gebhart/patrepeval huggingface dataset:
A recombinant humanized anti‐insulin‐like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti‐epidermal growth factor receptor therapy against human cancer xenografts (2004)

Interaction of insulin-like growth factor receptor I (IGF-IR) with its ligands has been reported to induce cell proliferation, transformation and blockade of cell apoptotic functions. IGF-IR is overexpressed on numerous tumor cell types and its blockade could be of importance for anti-cancer therapy. We have generated a humanized anti-IGF-IR antibody h7C10 that blocks in vitro IGF-I and IGF-II-induced cell proliferation of MCF-7 breast cancer cells. Analysis of the IGF-I transduction cascade demonstrated that the humanized anti-IGF-IR antibody and its murine parental form block IGF-I-induced tyrosine phosphorylation, both its beta-chain and IRS-1 tyrosine phosphorylation. This presumably leads to cell cycle arrest and, consequently, growth inhibition. Treatment of nude mice bearing either human breast cancer cells (MCF-7) or non small lung cancer cells (A549) with h7C10, or its murine parental form 7C10, inhibited significantly tumor growth. An almost complete inhibition of A549 tumor growth was observed when mice were treated with the anti-IGF-IR antibody combined with either a chemotherapeutic agent, Vinorelbine or an anti-epidermal growth factor receptor (EGFR) antibody, 225. Combined therapy prolonged significantly the life span of mice in an orthotopic in vivo model of A549; the combination of the anti-IGF-IR antibody with an anti-EGFR antibody was superior to the Vinorelbine combination. The present results indicate that the humanized anti-IGF-IR antibody h7C10 has a great potential for cancer therapy when combined with either a chemotherapeutic agent or an antibody that targets other growth factor receptors, such as the epidermal growth factor receptor.
MobiDB 2.0: an improved database of intrinsically disordered and mobile proteins (2014)

MobiDB (http://mobidb.bio.unipd.it/) is a database of intrinsically disordered and mobile proteins. Intrinsically disordered regions are key for the function of numerous proteins. Here we provide a new version of MobiDB, a centralized source aimed at providing the most complete picture on different flavors of disorder in protein structures covering all UniProt sequences (currently over 80 million). The database features three levels of annotation: manually curated, indirect and predicted. Manually curated data is extracted from the DisProt database. Indirect data is inferred from PDB structures that are considered an indication of intrinsic disorder. The 10 predictors currently included (three ESpritz flavors, two IUPred flavors, two DisEMBL flavors, GlobPlot, VSL2b and JRONN) enable MobiDB to provide disorder annotations for every protein in absence of more reliable data. The new version also features a consensus annotation and classification for long disordered regions. In order to complement the disorder annotations, MobiDB features additional annotations from external sources. Annotations from the UniProt database include post-translational modifications and linear motifs. Pfam annotations are displayed in graphical form and are link-enabled, allowing the user to visit the corresponding Pfam page for further information. Experimental protein-protein interactions from STRING are also classified for disorder content.
Software cache coherence for large scale multiprocessors (2002)

Shared memory is an appealing abstraction for parallel programming. It must be implemented with caches in order to perform well, however and caches require a coherence mechanism to ensure that processors reference current data. Hardware coherence mechanisms for large-scale machines are complex and costly, but existing software mechanisms for message-passing machines have not provided a performance-competitive solution. We claim that an intermediate hardware option-memory-mapped network interfaces that support a global physical address space-can provide most of the performance benefits of hardware cache coherence. We present a software coherence protocol that runs on this class of machines and greatly narrows the performance gap between hardware and software coherence. We compare the performance of the protocol to that of existing software and hardware alternatives and evaluate the tradeoffs among various cache-write policies. We also observe that simple program changes can greatly improve performance. For the programs in our test suite and with the changes in place, software coherence is often faster and never more than 55% slower than hardware coherence.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of Microglial Signal Transduction Pathways Mediating a Neurotoxic Response to Amyloidogenic Fragments of β-Amyloid and Prion Proteins (1999)

Microglial interaction with amyloid fibrils in the brains of Alzheimer's and prion disease patients results in the inflammatory activation of these cells. We observed that primary microglial cultures and the THP-1 monocytic cell line are stimulated by fibrillar beta-amyloid and prion peptides to activate identical tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine kinases Lyn and Syk are activated by the fibrillar peptides and initiate a signaling cascade resulting in a transient release of intracellular calcium that results in the activation of classical PKC and the recently described calcium-sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2 follows as a subsequent downstream signaling event. We demonstrate that PYK2 is positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate required for ERK activation. Importantly, the signaling response elicited by beta-amyloid and prion fibrils leads to the production of neurotoxic products. We have demonstrated in a tissue culture model that conditioned media from beta-amyloid- and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses.
Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [14C]-2-Deoxyglucose Autoradiographic Study (1997)

Metabotropic glutamate receptors (mGluRs) are a major class of excitatory amino acid receptors. Eight mGluR subtypes, coupled to a variety of effector systems, have been cloned. These receptors have been classified into three groups based on amino acid sequence homology, effector systems, and pharmacological profile. Group I mGluRs increase phosphoinositide turnover, whereas groups II and III mGluRs are negatively coupled to adenylyl cyclase. The striatum possesses a high density of mGluR binding sites, and several mGluR mRNAs and proteins are expressed by striatal neurons. In rats, unilateral striatal injection of the nonsubtype selective mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) results in contralateral rotation with delayed onset, thought to be secondary to an increase in dopamine release. We sought to determine the mGluR subtype(s) involved, the modulation of the rotation by other basal ganglia neurotransmitter systems, and the functional anatomy underlying the rotational behavior. The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced contralateral rotation in a dose-dependent manner, whereas group II and group III agonists were ineffective. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by group I antagonists, but not by group II or group III antagonists. This suggests that the rotation is mediated by group I mGluRs. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by pretreatment with antagonists at muscarinic cholinergic, adenosine A2, dopamine D2, or dopamine D1 receptors. Examination of FOS-like immunoreactivity after group I and group II mGluR agonist administration suggests increased activity in the striatopallidal pathway. However, [14C]-2-deoxyglucose uptake studies indicate increased activity in nuclei of the striatopallidal (indirect) pathway, particularly in the subthalamic nucleus, only after group I mGluR activation.
Measles Virus (1962)

Introduction Measles as a clinical entity was defined by Rhazes, the Arabian physician, about 900a.d.Only 7 years ago were techniques found whereby consistent propagation of the causative agent of this disease is assured. These techniques have permitted systematic studies of the nature and behavior of the measles virus. In turn, the knowledge thus gained has provided the means for a new approach to the old problem of active immunization against the disease. As a contribution to the background for contemporary investigations on immunization which are to be summarized in later sessions, I shall review the principal landmarks in the modern history of the virus and then comment briefly on its isolation from patients and its behavior in cell systems. Historical Summary Perhaps an expeditious way to summarize the history of the measles agent is to consider what had been established regarding its nature by the year 1939. At
Gastrointestinal tissue polyamine contents of patients with Barrett's esophagus treated with alpha-difluoromethylornithine. (1994)

alpha-Difluoromethylornithine (DFMO), an investigational chemopreventive agent, suppresses polyamine contents and decreases epithelial carcinogenesis in experimental models. The ability of this drug to decrease polyamine contents in human esophageal tissues has not yet been determined. Eight patients with Barrett's esophagus were treated with DFMO at a dose of 1.5 g/m2/day for 12 weeks. Four sites (Barrett's lesion, adjacent normal squamous esophagus, gastric tissue, and small bowel) were biopsied in each patient before, during, and after DFMO treatment in order to assess the effects of this drug on tissue polyamine levels. Ornithine decarboxylase activities and polyamine contents varied in each site analyzed. The rank orders were Barrett's > small bowel congruent to normal esophagus > gastric tissue for ODC activities, and small bowel > or = Barrett's congruent to normal esophagus > gastric tissue for putrescine contents. Spermidine, but not spermine, contents in the Barrett's lesions and normal squamous esophageal tissue were suppressed by systemic DFMO treatment and recovered to untreated control values when DFMO therapy was discontinued. Systemic DFMO treatment did not affect the levels of either of these two amines in gastric tissue and small bowel. Since DFMO can suppress polyamine contents in several gastrointestinal tissues, including Barrett's mucosa, we conclude that it is an effective agent with which to test the hypothesis that depletion of spermidine contents may prevent the development of adenocarcinoma of the esophagus in this specific patient group.
Water-Soluble Conjugated Oligomers:  Effect of Chain Length and Aggregation on Photoluminescence-Quenching Efficiencies (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTWater-Soluble Conjugated Oligomers: Effect of Chain Length and Aggregation on Photoluminescence-Quenching EfficienciesBrent S. Gaylord, Shujun Wang, Alan J. Heeger, and Guillermo C. BazanView Author Information Departments of Chemistry and Materials University of California, Santa Barbara, California 93106 Cite this: J. Am. Chem. Soc. 2001, 123, 26, 6417–6418Publication Date (Web):June 8, 2001Publication History Received12 February 2001Published online8 June 2001Published inissue 1 July 2001https://pubs.acs.org/doi/10.1021/ja010373fhttps://doi.org/10.1021/ja010373frapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2524Altmetric-Citations224LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Conjugated polymers,Differential thermal analysis,Fluorescence,Quenching,Surfactants Get e-Alerts
Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells (2014)

// Yue-Zhi Lee 1,* , Cheng-Wei Yang 1,* , Hsin-Yu Chang 1,* , Hsing-Yu Hsu 1,* , Ih-Shen Chen 2 , Hsun-Shuo Chang 2 , Chih-Hao Lee 3 , Jinq-chyi Lee 1 , Chidambaram Ramesh Kumar 1 , Ya-Qi Qiu 1,4 , Yu-Sheng Chao 1 and Shiow-Ju Lee 1 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan 2 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, Boston, Massachusetts, USA 4 Graduate Program of Biotechnology in Medicine, Institute of Molecular &amp; Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan * These authors equally contributed to this work Correspondence: Shiow-Ju Lee, email: // Keywords : AMPK; Autophagy; Glutaminase; mTOR; Raptor; ULK1 Received : April 26, 2014 Accepted : July 7, 2014 Published : July 8, 2014 Abstract Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS ( GLS1 ) and GLS2 . Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS ; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2 . While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target.
Immunotherapeutic Approaches for Glioma (2009)

The development of effective immunotherapy strategies for glioma requires adequate understanding of the unique immunological microenvironment in the central nervous system (CNS) and CNS tumors. Although the CNS is often considered to be an immunologically privileged site and poses unique challenges for the delivery of effector cells and molecules, recent advances in technology and discoveries in CNS immunology suggest novel mechanisms that may significantly improve the efficacy of immunotherapy against gliomas. In this review, we first summarize recent advances in the CNS and CNS tumor immunology. We address factors that may promote immune escape of gliomas. We also review advances in passive and active immunotherapy strategies for glioma, with an emphasis on lessons learned from recent early-phase clinical trials. We also discuss novel immunotherapy strategies that have been recently tested in non-CNS tumors and show great potential for application to gliomas. Finally, we discuss how each of these promising strategies can be combined to achieve clinical benefit for patients with gliomas.
Hydration Assessment of Athletes (2015)

• Although there is no scientific consensus for 1) how best to assess the hydration status of athletes, 2) what criteria to use as acceptable outcome measurements, or 3) the best time to apply practical assessment methods, there are methods that can be used to provide athletes with useful feedback about their hydration status • Hydration assessment techniques include 1) total body water measured by isotope dilution or estimated by bioelectrical impedance analysis, 2) plasma markers, such as osmolality, sodium, hematocrit and hemoglobin changes, or the concentrations of hormones that help regulate body fluids, 3) urine markers, such as osmolality, specific gravity, or color, 4) changes in body mass, and 5) other variables, such as salivary flow or gross, physical signs and symptoms of clinical dehydration. • In most athletic settings, the use of body mass measurements in combination with some measure of urine concentration at the first urination of the morning allows ample sensitivity for detecting daily deviations from normal hydration (euydration). The methods are simple, inexpensive, accurately distinguish euhydration from dehydration, and can therefore be used as a sole source for assessment. • When more precision of acute hydration changes is desired, plasma osmolality, isotope dilution, and body mass changes, used in appropriate context, provide for the accurate gradations in measurement often required in research. • Plasma markers (other than osmolality), bioelectrical impedance analysis, saliva measures, and gross physical signs and symptoms of dehydration are often confounded or too inaccurate to reliably assess hydration of athletes.
Chromosome 9p21 Genetic Variants are Associated with Myocardial Infarction but Not with Ischemic Stroke in a Taiwanese Population (2011)

Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs.
Nanometric Aluminum in Explosives (2002)

Aluminum nanopowders, because of their larger surface area, can increase the burning rate of propellants. It has been suggested that the powders could also enhance the detonation properties of certain explosives. For these reasons, an experimental study was undertaken to compare the performance of nanometric and micrometric aluminum in various explosives. No enhancement of performance was found in plastic-bonded explosives. In fact, a reduction of the detonation velocity was found in plastic-bonded explosives that are based on an energetic binder system. No increase of the detonation velocity was found in mixtures of aluminum and either Composition B or Ammonium Nitrate Fuel Oil, but a small increase in the heat of detonation was measured. The mixture of TNT and nano-aluminum demonstrated higher detonation velocities and heats of detonation. The increase was higher at small charge diameters. Nanometric aluminum was shown to reduce the critical diameter of such mixtures, and it is concluded that the nano-aluminum reacts faster than regular micron-size particles in TNT/Al compositions.
X-ray Crystal Structure of a Small Antagonist Peptide Bound to Interleukin-1 Receptor Type 1 (2000)

Interleukin (IL-1)alpha and IL-1beta are important mediators of inflammation. The binding of IL-1 to interleukin-1 receptor (IL-1R) type 1 is the initial step in IL-1 signal transduction and therefore is a tempting target for anti-inflammatory therapeutics. To advance our understanding of IL-1R1 binding interactions, we have determined the structure of the extracellular domains of IL-1R1 bound to a 21-amino acid IL-1 antagonist peptide at 3.0-A resolution. The antagonist peptide binds to the domain 1/2 junction of the receptor, which is a conserved binding site for IL-1beta and IL-1 receptor antagonist (IL-1ra). This co-crystal structure also reveals that considerable flexibility is present in IL-1R1 because the carboxyl-terminal domain of the receptor is rotated almost 170 degrees relative to the first two domains of the receptor compared with the previously solved IL-1R1.ligand structures. The structure shows an unexpected binding mode for the peptide and may contribute to the design of smaller IL-1R antagonists.
ARACHIDONIC ACID METABOLISM (1986)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Importance of Different Pathways of Cellular Cholesterol Efflux (2003)

The removal of excess free cholesterol from cells by HDL or its apolipoproteins is important for maintaining cellular cholesterol homeostasis. This process is most likely compromised in the atherosclerotic lesion because the development of atherosclerosis is associated with low HDL cholesterol. Multiple mechanisms for efflux of cell cholesterol exist. Efflux of free cholesterol via aqueous diffusion occurs with all cell types but is inefficient. Efflux of cholesterol is accelerated when scavenger receptor class-B type I (SR-BI) is present in the cell plasma membrane. Both diffusion-mediated and SR-BI-mediated efflux occur to phospholipid-containing acceptors (ie, HDL and lipidated apolipoproteins); in both cases, the flux of cholesterol is bidirectional, with the direction of net flux depending on the cholesterol gradient. The ATP-binding cassette transporter AI (ABCA1) mediates efflux of both cellular cholesterol and phospholipid. In contrast to SR-BI-mediated flux, efflux via ABCA1 is unidirectional, occurring to lipid-poor apolipoproteins. The relative importance of the SR-BI and ABCA1 efflux pathways in preventing the development of atherosclerotic plaque is not known but will depend on the expression levels of the two proteins and on the type of cholesterol acceptors available.
Mass Spectrometry of Low Molecular Mass Solids by Matrix-assisted Laser Desorption/Ionization (1997)

Matrix-assisted laser desorption/ionization combined with time-of-flight mass spectrometry (MALDI/TOF-MS) was used for the analysis of low molecular mass compounds. Three classes of molecules were studied: organic acids, salts of oxyanions and amine-based chelating compounds. Mass spectra from samples of citric, propionic, butyric, oxalic and stearic acid; ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA), ethylenediamine N,N′-diacetic acid (EDDA) and nitrilotriacetic acid (NTA); and sulfate, nitrate, nitrite and phosphate salts were obtained. These species were analyzed alone and as mixtures in both the positive and negative ion modes. The organic acids and oxyanion salts displayed much stronger signals in the negative ion detection mode whereas chelating compounds, which contain basic amine functional groups, yielded stronger signals in the positive ion mode. This implies that detection sensitivity is often better for a particular ion mode in the analysis of small molecules containing limited classes of functional groups. In all analyses, the presence of high concentrations of sodium was found to quench the MALDI signals. To increase the detection sensitivity, some samples were processed through an ion-exchange column to remove sodium ions. This step was found to enhance the signal by two orders of magnitude over untreated samples. © 1997 by John Wiley & Sons, Ltd.