_id='Induction of myelodysplasia by myeloid-derived suppressor cells. Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.' metadata=None\n"
]
}
],
"source": [
"for doc_id in corpus_ids[:2]:\n",
" doc_text = corpus_map[doc_id]\n",
" doc = Document(doc_id, doc_text)\n",
" print(doc)"
]
},
{
"cell_type": "code",
"execution_count": 191,
"metadata": {},
"outputs": [],
"source": [
"from typing import List\n",
"from rerankers.documents import Document\n",
"docs: List[Document] = [Document(doc_id, corpus_map[doc_id]) for doc_id in corpus_ids]"
]
},
{
"cell_type": "code",
"execution_count": 195,
"metadata": {},
"outputs": [],
"source": [
"# rinspect(Result, help=True)"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "180241b2b2d941f0a4e214221bac4267",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "edd8e27057014de1a97e31f68b606bff",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Retrieve: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"text/plain": [
"(array([['40212412', '43385013']], dtype='<U8'),\n",
" array([[3.8886156, 3.8745685]], dtype=float32))"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"query = queries[0]['text']\n",
"results, scores = retriever.retrieve(bm25s.tokenize(query), corpus=corpus_ids, k=2)\n",
"Result()\n",
"for idx, result in enumerate(results[0])\n",
"results, scores"
]
},
{
"cell_type": "code",
"execution_count": 200,
"metadata": {},
"outputs": [],
"source": [
"from typing import Dict\n",
"# Function to retrieve the top 100 results\n",
"def get_top_100(query, retriever, corpus_ids)->Dict[str, float]:\n",
" tokenized_query = bm25s.tokenize(query)\n",
" results, scores = retriever.retrieve(tokenized_query, corpus=corpus_ids, k=100, show_progress=False, leave_progress=False)\n",
" return {str(doc_id): float(score) for doc_id, score in zip(results[0], scores[0])}\n",
" # return results[0].tolist()"
]
},
{
"cell_type": "code",
"execution_count": 137,
"metadata": {},
"outputs": [
{
"data": {
"text/html": [
"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭────────────────── </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">bound</span><span style=\"color: #000000; text-decoration-color: #000000\"> method BM25.retrieve of &lt;bm25s.hf.BM25HF object at </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0x7fec4cf08fd0</span><span style=\"color: #000000; text-decoration-color: #000000\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080\"> ───────────────────╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #00ffff; text-decoration-color: #00ffff; font-style: italic\">def </span><span style=\"color: #800000; text-decoration-color: #800000; font-weight: bold\">BM25.retrieve</span><span style=\"font-weight: bold\">(</span>query_tokens: Union<span style=\"font-weight: bold\">[</span>List<span style=\"font-weight: bold\">[</span>List<span style=\"font-weight: bold\">[</span>str<span style=\"font-weight: bold\">]]</span>, bm25s.tokenization.Tokenized<span style=\"font-weight: bold\">]</span>, corpus: List<span style=\"font-weight: bold\">[</span>Any<span style=\"font-weight: bold\">]</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> k: int = <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">10</span>, sorted: bool = <span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span>, return_as: str = <span style=\"color: #008000; text-decoration-color: #008000\">'tuple'</span>, show_progress: bool = <span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span>, leave_progress: bool = <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #ff0000; text-decoration-color: #ff0000; font-style: italic\">False</span>, n_threads: int = <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0</span>, chunksize: int = <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">50</span>, backend_selection: str = <span style=\"color: #008000; text-decoration-color: #008000\">'auto'</span><span style=\"font-weight: bold\">)</span>: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">Retrieve the top-k documents for each query </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">tokenized</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span><span style=\"color: #008080; text-decoration-color: #008080\">.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">Parameters</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">----------</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">query_tokens : List</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">[</span><span style=\"color: #008080; text-decoration-color: #008080\">List</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">[</span><span style=\"color: #008080; text-decoration-color: #008080\">str</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">]]</span><span style=\"color: #008080; text-decoration-color: #008080\"> or bm25s.tokenization.Tokenized</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> List of list of tokens for each query. If a Tokenized object is provided,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> it will be converted to a list of list of tokens.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">corpus : List</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">[</span><span style=\"color: #008080; text-decoration-color: #008080\">str</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">]</span><span style=\"color: #008080; text-decoration-color: #008080\"> or np.ndarray</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> List of </span><span style=\"color: #008000; text-decoration-color: #008000\">\"documents\"</span><span style=\"color: #008080; text-decoration-color: #008080\"> or a numpy array of documents. If provided, the function</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> will return the documents instead of the indices. You do not have to provide</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> the original documents </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">for example, you can provide the unique IDs of the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> documents here and then retrieve the actual documents from another source</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span><span style=\"color: #008080; text-decoration-color: #008080\">.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">k : int</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> Number of documents to retrieve for each query.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">batch_size : int</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> Number of queries to process in each batch. Internally, the function will</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> process the queries in batches to speed up the computation.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">sorted : bool</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span><span style=\"color: #008080; text-decoration-color: #008080\">, the function will sort the results by score before returning them.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">return_as : str</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #808000; text-decoration-color: #808000\">return_as</span><span style=\"color: #008080; text-decoration-color: #008080\">=</span><span style=\"color: #008000; text-decoration-color: #008000\">\"tuple\"</span><span style=\"color: #008080; text-decoration-color: #008080\">, a named tuple with two fields will be returned:</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> `documents` and `scores`, which can be accessed as `result.documents` and</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> `result.scores`, or by unpacking, e.g. `documents, scores = </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">retrieve</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #808000; text-decoration-color: #808000\">...</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span><span style=\"color: #008080; text-decoration-color: #008080\">`.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #808000; text-decoration-color: #808000\">return_as</span><span style=\"color: #008080; text-decoration-color: #008080\">=</span><span style=\"color: #008000; text-decoration-color: #008000\">\"documents\"</span><span style=\"color: #008080; text-decoration-color: #008080\">, only the retrieved documents </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">(</span><span style=\"color: #008080; text-decoration-color: #008080\">or indices if `corpus`</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> is not provided</span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">)</span><span style=\"color: #008080; text-decoration-color: #008080\"> will be returned.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">show_progress : bool</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span><span style=\"color: #008080; text-decoration-color: #008080\">, a progress bar will be shown. If </span><span style=\"color: #ff0000; text-decoration-color: #ff0000; font-style: italic\">False</span><span style=\"color: #008080; text-decoration-color: #008080\">, no progress bar will be shown.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">leave_progress : bool</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span><span style=\"color: #008080; text-decoration-color: #008080\">, the progress bars will remain after the function completes.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">n_threads : int</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> Number of jobs to run in parallel. If </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">-1</span><span style=\"color: #008080; text-decoration-color: #008080\">, it will use all available CPUs.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0</span><span style=\"color: #008080; text-decoration-color: #008080\">, it will run the jobs sequentially, without using multiprocessing.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">chunksize : int</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> Number of batches to process in each job in the multiprocessing pool.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">backend_selection : str</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> The backend to use for the top-k retrieval. Choose from </span><span style=\"color: #008000; text-decoration-color: #008000\">\"auto\"</span><span style=\"color: #008080; text-decoration-color: #008080\">, </span><span style=\"color: #008000; text-decoration-color: #008000\">\"numpy\"</span><span style=\"color: #008080; text-decoration-color: #008080\">, </span><span style=\"color: #008000; text-decoration-color: #008000\">\"jax\"</span><span style=\"color: #008080; text-decoration-color: #008080\">.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\"> If </span><span style=\"color: #008000; text-decoration-color: #008000\">\"auto\"</span><span style=\"color: #008080; text-decoration-color: #008080\">, it will use JAX if it is available, otherwise it will use numpy.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">27</span><span style=\"font-style: italic\"> attribute(s) not shown.</span> Run <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">inspect</span><span style=\"font-weight: bold\">(</span>inspect<span style=\"font-weight: bold\">)</span> for options. <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯</span>\n",
"</pre>\n"
],
"text/plain": [
"\u001b[34m╭─\u001b[0m\u001b[34m─────────────────\u001b[0m\u001b[34m \u001b[0m\u001b[1;34m<\u001b[0m\u001b[1;95mbound\u001b[0m\u001b[39m method BM25.retrieve of <bm25s.hf.BM25HF object at \u001b[0m\u001b[1;36m0x7fec4cf08fd0\u001b[0m\u001b[39m>\u001b[0m\u001b[1;34m>\u001b[0m\u001b[34m \u001b[0m\u001b[34m──────────────────\u001b[0m\u001b[34m─╮\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;96mdef \u001b[0m\u001b[1;31mBM25.retrieve\u001b[0m\u001b[1m(\u001b[0mquery_tokens: Union\u001b[1m[\u001b[0mList\u001b[1m[\u001b[0mList\u001b[1m[\u001b[0mstr\u001b[1m]\u001b[0m\u001b[1m]\u001b[0m, bm25s.tokenization.Tokenized\u001b[1m]\u001b[0m, corpus: List\u001b[1m[\u001b[0mAny\u001b[1m]\u001b[0m = \u001b[3;35mNone\u001b[0m, \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m k: int = \u001b[1;36m10\u001b[0m, sorted: bool = \u001b[3;92mTrue\u001b[0m, return_as: str = \u001b[32m'tuple'\u001b[0m, show_progress: bool = \u001b[3;92mTrue\u001b[0m, leave_progress: bool = \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;91mFalse\u001b[0m, n_threads: int = \u001b[1;36m0\u001b[0m, chunksize: int = \u001b[1;36m50\u001b[0m, backend_selection: str = \u001b[32m'auto'\u001b[0m\u001b[1m)\u001b[0m: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mRetrieve the top-k documents for each query \u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mtokenized\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mParameters\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m----------\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mquery_tokens : List\u001b[0m\u001b[1;36m[\u001b[0m\u001b[36mList\u001b[0m\u001b[1;36m[\u001b[0m\u001b[36mstr\u001b[0m\u001b[1;36m]\u001b[0m\u001b[1;36m]\u001b[0m\u001b[36m or bm25s.tokenization.Tokenized\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m List of list of tokens for each query. If a Tokenized object is provided,\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m it will be converted to a list of list of tokens.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mcorpus : List\u001b[0m\u001b[1;36m[\u001b[0m\u001b[36mstr\u001b[0m\u001b[1;36m]\u001b[0m\u001b[36m or np.ndarray\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m List of \u001b[0m\u001b[32m\"documents\"\u001b[0m\u001b[36m or a numpy array of documents. If provided, the function\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m will return the documents instead of the indices. You do not have to provide\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m the original documents \u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mfor example, you can provide the unique IDs of the\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m documents here and then retrieve the actual documents from another source\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mk : int\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m Number of documents to retrieve for each query.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mbatch_size : int\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m Number of queries to process in each batch. Internally, the function will\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m process the queries in batches to speed up the computation.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36msorted : bool\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[3;92mTrue\u001b[0m\u001b[36m, the function will sort the results by score before returning them.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mreturn_as : str\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[33mreturn_as\u001b[0m\u001b[36m=\u001b[0m\u001b[32m\"tuple\"\u001b[0m\u001b[36m, a named tuple with two fields will be returned:\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m `documents` and `scores`, which can be accessed as `result.documents` and\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m `result.scores`, or by unpacking, e.g. `documents, scores = \u001b[0m\u001b[1;35mretrieve\u001b[0m\u001b[1;36m(\u001b[0m\u001b[33m...\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m`.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[33mreturn_as\u001b[0m\u001b[36m=\u001b[0m\u001b[32m\"documents\"\u001b[0m\u001b[36m, only the retrieved documents \u001b[0m\u001b[1;36m(\u001b[0m\u001b[36mor indices if `corpus`\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m is not provided\u001b[0m\u001b[1;36m)\u001b[0m\u001b[36m will be returned.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mshow_progress : bool\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[3;92mTrue\u001b[0m\u001b[36m, a progress bar will be shown. If \u001b[0m\u001b[3;91mFalse\u001b[0m\u001b[36m, no progress bar will be shown.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mleave_progress : bool\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[3;92mTrue\u001b[0m\u001b[36m, the progress bars will remain after the function completes.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mn_threads : int\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m Number of jobs to run in parallel. If \u001b[0m\u001b[1;36m-1\u001b[0m\u001b[36m, it will use all available CPUs.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[1;36m0\u001b[0m\u001b[36m, it will run the jobs sequentially, without using multiprocessing.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mchunksize : int\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m Number of batches to process in each job in the multiprocessing pool.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mbackend_selection : str\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m The backend to use for the top-k retrieval. Choose from \u001b[0m\u001b[32m\"auto\"\u001b[0m\u001b[36m, \u001b[0m\u001b[32m\"numpy\"\u001b[0m\u001b[36m, \u001b[0m\u001b[32m\"jax\"\u001b[0m\u001b[36m.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36m If \u001b[0m\u001b[32m\"auto\"\u001b[0m\u001b[36m, it will use JAX if it is available, otherwise it will use numpy.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[1;36m27\u001b[0m\u001b[3m attribute(s) not shown.\u001b[0m Run \u001b[1;35minspect\u001b[0m\u001b[1m(\u001b[0minspect\u001b[1m)\u001b[0m for options. \u001b[34m│\u001b[0m\n",
"\u001b[34m╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯\u001b[0m\n"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"rinspect(retriever.retrieve, help=True)"
]
},
{
"cell_type": "code",
"execution_count": 139,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"array(['40212412', '43385013'], dtype='<U8')"
]
},
"execution_count": 139,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"results[0]"
]
},
{
"cell_type": "code",
"execution_count": 140,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "5579dec5696540f19c687e922fe87550",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "e09a92583aa847fb8a80b58819c3a754",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"BM25S Retrieve: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"text/plain": [
"(array([[\"Periosteal bone formation--a neglected determinant of bone strength. Life forms that have low body mass can hunt for food on the undersurface of branches or along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for dinner and the struggle to avoid becoming someone else's meal require rapid movement against gravity. This need is met by the lever function of long bones, three-dimensional masterpieces of biomechanical engineering that, by their material composition and structural design, achieve the contradictory properties of stiffness and flexibility, strength and lightness.1 Material stiffness results from the encrusting of the triple-helical structure of collagen type I with hydroxyapatite crystals, which confers . . .\",\n",
" 'Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties. It has been proposed that epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin-low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal-like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation (\"EpCAM+,\" epithelial cell adhesion molecule positive [EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells (\"Fibros,\" EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three-dimensional acini-like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene expression profiling meta-analysis established that EpCAM+ cells show a luminal progenitor-like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal-like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial differentiation.']],\n",
" dtype='<U2097'),\n",
" array([[3.8886156, 3.8745685]], dtype=float32))"
]
},
"execution_count": 140,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"query = queries[0]['text']\n",
"results, scores = retriever.retrieve(bm25s.tokenize(query), k=2)\n",
"results, scores"
]
},
{
"cell_type": "code",
"execution_count": 141,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"array([\"Periosteal bone formation--a neglected determinant of bone strength. Life forms that have low body mass can hunt for food on the undersurface of branches or along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for dinner and the struggle to avoid becoming someone else's meal require rapid movement against gravity. This need is met by the lever function of long bones, three-dimensional masterpieces of biomechanical engineering that, by their material composition and structural design, achieve the contradictory properties of stiffness and flexibility, strength and lightness.1 Material stiffness results from the encrusting of the triple-helical structure of collagen type I with hydroxyapatite crystals, which confers . . .\",\n",
" 'Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties. It has been proposed that epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin-low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal-like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation (\"EpCAM+,\" epithelial cell adhesion molecule positive [EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells (\"Fibros,\" EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three-dimensional acini-like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene expression profiling meta-analysis established that EpCAM+ cells show a luminal progenitor-like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal-like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial differentiation.'],\n",
" dtype='<U2097')"
]
},
"execution_count": 141,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"results[0]"
]
},
{
"cell_type": "code",
"execution_count": 202,
"metadata": {},
"outputs": [
{
"data": {
"application/vnd.jupyter.widget-view+json": {
"model_id": "a7f3883d35d847f8a954b4557b664cbf",
"version_major": 2,
"version_minor": 0
},
"text/plain": [
"Split strings: 0%| | 0/1 [00:00<?, ?it/s]"
]
},
"metadata": {},
"output_type": "display_data"
},
{
"data": {
"text/plain": [
"('40212412', 3.888615608215332)"
]
},
"execution_count": 202,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"top_100_sample = get_top_100(queries[0]['text'], retriever, corpus_ids)\n",
"next(iter(top_100_sample.items()))"
]
},
{
"cell_type": "code",
"execution_count": null,
"metadata": {},
"outputs": [],
"source": [
"from tqdm import tqdm\n",
"# Retrieve the top 100 for each query\n",
"top_100 = {}\n",
"for q in tqdm(queries):\n",
" top_100[q['_id']]=get_top_100(query=q['text'], retriever=retriever, corpus_ids=corpus_ids)\n"
]
},
{
"cell_type": "code",
"execution_count": 197,
"metadata": {},
"outputs": [],
"source": [
"# next(iter(top_100.items()))"
]
},
{
"cell_type": "code",
"execution_count": 204,
"metadata": {},
"outputs": [],
"source": [
"qrels_dict = dict(qrels)"
]
},
{
"cell_type": "code",
"execution_count": 210,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"('1', {'31715818': 1})"
]
},
"execution_count": 210,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"next(iter(qrels_dict.items()))"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"### BM25 Baseline"
]
},
{
"cell_type": "code",
"execution_count": 213,
"metadata": {},
"outputs": [],
"source": [
"queries = [q for q in queries if q['_id'] in qrels_dict]\n",
"bm25_baseline_run = Run(run=top_100, name='bm25_baseline')"
]
},
{
"cell_type": "code",
"execution_count": 211,
"metadata": {},
"outputs": [],
"source": [
"from ranx import evaluate"
]
},
{
"cell_type": "code",
"execution_count": 214,
"metadata": {},
"outputs": [],
"source": [
"eval_scores = evaluate(qrels=qrels_dict, run=bm25_baseline_run, metrics=['recall@10', 'hit_rate@10', 'ndcg@10'])"
]
},
{
"cell_type": "code",
"execution_count": 215,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"{'recall@10': np.float64(0.7739444444444444),\n",
" 'hit_rate@10': np.float64(0.7966666666666666),\n",
" 'ndcg@10': np.float64(0.6616913885341652)}"
]
},
"execution_count": 215,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"eval_scores"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"### FlashRank reranker"
]
},
{
"cell_type": "code",
"execution_count": 216,
"metadata": {},
"outputs": [
{
"name": "stdout",
"output_type": "stream",
"text": [
"Loading default flashrank model for language en\n",
"Default Model: ms-marco-MiniLM-L-12-v2\n",
"Loading FlashRankRanker model ms-marco-MiniLM-L-12-v2\n",
"Loading model FlashRank model ms-marco-MiniLM-L-12-v2...\n"
]
}
],
"source": [
"queries = [q for q in queries if q['_id'] in qrels_dict]\n",
"from tqdm import tqdm\n",
"\n",
"ranker = Reranker('flashrank')"
]
},
{
"cell_type": "code",
"execution_count": 145,
"metadata": {},
"outputs": [
{
"data": {
"text/html": [
"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭─ </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">bound</span><span style=\"color: #000000; text-decoration-color: #000000\"> method FlashRankRanker.rank of &lt;rerankers.models.flashrank_ranker.FlashRankRanker object at </span><span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0x7fec4cf6b</span><span style=\"color: #000080; text-decoration-color: #000080\">─╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #00ffff; text-decoration-color: #00ffff; font-style: italic\">def </span><span style=\"color: #800000; text-decoration-color: #800000; font-weight: bold\">FlashRankRanker.rank</span><span style=\"font-weight: bold\">(</span>query: str, docs: Union<span style=\"font-weight: bold\">[</span>str, List<span style=\"font-weight: bold\">[</span>str<span style=\"font-weight: bold\">]</span>, rerankers.documents.Document, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> List<span style=\"font-weight: bold\">[</span>rerankers.documents.Document<span style=\"font-weight: bold\">]]</span>, doc_ids: Union<span style=\"font-weight: bold\">[</span>List<span style=\"font-weight: bold\">[</span>str<span style=\"font-weight: bold\">]</span>, List<span style=\"font-weight: bold\">[</span>int<span style=\"font-weight: bold\">]</span>, NoneType<span style=\"font-weight: bold\">]</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span>, metadata: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> Optional<span style=\"font-weight: bold\">[</span>List<span style=\"font-weight: bold\">[</span>dict<span style=\"font-weight: bold\">]]</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span><span style=\"font-weight: bold\">)</span> -&gt; rerankers.results.RankedResults: <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080\">End-to-end reranking of documents.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">27</span><span style=\"font-style: italic\"> attribute(s) not shown.</span> Run <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">inspect</span><span style=\"font-weight: bold\">(</span>inspect<span style=\"font-weight: bold\">)</span> for options. <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯</span>\n",
"</pre>\n"
],
"text/plain": [
"\u001b[34m╭─\u001b[0m\u001b[34m \u001b[0m\u001b[1;34m<\u001b[0m\u001b[1;95mbound\u001b[0m\u001b[39m method FlashRankRanker.rank of <rerankers.models.flashrank_ranker.FlashRankRanker object at \u001b[0m\u001b[1;36m0x7fec4cf6b\u001b[0m\u001b[34m─╮\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[3;96mdef \u001b[0m\u001b[1;31mFlashRankRanker.rank\u001b[0m\u001b[1m(\u001b[0mquery: str, docs: Union\u001b[1m[\u001b[0mstr, List\u001b[1m[\u001b[0mstr\u001b[1m]\u001b[0m, rerankers.documents.Document, \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m List\u001b[1m[\u001b[0mrerankers.documents.Document\u001b[1m]\u001b[0m\u001b[1m]\u001b[0m, doc_ids: Union\u001b[1m[\u001b[0mList\u001b[1m[\u001b[0mstr\u001b[1m]\u001b[0m, List\u001b[1m[\u001b[0mint\u001b[1m]\u001b[0m, NoneType\u001b[1m]\u001b[0m = \u001b[3;35mNone\u001b[0m, metadata: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m Optional\u001b[1m[\u001b[0mList\u001b[1m[\u001b[0mdict\u001b[1m]\u001b[0m\u001b[1m]\u001b[0m = \u001b[3;35mNone\u001b[0m\u001b[1m)\u001b[0m -> rerankers.results.RankedResults: \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[36mEnd-to-end reranking of documents.\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[34m│\u001b[0m\n",
"\u001b[34m│\u001b[0m \u001b[1;36m27\u001b[0m\u001b[3m attribute(s) not shown.\u001b[0m Run \u001b[1;35minspect\u001b[0m\u001b[1m(\u001b[0minspect\u001b[1m)\u001b[0m for options. \u001b[34m│\u001b[0m\n",
"\u001b[34m╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯\u001b[0m\n"
]
},
"metadata": {},
"output_type": "display_data"
}
],
"source": [
"rinspect(ranker.rank, help=True)"
]
},
{
"cell_type": "code",
"execution_count": 147,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"[45638119, 8963413, 24341590]"
]
},
"execution_count": 147,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"doc_ids[:3]"
]
},
{
"cell_type": "code",
"execution_count": 148,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"'4983'"
]
},
"execution_count": 148,
"metadata": {},
"output_type": "execute_result"
}
],
"source": [
"next(iter(corpus_map))"
]
},
{
"cell_type": "markdown",
"metadata": {},
"source": [
"Check if the reranker works using the first 10 queries"
]
},
{
"cell_type": "code",
"execution_count": 150,
"metadata": {},
"outputs": [
{
"name": "stderr",
"output_type": "stream",
"text": [
"100%|██████████| 10/10 [00:56<00:00, 5.61s/it]\n"
]
}
],
"source": [
"from rerankers.results import RankedResults\n",
"\n",
"scores = {}\n",
"for q in tqdm(queries[:10]):\n",
" doc_ids = top_100.get(q['_id'])\n",
" docs = [corpus_map[x] for x in doc_ids]\n",
" scores[q['_id']]: RankedResults = ranker.rank(query=q['text'], docs=docs, doc_ids=corpus_ids)\n",
" "
]
},
{
"cell_type": "code",
"execution_count": 152,
"metadata": {},
"outputs": [
{
"data": {
"text/plain": [
"('1',\n",
" RankedResults(results=[Result(document=Document(text=\"Periosteal bone formation--a neglected determinant of bone strength. Life forms that have low body mass can hunt for food on the undersurface of branches or along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for dinner and the struggle to avoid becoming someone else's meal require rapid movement against gravity. This need is met by the lever function of long bones, three-dimensional masterpieces of biomechanical engineering that, by their material composition and structural design, achieve the contradictory properties of stiffness and flexibility, strength and lightness.1 Material stiffness results from the encrusting of the triple-helical structure of collagen type I with hydroxyapatite crystals, which confers . . .\", doc_id='4983', metadata={}), score=0.024103358387947083, rank=1), Result(document=Document(text='Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties. It has been proposed that epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin-low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal-like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation (\"EpCAM+,\" epithelial cell adhesion molecule positive [EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells (\"Fibros,\" EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three-dimensional acini-like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene expression profiling meta-analysis established that EpCAM+ cells show a luminal progenitor-like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal-like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial differentiation.', doc_id='5836', metadata={}), score=0.004422821570187807, rank=2), Result(document=Document(text='Geometry, epistasis, and developmental patterning. Developmental signaling networks are composed of dozens of components whose interactions are very difficult to quantify in an embryo. Geometric reasoning enumerates a discrete hierarchy of phenotypic models with a few composite variables whose parameters may be defined by in vivo data. Vulval development in the nematode Caenorhabditis elegans is a classic model for the integration of two signaling pathways; induction by EGF and lateral signaling through Notch. Existing data for the relative probabilities of the three possible terminal cell types in diverse genetic backgrounds as well as timed ablation of the inductive signal favor one geometric model and suffice to fit most of its parameters. The model is fully dynamic and encompasses both signaling and commitment. It then predicts the correlated cell fate probabilities for a cross between any two backgrounds/conditions. The two signaling pathways are combined additively, without interactions, and epistasis only arises from the nonlinear dynamical flow in the landscape defined by the geometric model. In this way, the model quantitatively fits genetic experiments purporting to show mutual pathway repression. The model quantifies the contributions of extrinsic vs. intrinsic sources of noise in the penetrance of mutant phenotypes in signaling hypomorphs and explains available experiments with no additional parameters. Data for anchor cell ablation fix the parameters needed to define Notch autocrine signaling.', doc_id='7912', metadata={}), score=0.0034973807632923126, rank=3), Result(document=Document(text='Large deformation of red blood cell ghosts in a simple shear flow. Red blood cells are known to change shape in response to local flow conditions. Deformability affects red blood cell physiological function and the hydrodynamic properties of blood. The immersed boundary method is used to simulate three-dimensional membrane-fluid flow interactions for cells with the same internal and external fluid viscosities. The method has been validated for small deformations of an initially spherical capsule in simple shear flow for both neo-Hookean and the Evans-Skalak membrane models. Initially oblate spheroidal capsules are simulated and it is shown that the red blood cell membrane exhibits asymptotic behavior as the ratio of the dilation modulus to the extensional modulus is increased and a good approximation of local area conservation is obtained. Tank treading behavior is observed and its period calculated.', doc_id='18670', metadata={}), score=0.0010757819982245564, rank=4), Result(document=Document(text='The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis. US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human cytomegalovirus and has been shown to both signal and endocytose in a ligand-independent, constitutively active manner. Here we show that the constitutive activity and constitutive endocytosis properties of US28 are separable entities in this viral chemokine receptor. We generated chimeric and mutant US28 proteins that were altered in either their constitutive endocytic (US28 Delta 300, US28 Delta 317, US28-NK1-ctail, and US28-ORF74-ctail) or signaling properties (US28R129A). By using this series of mutants, we show that the cytoplasmic tail domain of US28 per se regulates receptor endocytosis, independent of the signaling ability of the core domain of US28. The constitutive endocytic property of the US28 c-tail was transposable to other 7TM receptors, the herpes virus 8-encoded ORF74 and the tachykinin NK1 receptor (ORF74-US28-ctail and NK1-US28-ctail). Deletion of the US28 C terminus resulted in reduced constitutive endocytosis and consequently enhanced signaling capacity of all receptors tested as assessed by inositol phosphate turnover, NF-kappa B, and cAMP-responsive element-binding protein transcription assays. We further show that the constitutive endocytic property of US28 affects the action of its chemokine ligand fractalkine/CX3CL1 and show that in the absence of the US28 C terminus, fractalkine/CX3CL1 acts as an agonist on US28. This demonstrates for the first time that the endocytic properties of a 7TM receptor can camouflage the agonist properties of a ligand.', doc_id='19238', metadata={}), score=0.0009564738720655441, rank=5), Result(document=Document(text='Cerebral organoids model human brain development and microcephaly The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.', doc_id='33370', metadata={}), score=0.0008705182699486613, rank=6), Result(document=Document(text='From Cell Differentiation to Cell Collectives: Bacillus subtilis Uses Division of Labor to Migrate The organization of cells, emerging from cell-cell interactions, can give rise to collective properties. These properties are adaptive when together cells can face environmental challenges that they separately cannot. One particular challenge that is important for microorganisms is migration. In this study, we show how flagellum-independent migration is driven by the division of labor of two cell types that appear during Bacillus subtilis sliding motility. Cell collectives organize themselves into bundles (called \"van Gogh bundles\") of tightly aligned cell chains that form filamentous loops at the colony edge. We show, by time-course microscopy, that these loops migrate by pushing themselves away from the colony. The formation of van Gogh bundles depends critically on the synergistic interaction of surfactin-producing and matrix-producing cells. We propose that surfactin-producing cells reduce the friction between cells and their substrate, thereby facilitating matrix-producing cells to form bundles. The folding properties of these bundles determine the rate of colony expansion. Our study illustrates how the simple organization of cells within a community can yield a strong ecological advantage. This is a key factor underlying the diverse origins of multicellularity.', doc_id='36474', metadata={}), score=0.0007751494995318353, rank=7), Result(document=Document(text='In situ regulation of DC subsets and T cells mediates tumor regression in mice. Vaccines are largely ineffective for patients with established cancer, as advanced disease requires potent and sustained activation of CD8(+) cytotoxic T lymphocytes (CTLs) to kill tumor cells and clear the disease. Recent studies have found that subsets of dendritic cells (DCs) specialize in antigen cross-presentation and in the production of cytokines, which regulate both CTLs and T regulatory (Treg) cells that shut down effector T cell responses. Here, we addressed the hypothesis that coordinated regulation of a DC network, and plasmacytoid DCs (pDCs) and CD8(+) DCs in particular, could enhance host immunity in mice. We used functionalized biomaterials incorporating various combinations of an inflammatory cytokine, immune danger signal, and tumor lysates to control the activation and localization of host DC populations in situ. The numbers of pDCs and CD8(+) DCs, and the endogenous production of interleukin-12, all correlated strongly with the magnitude of protective antitumor immunity and the generation of potent CD8(+) CTLs. Vaccination by this method maintained local and systemic CTL responses for extended periods while inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete regression of distant and established melanoma tumors. The efficacy of this vaccine as a monotherapy against large invasive tumors may be a result of the local activity of pDCs and CD8(+) DCs induced by persistent danger and antigen signaling at the vaccine site. These results indicate that a critical pattern of DC subsets correlates with the evolution of therapeutic antitumor responses and provide a template for future vaccine design.', doc_id='54440', metadata={}), score=0.0007493325392715633, rank=8), Result(document=Document(text='The effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie. Native mammalian prions exist in self-propagating strains that exhibit distinctive clinical, pathological and biochemical characteristics. Prion strain diversity is associated with variations in PrP(Sc) conformation, but it remains unknown precisely which physical properties of the PrP(Sc) molecules are required to encipher mammalian prion strain phenotypes. In this study, we subjected prion-infected brain homogenates derived from three different hamster scrapie strains to either (i) proteinase K digestion or (ii) sonication, and inoculated the modified samples into normal hamsters. The results show that the strain-specific clinical features and neuropathological profiles of inoculated animals were not affected by either treatment. Similarly, the strain-dependent biochemical characteristics of the PrP(Sc) molecules (including electrophoretic mobility, glycoform composition, conformational stability and susceptibility to protease digestion) in infected animals were unaffected by either proteolysis or sonication of the original inocula. These results indicate that the infectious strain properties of native prions do not appear to be altered by PrP(Sc) disaggregation, and that maintenance of such properties does not require the N-domain (approximately residues 23-90) of the protease-resistant PrP(Sc) molecules or protease-sensitive PrP(Sc) molecules.', doc_id='70115', metadata={}), score=0.000624156731646508, rank=9), Result(document=Document(text=\"High-performance neuroprosthetic control by an individual with tetraplegia. BACKGROUND Paralysis or amputation of an arm results in the loss of the ability to orient the hand and grasp, manipulate, and carry objects, functions that are essential for activities of daily living. Brain-machine interfaces could provide a solution to restoring many of these lost functions. We therefore tested whether an individual with tetraplegia could rapidly achieve neurological control of a high-performance prosthetic limb using this type of an interface. METHODS We implanted two 96-channel intracortical microelectrodes in the motor cortex of a 52-year-old individual with tetraplegia. Brain-machine-interface training was done for 13 weeks with the goal of controlling an anthropomorphic prosthetic limb with seven degrees of freedom (three-dimensional translation, three-dimensional orientation, one-dimensional grasping). The participant's ability to control the prosthetic limb was assessed with clinical measures of upper limb function. This study is registered with ClinicalTrials.gov, NCT01364480. FINDINGS The participant was able to move the prosthetic limb freely in the three-dimensional workspace on the second day of training. After 13 weeks, robust seven-dimensional movements were performed routinely. Mean success rate on target-based reaching tasks was 91·6% (SD 4·4) versus median chance level 6·2% (95% CI 2·0-15·3). Improvements were seen in completion time (decreased from a mean of 148 s [SD 60] to 112 s [6]) and path efficiency (increased from 0·30 [0·04] to 0·38 [0·02]). The participant was also able to use the prosthetic limb to do skilful and coordinated reach and grasp movements that resulted in clinically significant gains in tests of upper limb function. No adverse events were reported. INTERPRETATION With continued development of neuroprosthetic limbs, individuals with long-term paralysis could recover the natural and intuitive command signals for hand placement, orientation, and reaching, allowing them to perform activities of daily living. FUNDING Defense Advanced Research Projects Agency, National Institutes of Health, Department of Veterans Affairs, and UPMC Rehabilitation Institute.\", doc_id='70490', metadata={}), score=0.0006221356452442706, rank=10), Result(document=Document(text=\"Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia. BACKGROUND Microfluidic platforms for quantitative evaluation of cell biologic processes allow low cost and time efficient research studies of biological and pathological events, such as monitoring cell migration by real-time imaging. In healthy and disease states, cell migration is crucial in development and wound healing, as well as to maintain the body's homeostasis. NEW METHOD The microfluidic chambers allow precise measurements to investigate whether fibroblasts carrying a mutation in the TOR1A gene, underlying the hereditary neurologic disease--DYT1 dystonia, have decreased migration properties when compared to control cells. RESULTS We observed that fibroblasts from DYT1 patients showed abnormalities in basic features of cell migration, such as reduced velocity and persistence of movement. COMPARISON WITH EXISTING METHOD The microfluidic method enabled us to demonstrate reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside the moving DYT1 patient cells compared to control cells, as well as vectorial movement of single cells. CONCLUSION We report here different assays useful in determining various parameters of cell migration in DYT1 patient cells as a consequence of the TOR1A gene mutation, including a microfluidic platform, which provides a means to evaluate real-time vectorial movement with single cell resolution in a three-dimensional environment.\", doc_id='72159', metadata={}), score=0.0005953511572442949, rank=11), Result(document=Document(text='Mechanical modulation of receptor-ligand interactions at cell-cell interfaces. Cell surface receptors have been extensively studied because they initiate and regulate signal transduction cascades leading to a variety of functional cellular outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose ligands are anchored to the surfaces of other cells remain poorly understood. The mechanism by which ligand binding initiates receptor phosphorylation, a process termed \"receptor triggering\", remains controversial. Recently, direct measurements of the (two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found to be smaller than (three-dimensional) lifetimes in solution but the underlying mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose ectodomains span >40 nm and these LSMs include phosphatases (e.g., CD45) that dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear whether the mechanochemistry supports such small-scale segregation. Here we present a nanometer-scale mathematical model that couples membrane elasticity with the compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM redistribution will result in a time-dependent tension on the complex leading to a decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear relationship between the three- and two-dimensional lifetimes, which can enhance the ability of receptors to discriminate between similar ligands.', doc_id='79447', metadata={}), score=0.0005835893680341542, rank=12), Result(document=Document(text='Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis.', doc_id='87758', metadata={}), score=0.0005717248423025012, rank=13), Result(document=Document(text='microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus regulates keratinocyte differentiation. Notch plays a critical role in the transition from proliferation to differentiation in the epidermis and corneal epithelium. Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, nonmelanoma skin cancer, and melanoma where differentiation and proliferation are impaired. Whereas much is known about the downstream events following Notch signaling, factors responsible for negatively regulating Notch receptor signaling after ligand activation are incompletely understood. Notch can undergo hydroxylation by factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological significance of this phenomenon is unclear. Here we show that FIH-1 expression is up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes (HCEKs) impairs differentiation in submerged cultures and in a \"three-dimensional\" organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in vivo increased Notch activity in the limbal epithelium, resulting in a more differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of FIH-1 expression that results in keratinocyte differentiation, mediated by Notch activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial cell line promotes differentiation and recapitulates a corneal epithelium in a three-dimensional raft culture model. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus.', doc_id='92308', metadata={}), score=0.0004151232133153826, rank=14), Result(document=Document(text='Organization of the mitotic chromosome. Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.', doc_id='92499', metadata={}), score=0.000411765999160707, rank=15), Result(document=Document(text='Interleukin 6 plays a key role in the development of antigen-induced arthritis. To investigate the direct role of interleukin (IL) 6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight generations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.', doc_id='97884', metadata={}), score=0.0003154606674797833, rank=16), Result(document=Document(text='Three-Dimensional Modeling and Quantitative Analysis of Gap Junction Distributions in Cardiac Tissue Gap junctions play a fundamental role in intercellular communication in cardiac tissue. Various types of heart disease including hypertrophy and ischemia are associated with alterations of the spatial arrangement of gap junctions. Previous studies applied two-dimensional optical and electron-microscopy to visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were primarily found at cell ends, but can be found also in more central regions. In this study, we extended these approaches toward three-dimensional reconstruction of gap junction distributions based on high-resolution scanning confocal microscopy and image processing. We developed methods for quantitative characterization of gap junction distributions based on analysis of intensity profiles along the principal axes of myocytes. The analyses characterized gap junction polarization at cell ends and higher-order statistical image moments of intensity profiles. The methodology was tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on gap junction distributions. In particular, the analysis demonstrated that the distributions exhibit significant variability with respect to polarization, skewness, and kurtosis. We suggest that this methodology provides a quantitative alternative to current approaches based on visual inspection, with applications in particular in characterization of engineered and diseased myocardium. Furthermore, we propose that these data provide improved input for computational modeling of cardiac conduction.', doc_id='102662', metadata={}), score=0.00025019916938617826, rank=17), Result(document=Document(text='Nanoenzymology of the 20S proteasome: proteasomal actions are controlled by the allosteric transition. The proteasome is a major cytosolic proteolytic assembly, essential for the physiology of eukaryotic cells. Both the architecture and enzymatic properties of the 20S proteasome are relatively well understood. However, despite longstanding interest, the integration of structural and functional properties of the proteasome into a coherent model explaining the mechanism of its enzymatic actions has been difficult. Recently, we used tapping mode atomic force microscopy (AFM) in liquid to demonstrate that the alpha-rings of the proteasome imaged in a top-view position repeatedly switched between their open and closed conformations, apparently to control access to the central channel. Here, we show with AFM that the molecules in a side-view position acquired two stable conformations. The overall shapes of the 20S particles were classified as either barrel-like or cylinder-like. The relative abundance of the two conformers depended on the nature of their interactions with ligands. Similarly to the closed molecules in top view, the barrels predominated in control or inhibited molecules. The cylinders and open molecules prevailed when the proteasome was observed in the presence of peptide substrates. Based on these data, we developed the two-state model of allosteric transitions to explain the dynamics of proteasomal structure. This model helps to better understand the observed properties of the 20S molecule, and sets foundations for further studies of the structural dynamics of the proteasome.', doc_id='103007', metadata={}), score=0.00020507434965111315, rank=18), Result(document=Document(text=\"The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling Histone variants within the H2A family show high divergences in their C-terminal regions. In this work, we have studied how these divergences and in particular, how a part of the H2A COOH-terminus, the docking domain, is implicated in both structural and functional properties of the nucleosome. Using biochemical methods in combination with Atomic Force Microscopy and Electron Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within the nucleosome. Deletion of this domain or replacement with the incomplete docking domain from the variant H2A.Bbd results in significant structural alterations in the nucleosome, including an increase in overall accessibility to nucleases, un-wrapping of ∼10 bp of DNA from each end of the nucleosome and associated changes in the entry/exit angle of DNA ends. These structural alterations are associated with a reduced ability of the chromatin remodeler RSC to both remodel and mobilize the nucleosomes. Linker histone H1 binding is also abrogated in nucleosomes containing the incomplete docking domain of H2A.Bbd. Our data illustrate the unique role of the H2A-docking domain in coordinating the structural-functional aspects of the nucleosome properties. Moreover, our data suggest that incorporation of a 'defective' docking domain may be a primary structural role of H2A.Bbd in chromatin.\", doc_id='104130', metadata={}), score=0.00019022477499675006, rank=19), Result(document=Document(text='Direct observation of ligand recognition by T cells The activation of T cells through interaction of their T-cell receptors with antigenic peptide bound to major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a crucial step in adaptive immunity. Here we use three-dimensional fluorescence microscopy to visualize individual peptide–I-Ek class II MHC complexes labelled with the phycobiliprotein phycoerythrin in an effort to characterize T-cell sensitivity and the requirements for forming an immunological synapse in single cells. We show that T cells expressing the CD4 antigen respond with transient calcium signalling to even a single agonist peptide–MHC ligand, and that the organization of molecules in the contact zone of the T cell and APC takes on the characteristics of an immunological synapse when only about ten agonists are present. This sensitivity is highly dependant on CD4, because blocking this molecule with antibodies renders T cells unable to detect less than about 30 ligands.', doc_id='106301', metadata={}), score=0.00017890066374093294, rank=20), Result(document=Document(text=\"Data analysis methods for detection of differential protein expression in two-dimensional gel electrophoresis. The recent development of microarray technology has led statisticians and bioinformaticians to develop new statistical methodologies for comparing different biological samples. The objective is to identify a small number of differentially expressed genes from among thousands. In quantitative proteomics, analysis of protein expression using two-dimensional gel electrophoresis shows some similarities with transcriptomic studies. Thus, the goal of this study was to evaluate different data analysis methodologies widely used in array analysis using different proteomic data sets of hundreds of proteins. Even with few replications, the significance analysis of microarrays method appeared to be more powerful than the Student's t test in truly declaring differentially expressed proteins. This procedure will avoid wasting time due to false positives and losing information with false negatives.\", doc_id='116792', metadata={}), score=0.00017818412743508816, rank=21), Result(document=Document(text=\"Three-dimensional superresolution colocalization of intracellular protein superstructures and the cell surface in live Caulobacter crescentus. Recently, single-molecule imaging and photocontrol have enabled superresolution optical microscopy of cellular structures beyond Abbe's diffraction limit, extending the frontier of noninvasive imaging of structures within living cells. However, live-cell superresolution imaging has been challenged by the need to image three-dimensional (3D) structures relative to their biological context, such as the cellular membrane. We have developed a technique, termed superresolution by power-dependent active intermittency and points accumulation for imaging in nanoscale topography (SPRAIPAINT) that combines imaging of intracellular enhanced YFP (eYFP) fusions (SPRAI) with stochastic localization of the cell surface (PAINT) to image two different fluorophores sequentially with only one laser. Simple light-induced blinking of eYFP and collisional flux onto the cell surface by Nile red are used to achieve single-molecule localizations, without any antibody labeling, cell membrane permeabilization, or thiol-oxygen scavenger systems required. Here we demonstrate live-cell 3D superresolution imaging of Crescentin-eYFP, a cytoskeletal fluorescent protein fusion, colocalized with the surface of the bacterium Caulobacter crescentus using a double-helix point spread function microscope. Three-dimensional colocalization of intracellular protein structures and the cell surface with superresolution optical microscopy opens the door for the analysis of protein interactions in living cells with excellent precision (20-40 nm in 3D) over a large field of view (12 12 μm).\", doc_id='118568', metadata={}), score=0.00017008179565891623, rank=22), Result(document=Document(text='The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.', doc_id='120626', metadata={}), score=0.00013697220128960907, rank=23), Result(document=Document(text='An integrin β3–KRAS–RalB complex drives tumour stemness and resistance to EGFR inhibition Tumour cells, with stem-like properties, are highly aggressive and often show drug resistance. Here, we reveal that integrin αvβ3 serves as a marker of breast, lung and pancreatic carcinomas with stem-like properties that are highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This was observed in vitro and in mice bearing patient-derived tumour xenografts or in clinical specimens from lung cancer patients who had progressed on erlotinib. Mechanistically, αvβ3, in the unliganded state, recruits KRAS and RalB to the tumour cell plasma membrane, leading to the activation of TBK1 and NF-κB. In fact, αvβ3 expression and the resulting KRAS–RalB–NF-κB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance. Pharmacological targeting of this pathway with bortezomib reversed both tumour stemness and erlotinib resistance. These findings not only identify αvβ3 as a marker/driver of carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to RTK inhibition.', doc_id='123859', metadata={}), score=0.0001302049058722332, rank=24), Result(document=Document(text='An atlas of active enhancers across human cell types and tissues Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.', doc_id='140874', metadata={}), score=0.00012895374675281346, rank=25), Result(document=Document(text='Advances in high-resolution imaging--techniques for three-dimensional imaging of cellular structures. A fundamental goal in biology is to determine how cellular organization is coupled to function. To achieve this goal, a better understanding of organelle composition and structure is needed. Although visualization of cellular organelles using fluorescence or electron microscopy (EM) has become a common tool for the cell biologist, recent advances are providing a clearer picture of the cell than ever before. In particular, advanced light-microscopy techniques are achieving resolutions below the diffraction limit and EM tomography provides high-resolution three-dimensional (3D) images of cellular structures. The ability to perform both fluorescence and electron microscopy on the same sample (correlative light and electron microscopy, CLEM) makes it possible to identify where a fluorescently labeled protein is located with respect to organelle structures visualized by EM. Here, we review the current state of the art in 3D biological imaging techniques with a focus on recent advances in electron microscopy and fluorescence super-resolution techniques.', doc_id='143251', metadata={}), score=0.0001272441731998697, rank=26), Result(document=Document(text='Structural insights into calicivirus attachment and uncoating. The Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary significance. In humans, caliciviruses are a major cause of acute gastroenteritis, while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic disease are documented. Investigation of virus-host interactions is limited by a lack of culture systems for many viruses in this family. Feline calicivirus (FCV), a member of the Vesivirus genus, provides a tractable model, since it may be propagated in cell culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a functional receptor for FCV. We have analyzed the structure of this virus-receptor complex by cryo-electron microscopy and three-dimensional image reconstruction, combined with fitting of homology modeled high-resolution coordinates. We show that domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein VP1, inducing conformational changes in the viral capsid. This study provides the first structural view of a native calicivirus-protein receptor complex and insights into the mechanisms of virus attachment and uncoating.', doc_id='152245', metadata={}), score=0.00012399932893458754, rank=27), Result(document=Document(text=\"CDD: conserved domains and protein three-dimensional structure CDD, the Conserved Domain Database, is part of NCBI's Entrez query and retrieval system and is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD provides annotation of protein sequences with the location of conserved domain footprints and functional sites inferred from these footprints. Pre-computed annotation is available via Entrez, and interactive search services accept single protein or nucleotide queries, as well as batch submissions of protein query sequences, utilizing RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain and full-length protein model collections, and maintains an active curation effort that aims at providing fine grained classifications for major and well-characterized protein domain families, as supported by available protein three-dimensional (3D) structure and the published literature. To this date, the majority of protein 3D structures are represented by models tracked by CDD, and CDD curators are characterizing novel families that emerge from protein structure determination efforts.\", doc_id='153744', metadata={}), score=0.00012311134196352214, rank=28), Result(document=Document(text='2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size. Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.', doc_id='159469', metadata={}), score=0.00011527373862918466, rank=29), Result(document=Document(text='Three-dimensional structure of the AAH26994.1 protein from Mus musculus, a putative eukaryotic Urm1. We have used NMR spectroscopy to determine the solution structure of protein AAH26994.1 from Mus musculus and propose that it represents the first three-dimensional structure of a ubiquitin-related modifier 1 (Urm1) protein. Amino acid sequence comparisons indicate that AAH26994.1 belongs to the Urm1 family of ubiquitin-like modifier proteins. The best characterized member of this family has been shown to be involved in nutrient sensing, invasive growth, and budding in yeast. Proteins in this family have only a weak sequence similarity to ubiquitin, and the structure of AAH26994.1 showed a much closer resemblance to MoaD subunits of molybdopterin synthases (known structures are of three bacterial MoaD proteins with 14%-26% sequence identity to AAH26994.1). The structures of AAH26994.1 and the MoaD proteins each contain the signature ubiquitin secondary structure fold, but all differ from ubiquitin largely in regions outside of this fold. This structural similarity bolsters the hypothesis that ubiquitin and ubiquitin-related proteins evolved from a protein-based sulfide donor system of the molybdopterin synthase type.', doc_id='164189', metadata={}), score=0.00011244910274399444, rank=30), Result(document=Document(text='Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5α/β LL5beta has been identified as a microtubule-anchoring factor that attaches EB1/CLIP-associating protein (CLASP)-bound microtubule plus ends to the cell cortex. In this study, we show that LL5beta and its homologue LL5alpha (LL5s) colocalize with autocrine laminin-5 and its receptors, integrins alpha3beta1 and alpha6beta4, at the basal side of fully polarized epithelial sheets. Depletion of both laminin receptor integrins abolishes the cortical localization of LL5s, whereas LL5 depletion reduces the amount of integrin alpha3 at the basal cell cortex. Activation of integrin alpha3 is sufficient to initiate LL5 accumulation at the cell cortex. LL5s form a complex with the cytoplasmic tails of these integrins, but their interaction might be indirect. Analysis of the three-dimensional distribution of microtubule growth by visualizing EB1-GFP in epithelial sheets in combination with RNA interference reveals that LL5s are required to maintain the density of growing microtubules selectively at the basal cortex. These findings reveal that signaling from laminin-integrin associations attaches microtubule plus ends to the epithelial basal cell cortex.', doc_id='164985', metadata={}), score=0.00011107359023299068, rank=31), Result(document=Document(text='Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. Protoplasmic astrocytes are increasingly thought to interact extensively with neuronal elements in the brain and to influence their activity. Recent reports have also begun to suggest that physiologically, and perhaps functionally, diverse forms of these cells may be present in the CNS. Our current understanding of astrocyte form and distribution is based predominantly on studies that used the astrocytic marker glial fibrillary acidic protein (GFAP) and on studies using metal-impregnation techniques. The prevalent opinion, based on studies using these methods, is that astrocytic processes overlap extensively and primarily share the underlying neuropil. However, both of these techniques have serious shortcomings for visualizing the interactions among these structurally complex cells. In the present study, intracellular injection combined with immunohistochemistry for GFAP show that GFAP delineates only approximately 15% of the total volume of the astrocyte. As a result, GFAP-based images have led to incorrect conclusions regarding the interaction of processes of neighboring astrocytes. To investigate these interactions in detail, groups of adjacent protoplasmic astrocytes in the CA1 stratum radiatum were injected with fluorescent intracellular tracers of distinctive emissive wavelengths and analyzed using three-dimensional (3D) confocal analysis and electron microscopy. Our findings show that protoplasmic astrocytes establish primarily exclusive territories. The knowledge of how the complex morphology of protoplasmic astrocytes affects their 3D relationships with other astrocytes, oligodendroglia, neurons, and vasculature of the brain should have important implications for our understanding of nervous system function.', doc_id='169264', metadata={}), score=0.00010752250091172755, rank=32), Result(document=Document(text='The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes. The Saccharomyces cerevisiae DNA helicase Rrm3p is needed for normal fork progression through >1000 discrete sites scattered throughout the genome. Here we show that replication of all yeast chromosomes was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared similar to wild-type except at known Rrm3p-dependent sites. These data suggest that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult-to-replicate sites. By the criterion of chromatin immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent sites, and moved with the replication fork through both. In addition, Rrm3p interacted with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than being recruited to its sites of action when replication forks stall at these sites, Rrm3p is likely a component of the replication fork apparatus.', doc_id='175735', metadata={}), score=0.00010532455780776218, rank=33), Result(document=Document(text='Corresponding Author: In higher eukaryotes, introns are spliced out of protein-coding mRNAs by the spliceosome, a massive complex comprising five non-coding RNAs (ncRNAs) and about 200 proteins. By comparing the differences between spliceosomal proteins from many basal eukaryotic lineages, it is possible to infer properties of the splicing system in the last common ancestor of extant eukaryotes, the eukaryotic ancestor. We begin with the hypothesis that, similar to intron length (that appears to have increased in multicellular eukaryotes), the spliceosome has increased in complexity throughout eukaryotic evolution. However, examination of the distribution of spliceosomal components indicates that not only was a spliceosome present in the eukaryotic ancestor but it also contained most of the key components found in today\\'s eukaryotes. All the small nuclear ribonucleoproteins (snRNPs) protein components are likely to have been present, as well as many splicing-related proteins. Both major and trans-splicing are likely to have been present, and the spliceosome had already formed links with other cellular processes such as transcription and capping. However, there is no evidence as yet to suggest that minor (U12-dependent) splicing was present in the eukaryotic ancestor. Although the last common ancestor of extant eukaryotes appears to show much of the molecular complexity seen today, we do not, from this work, infer anything of the properties of the earlier \"first eukaryote. \"', doc_id='188911', metadata={}), score=9.985562792280689e-05, rank=34), Result(document=Document(text='High-resolution sperm typing of meiotic recombination in the mouse MHC Ebeta gene. Meiotic crossovers detected by pedigree analysis in the mouse MHC cluster into hotspots. To explore the properties of hotspots, we subjected the class II E(beta) gene to high-resolution sperm crossover analysis. We confirm the presence of a highly localized hotspot 1.0-1.6 kb wide in the second intron of E(beta) and show that it is flanked by DNA which is almost completely recombinationally inert. Mice heterozygous for haplotype s and another MHC haplotype show major haplotype-dependant variation in crossover rate but always the same hotspot, even in crosses including the highly diverged p haplotype. Crossovers in reciprocal orientations occur at similar rates but show different distributions across the hotspot, with the position of centre points in the two orientations shifted on average by 400 bp. This asymmetry results in crossover products showing biased gene conversion in favour of hotspot markers from the non-initiating haplotype, and supports the double-strand break repair model of recombination, with haplotype s as the most efficient crossover initiator. The detailed behaviour of the E(beta) hotspot, including evidence for highly localized recombination initiation, is strikingly similar to human hotspots.', doc_id='195352', metadata={}), score=9.964589844457805e-05, rank=35), Result(document=Document(text='Mechanisms that Specify Promoter Nucleosome Location and Identity The chromatin architecture of eukaryotic gene promoters is generally characterized by a nucleosome-free region (NFR) flanked by at least one H2A.Z variant nucleosome. Computational predictions of nucleosome positions based on thermodynamic properties of DNA-histone interactions have met with limited success. Here we show that the action of the essential RSC remodeling complex in S. cerevisiae helps explain the discrepancy between theory and experiment. In RSC-depleted cells, NFRs shrink such that the average positions of flanking nucleosomes move toward predicted sites. Nucleosome positioning at distinct subsets of promoters additionally requires the essential Myb family proteins Abf1 and Reb1, whose binding sites are enriched in NFRs. In contrast, H2A.Z deposition is dispensable for nucleosome positioning. By regulating H2A.Z deposition using a steroid-inducible protein splicing strategy, we show that NFR establishment is necessary for H2A.Z deposition. These studies suggest an ordered pathway for the assembly of promoter chromatin architecture.', doc_id='202259', metadata={}), score=9.755350038176402e-05, rank=36), Result(document=Document(text=\"Reserves, functional, immunoregulatory, and cytogenetic properties of bone marrow mesenchymal stem cells in patients with myelodysplastic syndromes. Defective hematopoiesis supporting capacity of bone marrow (BM) stroma has been implicated in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this study is to explore whether the BM stroma progenitors, namely the mesenchymal stem cells (MSCs), are primarily affected in MDS by evaluating the reserves, the functional properties, as well as the cytogenetic characteristics, in comparison to BM hematopoietic cells, in patients with de novo MDS (n = 13). The number, differentiation potential toward adipocytes/chondrocytes/osteoblasts and immunosuppressive function in terms of inhibition of mitogen-induced T-cell proliferation did not differ significantly between patient and normal (n = 20) MSCs. Patient MSCs did not show any aberrations in the production of proinflammatory or growth-promoting cytokines and did not harbor the cytogenetic abnormalities present in hematopoietic cells. Occasional patient and normal MSC cultures, however, developed irrelevant chromosomal alterations (trisomies 5 and 7) with uncertain pathophysiologic significance. Compared to controls, patient MSCs displayed impaired proliferative and clonogenic potential through passages that might represent a nonspecific abnormality associated with the chronic inflammatory process present in patients' BM. These data suggest that BM MSCs from MDS patients do not belong to the abnormal clone and do not represent the main cellular source contributing to the inflammatory marrow microenvironment.\", doc_id='207972', metadata={}), score=9.456238331040367e-05, rank=37), Result(document=Document(text='Computational and Statistical Analyses of Amino Acid Usage and Physico-Chemical Properties of the Twelve Late Embryogenesis Abundant Protein Classes Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to play major roles in desiccation tolerance. Little is known about their structure - function relationships because of the scarcity of 3-D structures for LEAPs. The previous building of LEAPdb, a database dedicated to LEAPs from plants and other organisms, led to the classification of 710 LEAPs into 12 non-overlapping classes with distinct properties. Using this resource, numerous physico-chemical properties of LEAPs and amino acid usage by LEAPs have been computed and statistically analyzed, revealing distinctive features for each class. This unprecedented analysis allowed a rigorous characterization of the 12 LEAP classes, which differed also in multiple structural and physico-chemical features. Although most LEAPs can be predicted as intrinsically disordered proteins, the analysis indicates that LEAP class 7 (PF03168) and probably LEAP class 11 (PF04927) are natively folded proteins. This study thus provides a detailed description of the structural properties of this protein family opening the path toward further LEAP structure - function analysis. Finally, since each LEAP class can be clearly characterized by a unique set of physico-chemical properties, this will allow development of software to predict proteins as LEAPs.', doc_id='213017', metadata={}), score=9.174412116408348e-05, rank=38), Result(document=Document(text='Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and mature adipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and human tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, using an original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of delipidation and decreased adipocyte markers associated with the occurrence of an activated state characterized by overexpression of proteases, including matrix metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1β]. In the case of IL-6, we show that it plays a key role in the acquired proinvasive effect by tumor cells. Equally important, we confirm the presence of these modified adipocytes in human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and in vivo evidence that (i) invasive cancer cells dramatically impact surrounding adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific biological features sufficient to be named cancer-associated adipocytes (CAA); and (iii) CAAs modify the cancer cell characteristics/phenotype leading to a more aggressive behavior. Our results strongly support the innovative concept that adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells to promote tumor progression that might be amplified in obese patients.', doc_id='219475', metadata={}), score=9.117244917433709e-05, rank=39), Result(document=Document(text='Three-dimensional chemical imaging of skin using stimulated Raman scattering microscopy Abstract. Stimulated Raman scattering (SRS) microscopy is used to generate structural and chemical three-dimensional images of native skin. We employed SRS microscopy to investigate the microanatomical features of skin and penetration of topically applied materials. Image depth stacks are collected at distinct wavelengths corresponding to vibrational modes of proteins, lipids, and water in the skin. We observed that corneocytes in stratum corneum are grouped together in clusters, 100 to 250 μm in diameter, separated by 10- to 25-μm-wide microanatomical skin-folds called canyons. These canyons occasionally extend down to depths comparable to that of the dermal–epidermal junction below the flat surface regions in porcine and human skin. SRS imaging shows the distribution of chemical species within cell clusters and canyons. Water is predominately located within the cell clusters, and its concentration rapidly increases at the transition from stratum corneum to viable epidermis. Canyons do not contain detectable levels of water and are rich in lipid material. Oleic acid-d34 applied to the skin surface lines the canyons down to a depth of 50 μm below the surface of the skin. This observation could have implications on the evaluation of penetration profiles of bioactive materials measured using traditional methods, such as tape-stripping.', doc_id='226488', metadata={}), score=9.109588427236304e-05, rank=40), Result(document=Document(text='Synaptic islands defined by the territory of a single astrocyte. In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals in vivo. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal dendrites. Together with the recent findings showing that glial Ca2+ signaling is restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain.', doc_id='236204', metadata={}), score=8.361691288882867e-05, rank=41), Result(document=Document(text='A 3D Map of the Yeast Kinetochore Reveals the Presence of Core and Accessory Centromere-Specific Histone The budding yeast kinetochore is ~68 nm in length with a diameter slightly larger than a 25 nm microtubule. The kinetochores from the 16 chromosomes are organized in a stereotypic cluster encircling central spindle microtubules. Quantitative analysis of the inner kinetochore cluster (Cse4, COMA) reveals structural features not apparent in singly attached kinetochores. The cluster of Cse4-containing kinetochores is physically larger perpendicular to the spindle axis relative to the cluster of Ndc80 molecules. If there was a single Cse4 (molecule or nucleosome) at the kinetochore attached to each microtubule plus end, the cluster of Cse4 would appear geometrically identical to Ndc80. Thus, the structure of the inner kinetochore at the surface of the chromosomes remains unsolved. We have used point fluorescence microscopy and statistical probability maps to deduce the two-dimensional mean position of representative components of the yeast kinetochore relative to the mitotic spindle in metaphase. Comparison of the experimental images to three-dimensional architectures from convolution of mathematical models reveals a pool of Cse4 radially displaced from Cse4 at the kinetochore and kinetochore microtubule plus ends. The pool of displaced Cse4 can be experimentally depleted in mRNA processing pat1Δ or xrn1Δ mutants. The peripheral Cse4 molecules do not template outer kinetochore components. This study suggests an inner kinetochore plate at the centromere-microtubule interface in budding yeast and yields information on the number of Ndc80 molecules at the microtubule attachment site.', doc_id='238409', metadata={}), score=7.476454629795626e-05, rank=42), Result(document=Document(text='Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Secreted Wnt proteins influence neural connectivity by regulating axon guidance, dendritic morphogenesis and synapse formation. We report a new role for Wnt and Frizzled proteins in establishing the anteroposterior polarity of the mechanosensory neurons ALM and PLM in C. elegans. Disruption of Wnt signaling leads to a complete inversion of ALM and PLM polarity: the anterior process adopts the length, branching pattern and synaptic properties of the wild-type posterior process, and vice versa. Different but overlapping sets of Wnt proteins regulate neuronal polarity in different body regions. Wnts act directly on PLM via the Frizzled LIN-17. In addition, we show that they are needed for axon branching and anteriorly directed axon growth. We also find that the retromer, a conserved protein complex that mediates transcytosis and endosome-to-Golgi protein trafficking, plays a key role in Wnt signaling. Deletion mutations of retromer subunits cause ALM and PLM polarity, and other Wnt-related defects. We show that retromer protein VPS-35 is required in Wnt-expressing cells and propose that retromer activity is needed to generate a fully active Wnt signal.', doc_id='243694', metadata={}), score=7.436614396283403e-05, rank=43), Result(document=Document(text='Immune complex relay by subcapsular sinus macrophages and non-cognate B cells drives antibody affinity maturation Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, noncognate B cells relayed antigen opsonized by newly produced antibodies from the subcapsular region to the germinal center, and affinity maturation was impaired when this transport process was disrupted. Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity.', doc_id='253672', metadata={}), score=6.547493831021711e-05, rank=44), Result(document=Document(text='Unique response pathways are established by allosteric interactions among nuclear hormone receptors Heterodimerization is a common paradigm among eukaryotic transcription factors. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors, including the thyroid hormone receptor (T3R) and retinoic acid receptor (RAR). This raises the question as to whether these complexes possess dual hormonal responsiveness. We devised a strategy to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. We find that the intrinsic binding properties of RXR are masked in T3R-RXR and RAR-RXR heterodimers. In contrast, RXR is active as a non-DNA-binding cofactor with the NGFI-B/Nurr1 orphan receptors. Heterodimerization of RXR with constitutively active NGFI-B/Nurr1 creates a novel hormone-dependent complex. These findings suggest that allosteric interactions among heterodimers create complexes with unique properties. We suggest that allostery is a critical feature underlying the generation of diversity in hormone response networks.', doc_id='263364', metadata={}), score=6.47211927571334e-05, rank=45), Result(document=Document(text='Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.', doc_id='266641', metadata={}), score=6.296775245573372e-05, rank=46), Result(document=Document(text='sasCIF: an extension of core Crystallographic Information File for SAS Data acquisition packages developed at different small angle scattering facilities use different formats both for raw and processed data storage. To facilitate the data exchange between laboratories, a consensus in the small angle scattering community has been reached on an ASCII format for one-dimensional data which includes a self-describing header containing relevant information about the sample and instrumental conditions followed by raw or reduced data in a tabular form. This format called sasCIF was implemented as an extension of core CIF (Crystallographic Information File) dictionary.', doc_id='275294', metadata={}), score=6.06991998211015e-05, rank=47), Result(document=Document(text='Characterization of the interaction between retinoic acid receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators through structural and fluorescence anisotropy studies. Retinoid receptors (RARs and RXRs) are ligand-activated transcription factors that regulate the transcription of target genes by recruiting coregulator complexes at cognate promoters. To understand the effects of heterodimerization and ligand binding on coactivator recruitment, we solved the crystal structure of the complex between the RARbeta/RXRalpha ligand-binding domain heterodimer, its 9-cis retinoic acid ligand, and an LXXLL-containing peptide (termed NR box 2) derived from the nuclear receptor interaction domain (NID) of the TRAP220 coactivator. In parallel, we measured the binding affinities of the isolated NR box 2 peptide or the full-length NID of the coactivator SRC-1 for retinoid receptors in the presence of various types of ligands. Our correlative analysis of three-dimensional structures and fluorescence data reveals that heterodimerization does not significantly alter the structure of individual subunits or their intrinsic capacity to interact with NR box 2. Similarly, we show that the ability of a protomer to recruit NR box 2 does not vary as a function of the ligand binding status of the partner receptor. In contrast, the strength of the overall association between the heterodimer and the full-length SRC-1 NID is dictated by the combinatorial action of RAR and RXR ligands, the simultaneous presence of the two receptor agonists being required for highest binding affinity. We identified an LXXLL peptide-driven mechanism by which the concerted reorientation of three phenylalanine side chains generates an \"aromatic clamp\" that locks the RXR activation helix H12 in the transcriptionally active conformation. Finally, we show how variations of helix H11-ligand interactions can alter the communication pathway linking helices H11, H12, and the connecting loop L11-12 to the coactivator-binding site. Together, our results reveal molecular and structural features that impact on the ligand-dependent interaction of the RAR/RXR heterodimer with nuclear receptor coactivators.', doc_id='279052', metadata={}), score=6.0122129070805386e-05, rank=48), Result(document=Document(text='Optogenetics reveal delayed afferent synaptogenesis on grafted human-induced pluripotent stem cell-derived neural progenitors. Reprogramming of somatic cells into pluripotency stem cell state has opened new opportunities in cell replacement therapy and disease modeling in a number of neurological disorders. It still remains unknown, however, to what degree the grafted human-induced pluripotent stem cells (hiPSCs) differentiate into a functional neuronal phenotype and if they integrate into the host circuitry. Here, we present a detailed characterization of the functional properties and synaptic integration of hiPSC-derived neurons grafted in an in vitro model of hyperexcitable epileptic tissue, namely organotypic hippocampal slice cultures (OHSCs), and in adult rats in vivo. The hiPSCs were first differentiated into long-term self-renewing neuroepithelial stem (lt-NES) cells, which are known to form primarily GABAergic neurons. When differentiated in OHSCs for 6 weeks, lt-NES cell-derived neurons displayed neuronal properties such as tetrodotoxin-sensitive sodium currents and action potentials (APs), as well as both spontaneous and evoked postsynaptic currents, indicating functional afferent synaptic inputs. The grafted cells had a distinct electrophysiological profile compared to host cells in the OHSCs with higher input resistance, lower resting membrane potential, and APs with lower amplitude and longer duration. To investigate the origin of synaptic afferents to the grafted lt-NES cell-derived neurons, the host neurons were transduced with Channelrhodopsin-2 (ChR2) and optogenetically activated by blue light. Simultaneous recordings of synaptic currents in grafted lt-NES cell-derived neurons using whole-cell patch-clamp technique at 6 weeks after grafting revealed limited synaptic connections from host neurons. Longer differentiation times, up to 24 weeks after grafting in vivo, revealed more mature intrinsic properties and extensive synaptic afferents from host neurons to the lt-NES cell-derived neurons, suggesting that these cells require extended time for differentiation/maturation and synaptogenesis. However, even at this later time point, the grafted cells maintained a higher input resistance. These data indicate that grafted lt-NES cell-derived neurons receive ample afferent input from the host brain. Since the lt-NES cells used in this study show a strong propensity for GABAergic differentiation, the host-to-graft synaptic afferents may facilitate inhibitory neurotransmitter release, and normalize hyperexcitable neuronal networks in brain diseases, for example, such as epilepsy.', doc_id='285794', metadata={}), score=5.704353316104971e-05, rank=49), Result(document=Document(text='Dodecameric structure and ATPase activity of the human TIP48/TIP49 complex. TIP48 and TIP49 are two related and highly conserved eukaryotic AAA(+) proteins with an essential biological function and a critical role in major pathways that are closely linked to cancer. They are found together as components of several highly conserved chromatin-modifying complexes. Both proteins show sequence homology to bacterial RuvB but the nature and mechanism of their biochemical role remain unknown. Recombinant human TIP48 and TIP49 were assembled into a stable high molecular mass equimolar complex and tested for activity in vitro. TIP48/TIP49 complex formation resulted in synergistic increase in ATPase activity but ATP hydrolysis was not stimulated in the presence of single-stranded, double-stranded or four-way junction DNA and no DNA helicase or branch migration activity could be detected. Complexes with catalytic defects in either TIP48 or TIP49 had no ATPase activity showing that both proteins within the TIP48/TIP49 complex are required for ATP hydrolysis. The structure of the TIP48/TIP49 complex was examined by negative stain electron microscopy. Three-dimensional reconstruction at 20 A resolution revealed that the TIP48/TIP49 complex consisted of two stacked hexameric rings with C6 symmetry. The top and bottom rings showed substantial structural differences. Interestingly, TIP48 formed oligomers in the presence of adenine nucleotides, whilst TIP49 did not. The results point to biochemical differences between TIP48 and TIP49, which may explain the structural differences between the two hexameric rings and could be significant for specialised functions that the proteins perform individually.', doc_id='293661', metadata={}), score=5.702128692064434e-05, rank=50), Result(document=Document(text='A core subunit of Polycomb repressive complex 1 is broadly conserved in function but not primary sequence. Polycomb Group (PcG) proteins mediate heritable gene silencing by modifying chromatin structure. An essential PcG complex, PRC1, compacts chromatin and inhibits chromatin remodeling. In Drosophila melanogaster, the intrinsically disordered C-terminal region of PSC (PSC-CTR) mediates these noncovalent effects on chromatin, and is essential for viability. Because the PSC-CTR sequence is poorly conserved, the significance of its effects on chromatin outside of Drosophila was unclear. The absence of folded domains also made it difficult to understand how the sequence of PSC-CTR encodes its function. To determine the mechanistic basis and extent of conservation of PSC-CTR activity, we identified 17 metazoan PSC-CTRs spanning chordates to arthropods, and examined their sequence features and biochemical properties. PSC-CTR sequences are poorly conserved, but are all highly charged and structurally disordered. We show that active PSC-CTRs--which bind DNA tightly and inhibit chromatin remodeling efficiently--are distinguished from less active ones by the absence of extended negatively charged stretches. PSC-CTR activity can be increased by dispersing its contiguous negative charge, confirming the importance of this property. Using the sequence properties defined as important for PSC-CTR activity, we predicted the presence of active PSC-CTRs in additional diverse genomes. Our analysis reveals broad conservation of PSC-CTR activity across metazoans. This conclusion could not have been determined from sequence alignments. We further find that plants that lack active PSC-CTRs instead possess a functionally analogous PcG protein, EMF1. Thus, our study suggests that a disordered domain with dispersed negative charges underlies PRC1 activity, and is conserved across metazoans and plants.', doc_id='301838', metadata={}), score=5.444479393190704e-05, rank=51), Result(document=Document(text='A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Epidermal growth factor receptor (EGFR) and HER3 each form heterodimers with HER2 and have independently been implicated as key coreceptors that drive HER2-amplified breast cancer. Some studies suggest a dominant role for EGFR, a notion of renewed interest given the development of dual HER2/EGFR small-molecule inhibitors. Other studies point to HER3 as the primary coreceptor. To clarify the relative contributions of EGFR and HER3 to HER2 signaling, we studied receptor knockdown via small interfering RNA technology across a panel of six HER2-overexpressing cell lines. Interestingly, HER3 was as critical as HER2 for maintaining cell proliferation in most cell lines, whereas EGFR was dispensable. Induction of HER3 knockdown in the HER2-overexpressing BT474M1 cell line was found to inhibit growth in three-dimensional culture and induce rapid tumor regression of in vivo xenografts. Furthermore, preferential phosphorylation of HER3, but not EGFR, was observed in HER2-amplified breast cancer tissues. Given these data suggesting HER3 as an important therapeutic target, we examined the activity of pertuzumab, a HER2 antibody that inhibits HER3 signaling by blocking ligand-induced HER2/HER3 heterodimerization. Pertuzumab inhibited ligand-dependent morphogenesis in three-dimensional culture and induced tumor regression in the heregulin-dependent MDA-MB-175 xenograft model. Importantly, these activities of pertuzumab were distinct from those of trastuzumab, a monoclonal antibody currently used for treatment of HER2-amplified breast cancer patients. Our data suggest that inhibition of HER3 may be more clinically relevant than inhibition of EGFR in HER2-amplified breast cancer and also suggest that adding pertuzumab to trastuzumab may augment therapeutic benefit by blocking HER2/HER3 signaling.', doc_id='301866', metadata={}), score=5.191130912862718e-05, rank=52), Result(document=Document(text='A three-dimensional cell biology model of human hepatocellular carcinoma in vitro We established an in vitro 3-D model of metastatic hepatocellular carcinoma (HCC) by culturing MHCC97H cells on molecular scaffolds within a rotating wall vessel bioreactor. Morphological and biochemical analyses revealed that the 3-D HCC model mirrored many clinical pathological features of HCC in vivo, including cancer cell morphology, tissue ultrastructure, protein production and secretion, glucose metabolism, tissue-specific gene expression, and apoptosis. Xenografts into livers of nude mice resulted in tumorigenesis and distant metastasis. This 3-D HCC spheroid is a promising model for HCC tumor biology, anticancer drug screening, and for the establishment of HCC animal models.', doc_id='306006', metadata={}), score=5.150652214069851e-05, rank=53), Result(document=Document(text=\"Nicotinic Acid Adenine Dinucleotide 2'-Phosphate (NAADP) Binding Proteins in T-Lymphocytes. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a messenger that regulates calcium release from intracellular acidic stores. Although several channels, including two-pore channels (TPC), ryanodine receptor (RYR) and mucolipin (TRP-ML1) have been implicated in NAADP regulation of calcium signaling, the NAADP receptor has not been identified. In this study, the photoaffinity probe, [32P]-5-azido-NAADP ([32P]-5-N3-NAADP), was used to study NAADP binding proteins in extracts from NAADP responsive Jurkat T-lymphocytes. [32P]-5-N3-NAADP photolabeling of Jurkat S100 cytosolic fractions resulted in the labeling of at least ten distinct proteins. Several of these S100 proteins, including a doublet at 22/23 kDa and small protein at 15 kDa displayed selectivity for NAADP as the labeling was protected by inclusion of unlabeled NAADP, whereas the structurally similar NADP required much higher concentrations for protection. Interestingly, the labeling of several S100 proteins (60, 45, 33 and 28 kDa) was stimulated by low concentrations of unlabeled NAADP, but not by NADP. The effect of NAADP on the labeling of the 60 kDa protein was biphasic, peaking at 100 nM with a five-fold increase and displaying no change at 1 µM NAADP. Several proteins were also photolabeled when the P100 membrane fraction from Jurkat cells was examined. Similar to the results with S100, a 22/23 kDa doublet and a 15 kDa protein appeared to be selectively labeled. NAADP did not increase the labeling of any P100 proteins as it did in the S100 fraction. The photolabeled S100 and P100 proteins were successfully resolved by two-dimensional gel electrophoresis. [32P]-5-N3-NAADP photolabeling and two-dimensional electrophoresis should represent a suitable strategy in which to identify and characterize NAADP binding proteins.\", doc_id='306311', metadata={}), score=4.9371348723070696e-05, rank=54), Result(document=Document(text='RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. L-glutamate, the principal excitatory transmitter in the brain, gates ion channels mediating fast neurotransmission. Subunit components of two related classes of glutamate receptor channels have been characterized by cDNA cloning and shown to carry either an arginine or a glutamine residue in a defined position of their putative channel-forming segment. The arginine residue in this segment profoundly alters, and dominates, the properties of ion flow, as demonstrated for one channel class. We now show that the genomic DNA sequences encoding the particular channel segment of all subunits harbor a glutamine codon (CAG), even though an arginine codon (CGG) is found in mRNAs of three subunits. Multiple genes and alternative exons were excluded as sources for the arginine codon; hence, we propose that transcripts for three subunits are altered by RNA editing. This process apparently edits subunit transcripts of the two glutamate receptor classes with different efficiency and selectivity.', doc_id='308862', metadata={}), score=4.8481608246220276e-05, rank=55), Result(document=Document(text='ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Application of stem cell biology to breast cancer research has been limited by the lack of simple methods for identification and isolation of normal and malignant stem cells. Utilizing in vitro and in vivo experimental systems, we show that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. These cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell fraction, capable of self-renewal and of generating tumors that recapitulate the heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression of ALDH1 detected by immunostaining correlated with poor prognosis. These findings offer an important new tool for the study of normal and malignant breast stem cells and facilitate the clinical application of stem cell concepts.', doc_id='313394', metadata={}), score=4.7295216063503176e-05, rank=56), Result(document=Document(text='BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells. Several components of the Wnt signaling cascade have been shown to function either as tumor suppressor proteins or as oncogenes in multiple human cancers, underscoring the relevance of this pathway in oncogenesis and the need for further investigation of Wnt signaling components as potential targets for cancer therapy. Here, using expression profiling analysis as well as in vitro and in vivo functional studies, we show that the Wnt pathway component BCL9 is a novel oncogene that is aberrantly expressed in human multiple myeloma as well as colon carcinoma. We show that BCL9 enhances beta-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases cell proliferation, migration, invasion, and the metastatic potential of tumor cells by promoting loss of epithelial and gain of mesenchymal-like phenotype. Most importantly, BCL9 knockdown significantly increased the survival of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis through down-regulation of c-Myc, cyclin D1, CD44, and vascular endothelial growth factor expression by tumor cells. Together, these findings suggest that deregulation of BCL9 is an important contributing factor to tumor progression. The pleiotropic roles of BCL9 reported in this study underscore its value as a drug target for therapeutic intervention in several malignancies associated with aberrant Wnt signaling.', doc_id='313403', metadata={}), score=4.665535016101785e-05, rank=57), Result(document=Document(text='Accurate coarse-grained modeling of red blood cells. We develop a systematic coarse-graining procedure for modeling red blood cells (RBCs) using arguments based on mean-field theory. The three-dimensional RBC membrane model takes into account the bending energy, in-plane shear energy, and constraints of fixed surface area and fixed enclosed volume. The coarse-graining procedure is general, it can be used for arbitrary level of coarse-graining and does not employ any fitting parameters. The sensitivity of the coarse-grained model is investigated and its behavior is validated against available experimental data and in dissipative particle dynamics (DPD) simulations of RBCs in capillary and shear flows.', doc_id='317204', metadata={}), score=4.662750507122837e-05, rank=58), Result(document=Document(text=\"PICH: a DNA translocase specially adapted for processing anaphase bridge DNA. The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins, including the Bloom's syndrome protein (BLM). However, very little is known about the function of PICH or how it is recruited to UFBs. Using a combination of microfluidics, fluorescence microscopy, and optical tweezers, we have defined the properties of PICH in an in vitro model of an anaphase bridge. We show that PICH binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent protein translocation and extension of the DNA. Most strikingly, the affinity of PICH for binding DNA increases with tension-induced DNA stretching, which mimics the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish force-induced DNA melting. We propose a model in which PICH recognizes and stabilizes DNA under tension during anaphase, thereby facilitating the resolution of entangled sister chromatids.\", doc_id='323030', metadata={}), score=4.601478576660156e-05, rank=59), Result(document=Document(text='Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle. An outstanding biological question is why tissue regeneration in mammals is limited, whereas urodele amphibians and teleost fish regenerate major structures, largely by cell cycle reentry. Upon inactivation of Rb, proliferation of postmitotic urodele skeletal muscle is induced, whereas in mammalian muscle this mechanism does not exist. We postulated that a tumor suppressor present in mammals but absent in regenerative vertebrates, the Ink4a product ARF (alternative reading frame), is a regeneration suppressor. Concomitant inactivation of Arf and Rb led to mammalian muscle cell cycle reentry, loss of differentiation properties, and upregulation of cytokinetic machinery. Single postmitotic myocytes were isolated by laser micro-dissection-catapulting, and transient suppression of Arf and Rb yielded myoblast colonies that retained the ability to differentiate and fuse into myofibers upon transplantation in vivo. These results show that differentiation of mammalian cells is reversed by inactivation of Arf and Rb and support the hypothesis that Arf evolved at the expense of regeneration.', doc_id='323335', metadata={}), score=4.5527282054536045e-05, rank=60), Result(document=Document(text='Hierarchical organization of the plasma membrane: investigations by single-molecule tracking vs. fluorescence correlation spectroscopy. Single-molecule tracking and fluorescence correlation spectroscopy (FCS) applied to the plasma membrane in living cells have allowed a number of unprecedented observations, thus fostering a new basic understanding of molecular diffusion, interaction, and signal transduction in the plasma membrane. It is becoming clear that the plasma membrane is a heterogeneous entity, containing diverse structures on nano-meso-scales (2-200 nm) with a variety of lifetimes, where certain membrane molecules stay together for limited durations. Molecular interactions occur in the time-dependent inhomogeneous two-dimensional liquid of the plasma membrane, which might be a key for plasma membrane functions.', doc_id='327319', metadata={}), score=4.3224335968261585e-05, rank=61), Result(document=Document(text='IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells. Thymic-derived natural T regulatory cells (Tregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs has been shown to express Klrg1, but it remains unclear as to what extent Klrg1 defines a unique Treg subset. In this study, we show that Klrg1(+) Tregs represent a terminally differentiated Treg subset derived from Klrg1(-) Tregs. This subset is a recent Ag-responsive and highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1(+) Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8(+) T effector cells. Our findings suggest that an important pathway driving Ag-activated conventional T lymphocytes also operates for Tregs.', doc_id='335029', metadata={}), score=4.165179780102335e-05, rank=62), Result(document=Document(text=' PHENIX: a comprehensive Python-based system for macromolecular structure solution Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.', doc_id='341324', metadata={}), score=4.148431617068127e-05, rank=63), Result(document=Document(text='Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5 The three-dimensional structure of an HNF-3/fork head DNA-recognition motif complexed with DNA has been determined by X-ray crystallography at 2.5 Å resolution. This α/β protein binds B-DNA as a monomer, through interactions with the DNA backbone and through both direct and water-mediated major and minor groove base contacts, inducing a 13° bend. The transcription factor fold is very similar to the structure of histone H5. In its amino-terminal half, three α-helices adopt a compact structure that presents the third helix to the major groove. The remainder of the protein includes a twisted, antiparallel β-structure and random coil that interacts with the minor groove.', doc_id='343052', metadata={}), score=4.1311872337246314e-05, rank=64), Result(document=Document(text='Adipose stem cells originate from perivascular cells. Recent research has shown that adipose tissues contain abundant MSCs (mesenchymal stem cells). The origin and location of the adipose stem cells, however, remain unknown, presenting an obstacle to the further purification and study of these cells. In the present study, we aimed at investigating the origins of adipose stem cells. α-SMA (α-smooth muscle actin) is one of the markers of pericytes. We harvested ASCs (adipose stromal cells) from α-SMA-GFP (green fluorescent protein) transgenic mice and sorted them into GFP-positive and GFP-negative cells by FACS. Multilineage differentiation tests were applied to examine the pluripotent ability of the α-SMA-GFP-positive and -negative cells. Immunofluorescent staining for α-SMA and PDGF-Rβ (platelet-derived growth factor receptor β) were applied to identify the α-SMA-GFP-positive cells. Then α-SMA-GFP-positive cells were loaded on a collagen-fibronectin gel with endothelial cells to test their vascularization ability both in vitro and in vivo. Results show that, in adipose tissue, all of the α-SMA-GFP-positive cells congregate around the blood vessels. Only the α-SMA-GFP-positive cells have multilineage differentiation ability, while the α-SMA-GFP-negative cells can only differentiate in an adipogenic direction. The α-SMA-GFP-positive cells maintained expression of α-SMA during multilineage differentiation. The α-SMA-GFP-positive cells can promote the vascularization of endothelial cells in three-dimensional culture both in vitro and in vivo. We conclude that the adipose stem cells originate from perivascular cells and congregate around blood vessels.', doc_id='344240', metadata={}), score=4.092223753104918e-05, rank=65), Result(document=Document(text='The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Free radicals vary widely in their thermodynamic properties, ranging from very oxidizing to very reducing. These thermodynamic properties can be used to predict a pecking order, or hierarchy, for free radical reactions. Using one-electron reduction potentials, the predicted pecking order is in agreement with experimentally observed free radical electron (hydrogen atom) transfer reactions. These potentials are also in agreement with experimental data that suggest that vitamin E, the primary lipid soluble small molecule antioxidant, and vitamin C, the terminal water soluble small molecule antioxidant, cooperate to protect lipids and lipid structures against peroxidation. Although vitamin E is located in membranes and vitamin C is located in aqueous phases, vitamin C is able to recycle vitamin E; i.e., vitamin C repairs the tocopheroxyl (chromanoxyl) radical of vitamin E, thereby permitting vitamin E to function again as a free radical chain-breaking antioxidant. This review discusses: (i) the thermodynamics of free radical reactions that are of interest to the health sciences; (ii) the fundamental thermodynamic and kinetic properties that are associated with chain-breaking antioxidants; (iii) the unique interfacial nature of the apparent reaction of the tocopherol free radical (vitamin E radical) and vitamin C; and (iv) presents a hierarchy, or pecking order, for free radical electron (hydrogen atom) transfer reactions.', doc_id='350542', metadata={}), score=4.0881011955207214e-05, rank=66), Result(document=Document(text='High Km soluble 5\\'-nucleotidase from human placenta. Properties and allosteric regulation by IMP and ATP. A human placental soluble \"high Km\" 5\\'-nucleotidase has been separated from \"low Km\" 5\\'-nucleotidase and nonspecific phosphatase by AMP-Sepharose affinity chromatography. The enzyme was purified 8000-fold to a specific activity of 25.6 mumol/min/mg. The subunit molecular mass is 53 kDa, and the native molecular mass is 210 kDa, suggesting a tetrameric structure. Soluble high Km 5\\'-nucleotidase is most active with IMP and GMP and their deoxy derivatives. IMP is hydrolyzed 15 times faster than AMP. The enzyme has a virtually absolute requirement for magnesium ions and is regulated by them. Purine nucleoside 5\\'-triphosphates strongly activate the enzyme with the potency order dATP greater than ATP greater than GTP. 2,3-Diphosphoglycerate activates the enzyme as potently as ATP. Three millimolar ATP decreased the Km for IMP from 0.33 to 0.09 mM and increased the Vmax 12-fold. ATP activation was modified by the IMP concentration. At 20 microM IMP the ATP-dependent activation curve was sigmoidal, while at 2 mM IMP it was hyperbolic. The A0.5 values for ATP were 2.26 and 0.70 mM, and the relative maximal velocities were 32.9 and 126.0 nmol/min, respectively. Inorganic phosphate shifts the hyperbolic substrate velocity relationship for IMP to a sigmoidal one. With physiological concentrations of cofactors (3 mM ATP, 1-4 mM Pi, 150 mM KCl) at pH 7.4, the enzyme is 25-35 times more active toward 100 microM IMP than 100 microM AMP. These data show that: (a) soluble human placental high Km 5\\'-nucleotidase coexists in human placenta with the low Km enzyme; (b) under physiological conditions the enzyme favors the hydrolysis of IMP and is critically regulated by IMP, ATP, and Pi levels; and (c) kinetic properties of ATP and IMP are each modified by the other compound suggesting complex interaction of the associated binding sites.', doc_id='356218', metadata={}), score=3.88347398256883e-05, rank=67), Result(document=Document(text='A three-dimensional human neural cell culture model of Alzheimer’s disease Alzheimer’s disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer’s disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer’s disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer’s disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer’s disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-β generation with β- or γ-secretase inhibitors not only decreased amyloid-β pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-β-mediated tau phosphorylation. We have successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer’s disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.', doc_id='364522', metadata={}), score=3.773146454477683e-05, rank=68), Result(document=Document(text='Comparative Protein Structure Modeling Using MODELLER. Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley & Sons, Inc.', doc_id='365896', metadata={}), score=3.7290861655492336e-05, rank=69), Result(document=Document(text='Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.', doc_id='368506', metadata={}), score=3.674955587484874e-05, rank=70), Result(document=Document(text=\"Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe Eukaryotic genomes are folded into three-dimensional structures, such as self-associating topological domains, the borders of which are enriched in cohesin and CCCTC-binding factor (CTCF) required for long-range interactions. How local chromatin interactions govern higher-order folding of chromatin fibres and the function of cohesin in this process remain poorly understood. Here we perform genome-wide chromatin conformation capture (Hi-C) analysis to explore the high-resolution organization of the Schizosaccharomyces pombe genome, which despite its small size exhibits fundamental features found in other eukaryotes. Our analyses of wild-type and mutant strains reveal key elements of chromosome architecture and genome organization. On chromosome arms, small regions of chromatin locally interact to form 'globules'. This feature requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structures and global chromosome territories. By contrast, heterochromatin, which loads cohesin at specific sites including pericentromeric and subtelomeric domains, is dispensable for globule formation but nevertheless affects genome organization. We show that heterochromatin mediates chromatin fibre compaction at centromeres and promotes prominent inter-arm interactions within centromere-proximal regions, providing structural constraints crucial for proper genome organization. Loss of heterochromatin relaxes constraints on chromosomes, causing an increase in intra- and inter-chromosomal interactions. Together, our analyses uncover fundamental genome folding principles that drive higher-order chromosome organization crucial for coordinating nuclear functions.\", doc_id='371289', metadata={}), score=3.627258774940856e-05, rank=71), Result(document=Document(text='Margination of white blood cells in microcapillary flow. Margination of white blood cells (WBCs) towards vessel walls is an essential precondition for their efficient adhesion to the vascular endothelium. We perform numerical simulations with a two-dimensional blood flow model to investigate the dependence of WBC margination on hydrodynamic interactions of blood cells with the vessel walls, as well as on their collective behavior and deformability. We find WBC margination to be optimal in intermediate ranges of red blood cell (RBC) volume fractions and flow rates, while, beyond these ranges, it is substantially attenuated. RBC aggregation enhances WBC margination, while WBC deformability reduces it. These results are combined in state diagrams, which identify WBC margination for a wide range of flow and cell suspension conditions.', doc_id='374902', metadata={}), score=3.5269469663035125e-05, rank=72), Result(document=Document(text=\"The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding How follicular helper T cells (TFH cells) differentiate to regulate B cell immunity is critical for effective protein vaccination. Here we define three transcription factor T-bet–expressing antigen-specific effector helper T cell subsets with distinguishable function, migratory properties and developmental programming in vivo. Expression of the transcriptional repressor Blimp-1 distinguished T zone 'lymphoid' effector helper T cells (CD62LhiCCR7hi) from CXCR5lo 'emigrant' effector helper T cells and CXCR5hi 'resident' TFH cells expressing the transcriptional repressor Bcl-6 (CD62LloCCR7lo). We then show by adoptive transfer and intact polyclonal responses that helper T cells with the highest specific binding of peptide–major histocompatibility complex class II and the most restricted T cell antigen receptor junctional diversity 'preferentially' developed into the antigen-specific effector TFH compartment. Our studies demonstrate a central function for differences in the binding strength of the T cell antigen receptor in the antigen-specific mechanisms that 'program' specialized effector TFH function in vivo.\", doc_id='380526', metadata={}), score=3.492526229820214e-05, rank=73), Result(document=Document(text='Purification and activation properties of UreD-UreF-urease apoprotein complexes. In vivo assembly of the Klebsiella aerogenes urease nickel metallocenter requires the presence of UreD, UreF, and UreG accessory proteins and is further facilitated by UreE. Prior studies had shown that urease apoprotein exists in an uncomplexed form as well as in a series of UreD-urease (I.-S. Park, M.B. Carr, and R.P. Hausinger, Proc. Natl. Acad. Sci. USA 91:3233-3237, 1994) and UreD-UreF-UreG-urease (I.-S. Park and R.P. Hausinger, J. Bacteriol. 177:1947-1951, 1995) apoprotein complexes. This study demonstrates the existence of a distinct series of complexes consisting of UreD, UreF, and urease apoprotein. These novel complexes exhibited activation properties that were distinct from urease and UreD-urease apoprotein complexes. Unlike the previously described species, the UreD-UreF-urease apoprotein complexes were resistant to inactivation by NiCl2. The bicarbonate concentration dependence for UreD-UreF-urease apoenzyme activation was significantly decreased compared with that of the urease and UreD-urease apoproteins. Western blot (immunoblot) analyses with polyclonal anti-urease and anti-UreD antibodies indicated that UreD is masked in the UreD-UreF-urease complexes, presumably by UreF. We propose that the binding of UreF modulates the UreD-urease apoprotein activation properties by excluding nickel ions from binding to the active site until after formation of the carbamylated lysine metallocenter ligand.', doc_id='381602', metadata={}), score=3.422097142902203e-05, rank=74), Result(document=Document(text='Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells. This top-down engineering approach can be applied toward the development of novel therapeutic strategies owing to the unique interactions enabled through the retention of complex antigenic information. Herein, we report on the biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells. The resulting core-shell nanostructures, which carry the full array of cancer cell membrane antigens, offer a robust platform with applicability toward multiple modes of anticancer therapy. We demonstrate that by coupling the particles with an immunological adjuvant, the resulting formulation can be used to promote a tumor-specific immune response for use in vaccine applications. Moreover, we show that by taking advantage of the inherent homotypic binding phenomenon frequently observed among tumor cells the membrane functionalization allows for a unique cancer targeting strategy that can be utilized for drug delivery applications.', doc_id='393001', metadata={}), score=3.407576878089458e-05, rank=75), Result(document=Document(text='Neuromodulation of neurons and synapses. Neuromodulation underlies the flexibility of neural circuit operation and behavior. Individual neuromodulators can have divergent actions in a neuron by targeting multiple physiological mechanisms. Conversely, multiple neuromodulators may have convergent actions through overlapping targets. The divergent and convergent neuromodulator actions can be unambiguously synergistic or antagonistic, but neuromodulation often entails balanced adjustment of nonlinear membrane and synaptic properties by targeting ion channel and synaptic dynamics rather than just excitability or synaptic strength. In addition, neuromodulators can exert effects at multiple timescales, from short-term adjustments of neuron and synapse function to persistent long-term regulation. This short review summarizes some highlights of the diverse actions of neuromodulators on ion channel and synaptic properties.', doc_id='406733', metadata={}), score=3.356976230861619e-05, rank=76), Result(document=Document(text='Phosphorylation site mutations in heterochromatin protein 1 (HP1) reduce or eliminate silencing activity. HP1 is an essential heterochromatin-associated protein in Drosophila. HP1 has dosage-dependent effects on the silencing of euchromatic genes that are mislocalized to heterochromatin and is required for the normal expression of at least two heterochromatic genes. HP1 is multiply phosphorylated in vivo, and HP1 hyperphosphorylation is correlated with heterochromatin assembly during development. The purpose of this study was to test whether HP1 phosphorylation modifies biological activity and biochemical properties of HP1. To determine sites of HP1 phosphorylation in vivo and whether phosphorylation affects any biochemical properties of HP1, we expressed Drosophila HP1 in lepidopteran cultured cells using a recombinant baculovirus vector. Phosphopeptides were identified by matrix-assisted laser desorption ionization/time of flight mass spectroscopy; these peptides contain target sites for casein kinase II, protein tyrosine kinase, and PIM-1 kinase. Purified HP1 from bacterial (unphosphorylated) and lepidopteran (phosphorylated) cells has similar secondary structure. Phosphorylation has no effect on HP1 self-association but alters the DNA binding properties of HP1, suggesting that phosphorylation could differentially regulate HP1-dependent interactions. Serine-to-alanine and serine-to-glutamate substitutions at consensus protein kinase motifs resulted in reduction or loss of silencing activity of mutant HP1 in transgenic flies. These results suggest that dynamic phosphorylation/dephosphorylation regulates HP1 activity in heterochromatic silencing.', doc_id='409280', metadata={}), score=3.244985418859869e-05, rank=77), Result(document=Document(text='Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci. Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity. PARP-1-dependent Sox2-binding sites reside in euchromatic regions of the genome with relatively high nucleosome occupancy and low co-occupancy by other transcription factors. PARP-1 stabilizes Sox2 binding to nucleosomes at suboptimal sites through cooperative interactions on DNA. Our results define intrinsic and extrinsic features that determine Sox2 pioneer activity. The conditional pioneer activity observed with Sox2 at a subset of binding sites may be a key feature of other pioneer TFs operating at intractable genomic loci.', doc_id='410286', metadata={}), score=3.074432606808841e-05, rank=78), Result(document=Document(text='Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3beta (GSK3beta) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated \"naïve\" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.', doc_id='418246', metadata={}), score=2.9054999686195515e-05, rank=79), Result(document=Document(text='Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine. The large Trp gene family encodes transient receptor potential (TRP) proteins that form novel cation-selective ion channels. In mammals, 28 Trp channel genes have been identified. TRP proteins exhibit diverse permeation and gating properties and are involved in a plethora of physiologic functions with a strong impact on cellular sensing and signaling pathways. Indeed, mutations in human genes encoding TRP channels, the so-called \"TRP channelopathies,\" are responsible for a number of hereditary diseases that affect the musculoskeletal, cardiovascular, genitourinary, and nervous systems. This review gives an overview of the functional properties of mammalian TRP channels, describes their roles in acquired and hereditary diseases, and discusses their potential as drug targets for therapeutic intervention.', doc_id='427082', metadata={}), score=2.8101698262616992e-05, rank=80), Result(document=Document(text='A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay. In eukaryotes, a surveillance mechanism known as nonsense-mediated decay (NMD) degrades the mRNA when a premature-termination codon (PTC) is present. NMD requires translation to read the frame of the mRNA and detect the PTC. During pre-mRNA splicing, the exon-exon junction complex (EJC) is recruited to a region 20-24 nt upstream of the exon junction on the mature mRNA. The presence of a PTC upstream from the EJC elicits NMD. Eukaryotic initiation factor 4A (eIF4A) III is a nuclear protein that interacts physically or functionally with translation initiation factors eIF4G and eIF4B, respectively, and shares strikingly high identity with the initiation factors eIF4AI/II. Here we show that siRNA against eIF4AIII, but not against eIF4AI/II, inhibits NMD. Moreover, eIF4AIII, but not eIF4AI, is specifically recruited to the EJC during splicing. The observations that eIF4AIII is loaded onto the mRNA during splicing in the nucleus, has properties related to a translation initiation factor, and functions in NMD raises the possibility that eIF4AIII substitutes for eIF4AI/II during NMD.', doc_id='427865', metadata={}), score=2.7155427233083174e-05, rank=81), Result(document=Document(text='Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible \"wait anaphase\" signal to the vicinity of the spindle.', doc_id='432261', metadata={}), score=2.692759153433144e-05, rank=82), Result(document=Document(text='A 40-Hz auditory potential recorded from the human scalp. Computer techniques readily extract from the brainwaves an orderly sequence of brain potentials locked in time to sound stimuli. The potentials that appear 8 to 80 msec after the stimulus resemble 3 or 4 cycles of a 40-Hz sine wave; we show here that these waves combined to form a single, stable, composite wave when the sounds are repeated at rates around 40 per sec. This phenomenon, the 40-Hz event-related potential (ERP), displays several properties of theoretical and practical interest. First, it reportedly disappears with surgical anesthesia, and it resembles similar phenomena in the visual and olfactory system, facts which suggest that adequate processing of sensory information may require cyclical brain events in the 30- to 50-Hz range. Second, latency and amplitude measurements on the 40-Hz ERP indicate it may contain useful information on the number and basilar membrane location of the auditory nerve fibers a given tone excites. Third, the response is present at sound intensities very close to normal adult thresholds for the audiometric frequencies, a fact that could have application in clinical hearing testing.', doc_id='435529', metadata={}), score=2.6912059183814563e-05, rank=83), Result(document=Document(text='Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(kappa)] is in preclinical development for treatment of Cryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.', doc_id='437924', metadata={}), score=2.5558760171406902e-05, rank=84), Result(document=Document(text='Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model. We used a mouse nasal model of herpes simplex virus 2 (HSV-2) infection to examine the biological properties of HSV-2 wild-type (wt), TK-negative, and replication-defective strains in vivo. Nasal septa tissue is the major site of wt viral replication post intranasal (i.n.) inoculation. The HSV-2 strain 186 syn(+)-1 wt virus caused lethal encephalitis at doses of 10(4) PFU and above per nostril, and at lower doses no neurons in the trigeminal ganglia were positive for the latency-associated transcript, indicating a lack of latent infection. The 186DeltaKpn TK-negative mutant virus replicated in nasal septa tissue but showed low-level replication in trigeminal ganglia at only one timepoint. In situ hybridization of trigeminal ganglia showed that the number of LAT-positive neurons was proportional to the inoculum dose from 10(3) to 10(6) PFU per nare. The replication-defective mutant virus 5BlacZ showed no replication in nasal septa tissue and no persistence of viral DNA at the inoculation site or the trigeminal ganglia. Nevertheless, inoculation of 5BlacZ or the double-mutant dl5-29 at distal sites reduced acute replication and latent infection of 186DeltaKpn following intranasal challenge. This infection model provides a biological system to test the properties of HSV-2 strains and shows that replication-defective mutant strains do not persist at sites of inoculation or in sensory ganglia but can induce immune protection that reduces the latent viral load of a challenge virus.', doc_id='439670', metadata={}), score=2.4273142116726376e-05, rank=85), Result(document=Document(text='Crystal structure of the first plant urease from jack bean: 83 years of journey from its first crystal to molecular structure. Urease, a nickel-dependent metalloenzyme, is synthesized by plants, some bacteria, and fungi. It catalyzes the hydrolysis of urea into ammonia and carbon dioxide. Although the amino acid sequences of plant and bacterial ureases are closely related, some biological activities differ significantly. Plant ureases but not bacterial ureases possess insecticidal properties independent of its ureolytic activity. To date, the structural information is available only for bacterial ureases although the jack bean urease (Canavalia ensiformis; JBU), the best-studied plant urease, was the first enzyme to be crystallized in 1926. To better understand the biological properties of plant ureases including the mechanism of insecticidal activity, we initiated the structural studies on some of them. Here, we report the crystal structure of JBU, the first plant urease structure, at 2.05 A resolution. The active-site architecture of JBU is similar to that of bacterial ureases containing a bi-nickel center. JBU has a bound phosphate and covalently modified residue (Cys592) by beta-mercaptoethanol at its active site, and the concomitant binding of multiple inhibitors (phosphate and beta-mercaptoethanol) is not observed so far in bacterial ureases. By correlating the structural information of JBU with the available biophysical and biochemical data on insecticidal properties of plant ureases, we hypothesize that the amphipathic beta-hairpin located in the entomotoxic peptide region of plant ureases might form a membrane insertion beta-barrel as found in beta-pore-forming toxins.', doc_id='456304', metadata={}), score=2.3493843400501646e-05, rank=86), Result(document=Document(text='Extracellular vesicles for drug delivery. Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained considerable scientific interest. EVs may have multiple advantages over currently available drug delivery vehicles, such as their ability to overcome natural barriers, their intrinsic cell targeting properties, and stability in the circulation. However, therapeutic applications of EVs as drug delivery systems have been limited due to a lack of methods for scalable EV isolation and efficient drug loading. Furthermore, in order to achieve targeted drug delivery, their intrinsic cell targeting properties should be tuned through EV engineering. Here, we review and discuss recent progress and remaining challenges in the development of EVs as drug delivery vehicles.', doc_id='457630', metadata={}), score=2.344525455555413e-05, rank=87), Result(document=Document(text='A core Klf circuitry regulates self-renewal of embryonic stem cells Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely and maintain pluripotency. These properties require transcription factors that specify the gene expression programme of ES cells. It has been possible to reverse the highly differentiated state of somatic cells back to a pluripotent state with a combination of four transcription factors: Klf4 is one of the reprogramming factors required, in conjunction with Oct4, Sox2 and c-Myc. Maintenance of self-renewal and pluripotency of ES cells requires Oct4, Sox2 and c-Myc, but Klf4 is dispensable. Here, we show that Krüppel-like factors are required for the self-renewal of ES cells. Simultaneous depletion of Klf2, Klf4 and Klf5 lead to ES cell differentiation. Chromatin immunoprecipitation coupled to microarray assay reveals that these Klf proteins share many common targets of Nanog, suggesting a close functional relationship between these factors. Expression analysis after triple RNA interference (RNAi) of the Klfs shows that they regulate key pluripotency genes, such as Nanog. Taken together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression that is unique to ES cells.', doc_id='461550', metadata={}), score=2.260063774883747e-05, rank=88), Result(document=Document(text='Correlation and variable importance in random forests This paper is about variable selection with the random forests algorithm in presence of correlated predictors. In high-dimensional regression or classification frameworks, variable selection is a difficult task, that becomes even more challenging in the presence of highly correlated predictors. Firstly we provide a theoretical study of the permutation importance measure for an additive regression model. This allows us to describe how the correlation between predictors impacts the permutation importance. Our results motivate the use of the Recursive Feature Elimination (RFE) algorithm for variable selection in this context. This algorithm recursively eliminates the variables using permutation importance measure as a ranking criterion. Next various simulation experiments illustrate the efficiency of the RFE algorithm for selecting a small number of variables together with a good prediction error. Finally, this selection algorithm is tested on the Landsat Satellite data from the UCI Machine Learning Repository.', doc_id='463309', metadata={}), score=2.1846226445632055e-05, rank=89), Result(document=Document(text='New developments in the ATSAS program package for small-angle scattering data analysis New developments in the program package ATSAS (version 2.4) for the processing and analysis of isotropic small-angle X-ray and neutron scattering data are described. They include (i) multiplatform data manipulation and display tools, (ii) programs for automated data processing and calculation of overall parameters, (iii) improved usage of high- and low-resolution models from other structural methods, (iv) new algorithms to build three-dimensional models from weakly interacting oligomeric systems and complexes, and (v) enhanced tools to analyse data from mixtures and flexible systems. The new ATSAS release includes installers for current major platforms (Windows, Linux and Mac OSX) and provides improved indexed user documentation. The web-related developments, including a user discussion forum and a widened online access to run ATSAS programs, are also presented.', doc_id='463533', metadata={}), score=2.082689752569422e-05, rank=90), Result(document=Document(text='Genomic organisation and transcription characterisation of the gene encoding Leishmania (Leishmania) amazonensis arginase and its protein structure prediction. The genomic organisation of the gene encoding Leishmania (Leishmania) amazonensis arginase as well as its flanking regions were characterised. The size of the transcribed RNA was determined, allowing us to map the genomic sites signalling for RNA trans-splicing and putative polyadenylation regions. The general organisation was compared with genes encoding other proteins already described in organisms of the Trypanosomatid family. The complete nucleotide sequence of the arginase open reading frame was obtained and the three-dimensional structure of the enzyme was inferred by a computational analysis of the deduced amino acid sequence, based on the established crystal structure described for Rattus norvergicus arginase. The human liver arginase sequence was analysed in the same way and the comparison of the presumed structure of both the Leishmania and human enzymes identified some differences that may be exploited in chemotherapeutic studies.', doc_id='464511', metadata={}), score=2.0483179469010793e-05, rank=91), Result(document=Document(text='A general model to explore complex dominance patterns in plant sporophytic self-incompatibility systems. We developed a general model of sporophytic self-incompatibility under negative frequency-dependent selection allowing complex patterns of dominance among alleles. We used this model deterministically to investigate the effects on equilibrium allelic frequencies of the number of dominance classes, the number of alleles per dominance class, the asymmetry in dominance expression between pollen and pistil, and whether selection acts on male fitness only or both on male and on female fitnesses. We show that the so-called \"recessive effect\" occurs under a wide variety of situations. We found emerging properties of finite population models with several alleles per dominance class such as that higher numbers of alleles are maintained in more dominant classes and that the number of dominance classes can evolve. We also investigated the occurrence of homozygous genotypes and found that substantial proportions of those can occur for the most recessive alleles. We used the model for two species with complex dominance patterns to test whether allelic frequencies in natural populations are in agreement with the distribution predicted by our model. We suggest that the model can be used to test explicitly for additional, allele-specific, selective forces.', doc_id='469066', metadata={}), score=2.039114770013839e-05, rank=92), Result(document=Document(text='A nano-positioning system for macromolecular structural analysis Very often, the positions of flexible domains within macromolecules as well as within macromolecular complexes cannot be determined by standard structural biology methods. To overcome this problem, we developed a method that uses probabilistic data analysis to combine single-molecule measurements with X-ray crystallography data. The method determines not only the most likely position of a fluorescent dye molecule attached to the domain but also the complete three-dimensional probability distribution depicting the experimental uncertainty. With this approach, single-pair fluorescence resonance energy transfer measurements can now be used as a quantitative tool for investigating the position and dynamics of flexible domains within macromolecular complexes. We applied this method to find the position of the 5′ end of the nascent RNA exiting transcription elongation complexes of yeast (Saccharomyces cerevisiae) RNA polymerase II and studied the influence of transcription factor IIB on the position of the RNA.', doc_id='470625', metadata={}), score=2.0214338292134926e-05, rank=93), Result(document=Document(text='Plant products as antimicrobial agents. The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and \"leads\" which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.', doc_id='471735', metadata={}), score=1.971597521333024e-05, rank=94), Result(document=Document(text='Biochemical Properties of Highly Neuroinvasive Prion Strains Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrP(Sc). Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrP(Sc) over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrP(Sc) over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS.', doc_id='471921', metadata={}), score=1.9233732018619776e-05, rank=95), Result(document=Document(text='Diaphragm Atrophy and Contractile Dysfunction in a Murine Model of Pulmonary Hypertension Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced by MCT in mice reproduces the loss of body weight and diaphragm muscle dysfunction seen in patients. This is a pre-requisite for widespread use of mice to examine mechanisms of cachexia and diaphragm abnormalities in PH. Thus, we measured body and soleus muscle weight, food intake, and diaphragm contractile properties in mice after 6-8 weeks of saline (control) or MCT (600 mg/kg) injections. Body weight progressively decreased in PH mice, while food intake was similar in both groups. PH decreased (P<0.05) diaphragm maximal isometric specific force, maximal shortening velocity, and peak power. Protein carbonyls in whole-diaphragm lysates and the abundance of select myofibrillar proteins were unchanged by PH. Our findings show diaphragm isometric and isotonic contractile abnormalities in a murine model of PH induced by MCT. Overall, the murine model of PH elicited by MCT mimics loss of body weight and diaphragm muscle weakness reported in PH patients.', doc_id='474325', metadata={}), score=1.9109371351078153e-05, rank=96), Result(document=Document(text='A unified concept of species and its consequences for the future of taxonomy Contemporary species concepts are diverse. Nonetheless, all share the fundamental idea that species are segments of lineages at the population level of biological organization. They differ in the secondary properties (e.g., intrinsic reproductive isolation, monophyly, diagnosability) that are treated as necessary for considering lineages to be species. A unified species concept can be achieved by interpreting the common fundamental idea of being a separately evolving lineage segment as the only necessary property of species and viewing the various secondary properties either as lines of evidence relevant to assessing lineage separation or as properties that define different subcategories of the species category (e.g., reproductively isolated species, monophyletic species, diagnosable species). This unified species concept has a number of consequences for taxonomy, including the need to acknowledge that undifferentiated and undiagnosable lineages are species, that species can fuse, that species can be nested within other species, that the species category is not a taxonomic rank, and that new taxonomic practices and conventions are needed to accommodate these conclusions. Although acceptance of a unified species concept has some radical consequences for taxonomy, it also reflects a change in the general conceptualization of the species category that has been underway for more than a half-century — a shift from viewing the species category as one member of the hierarchy of taxonomic ranks to viewing it as a natural kind whose members are the units at one of the levels of biological organization. This change is related to a more general shift in the primary concern of the discipline of systematics (including taxonomy), from the utilitarian activity of classifying organisms to the scientific activity of testing hypotheses about lineage boundaries and phylogenetic relationships. The unified species concept is a natural outcome of this conceptual shift and represents the more complete acceptance of the idea that species are one of the fundamental units of biology. As such, the unified species concept is central to the future of taxonomy.', doc_id='485020', metadata={}), score=1.646330019866582e-05, rank=97), Result(document=Document(text='The binding of maize DHN1 to lipid vesicles. Gain of structure and lipid specificity. Dehydrins (DHNs; late embryogenesis abundant D-11) are a family of plant proteins induced in response to abiotic stresses such as drought, low temperature, and salinity or during the late stages of embryogenesis. Spectral and thermal properties of these proteins in purified form suggest that they are \"intrinsically unstructured. \" However, DHNs contain at least one copy of a consensus 15-amino acid sequence, the \"K segment,\" which resembles a class A2 amphipathic alpha-helical, lipid-binding domain found in other proteins such as apolipoproteins and alpha-synuclein. The presence of the K segment raises the question of whether DHNs bind lipids, bilayers, or phospholipid vesicles. Here, we show that maize (Zea mays) DHN DHN1 can bind to lipid vesicles that contain acidic phospholipids. We also observe that DHN1 binds more favorably to vesicles of smaller diameter than to larger vesicles, and that the association of DHN1 with vesicles results in an apparent increase of alpha-helicity of the protein. Therefore, DHNs, and presumably somewhat similar plant stress proteins in the late embryogenesis abundant and cold-regulated classes may undergo function-related conformational changes at the water/membrane interface, perhaps related to the stabilization of vesicles or other endomembrane structures under stress conditions.', doc_id='493346', metadata={}), score=1.607399281056132e-05, rank=98), Result(document=Document(text='Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms represents diverse pathophysiologies. Human epithelium contains keratin, which is expressed during differentiation. Depending on the target cell type, different types of keratin are expressed, and their alterations seem to represent changes in cell properties. The basal cells of oral epithelium express keratin 5 (K5), K14, K15 and K19, but their alterations in tumors are unclear. To address this issue and to seek possible diagnostic application, we examined the expression of these keratins in oral squamous cell carcinoma (OSCC) and squamous intraepithelial neoplasm (SIN). cDNA microarray analysis of 43 OSCC revealed slight upregulation of KRT14, downregulation of KRT15 and KRT19, and unaltered KRT5 expression. There were great variations in KRT15 and KRT19 expression across each cancer. Well-differentiated OSCC tended to express more KRT15 and less KRT19 compared to moderately- or poorly-differentiated OSCC. KRT15 was positively correlated with differentiation-related keratin, KRT13. These observations were further investigated by immunohistochemical examination. K5 and K14 were ubiquitously expressed in all 50 OSCC and 50 SIN examined. K15 and K19 were generally downregulated, but were considerably retained in about half of the cases and showed diverse expression patterns. K15-positive cancers tended to show a well-differentiated phenotype, and K19-positive cancers tended to show more invasive tumor fronts. Most K19-positive cancers appeared to develop with little associating SIN. K19 was consistently downregulated in SIN, while K15 was downregulated mainly in high grade SIN. In summary, K15 and K19, unlike K5 or K14, are expressed variably in both SIN and OSCC, which reflects the differences in their pathogenesis and biological behaviors, suggesting their prospective applications as markers for subclassifying OSCC and SIN.', doc_id='496873', metadata={}), score=1.5373974747490138e-05, rank=99), Result(document=Document(text='The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists.', doc_id='502591', metadata={}), score=1.5081539459060878e-05, rank=100)], query='0-dimensional biomaterials show inductive properties.', has_scores=True))"
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"source": [
"q_id, ranked_results = next(iter(scores.items()))\n",
"q_id, ranked_results"
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{
"cell_type": "code",
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"[Result(document=Document(text=\"Periosteal bone formation--a neglected determinant of bone strength. Life forms that have low body mass can hunt for food on the undersurface of branches or along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for dinner and the struggle to avoid becoming someone else's meal require rapid movement against gravity. This need is met by the lever function of long bones, three-dimensional masterpieces of biomechanical engineering that, by their material composition and structural design, achieve the contradictory properties of stiffness and flexibility, strength and lightness.1 Material stiffness results from the encrusting of the triple-helical structure of collagen type I with hydroxyapatite crystals, which confers . . .\", doc_id='4983', metadata={}), score=0.024103358387947083, rank=1),\n",
" Result(document=Document(text='Epithelial and mesenchymal subpopulations within normal basal breast cell lines exhibit distinct stem cell/progenitor properties. It has been proposed that epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells generates stem cell features, and that the presence of EMT characteristics in claudin-low breast tumors reveals their origin in basal stem cells. It remains to be determined, however, whether EMT is an inherent property of normal basal stem cells, and if the presence of a mesenchymal-like phenotype is required for the maintenance of all their stem cell properties. We used nontumorigenic basal cell lines as models of normal stem cells/progenitors and demonstrate that these cell lines contain an epithelial subpopulation (\"EpCAM+,\" epithelial cell adhesion molecule positive [EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells (\"Fibros,\" EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and formation of three-dimensional acini-like structures predominantly reside within EpCAM+ cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene expression profiling meta-analysis established that EpCAM+ cells show a luminal progenitor-like expression pattern, while Fibros most closely resemble stromal fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a mesenchymal-like phenotype does not correlate with the acquisition of global stem cell/progenitor features. Based on our findings, we propose that EMT in normal basal cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial differentiation.', doc_id='5836', metadata={}), score=0.004422821570187807, rank=2),\n",
" Result(document=Document(text='Geometry, epistasis, and developmental patterning. Developmental signaling networks are composed of dozens of components whose interactions are very difficult to quantify in an embryo. Geometric reasoning enumerates a discrete hierarchy of phenotypic models with a few composite variables whose parameters may be defined by in vivo data. Vulval development in the nematode Caenorhabditis elegans is a classic model for the integration of two signaling pathways; induction by EGF and lateral signaling through Notch. Existing data for the relative probabilities of the three possible terminal cell types in diverse genetic backgrounds as well as timed ablation of the inductive signal favor one geometric model and suffice to fit most of its parameters. The model is fully dynamic and encompasses both signaling and commitment. It then predicts the correlated cell fate probabilities for a cross between any two backgrounds/conditions. The two signaling pathways are combined additively, without interactions, and epistasis only arises from the nonlinear dynamical flow in the landscape defined by the geometric model. In this way, the model quantitatively fits genetic experiments purporting to show mutual pathway repression. The model quantifies the contributions of extrinsic vs. intrinsic sources of noise in the penetrance of mutant phenotypes in signaling hypomorphs and explains available experiments with no additional parameters. Data for anchor cell ablation fix the parameters needed to define Notch autocrine signaling.', doc_id='7912', metadata={}), score=0.0034973807632923126, rank=3)]"
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"execution_count": 153,
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"source": [
"ranked_results.top_k(3)"
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{
"cell_type": "code",
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"execution_count": 154,
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"source": [
"{each.doc_id: each.score for each in ranked_results.top_k(3)} "
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"cell_type": "code",
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"<pre style=\"white-space:pre;overflow-x:auto;line-height:normal;font-family:Menlo,'DejaVu Sans Mono',consolas,'Courier New',monospace\"><span style=\"color: #000080; text-decoration-color: #000080\">╭─────────────────────────────────── </span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&lt;</span><span style=\"color: #ff00ff; text-decoration-color: #ff00ff; font-weight: bold\">class</span><span style=\"color: #000000; text-decoration-color: #000000\"> </span><span style=\"color: #008000; text-decoration-color: #008000\">'rerankers.results.RankedResults'</span><span style=\"color: #000080; text-decoration-color: #000080; font-weight: bold\">&gt;</span><span style=\"color: #000080; text-decoration-color: #000080\"> ───────────────────────────────────╮</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">╭─────────────────────────────────────────────────────────────────────────────────────────────────────────────╮</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">RankedResults</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ </span><span style=\"color: #808000; text-decoration-color: #808000\">results</span>=<span style=\"font-weight: bold\">[</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Periosteal bone formation--a neglected determinant of bone s'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">698</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4983</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.024103358387947083</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Epithelial and mesenchymal subpopulations within normal basa'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2037</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5836</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.004422821570187807</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Geometry, epistasis, and developmental patterning. Developme'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1471</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7912</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0034973807632923126</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">3</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Large deformation of red blood cell ghosts in a simple shear'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">853</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">18670</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0010757819982245564</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The carboxyl terminus of human cytomegalovirus-encoded 7 tra'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1660</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">19238</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0009564738720655441</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Cerebral organoids model human brain development and microce'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1143</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">33370</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0008705182699486613</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'From Cell Differentiation to Cell Collectives: Bacillus subt'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1326</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">36474</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0007751494995318353</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'In situ regulation of DC subsets and T cells mediates tumor '</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1682</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">54440</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0007493325392715633</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">8</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The effects of prion protein proteolysis and disaggregation '</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1414</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">70115</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.000624156731646508</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'High-performance neuroprosthetic control by an individual wi'</span>+<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2161</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">70490</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0006221356452442706</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">10</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ │ </span><span style=\"color: #808000; text-decoration-color: #808000\">...</span> +<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">90</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ </span><span style=\"font-weight: bold\">]</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ </span><span style=\"color: #808000; text-decoration-color: #808000\">query</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'0-dimensional biomaterials show inductive properties.'</span>, <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #7fbf7f; text-decoration-color: #7fbf7f\">│ </span><span style=\"color: #808000; text-decoration-color: #808000\">has_scores</span>=<span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"font-weight: bold\">)</span> <span style=\"color: #008000; text-decoration-color: #008000\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────╯</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">has_scores</span> = <span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">model_computed_fields</span> = <span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">model_config</span> = <span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">model_extra</span> = <span style=\"color: #800080; text-decoration-color: #800080; font-style: italic\">None</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">model_fields</span> = <span style=\"font-weight: bold\">{</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">'results'</span>: <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">FieldInfo</span><span style=\"font-weight: bold\">(</span><span style=\"color: #808000; text-decoration-color: #808000\">annotation</span>=<span style=\"color: #800080; text-decoration-color: #800080\">List</span><span style=\"font-weight: bold\">[</span>Result<span style=\"font-weight: bold\">]</span>, <span style=\"color: #808000; text-decoration-color: #808000\">required</span>=<span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">'query'</span>: <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">FieldInfo</span><span style=\"font-weight: bold\">(</span><span style=\"color: #808000; text-decoration-color: #808000\">annotation</span>=<span style=\"color: #800080; text-decoration-color: #800080\">str</span>, <span style=\"color: #808000; text-decoration-color: #808000\">required</span>=<span style=\"color: #00ff00; text-decoration-color: #00ff00; font-style: italic\">True</span><span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">'has_scores'</span>: <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">FieldInfo</span><span style=\"font-weight: bold\">(</span><span style=\"color: #808000; text-decoration-color: #808000\">annotation</span>=<span style=\"color: #800080; text-decoration-color: #800080\">bool</span>, <span style=\"color: #808000; text-decoration-color: #808000\">required</span>=<span style=\"color: #ff0000; text-decoration-color: #ff0000; font-style: italic\">False</span>, <span style=\"color: #808000; text-decoration-color: #808000\">default</span>=<span style=\"color: #ff0000; text-decoration-color: #ff0000; font-style: italic\">False</span><span style=\"font-weight: bold\">)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">model_fields_set</span> = <span style=\"font-weight: bold\">{</span><span style=\"color: #008000; text-decoration-color: #008000\">'results'</span>, <span style=\"color: #008000; text-decoration-color: #008000\">'has_scores'</span>, <span style=\"color: #008000; text-decoration-color: #008000\">'query'</span><span style=\"font-weight: bold\">}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">query</span> = <span style=\"color: #008000; text-decoration-color: #008000\">'0-dimensional biomaterials show inductive properties.'</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000; font-style: italic\">results</span> = <span style=\"font-weight: bold\">[</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Periosteal bone formation--a neglected determinant of bone strength. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Life forms that have low body mass can hunt for food on the undersurface of branches or</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">along shear cliff faces quite unperturbed by gravity. For larger animals, the hunt for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dinner and the struggle to avoid becoming someone else's meal require rapid movement </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">against gravity. This need is met by the lever function of long bones, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional masterpieces of biomechanical engineering that, by their material </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">composition and structural design, achieve the contradictory properties of stiffness </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and flexibility, strength and lightness.1 Material stiffness results from the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">encrusting of the triple-helical structure of collagen type I with hydroxyapatite </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">crystals, which confers . . .\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4983</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.024103358387947083</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">1</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Epithelial and mesenchymal subpopulations within normal basal breast </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell lines exhibit distinct stem cell/progenitor properties. It has been proposed that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">epithelial-mesenchymal transition (EMT) in mammary epithelial cells and breast cancer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells generates stem cell features, and that the presence of EMT characteristics in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">claudin-low breast tumors reveals their origin in basal stem cells. It remains to be </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">determined, however, whether EMT is an inherent property of normal basal stem cells, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and if the presence of a mesenchymal-like phenotype is required for the maintenance of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">all their stem cell properties. We used nontumorigenic basal cell lines as models of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">normal stem cells/progenitors and demonstrate that these cell lines contain an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">epithelial subpopulation (\"EpCAM+,\" epithelial cell adhesion molecule positive </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">[EpCAM(pos)]/CD49f(high)) that spontaneously generates mesenchymal-like cells </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(\"Fibros,\" EpCAM(neg)/CD49f(med/low)) through EMT. Importantly, stem cell/progenitor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties such as regenerative potential, high aldehyde dehydrogenase 1 activity, and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">formation of three-dimensional acini-like structures predominantly reside within EpCAM+</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells, while Fibros exhibit invasive behavior and mammosphere-forming ability. A gene </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">expression profiling meta-analysis established that EpCAM+ cells show a luminal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">progenitor-like expression pattern, while Fibros most closely resemble stromal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fibroblasts but not stem cells. Moreover, Fibros exhibit partial myoepithelial traits </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and strong similarities with claudin-low breast cancer cells. Finally, we demonstrate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that Slug and Zeb1 EMT-inducers control the progenitor and mesenchymal-like phenotype </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in EpCAM+ cells and Fibros, respectively, by inhibiting luminal differentiation. In </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">conclusion, nontumorigenic basal cell lines have intrinsic capacity for EMT, but a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mesenchymal-like phenotype does not correlate with the acquisition of global stem </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell/progenitor features. Based on our findings, we propose that EMT in normal basal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells and claudin-low breast cancers reflects aberrant/incomplete myoepithelial </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differentiation.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5836</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.004422821570187807</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">2</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Geometry, epistasis, and developmental patterning. Developmental </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signaling networks are composed of dozens of components whose interactions are very </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">difficult to quantify in an embryo. Geometric reasoning enumerates a discrete hierarchy</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of phenotypic models with a few composite variables whose parameters may be defined by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in vivo data. Vulval development in the nematode Caenorhabditis elegans is a classic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">model for the integration of two signaling pathways; induction by EGF and lateral </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signaling through Notch. Existing data for the relative probabilities of the three </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">possible terminal cell types in diverse genetic backgrounds as well as timed ablation </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of the inductive signal favor one geometric model and suffice to fit most of its </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">parameters. The model is fully dynamic and encompasses both signaling and commitment. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">It then predicts the correlated cell fate probabilities for a cross between any two </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">backgrounds/conditions. The two signaling pathways are combined additively, without </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">interactions, and epistasis only arises from the nonlinear dynamical flow in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">landscape defined by the geometric model. In this way, the model quantitatively fits </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">genetic experiments purporting to show mutual pathway repression. The model quantifies </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the contributions of extrinsic vs. intrinsic sources of noise in the penetrance of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mutant phenotypes in signaling hypomorphs and explains available experiments with no </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">additional parameters. Data for anchor cell ablation fix the parameters needed to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">define Notch autocrine signaling.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7912</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0034973807632923126</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">3</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Large deformation of red blood cell ghosts in a simple shear flow. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Red blood cells are known to change shape in response to local flow conditions. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Deformability affects red blood cell physiological function and the hydrodynamic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties of blood. The immersed boundary method is used to simulate three-dimensional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">membrane-fluid flow interactions for cells with the same internal and external fluid </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">viscosities. The method has been validated for small deformations of an initially </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">spherical capsule in simple shear flow for both neo-Hookean and the Evans-Skalak </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">membrane models. Initially oblate spheroidal capsules are simulated and it is shown </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that the red blood cell membrane exhibits asymptotic behavior as the ratio of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dilation modulus to the extensional modulus is increased and a good approximation of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">local area conservation is obtained. Tank treading behavior is observed and its period </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">calculated.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">18670</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0010757819982245564</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The carboxyl terminus of human cytomegalovirus-encoded 7 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">US28 is one of four 7 transmembrane (7TM) chemokine receptors encoded by human </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cytomegalovirus and has been shown to both signal and endocytose in a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ligand-independent, constitutively active manner. Here we show that the constitutive </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activity and constitutive endocytosis properties of US28 are separable entities in this</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">viral chemokine receptor. We generated chimeric and mutant US28 proteins that were </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">altered in either their constitutive endocytic (US28 Delta 300, US28 Delta 317, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">US28-NK1-ctail, and US28-ORF74-ctail) or signaling properties (US28R129A). By using </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">this series of mutants, we show that the cytoplasmic tail domain of US28 per se </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regulates receptor endocytosis, independent of the signaling ability of the core domain</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of US28. The constitutive endocytic property of the US28 c-tail was transposable to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">other 7TM receptors, the herpes virus 8-encoded ORF74 and the tachykinin NK1 receptor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(ORF74-US28-ctail and NK1-US28-ctail). Deletion of the US28 C terminus resulted in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reduced constitutive endocytosis and consequently enhanced signaling capacity of all </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">receptors tested as assessed by inositol phosphate turnover, NF-kappa B, and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cAMP-responsive element-binding protein transcription assays. We further show that the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">constitutive endocytic property of US28 affects the action of its chemokine ligand </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fractalkine/CX3CL1 and show that in the absence of the US28 C terminus, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fractalkine/CX3CL1 acts as an agonist on US28. This demonstrates for the first time </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that the endocytic properties of a 7TM receptor can camouflage the agonist properties </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of a ligand.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">19238</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0009564738720655441</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Cerebral organoids model human brain development and microcephaly The</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">complexity of the human brain has made it difficult to study many brain disorders in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">model organisms, highlighting the need for an in vitro model of human brain </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">development. Here we have developed a human pluripotent stem cell-derived </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional organoid culture system, termed cerebral organoids, that develop </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">various discrete, although interdependent, brain regions. These include a cerebral </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cortex containing progenitor populations that organize and produce mature cortical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">human cortical development, namely characteristic progenitor zone organization with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">abundant outer radial glial stem cells. Finally, we use RNA interference and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">patient-specific induced pluripotent stem cells to model microcephaly, a disorder that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">has been difficult to recapitulate in mice. We demonstrate premature neuronal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differentiation in patient organoids, a defect that could help to explain the disease </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">phenotype. Together, these data show that three-dimensional organoids can recapitulate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">development and disease even in this most complex human tissue.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">33370</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0008705182699486613</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'From Cell Differentiation to Cell Collectives: Bacillus subtilis Uses</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Division of Labor to Migrate The organization of cells, emerging from cell-cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">interactions, can give rise to collective properties. These properties are adaptive </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">when together cells can face environmental challenges that they separately cannot. One </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">particular challenge that is important for microorganisms is migration. In this study, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">we show how flagellum-independent migration is driven by the division of labor of two </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell types that appear during Bacillus subtilis sliding motility. Cell collectives </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organize themselves into bundles (called \"van Gogh bundles\") of tightly aligned cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">chains that form filamentous loops at the colony edge. We show, by time-course </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microscopy, that these loops migrate by pushing themselves away from the colony. The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">formation of van Gogh bundles depends critically on the synergistic interaction of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">surfactin-producing and matrix-producing cells. We propose that surfactin-producing </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells reduce the friction between cells and their substrate, thereby facilitating </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">matrix-producing cells to form bundles. The folding properties of these bundles </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">determine the rate of colony expansion. Our study illustrates how the simple </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organization of cells within a community can yield a strong ecological advantage. This </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is a key factor underlying the diverse origins of multicellularity.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">36474</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0007751494995318353</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'In situ regulation of DC subsets and T cells mediates tumor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regression in mice. Vaccines are largely ineffective for patients with established </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cancer, as advanced disease requires potent and sustained activation of CD8(+) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cytotoxic T lymphocytes (CTLs) to kill tumor cells and clear the disease. Recent </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">studies have found that subsets of dendritic cells (DCs) specialize in antigen </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cross-presentation and in the production of cytokines, which regulate both CTLs and T </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regulatory (Treg) cells that shut down effector T cell responses. Here, we addressed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the hypothesis that coordinated regulation of a DC network, and plasmacytoid DCs (pDCs)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and CD8(+) DCs in particular, could enhance host immunity in mice. We used </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">functionalized biomaterials incorporating various combinations of an inflammatory </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cytokine, immune danger signal, and tumor lysates to control the activation and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">localization of host DC populations in situ. The numbers of pDCs and CD8(+) DCs, and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the endogenous production of interleukin-12, all correlated strongly with the magnitude</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of protective antitumor immunity and the generation of potent CD8(+) CTLs. Vaccination </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">by this method maintained local and systemic CTL responses for extended periods while </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regression of distant and established melanoma tumors. The efficacy of this vaccine as </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">a monotherapy against large invasive tumors may be a result of the local activity of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">pDCs and CD8(+) DCs induced by persistent danger and antigen signaling at the vaccine </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">site. These results indicate that a critical pattern of DC subsets correlates with the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">evolution of therapeutic antitumor responses and provide a template for future vaccine </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">design.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">54440</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0007493325392715633</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">8</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The effects of prion protein proteolysis and disaggregation on the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">strain properties of hamster scrapie. Native mammalian prions exist in self-propagating</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">strains that exhibit distinctive clinical, pathological and biochemical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">characteristics. Prion strain diversity is associated with variations in PrP(Sc) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">conformation, but it remains unknown precisely which physical properties of the PrP(Sc)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">molecules are required to encipher mammalian prion strain phenotypes. In this study, we</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">subjected prion-infected brain homogenates derived from three different hamster scrapie</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">strains to either (i) proteinase K digestion or (ii) sonication, and inoculated the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">modified samples into normal hamsters. The results show that the strain-specific </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">clinical features and neuropathological profiles of inoculated animals were not </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">affected by either treatment. Similarly, the strain-dependent biochemical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">characteristics of the PrP(Sc) molecules (including electrophoretic mobility, glycoform</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">composition, conformational stability and susceptibility to protease digestion) in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">infected animals were unaffected by either proteolysis or sonication of the original </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inocula. These results indicate that the infectious strain properties of native prions </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">do not appear to be altered by PrP(Sc) disaggregation, and that maintenance of such </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties does not require the N-domain (approximately residues 23-90) of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">protease-resistant PrP(Sc) molecules or protease-sensitive PrP(Sc) molecules.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">70115</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.000624156731646508</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"High-performance neuroprosthetic control by an individual with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tetraplegia. BACKGROUND Paralysis or amputation of an arm results in the loss of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ability to orient the hand and grasp, manipulate, and carry objects, functions that are</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">essential for activities of daily living. Brain-machine interfaces could provide a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">solution to restoring many of these lost functions. We therefore tested whether an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">individual with tetraplegia could rapidly achieve neurological control of a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">high-performance prosthetic limb using this type of an interface. METHODS We implanted </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">two 96-channel intracortical microelectrodes in the motor cortex of a 52-year-old </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">individual with tetraplegia. Brain-machine-interface training was done for 13 weeks </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with the goal of controlling an anthropomorphic prosthetic limb with seven degrees of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">freedom (three-dimensional translation, three-dimensional orientation, one-dimensional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">grasping). The participant's ability to control the prosthetic limb was assessed with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">clinical measures of upper limb function. This study is registered with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ClinicalTrials.gov, NCT01364480. FINDINGS The participant was able to move the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">prosthetic limb freely in the three-dimensional workspace on the second day of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">training. After 13 weeks, robust seven-dimensional movements were performed routinely. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Mean success rate on target-based reaching tasks was 91·6% (SD 4·4) versus median </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">chance level 6·2% (95% CI 2·0-15·3). Improvements were seen in completion time </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(decreased from a mean of 148 s [SD 60] to 112 s [6]) and path efficiency (increased </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from 0·30 [0·04] to 0·38 [0·02]). The participant was also able to use the prosthetic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">limb to do skilful and coordinated reach and grasp movements that resulted in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">clinically significant gains in tests of upper limb function. No adverse events were </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reported. INTERPRETATION With continued development of neuroprosthetic limbs, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">individuals with long-term paralysis could recover the natural and intuitive command </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signals for hand placement, orientation, and reaching, allowing them to perform </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activities of daily living. FUNDING Defense Advanced Research Projects Agency, National</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Institutes of Health, Department of Veterans Affairs, and UPMC Rehabilitation </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Institute.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">70490</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0006221356452442706</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">10</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Microfluidic platform to evaluate migration of cells from patients </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with DYT1 dystonia. BACKGROUND Microfluidic platforms for quantitative evaluation of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell biologic processes allow low cost and time efficient research studies of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">biological and pathological events, such as monitoring cell migration by real-time </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">imaging. In healthy and disease states, cell migration is crucial in development and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">wound healing, as well as to maintain the body's homeostasis. NEW METHOD The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microfluidic chambers allow precise measurements to investigate whether fibroblasts </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">carrying a mutation in the TOR1A gene, underlying the hereditary neurologic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">disease--DYT1 dystonia, have decreased migration properties when compared to control </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells. RESULTS We observed that fibroblasts from DYT1 patients showed abnormalities in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">basic features of cell migration, such as reduced velocity and persistence of movement.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">COMPARISON WITH EXISTING METHOD The microfluidic method enabled us to demonstrate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reduced polarization of the nucleus and abnormal orientation of nuclei and Golgi inside</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the moving DYT1 patient cells compared to control cells, as well as vectorial movement </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of single cells. CONCLUSION We report here different assays useful in determining </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">various parameters of cell migration in DYT1 patient cells as a consequence of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">TOR1A gene mutation, including a microfluidic platform, which provides a means to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">evaluate real-time vectorial movement with single cell resolution in a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional environment.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">72159</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0005953511572442949</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">11</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Mechanical modulation of receptor-ligand interactions at cell-cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">interfaces. Cell surface receptors have been extensively studied because they initiate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and regulate signal transduction cascades leading to a variety of functional cellular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">outcomes. An important class of immune receptors (e.g., T-cell antigen receptors) whose</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ligands are anchored to the surfaces of other cells remain poorly understood. The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mechanism by which ligand binding initiates receptor phosphorylation, a process termed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">\"receptor triggering\", remains controversial. Recently, direct measurements of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(two-dimensional) receptor-ligand complex lifetimes at cell-cell interface were found </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to be smaller than (three-dimensional) lifetimes in solution but the underlying </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mechanism is unknown. At the cell-cell interface, the receptor-ligand complex spans a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">short intermembrane distance (15 nm) compared to long surface molecules (LSMs) whose </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ectodomains span &gt;40 nm and these LSMs include phosphatases (e.g., CD45) that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dephosphorylate the receptor. It has been proposed that size-based segregation of LSMs </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from a receptor-ligand complex is a mechanism of receptor triggering but it is unclear </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">whether the mechanochemistry supports such small-scale segregation. Here we present a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nanometer-scale mathematical model that couples membrane elasticity with the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">compressional stiffness and lateral mobility of LSMs. We find robust supradiffusive </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">segregation of LSMs from a single receptor-ligand complex. The model predicts that LSM </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">redistribution will result in a time-dependent tension on the complex leading to a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">decreased two-dimensional lifetime. Interestingly, the model predicts a nonlinear </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">relationship between the three- and two-dimensional lifetimes, which can enhance the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ability of receptors to discriminate between similar ligands.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">79447</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0005835893680341542</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">12</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Metastatic colonization requires the repression of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">epithelial-mesenchymal transition inducer Prrx1. The epithelial-mesenchymal transition </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(EMT) is required in the embryo for the formation of tissues for which cells originate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">far from their final destination. Carcinoma cells hijack this program for tumor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dissemination. The relevance of the EMT in cancer is still debated because it is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">unclear how these migratory cells colonize distant tissues to form macrometastases. We </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">which revert to the epithelial phenotype concomitant with the acquisition of stem cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and stemness, and is a biomarker associated with patient survival and lack of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">metastasis.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">87758</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0005717248423025012</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">13</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'microRNA-31/factor-inhibiting hypoxia-inducible factor 1 nexus </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regulates keratinocyte differentiation. Notch plays a critical role in the transition </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from proliferation to differentiation in the epidermis and corneal epithelium. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Furthermore, aberrant Notch signaling is a feature of diseases like psoriasis, eczema, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nonmelanoma skin cancer, and melanoma where differentiation and proliferation are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">impaired. Whereas much is known about the downstream events following Notch signaling, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">factors responsible for negatively regulating Notch receptor signaling after ligand </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activation are incompletely understood. Notch can undergo hydroxylation by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">factor-inhibiting hypoxia-inducible factor 1 (FIH-1); however, the biological </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">significance of this phenomenon is unclear. Here we show that FIH-1 expression is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">up-regulated in diseased epidermis and corneal epithelium. Elevating FIH-1 levels in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">primary human epidermal keratinocytes (HEKs) and human corneal epithelial keratinocytes</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(HCEKs) impairs differentiation in submerged cultures and in a \"three-dimensional\" </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organotypic raft model of human epidermis, in part, via a coordinate decrease in Notch </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signaling. Knockdown of FIH-1 enhances keratinocyte differentiation. Loss of FIH-1 in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">vivo increased Notch activity in the limbal epithelium, resulting in a more </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differentiated phenotype. microRNA-31 (miR-31) is an endogenous negative regulator of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">FIH-1 expression that results in keratinocyte differentiation, mediated by Notch </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activation. Ectopically expressing miR-31 in an undifferentiated corneal epithelial </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell line promotes differentiation and recapitulates a corneal epithelium in a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional raft culture model. Our results define a previously unknown mechanism</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">for keratinocyte fate decisions where Notch signaling potential is, in part, controlled</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">through a miR-31/FIH-1 nexus.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">92308</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0004151232133153826</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">14</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Organization of the mitotic chromosome. Mitotic chromosomes are among</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the most recognizable structures in the cell, yet for over a century their internal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organization remains largely unsolved. We applied chromosome conformation capture </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">folding states of the human genome. We show that the highly compartmentalized and cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">type-specific organization described previously for nonsynchronous cells is restricted </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to interphase. In metaphase, we identified a homogenous folding state that is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">locus-independent, common to all chromosomes, and consistent among cell types, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">suggesting a general principle of metaphase chromosome organization. Using polymer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">simulations, we found that metaphase Hi-C data are inconsistent with classic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">hierarchical models and are instead best described by a linearly organized </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">longitudinally compressed array of consecutive chromatin loops.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">92499</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.000411765999160707</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">15</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Interleukin 6 plays a key role in the development of antigen-induced </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">arthritis. To investigate the direct role of interleukin (IL) 6 in the development of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">generations into C57BL/6 mice, a strain of mice with a genetic background of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">susceptibility for antigen-induced arthritis (AIA). Both histological and immunological</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">littermates after the induction of AIA. Although all IL-6 +/+ mice developed severe </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">both IL-1beta and tumor necrosis factor alpha, but not for IL-6, was detected in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cartilage destruction than either IL-1beta or tumor necrosis factor alpha. In </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">immunological comparisons, both antigen-specific in vitro proliferative response in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">IL-6 -/- mice produced many more Th2 cytokines than did IL-6 +/+ mice with either </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">results indicate that IL-6 may play a key role in the development of AIA at the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inductive as well as the effector phase, and the blockade of IL-6 is possibly </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">beneficial in the treatment of rheumatoid arthritis.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">97884</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0003154606674797833</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">16</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Three-Dimensional Modeling and Quantitative Analysis of Gap Junction </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Distributions in Cardiac Tissue Gap junctions play a fundamental role in intercellular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">communication in cardiac tissue. Various types of heart disease including hypertrophy </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and ischemia are associated with alterations of the spatial arrangement of gap </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">junctions. Previous studies applied two-dimensional optical and electron-microscopy to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">primarily found at cell ends, but can be found also in more central regions. In this </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">study, we extended these approaches toward three-dimensional reconstruction of gap </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">junction distributions based on high-resolution scanning confocal microscopy and image </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">processing. We developed methods for quantitative characterization of gap junction </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">distributions based on analysis of intensity profiles along the principal axes of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">myocytes. The analyses characterized gap junction polarization at cell ends and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">higher-order statistical image moments of intensity profiles. The methodology was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">gap junction distributions. In particular, the analysis demonstrated that the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">distributions exhibit significant variability with respect to polarization, skewness, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and kurtosis. We suggest that this methodology provides a quantitative alternative to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">current approaches based on visual inspection, with applications in particular in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">characterization of engineered and diseased myocardium. Furthermore, we propose that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">these data provide improved input for computational modeling of cardiac conduction.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">102662</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00025019916938617826</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">17</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Nanoenzymology of the 20S proteasome: proteasomal actions are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">controlled by the allosteric transition. The proteasome is a major cytosolic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteolytic assembly, essential for the physiology of eukaryotic cells. Both the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">architecture and enzymatic properties of the 20S proteasome are relatively well </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">understood. However, despite longstanding interest, the integration of structural and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">functional properties of the proteasome into a coherent model explaining the mechanism </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of its enzymatic actions has been difficult. Recently, we used tapping mode atomic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">force microscopy (AFM) in liquid to demonstrate that the alpha-rings of the proteasome </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">imaged in a top-view position repeatedly switched between their open and closed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">conformations, apparently to control access to the central channel. Here, we show with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">AFM that the molecules in a side-view position acquired two stable conformations. The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">overall shapes of the 20S particles were classified as either barrel-like or </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cylinder-like. The relative abundance of the two conformers depended on the nature of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">their interactions with ligands. Similarly to the closed molecules in top view, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">barrels predominated in control or inhibited molecules. The cylinders and open </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">molecules prevailed when the proteasome was observed in the presence of peptide </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">substrates. Based on these data, we developed the two-state model of allosteric </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">transitions to explain the dynamics of proteasomal structure. This model helps to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">better understand the observed properties of the 20S molecule, and sets foundations for</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">further studies of the structural dynamics of the proteasome.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">103007</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00020507434965111315</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">18</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"The docking domain of histone H2A is required for H1 binding and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">RSC-mediated nucleosome remodeling Histone variants within the H2A family show high </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">divergences in their C-terminal regions. In this work, we have studied how these </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">divergences and in particular, how a part of the H2A COOH-terminus, the docking domain,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is implicated in both structural and functional properties of the nucleosome. Using </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">biochemical methods in combination with Atomic Force Microscopy and Electron </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the nucleosome. Deletion of this domain or replacement with the incomplete docking </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">domain from the variant H2A.Bbd results in significant structural alterations in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nucleosome, including an increase in overall accessibility to nucleases, un-wrapping of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">∼10 bp of DNA from each end of the nucleosome and associated changes in the entry/exit </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">angle of DNA ends. These structural alterations are associated with a reduced ability </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of the chromatin remodeler RSC to both remodel and mobilize the nucleosomes. Linker </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">histone H1 binding is also abrogated in nucleosomes containing the incomplete docking </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">domain of H2A.Bbd. Our data illustrate the unique role of the H2A-docking domain in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">coordinating the structural-functional aspects of the nucleosome properties. Moreover, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">our data suggest that incorporation of a 'defective' docking domain may be a primary </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structural role of H2A.Bbd in chromatin.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">104130</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00019022477499675006</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">19</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Direct observation of ligand recognition by T cells The activation of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">T cells through interaction of their T-cell receptors with antigenic peptide bound to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">major histocompatibility complex (MHC) on the surface of antigen presenting cells </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(APCs) is a crucial step in adaptive immunity. Here we use three-dimensional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fluorescence microscopy to visualize individual peptide–I-Ek class II MHC complexes </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">labelled with the phycobiliprotein phycoerythrin in an effort to characterize T-cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sensitivity and the requirements for forming an immunological synapse in single cells. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">We show that T cells expressing the CD4 antigen respond with transient calcium </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signalling to even a single agonist peptide–MHC ligand, and that the organization of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">molecules in the contact zone of the T cell and APC takes on the characteristics of an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">immunological synapse when only about ten agonists are present. This sensitivity is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">highly dependant on CD4, because blocking this molecule with antibodies renders T cells</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">unable to detect less than about 30 ligands.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">106301</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00017890066374093294</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">20</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Data analysis methods for detection of differential protein </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">expression in two-dimensional gel electrophoresis. The recent development of microarray</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">technology has led statisticians and bioinformaticians to develop new statistical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">methodologies for comparing different biological samples. The objective is to identify </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">a small number of differentially expressed genes from among thousands. In quantitative </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteomics, analysis of protein expression using two-dimensional gel electrophoresis </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">shows some similarities with transcriptomic studies. Thus, the goal of this study was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to evaluate different data analysis methodologies widely used in array analysis using </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">different proteomic data sets of hundreds of proteins. Even with few replications, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">significance analysis of microarrays method appeared to be more powerful than the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Student's t test in truly declaring differentially expressed proteins. This procedure </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">will avoid wasting time due to false positives and losing information with false </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">negatives.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">116792</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00017818412743508816</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">21</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Three-dimensional superresolution colocalization of intracellular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">protein superstructures and the cell surface in live Caulobacter crescentus. Recently, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">single-molecule imaging and photocontrol have enabled superresolution optical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microscopy of cellular structures beyond Abbe's diffraction limit, extending the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">frontier of noninvasive imaging of structures within living cells. However, live-cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">superresolution imaging has been challenged by the need to image three-dimensional (3D)</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structures relative to their biological context, such as the cellular membrane. We have</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">developed a technique, termed superresolution by power-dependent active intermittency </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and points accumulation for imaging in nanoscale topography (SPRAIPAINT) that combines </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">imaging of intracellular enhanced YFP (eYFP) fusions (SPRAI) with stochastic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">localization of the cell surface (PAINT) to image two different fluorophores </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sequentially with only one laser. Simple light-induced blinking of eYFP and collisional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">flux onto the cell surface by Nile red are used to achieve single-molecule </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">localizations, without any antibody labeling, cell membrane permeabilization, or </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">thiol-oxygen scavenger systems required. Here we demonstrate live-cell 3D </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">superresolution imaging of Crescentin-eYFP, a cytoskeletal fluorescent protein fusion, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">colocalized with the surface of the bacterium Caulobacter crescentus using a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">double-helix point spread function microscope. Three-dimensional colocalization of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">intracellular protein structures and the cell surface with superresolution optical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microscopy opens the door for the analysis of protein interactions in living cells with</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">excellent precision (20-40 nm in 3D) over a large field of view (12 12 μm).\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">118568</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00017008179565891623</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">22</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The Epithelial-Mesenchymal Transition Generates Cells with Properties</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of Stem Cells The epithelial-mesenchymal transition (EMT) is a key developmental </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">program that is often activated during cancer invasion and metastasis. We here report </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">results in the acquisition of mesenchymal traits and in the expression of stem-cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">markers. Furthermore, we show that those cells have an increased ability to form </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mammospheres, a property associated with mammary epithelial stem cells. Independent of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">this, stem cell-like cells isolated from HMLE cultures form mammospheres and express </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">isolated either from mouse or human mammary glands or mammary carcinomas express EMT </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">markers. Finally, transformed human mammary epithelial cells that have undergone an EMT</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">form mammospheres, soft agar colonies, and tumors more efficiently. These findings </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">illustrate a direct link between the EMT and the gain of epithelial stem cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">120626</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00013697220128960907</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">23</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'An integrin β3–KRAS–RalB complex drives tumour stemness and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">resistance to EGFR inhibition Tumour cells, with stem-like properties, are highly </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">aggressive and often show drug resistance. Here, we reveal that integrin αvβ3 serves as</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">a marker of breast, lung and pancreatic carcinomas with stem-like properties that are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">highly resistant to receptor tyrosine kinase inhibitors such as erlotinib. This was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">observed in vitro and in mice bearing patient-derived tumour xenografts or in clinical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">specimens from lung cancer patients who had progressed on erlotinib. Mechanistically, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">αvβ3, in the unliganded state, recruits KRAS and RalB to the tumour cell plasma </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">membrane, leading to the activation of TBK1 and NF-κB. In fact, αvβ3 expression and the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">resulting KRAS–RalB–NF-κB pathway were both necessary and sufficient for tumour </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">initiation, anchorage independence, self-renewal and erlotinib resistance. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Pharmacological targeting of this pathway with bortezomib reversed both tumour stemness</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and erlotinib resistance. These findings not only identify αvβ3 as a marker/driver of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">carcinoma stemness but also reveal a therapeutic strategy to sensitize such tumours to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">RTK inhibition.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">123859</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0001302049058722332</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">24</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'An atlas of active enhancers across human cell types and tissues </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Enhancers control the correct temporal and cell-type-specific activation of gene </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">expression in multicellular eukaryotes. Knowing their properties, regulatory activity </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and targets is crucial to understand the regulation of differentiation and homeostasis.</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Here we use the FANTOM5 panel of samples, covering the majority of human tissues and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">enhancers share properties with CpG-poor messenger RNA promoters but produce </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">which is strongly related to enhancer activity. The atlas is used to compare regulatory</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">programs between different cells at unprecedented depth, to identify disease-associated</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regulatory single nucleotide polymorphisms, and to classify cell-type-specific and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">ubiquitous enhancers. We further explore the utility of enhancer redundancy, which </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">explains gene expression strength rather than expression patterns. The online FANTOM5 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">enhancer atlas represents a unique resource for studies on cell-type-specific enhancers</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and gene regulation.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">140874</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00012895374675281346</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">25</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Advances in high-resolution imaging--techniques for three-dimensional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">imaging of cellular structures. A fundamental goal in biology is to determine how </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cellular organization is coupled to function. To achieve this goal, a better </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">understanding of organelle composition and structure is needed. Although visualization </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of cellular organelles using fluorescence or electron microscopy (EM) has become a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">common tool for the cell biologist, recent advances are providing a clearer picture of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the cell than ever before. In particular, advanced light-microscopy techniques are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">achieving resolutions below the diffraction limit and EM tomography provides </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">high-resolution three-dimensional (3D) images of cellular structures. The ability to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">perform both fluorescence and electron microscopy on the same sample (correlative light</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and electron microscopy, CLEM) makes it possible to identify where a fluorescently </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">labeled protein is located with respect to organelle structures visualized by EM. Here,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">we review the current state of the art in 3D biological imaging techniques with a focus</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">on recent advances in electron microscopy and fluorescence super-resolution </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">techniques.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">143251</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.0001272441731998697</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">26</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Structural insights into calicivirus attachment and uncoating. The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">significance. In humans, caliciviruses are a major cause of acute gastroenteritis, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">disease are documented. Investigation of virus-host interactions is limited by a lack </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of culture systems for many viruses in this family. Feline calicivirus (FCV), a member </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of the Vesivirus genus, provides a tractable model, since it may be propagated in cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">functional receptor for FCV. We have analyzed the structure of this virus-receptor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">complex by cryo-electron microscopy and three-dimensional image reconstruction, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">combined with fitting of homology modeled high-resolution coordinates. We show that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">VP1, inducing conformational changes in the viral capsid. This study provides the first</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structural view of a native calicivirus-protein receptor complex and insights into the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mechanisms of virus attachment and uncoating.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">152245</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00012399932893458754</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">27</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"CDD: conserved domains and protein three-dimensional structure CDD, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the Conserved Domain Database, is part of NCBI's Entrez query and retrieval system and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">provides annotation of protein sequences with the location of conserved domain </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">footprints and functional sites inferred from these footprints. Pre-computed annotation</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is available via Entrez, and interactive search services accept single protein or </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nucleotide queries, as well as batch submissions of protein query sequences, utilizing </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and full-length protein model collections, and maintains an active curation effort that</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">aims at providing fine grained classifications for major and well-characterized protein</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">domain families, as supported by available protein three-dimensional (3D) structure and</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the published literature. To this date, the majority of protein 3D structures are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">represented by models tracked by CDD, and CDD curators are characterizing novel </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">families that emerge from protein structure determination efforts.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">153744</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00012311134196352214</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">28</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'2D and 3D Stem Cell Models of Primate Cortical Development Identify </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Species-Specific Differences in Progenitor Behavior Contributing to Brain Size. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Variation in cerebral cortex size and complexity is thought to contribute to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differences in cognitive ability between humans and other animals. Here we compare </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cortical progenitor cell output in humans and three nonhuman primates using directed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">primate cortical progenitors proliferate for a protracted period of time, during which </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">they generate early-born neurons, in contrast to rodents, where this expansion phase </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">largely ceases before neurogenesis begins. The extent of this additional cortical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">progenitor expansion differs among primates, leading to differences in the number of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">neurons generated by each progenitor cell. We found that this mechanism for controlling</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cortical size is regulated cell autonomously in culture, suggesting that primate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cerebral cortex size is regulated at least in part at the level of individual cortical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">progenitor cell clonal output.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">159469</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00011527373862918466</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">29</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Three-dimensional structure of the AAH26994.1 protein from Mus </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">musculus, a putative eukaryotic Urm1. We have used NMR spectroscopy to determine the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">solution structure of protein AAH26994.1 from Mus musculus and propose that it </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">represents the first three-dimensional structure of a ubiquitin-related modifier 1 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(Urm1) protein. Amino acid sequence comparisons indicate that AAH26994.1 belongs to the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Urm1 family of ubiquitin-like modifier proteins. The best characterized member of this </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">family has been shown to be involved in nutrient sensing, invasive growth, and budding </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in yeast. Proteins in this family have only a weak sequence similarity to ubiquitin, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and the structure of AAH26994.1 showed a much closer resemblance to MoaD subunits of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">molybdopterin synthases (known structures are of three bacterial MoaD proteins with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">14%-26% sequence identity to AAH26994.1). The structures of AAH26994.1 and the MoaD </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins each contain the signature ubiquitin secondary structure fold, but all differ </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from ubiquitin largely in regions outside of this fold. This structural similarity </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">bolsters the hypothesis that ubiquitin and ubiquitin-related proteins evolved from a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">protein-based sulfide donor system of the molybdopterin synthase type.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">164189</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00011244910274399444</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">30</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Laminin-based cell adhesion anchors microtubule plus ends to the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">epithelial cell basal cortex through LL5α/β LL5beta has been identified as a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microtubule-anchoring factor that attaches EB1/CLIP-associating protein (CLASP)-bound </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microtubule plus ends to the cell cortex. In this study, we show that LL5beta and its </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">homologue LL5alpha (LL5s) colocalize with autocrine laminin-5 and its receptors, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">integrins alpha3beta1 and alpha6beta4, at the basal side of fully polarized epithelial </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sheets. Depletion of both laminin receptor integrins abolishes the cortical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">localization of LL5s, whereas LL5 depletion reduces the amount of integrin alpha3 at </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the basal cell cortex. Activation of integrin alpha3 is sufficient to initiate LL5 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">accumulation at the cell cortex. LL5s form a complex with the cytoplasmic tails of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">these integrins, but their interaction might be indirect. Analysis of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional distribution of microtubule growth by visualizing EB1-GFP in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">epithelial sheets in combination with RNA interference reveals that LL5s are required </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to maintain the density of growing microtubules selectively at the basal cortex. These </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">findings reveal that signaling from laminin-integrin associations attaches microtubule </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">plus ends to the epithelial basal cell cortex.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">164985</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00011107359023299068</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">31</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Protoplasmic astrocytes in CA1 stratum radiatum occupy separate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">anatomical domains. Protoplasmic astrocytes are increasingly thought to interact </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">extensively with neuronal elements in the brain and to influence their activity. Recent</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reports have also begun to suggest that physiologically, and perhaps functionally, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">diverse forms of these cells may be present in the CNS. Our current understanding of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">astrocyte form and distribution is based predominantly on studies that used the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">astrocytic marker glial fibrillary acidic protein (GFAP) and on studies using </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">metal-impregnation techniques. The prevalent opinion, based on studies using these </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">methods, is that astrocytic processes overlap extensively and primarily share the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">underlying neuropil. However, both of these techniques have serious shortcomings for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">visualizing the interactions among these structurally complex cells. In the present </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">study, intracellular injection combined with immunohistochemistry for GFAP show that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">GFAP delineates only approximately 15% of the total volume of the astrocyte. As a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">result, GFAP-based images have led to incorrect conclusions regarding the interaction </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of processes of neighboring astrocytes. To investigate these interactions in detail, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">groups of adjacent protoplasmic astrocytes in the CA1 stratum radiatum were injected </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with fluorescent intracellular tracers of distinctive emissive wavelengths and analyzed</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">using three-dimensional (3D) confocal analysis and electron microscopy. Our findings </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">show that protoplasmic astrocytes establish primarily exclusive territories. The </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">knowledge of how the complex morphology of protoplasmic astrocytes affects their 3D </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">relationships with other astrocytes, oligodendroglia, neurons, and vasculature of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">brain should have important implications for our understanding of nervous system </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">function.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">169264</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00010752250091172755</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">32</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'The S. cerevisiae Rrm3p DNA helicase moves with the replication fork </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and affects replication of all yeast chromosomes. The Saccharomyces cerevisiae DNA </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">helicase Rrm3p is needed for normal fork progression through &gt;1000 discrete sites </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">scattered throughout the genome. Here we show that replication of all yeast chromosomes</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">was markedly delayed in rrm3 cells. Delayed replication was seen even in a region that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">lacks any predicted Rrm3p-dependent sites. Based on the pattern of replication </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">intermediates in two-dimensional gels, the rate of fork movement in rrm3 cells appeared</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">similar to wild-type except at known Rrm3p-dependent sites. These data suggest that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">although Rrm3p has a global role in DNA replication, its activity is needed only or </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">primarily at specific, difficult-to-replicate sites. By the criterion of chromatin </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">immunoprecipitation, Rrm3p was associated with both Rrm3p-dependent and -independent </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sites, and moved with the replication fork through both. In addition, Rrm3p interacted </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with Pol2p, the catalytic subunit of DNA polymerase epsilon, in vivo. Thus, rather than</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">being recruited to its sites of action when replication forks stall at these sites, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Rrm3p is likely a component of the replication fork apparatus.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">175735</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">0.00010532455780776218</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">33</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Corresponding Author: In higher eukaryotes, introns are spliced out </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of protein-coding mRNAs by the spliceosome, a massive complex comprising five </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">non-coding RNAs (ncRNAs) and about 200 proteins. By comparing the differences between </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">spliceosomal proteins from many basal eukaryotic lineages, it is possible to infer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties of the splicing system in the last common ancestor of extant eukaryotes, the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">eukaryotic ancestor. We begin with the hypothesis that, similar to intron length (that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">appears to have increased in multicellular eukaryotes), the spliceosome has increased </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in complexity throughout eukaryotic evolution. However, examination of the distribution</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of spliceosomal components indicates that not only was a spliceosome present in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">eukaryotic ancestor but it also contained most of the key components found in today\\'s </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">eukaryotes. All the small nuclear ribonucleoproteins (snRNPs) protein components are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">likely to have been present, as well as many splicing-related proteins. Both major and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">trans-splicing are likely to have been present, and the spliceosome had already formed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">links with other cellular processes such as transcription and capping. However, there </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is no evidence as yet to suggest that minor (U12-dependent) splicing was present in the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">eukaryotic ancestor. Although the last common ancestor of extant eukaryotes appears to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">show much of the molecular complexity seen today, we do not, from this work, infer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">anything of the properties of the earlier \"first eukaryote. \"'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">188911</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.985562792280689e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">34</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'High-resolution sperm typing of meiotic recombination in the mouse </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">MHC Ebeta gene. Meiotic crossovers detected by pedigree analysis in the mouse MHC </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cluster into hotspots. To explore the properties of hotspots, we subjected the class II</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">E(beta) gene to high-resolution sperm crossover analysis. We confirm the presence of a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">highly localized hotspot 1.0-1.6 kb wide in the second intron of E(beta) and show that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">it is flanked by DNA which is almost completely recombinationally inert. Mice </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">heterozygous for haplotype s and another MHC haplotype show major haplotype-dependant </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">variation in crossover rate but always the same hotspot, even in crosses including the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">highly diverged p haplotype. Crossovers in reciprocal orientations occur at similar </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">rates but show different distributions across the hotspot, with the position of centre </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">points in the two orientations shifted on average by 400 bp. This asymmetry results in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">crossover products showing biased gene conversion in favour of hotspot markers from the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">non-initiating haplotype, and supports the double-strand break repair model of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">recombination, with haplotype s as the most efficient crossover initiator. The detailed</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">behaviour of the E(beta) hotspot, including evidence for highly localized recombination</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">initiation, is strikingly similar to human hotspots.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">195352</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.964589844457805e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">35</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Mechanisms that Specify Promoter Nucleosome Location and Identity The</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">chromatin architecture of eukaryotic gene promoters is generally characterized by a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nucleosome-free region (NFR) flanked by at least one H2A.Z variant nucleosome. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Computational predictions of nucleosome positions based on thermodynamic properties of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">DNA-histone interactions have met with limited success. Here we show that the action of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the essential RSC remodeling complex in S. cerevisiae helps explain the discrepancy </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">between theory and experiment. In RSC-depleted cells, NFRs shrink such that the average</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">positions of flanking nucleosomes move toward predicted sites. Nucleosome positioning </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">at distinct subsets of promoters additionally requires the essential Myb family </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins Abf1 and Reb1, whose binding sites are enriched in NFRs. In contrast, H2A.Z </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">deposition is dispensable for nucleosome positioning. By regulating H2A.Z deposition </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">using a steroid-inducible protein splicing strategy, we show that NFR establishment is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">necessary for H2A.Z deposition. These studies suggest an ordered pathway for the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">assembly of promoter chromatin architecture.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">202259</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.755350038176402e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">36</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Reserves, functional, immunoregulatory, and cytogenetic properties of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">bone marrow mesenchymal stem cells in patients with myelodysplastic syndromes. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Defective hematopoiesis supporting capacity of bone marrow (BM) stroma has been </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">implicated in the pathophysiology of myelodysplastic syndromes (MDS). The aim of this </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">study is to explore whether the BM stroma progenitors, namely the mesenchymal stem </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells (MSCs), are primarily affected in MDS by evaluating the reserves, the functional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties, as well as the cytogenetic characteristics, in comparison to BM </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">hematopoietic cells, in patients with de novo MDS (n = 13). The number, differentiation</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">potential toward adipocytes/chondrocytes/osteoblasts and immunosuppressive function in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">terms of inhibition of mitogen-induced T-cell proliferation did not differ </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">significantly between patient and normal (n = 20) MSCs. Patient MSCs did not show any </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">aberrations in the production of proinflammatory or growth-promoting cytokines and did </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">not harbor the cytogenetic abnormalities present in hematopoietic cells. Occasional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">patient and normal MSC cultures, however, developed irrelevant chromosomal alterations </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(trisomies 5 and 7) with uncertain pathophysiologic significance. Compared to controls,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">patient MSCs displayed impaired proliferative and clonogenic potential through passages</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that might represent a nonspecific abnormality associated with the chronic inflammatory</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">process present in patients' BM. These data suggest that BM MSCs from MDS patients do </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">not belong to the abnormal clone and do not represent the main cellular source </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">contributing to the inflammatory marrow microenvironment.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">207972</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.456238331040367e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">37</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Computational and Statistical Analyses of Amino Acid Usage and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Physico-Chemical Properties of the Twelve Late Embryogenesis Abundant Protein Classes </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to play </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">major roles in desiccation tolerance. Little is known about their structure - function </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">relationships because of the scarcity of 3-D structures for LEAPs. The previous </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">building of LEAPdb, a database dedicated to LEAPs from plants and other organisms, led </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to the classification of 710 LEAPs into 12 non-overlapping classes with distinct </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties. Using this resource, numerous physico-chemical properties of LEAPs and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">amino acid usage by LEAPs have been computed and statistically analyzed, revealing </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">distinctive features for each class. This unprecedented analysis allowed a rigorous </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">characterization of the 12 LEAP classes, which differed also in multiple structural and</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">physico-chemical features. Although most LEAPs can be predicted as intrinsically </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">disordered proteins, the analysis indicates that LEAP class 7 (PF03168) and probably </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">LEAP class 11 (PF04927) are natively folded proteins. This study thus provides a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">detailed description of the structural properties of this protein family opening the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">path toward further LEAP structure - function analysis. Finally, since each LEAP class </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">can be clearly characterized by a unique set of physico-chemical properties, this will </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">allow development of software to predict proteins as LEAPs.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">213017</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.174412116408348e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">38</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Cancer-associated adipocytes exhibit an activated phenotype and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">contribute to breast cancer invasion. Early local tumor invasion in breast cancer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">results in a likely encounter between cancer cells and mature adipocytes, but the role </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of these fat cells in tumor progression remains unclear. We show that murine and human </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in vitro and in vivo, using an original two-dimensional coculture system. Likewise, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">delipidation and decreased adipocyte markers associated with the occurrence of an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activated state characterized by overexpression of proteases, including matrix </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1β]. In the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">case of IL-6, we show that it plays a key role in the acquired proinvasive effect by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tumor cells. Equally important, we confirm the presence of these modified adipocytes in</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in vivo evidence that (i) invasive cancer cells dramatically impact surrounding </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">biological features sufficient to be named cancer-associated adipocytes (CAA); and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(iii) CAAs modify the cancer cell characteristics/phenotype leading to a more </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">aggressive behavior. Our results strongly support the innovative concept that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to promote tumor progression that might be amplified in obese patients.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">219475</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.117244917433709e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">39</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Three-dimensional chemical imaging of skin using stimulated Raman </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">scattering microscopy Abstract. Stimulated Raman scattering (SRS) microscopy is used to</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">generate structural and chemical three-dimensional images of native skin. We employed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">SRS microscopy to investigate the microanatomical features of skin and penetration of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">topically applied materials. Image depth stacks are collected at distinct wavelengths </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">corresponding to vibrational modes of proteins, lipids, and water in the skin. We </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">observed that corneocytes in stratum corneum are grouped together in clusters, 100 to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">250 μm in diameter, separated by 10- to 25-μm-wide microanatomical skin-folds called </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">canyons. These canyons occasionally extend down to depths comparable to that of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dermal–epidermal junction below the flat surface regions in porcine and human skin. SRS</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">imaging shows the distribution of chemical species within cell clusters and canyons. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Water is predominately located within the cell clusters, and its concentration rapidly </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">increases at the transition from stratum corneum to viable epidermis. Canyons do not </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">contain detectable levels of water and are rich in lipid material. Oleic acid-d34 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">applied to the skin surface lines the canyons down to a depth of 50 μm below the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">surface of the skin. This observation could have implications on the evaluation of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">penetration profiles of bioactive materials measured using traditional methods, such as</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tape-stripping.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">226488</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">9.109588427236304e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">40</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Synaptic islands defined by the territory of a single astrocyte. In </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">neuronal firing and coordinating synaptic networks. Little, however, is known about how</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">this is accomplished from a structural standpoint. To investigate the structural basis </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of astrocyte-mediated neuronal synchrony and synaptic coordination, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional relationships between cortical astrocytes and neurons was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">investigated. Using a transgenic and viral approach to label astrocytes with enhanced </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">green fluorescent protein, we performed a three-dimensional reconstruction of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">astrocytes from tissue sections or live animals in vivo. We found that cortical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">astrocytes occupy nonoverlapping territories similar to those described in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">enwraps on average four neuronal somata with an upper limit of eight. Single-neuron </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">dendrites. Together with the recent findings showing that glial Ca2+ signaling is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">gliotransmission, we propose the concept of functional islands of synapses in which </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">groups of synapses confined within the boundaries of an individual astrocyte are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">modulated by the gliotransmitter environment controlled by that astrocyte. Our </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">description offers a new structurally based conceptual framework to evaluate functional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">data involving interactions between neurons and astrocytes in the mammalian brain.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">236204</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">8.361691288882867e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">41</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'A 3D Map of the Yeast Kinetochore Reveals the Presence of Core and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Accessory Centromere-Specific Histone The budding yeast kinetochore is ~68 nm in length</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with a diameter slightly larger than a 25 nm microtubule. The kinetochores from the 16 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">chromosomes are organized in a stereotypic cluster encircling central spindle </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microtubules. Quantitative analysis of the inner kinetochore cluster (Cse4, COMA) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reveals structural features not apparent in singly attached kinetochores. The cluster </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of Cse4-containing kinetochores is physically larger perpendicular to the spindle axis </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">relative to the cluster of Ndc80 molecules. If there was a single Cse4 (molecule or </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nucleosome) at the kinetochore attached to each microtubule plus end, the cluster of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Cse4 would appear geometrically identical to Ndc80. Thus, the structure of the inner </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">kinetochore at the surface of the chromosomes remains unsolved. We have used point </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fluorescence microscopy and statistical probability maps to deduce the two-dimensional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mean position of representative components of the yeast kinetochore relative to the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mitotic spindle in metaphase. Comparison of the experimental images to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional architectures from convolution of mathematical models reveals a pool </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of Cse4 radially displaced from Cse4 at the kinetochore and kinetochore microtubule </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">plus ends. The pool of displaced Cse4 can be experimentally depleted in mRNA processing</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">pat1Δ or xrn1Δ mutants. The peripheral Cse4 molecules do not template outer kinetochore</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">components. This study suggests an inner kinetochore plate at the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">centromere-microtubule interface in budding yeast and yields information on the number </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of Ndc80 molecules at the microtubule attachment site.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">238409</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7.476454629795626e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">42</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Wnt signaling establishes anteroposterior neuronal polarity and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">requires retromer in C. elegans. Secreted Wnt proteins influence neural connectivity by</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">regulating axon guidance, dendritic morphogenesis and synapse formation. We report a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">new role for Wnt and Frizzled proteins in establishing the anteroposterior polarity of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the mechanosensory neurons ALM and PLM in C. elegans. Disruption of Wnt signaling leads</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to a complete inversion of ALM and PLM polarity: the anterior process adopts the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">length, branching pattern and synaptic properties of the wild-type posterior process, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and vice versa. Different but overlapping sets of Wnt proteins regulate neuronal </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">polarity in different body regions. Wnts act directly on PLM via the Frizzled LIN-17. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">In addition, we show that they are needed for axon branching and anteriorly directed </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">axon growth. We also find that the retromer, a conserved protein complex that mediates </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">transcytosis and endosome-to-Golgi protein trafficking, plays a key role in Wnt </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signaling. Deletion mutations of retromer subunits cause ALM and PLM polarity, and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">other Wnt-related defects. We show that retromer protein VPS-35 is required in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Wnt-expressing cells and propose that retromer activity is needed to generate a fully </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">active Wnt signal.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">243694</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">7.436614396283403e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">43</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Immune complex relay by subcapsular sinus macrophages and non-cognate</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">B cells drives antibody affinity maturation Subcapsular sinus (SCS) macrophages capture</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">antigens from lymph and present them intact for B cell encounter and follicular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">delivery. However, the properties of SCS macrophages are poorly defined. Here we show </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">lysosomal enzyme expression and retained opsonized antigens on their surface. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Intravital imaging revealed immune complexes moving along macrophage processes into the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">follicle. Moreover, noncognate B cells relayed antigen opsonized by newly produced </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">antibodies from the subcapsular region to the germinal center, and affinity maturation </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">was impaired when this transport process was disrupted. Thus, we characterize SCS </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">macrophages as specialized antigen-presenting cells functioning at the apex of an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">antigen transport chain that promotes humoral immunity.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">253672</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6.547493831021711e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">44</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Unique response pathways are established by allosteric interactions </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">among nuclear hormone receptors Heterodimerization is a common paradigm among </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">eukaryotic transcription factors. The 9-cis retinoic acid receptor (RXR) serves as a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">common heterodimerization partner for several nuclear receptors, including the thyroid </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">hormone receptor (T3R) and retinoic acid receptor (RAR). This raises the question as to</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">whether these complexes possess dual hormonal responsiveness. We devised a strategy to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">examine the transcriptional properties of each receptor individually or when tethered </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">to a heterodimeric partner. We find that the intrinsic binding properties of RXR are </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">masked in T3R-RXR and RAR-RXR heterodimers. In contrast, RXR is active as a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">non-DNA-binding cofactor with the NGFI-B/Nurr1 orphan receptors. Heterodimerization of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">RXR with constitutively active NGFI-B/Nurr1 creates a novel hormone-dependent complex. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">These findings suggest that allosteric interactions among heterodimers create complexes</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with unique properties. We suggest that allostery is a critical feature underlying the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">generation of diversity in hormone response networks.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">263364</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6.47211927571334e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">45</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Dynein is required for polarized dendritic transport and uniform </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microtubule orientation in axons Axons and dendrites differ in both microtubule </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organization and in the organelles and proteins they contain. Here we show that the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">microtubule motor dynein has a crucial role in polarized transport and in controlling </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the orientation of axonal microtubules in Drosophila melanogaster dendritic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">arborization (da) neurons. Changes in organelle distribution within the dendritic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">position. Dynein is also necessary for the dendrite-specific localization of Golgi </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">uniformly plus-end-distal; however, without dynein, axons contain both plus- and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">minus-end distal microtubules. These data suggest that dynein is required for the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">distinguishing properties of the axon and dendrites: without dynein, dendritic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">organelles and proteins enter the axon and the axonal microtubules are no longer </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">uniform in polarity.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">266641</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6.296775245573372e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">46</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'sasCIF: an extension of core Crystallographic Information File for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">SAS Data acquisition packages developed at different small angle scattering facilities </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">use different formats both for raw and processed data storage. To facilitate the data </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">exchange between laboratories, a consensus in the small angle scattering community has </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">been reached on an ASCII format for one-dimensional data which includes a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">self-describing header containing relevant information about the sample and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">instrumental conditions followed by raw or reduced data in a tabular form. This format </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">called sasCIF was implemented as an extension of core CIF (Crystallographic Information</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">File) dictionary.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">275294</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6.06991998211015e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">47</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Characterization of the interaction between retinoic acid </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">receptor/retinoid X receptor (RAR/RXR) heterodimers and transcriptional coactivators </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">through structural and fluorescence anisotropy studies. Retinoid receptors (RARs and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">RXRs) are ligand-activated transcription factors that regulate the transcription of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">target genes by recruiting coregulator complexes at cognate promoters. To understand </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the effects of heterodimerization and ligand binding on coactivator recruitment, we </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">solved the crystal structure of the complex between the RARbeta/RXRalpha ligand-binding</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">domain heterodimer, its 9-cis retinoic acid ligand, and an LXXLL-containing peptide </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(termed NR box 2) derived from the nuclear receptor interaction domain (NID) of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">TRAP220 coactivator. In parallel, we measured the binding affinities of the isolated NR</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">box 2 peptide or the full-length NID of the coactivator SRC-1 for retinoid receptors in</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the presence of various types of ligands. Our correlative analysis of three-dimensional</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structures and fluorescence data reveals that heterodimerization does not significantly</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">alter the structure of individual subunits or their intrinsic capacity to interact with</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">NR box 2. Similarly, we show that the ability of a protomer to recruit NR box 2 does </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">not vary as a function of the ligand binding status of the partner receptor. In </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">contrast, the strength of the overall association between the heterodimer and the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">full-length SRC-1 NID is dictated by the combinatorial action of RAR and RXR ligands, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the simultaneous presence of the two receptor agonists being required for highest </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">binding affinity. We identified an LXXLL peptide-driven mechanism by which the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">concerted reorientation of three phenylalanine side chains generates an \"aromatic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">clamp\" that locks the RXR activation helix H12 in the transcriptionally active </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">conformation. Finally, we show how variations of helix H11-ligand interactions can </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">alter the communication pathway linking helices H11, H12, and the connecting loop </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">L11-12 to the coactivator-binding site. Together, our results reveal molecular and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structural features that impact on the ligand-dependent interaction of the RAR/RXR </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">heterodimer with nuclear receptor coactivators.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">279052</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">6.0122129070805386e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">48</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Optogenetics reveal delayed afferent synaptogenesis on grafted </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">human-induced pluripotent stem cell-derived neural progenitors. Reprogramming of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">somatic cells into pluripotency stem cell state has opened new opportunities in cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">replacement therapy and disease modeling in a number of neurological disorders. It </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">still remains unknown, however, to what degree the grafted human-induced pluripotent </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">stem cells (hiPSCs) differentiate into a functional neuronal phenotype and if they </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">integrate into the host circuitry. Here, we present a detailed characterization of the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">functional properties and synaptic integration of hiPSC-derived neurons grafted in an </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in vitro model of hyperexcitable epileptic tissue, namely organotypic hippocampal slice</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cultures (OHSCs), and in adult rats in vivo. The hiPSCs were first differentiated into </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">long-term self-renewing neuroepithelial stem (lt-NES) cells, which are known to form </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">primarily GABAergic neurons. When differentiated in OHSCs for 6 weeks, lt-NES </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell-derived neurons displayed neuronal properties such as tetrodotoxin-sensitive </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sodium currents and action potentials (APs), as well as both spontaneous and evoked </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">postsynaptic currents, indicating functional afferent synaptic inputs. The grafted </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cells had a distinct electrophysiological profile compared to host cells in the OHSCs </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with higher input resistance, lower resting membrane potential, and APs with lower </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">amplitude and longer duration. To investigate the origin of synaptic afferents to the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">grafted lt-NES cell-derived neurons, the host neurons were transduced with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Channelrhodopsin-2 (ChR2) and optogenetically activated by blue light. Simultaneous </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">recordings of synaptic currents in grafted lt-NES cell-derived neurons using whole-cell</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">patch-clamp technique at 6 weeks after grafting revealed limited synaptic connections </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from host neurons. Longer differentiation times, up to 24 weeks after grafting in vivo,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">revealed more mature intrinsic properties and extensive synaptic afferents from host </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">neurons to the lt-NES cell-derived neurons, suggesting that these cells require </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">extended time for differentiation/maturation and synaptogenesis. However, even at this </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">later time point, the grafted cells maintained a higher input resistance. These data </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">indicate that grafted lt-NES cell-derived neurons receive ample afferent input from the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">host brain. Since the lt-NES cells used in this study show a strong propensity for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">GABAergic differentiation, the host-to-graft synaptic afferents may facilitate </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inhibitory neurotransmitter release, and normalize hyperexcitable neuronal networks in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">brain diseases, for example, such as epilepsy.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">285794</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5.704353316104971e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">49</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'Dodecameric structure and ATPase activity of the human TIP48/TIP49 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">complex. TIP48 and TIP49 are two related and highly conserved eukaryotic AAA(+) </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins with an essential biological function and a critical role in major pathways </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">that are closely linked to cancer. They are found together as components of several </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">highly conserved chromatin-modifying complexes. Both proteins show sequence homology to</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">bacterial RuvB but the nature and mechanism of their biochemical role remain unknown. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Recombinant human TIP48 and TIP49 were assembled into a stable high molecular mass </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">equimolar complex and tested for activity in vitro. TIP48/TIP49 complex formation </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">resulted in synergistic increase in ATPase activity but ATP hydrolysis was not </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">stimulated in the presence of single-stranded, double-stranded or four-way junction DNA</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and no DNA helicase or branch migration activity could be detected. Complexes with </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">catalytic defects in either TIP48 or TIP49 had no ATPase activity showing that both </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins within the TIP48/TIP49 complex are required for ATP hydrolysis. The structure </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of the TIP48/TIP49 complex was examined by negative stain electron microscopy. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Three-dimensional reconstruction at 20 A resolution revealed that the TIP48/TIP49 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">complex consisted of two stacked hexameric rings with C6 symmetry. The top and bottom </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">rings showed substantial structural differences. Interestingly, TIP48 formed oligomers </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in the presence of adenine nucleotides, whilst TIP49 did not. The results point to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">biochemical differences between TIP48 and TIP49, which may explain the structural </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">differences between the two hexameric rings and could be significant for specialised </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">functions that the proteins perform individually.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">293661</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5.702128692064434e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">50</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'A core subunit of Polycomb repressive complex 1 is broadly conserved </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">in function but not primary sequence. Polycomb Group (PcG) proteins mediate heritable </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">gene silencing by modifying chromatin structure. An essential PcG complex, PRC1, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">compacts chromatin and inhibits chromatin remodeling. In Drosophila melanogaster, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">intrinsically disordered C-terminal region of PSC (PSC-CTR) mediates these noncovalent </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">effects on chromatin, and is essential for viability. Because the PSC-CTR sequence is </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">poorly conserved, the significance of its effects on chromatin outside of Drosophila </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">was unclear. The absence of folded domains also made it difficult to understand how the</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">sequence of PSC-CTR encodes its function. To determine the mechanistic basis and extent</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of conservation of PSC-CTR activity, we identified 17 metazoan PSC-CTRs spanning </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">chordates to arthropods, and examined their sequence features and biochemical </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">properties. PSC-CTR sequences are poorly conserved, but are all highly charged and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">structurally disordered. We show that active PSC-CTRs--which bind DNA tightly and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inhibit chromatin remodeling efficiently--are distinguished from less active ones by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">the absence of extended negatively charged stretches. PSC-CTR activity can be increased</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">by dispersing its contiguous negative charge, confirming the importance of this </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">property. Using the sequence properties defined as important for PSC-CTR activity, we </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">predicted the presence of active PSC-CTRs in additional diverse genomes. Our analysis </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">reveals broad conservation of PSC-CTR activity across metazoans. This conclusion could </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">not have been determined from sequence alignments. We further find that plants that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">lack active PSC-CTRs instead possess a functionally analogous PcG protein, EMF1. Thus, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">our study suggests that a disordered domain with dispersed negative charges underlies </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">PRC1 activity, and is conserved across metazoans and plants.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">301838</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5.444479393190704e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">51</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'A central role for HER3 in HER2-amplified breast cancer: implications</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">for targeted therapy. Epidermal growth factor receptor (EGFR) and HER3 each form </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">heterodimers with HER2 and have independently been implicated as key coreceptors that </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">drive HER2-amplified breast cancer. Some studies suggest a dominant role for EGFR, a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">notion of renewed interest given the development of dual HER2/EGFR small-molecule </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inhibitors. Other studies point to HER3 as the primary coreceptor. To clarify the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">relative contributions of EGFR and HER3 to HER2 signaling, we studied receptor </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">knockdown via small interfering RNA technology across a panel of six </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">HER2-overexpressing cell lines. Interestingly, HER3 was as critical as HER2 for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">maintaining cell proliferation in most cell lines, whereas EGFR was dispensable. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Induction of HER3 knockdown in the HER2-overexpressing BT474M1 cell line was found to </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inhibit growth in three-dimensional culture and induce rapid tumor regression of in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">vivo xenografts. Furthermore, preferential phosphorylation of HER3, but not EGFR, was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">observed in HER2-amplified breast cancer tissues. Given these data suggesting HER3 as </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">an important therapeutic target, we examined the activity of pertuzumab, a HER2 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">antibody that inhibits HER3 signaling by blocking ligand-induced HER2/HER3 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">heterodimerization. Pertuzumab inhibited ligand-dependent morphogenesis in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three-dimensional culture and induced tumor regression in the heregulin-dependent </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">MDA-MB-175 xenograft model. Importantly, these activities of pertuzumab were distinct </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">from those of trastuzumab, a monoclonal antibody currently used for treatment of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">HER2-amplified breast cancer patients. Our data suggest that inhibition of HER3 may be </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">more clinically relevant than inhibition of EGFR in HER2-amplified breast cancer and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">also suggest that adding pertuzumab to trastuzumab may augment therapeutic benefit by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">blocking HER2/HER3 signaling.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">301866</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5.191130912862718e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">52</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'A three-dimensional cell biology model of human hepatocellular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">carcinoma in vitro We established an in vitro 3-D model of metastatic hepatocellular </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">carcinoma (HCC) by culturing MHCC97H cells on molecular scaffolds within a rotating </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">wall vessel bioreactor. Morphological and biochemical analyses revealed that the 3-D </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">HCC model mirrored many clinical pathological features of HCC in vivo, including cancer</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cell morphology, tissue ultrastructure, protein production and secretion, glucose </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">metabolism, tissue-specific gene expression, and apoptosis. Xenografts into livers of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">nude mice resulted in tumorigenesis and distant metastasis. This 3-D HCC spheroid is a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">promising model for HCC tumor biology, anticancer drug screening, and for the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">establishment of HCC animal models.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">306006</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">5.150652214069851e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">53</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">\"Nicotinic Acid Adenine Dinucleotide 2'-Phosphate (NAADP) Binding </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Proteins in T-Lymphocytes. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">messenger that regulates calcium release from intracellular acidic stores. Although </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">several channels, including two-pore channels (TPC), ryanodine receptor (RYR) and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mucolipin (TRP-ML1) have been implicated in NAADP regulation of calcium signaling, the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">NAADP receptor has not been identified. In this study, the photoaffinity probe, </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">[32P]-5-azido-NAADP ([32P]-5-N3-NAADP), was used to study NAADP binding proteins in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">extracts from NAADP responsive Jurkat T-lymphocytes. [32P]-5-N3-NAADP photolabeling of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Jurkat S100 cytosolic fractions resulted in the labeling of at least ten distinct </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins. Several of these S100 proteins, including a doublet at 22/23 kDa and small </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">protein at 15 kDa displayed selectivity for NAADP as the labeling was protected by </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">inclusion of unlabeled NAADP, whereas the structurally similar NADP required much </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">higher concentrations for protection. Interestingly, the labeling of several S100 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins (60, 45, 33 and 28 kDa) was stimulated by low concentrations of unlabeled </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">NAADP, but not by NADP. The effect of NAADP on the labeling of the 60 kDa protein was </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">biphasic, peaking at 100 nM with a five-fold increase and displaying no change at 1 µM </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">NAADP. Several proteins were also photolabeled when the P100 membrane fraction from </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Jurkat cells was examined. Similar to the results with S100, a 22/23 kDa doublet and a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">15 kDa protein appeared to be selectively labeled. NAADP did not increase the labeling </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of any P100 proteins as it did in the S100 fraction. The photolabeled S100 and P100 </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">proteins were successfully resolved by two-dimensional gel electrophoresis. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">[32P]-5-N3-NAADP photolabeling and two-dimensional electrophoresis should represent a </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">suitable strategy in which to identify and characterize NAADP binding proteins.\"</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">306311</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4.9371348723070696e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">54</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'RNA editing in brain controls a determinant of ion flow in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">glutamate-gated channels. L-glutamate, the principal excitatory transmitter in the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">brain, gates ion channels mediating fast neurotransmission. Subunit components of two </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">related classes of glutamate receptor channels have been characterized by cDNA cloning </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and shown to carry either an arginine or a glutamine residue in a defined position of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">their putative channel-forming segment. The arginine residue in this segment profoundly</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">alters, and dominates, the properties of ion flow, as demonstrated for one channel </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">class. We now show that the genomic DNA sequences encoding the particular channel </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">segment of all subunits harbor a glutamine codon (CAG), even though an arginine codon </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">(CGG) is found in mRNAs of three subunits. Multiple genes and alternative exons were </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">excluded as sources for the arginine codon; hence, we propose that transcripts for </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">three subunits are altered by RNA editing. This process apparently edits subunit </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">transcripts of the two glutamate receptor classes with different efficiency and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">selectivity.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">308862</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4.8481608246220276e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">55</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'ALDH1 is a marker of normal and malignant human mammary stem cells </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">and a predictor of poor clinical outcome. Application of stem cell biology to breast </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">cancer research has been limited by the lack of simple methods for identification and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">isolation of normal and malignant stem cells. Utilizing in vitro and in vivo </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">experimental systems, we show that normal and cancer human mammary epithelial cells </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">These cells contain the subpopulation of normal breast epithelium with the broadest </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">lineage differentiation potential and greatest growth capacity in a xenotransplant </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">model. In breast carcinomas, high ALDH activity identifies the tumorigenic cell </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">fraction, capable of self-renewal and of generating tumors that recapitulate the </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">heterogeneity of the parental tumor. In a series of 577 breast carcinomas, expression </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">of ALDH1 detected by immunostaining correlated with poor prognosis. These findings </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">offer an important new tool for the study of normal and malignant breast stem cells and</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">facilitate the clinical application of stem cell concepts.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">313394</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">score</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">4.7295216063503176e-05</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">rank</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">56</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Result</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">document</span>=<span style=\"color: #800080; text-decoration-color: #800080; font-weight: bold\">Document</span><span style=\"font-weight: bold\">(</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">text</span>=<span style=\"color: #008000; text-decoration-color: #008000\">'BCL9 promotes tumor progression by conferring enhanced proliferative,</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">metastatic, and angiogenic properties to cancer cells. Several components of the Wnt </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">signaling cascade have been shown to function either as tumor suppressor proteins or as</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">oncogenes in multiple human cancers, underscoring the relevance of this pathway in </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">oncogenesis and the need for further investigation of Wnt signaling components as </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">potential targets for cancer therapy. Here, using expression profiling analysis as well</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">as in vitro and in vivo functional studies, we show that the Wnt pathway component BCL9</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">is a novel oncogene that is aberrantly expressed in human multiple myeloma as well as </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">colon carcinoma. We show that BCL9 enhances beta-catenin-mediated transcriptional </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">activity regardless of the mutational status of the Wnt signaling components and </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">increases cell proliferation, migration, invasion, and the metastatic potential of </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">tumor cells by promoting loss of epithelial and gain of mesenchymal-like phenotype. </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">Most importantly, BCL9 knockdown significantly increased the survival of xenograft </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">through down-regulation of c-Myc, cyclin D1, CD44, and vascular endothelial growth </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">factor expression by tumor cells. Together, these findings suggest that deregulation of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">BCL9 is an important contributing factor to tumor progression. The pleiotropic roles of</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">BCL9 reported in this study underscore its value as a drug target for therapeutic </span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #008000; text-decoration-color: #008000\">intervention in several malignancies associated with aberrant Wnt signaling.'</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">doc_id</span>=<span style=\"color: #008080; text-decoration-color: #008080; font-weight: bold\">313403</span>, <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"color: #808000; text-decoration-color: #808000\">metadata</span>=<span style=\"font-weight: bold\">{}</span> <span style=\"color: #000080; text-decoration-color: #000080\">│</span>\n",
"<span style=\"color: #000080; text-decoration-color: #000080\">│</span> <span style=\"font-weight: bold\">)</span>,
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