gebhart/patrepeval huggingface dataset:
In Vitro Characterization of the Anti-PD-1 Antibody Nivolumab, BMS-936558, and In Vivo Toxicology in Non-Human Primates (2014)

The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.
Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest (2006)

Metazoans are composed of a finite number of recognisable cell types. Similar to the relationship between species and ecosystems, knowledge of cell type diversity contributes to studies of complexity and evolution. However, as with other units of evolution, the cell type often resists definition. This review proposes guidelines for characterising cell types and discusses cell homology and the various developmental pathways by which cell types arise, including germ layers, blastemata (secondary development/neurulation), stem cells, and transdifferentiation. An updated list of cell types is presented for a familiar, albeit overlooked model taxon, adult Homo sapiens, with 411 cell types, including 145 types of neurons, recognised. Two methods for organising these cell types are explored. One is the artificial classification technique, clustering cells using commonly accepted criteria of similarity. The second approach, an empirical method modeled after cladistics, resolves the classification in terms of shared features rather than overall similarity. While the results of each scheme differ, both methods address important questions. The artificial classification provides compelling (and independent) support for the neural crest as the fourth germ layer, while the cladistic approach permits the evaluation of cell type evolution. Using the cladistic approach we observe a correlation between the developmental and evolutionary origin of a cell, suggesting that this method is useful for predicting which cell types share common (multipotential) progenitors. Whereas the current effort is restricted by the availability of phenotypic details for most cell types, the present study demonstrates that a comprehensive cladistic classification is practical, attainable, and warranted. The use of cell types and cell type comparative classification schemes has the potential to offer new and alternative models for therapeutic evaluation.
Diazo Groups Endure Metabolism and Enable Chemoselectivity in Cellulo (2015)

We introduce a stabilized diazo group as a reporter for chemical biology. ManDiaz, which is a diazo derivative of N-acetylmannosamine, is found to endure cellular metabolism and label the surface of a mammalian cell. There its diazo group can undergo a 1,3-dipolar cycloaddition with a strained alkyne, providing a signal comparable to that from the azido congener, ManNAz. The chemoselectivity of diazo and alkynyl groups enables dual labeling of cells that is not possible with azido and alkynyl groups. Thus, the diazo group, which is approximately half the size of an azido group, provides unique opportunities for orthogonal labeling of cellular components.
SOCS1 regulates interferon-γ mediated sensory neuron survival (2001)

Differentiation and survival of sensory neurons is regulated by factors such as NGF and LIF. Regulation of signal transduction pathways downstream of such factor signalling by suppressor of cytokine signalling (SOCS) proteins, which negatively regulate the JAK/STAT pathway, may modulate biological outcome. In this study, SOCS1 regulation of growth factor mediated sensory neuron survival was examined. SOCS1 expression by sensory neurons was up-regulated by IFNgamma. Survival of sensory neurons from SOCS1 null mice in NGF or LIF was similar to wildtype mice. IFNgamma partially supported survival of wildtype neurons but supported survival of SOCS1 null neurons as effectively as NGF or LIF. Thus it appears that SOCS1 is a major regulator of sensory neuron responses to the inflammatory cytokine, IFNgamma.
Comparison Between the Escherichia coli and Bacillus subtilis Genomes Suggests That a Major Function of Polynucleotide Phosphorylase is to Synthesize CDP (1997)

Genome comparison permits identification of chromosome regions conserved during evolution. Bacillus subtilis and Escherichia coli are so distant that there exists very few conserved landmarks in their genome organisation. Analysis of the conserved cmk rpsA cluster pinpointed the importance of cytosine nucleotide metabolism. In these bacteria, mRNA turnover provides an efficient means to fulfil the need for CDP as a precursor of DNA synthesis. The cmk rpsA operon is responsible for CDP synthesis. This function is self-explained in the case of the cmk gene (which codes for cytidylate kinase). The case of rpsA, that codes for ribosomal protein S1, is more subtle. It is suggested here that S1 is a RNA-binding protein helping polynucleotide phosphorylase (PNPase, known to be phylogenetically related to S1) to degrade mRNA, or helper molecule involved in other RNase activities. This provides an explanation for the elusive function of PNPase, which generates nucleoside diphosphates (not monophosphates) when degrading RNA. This also accounts for the discovery that the B. subtilis comR gene product is PNPase. This article briefly discusses the availability of cytosine nucleotides in eukaryotes, and suggests that they are derived from phospholipids turnover. Finally, the GC content of genomes is discussed in this new light.
PACE/furin can process the vitamin K-dependent pro-factor IX precursor within the secretory pathway. (1993)

Factor IX is synthesized as a precursor polypeptide which requires proteolytic cleavage of the propeptide for functional activity. Expression of factor IX at high levels in Chinese hamster ovary (CHO) cells results in the secretion of a mixture of profactor IX and mature factor IX. We have studied whether the processing of profactor IX may be mediated by the recently discovered subtilisin-like serine proteases PACE/furin and/or PACE4. Co-transfection of a PACE expression vector with a profactor IX expression vector resulted in the secretion of fully processed factor IX. In contrast, co-transfection of a PACE4 expression vector with a profactor IX expression vector did not increase processing of profactor IX to the mature form. A factor IX Arg-to-Thr mutation at the P1 position (residue 39) destroyed the ability for PACE to process profactor IX. Amino-terminal sequence analysis demonstrated that processing mediated by PACE occurred at the authentic site within profactor IX. The specificity of profactor IX processing by PACE was also evaluated by transfection of a vector encoding the serine protease inhibitor alpha 1-antitrypsin. Expression of wild-type alpha 1-antitrypsin, which does not inhibit PACE, did not influence processing of profactor IX mediated by co-expression of PACE. In contrast, the alpha 1-antitrypsin Pittsburgh mutant, which inhibits PACE, inhibited profactor IX processing activity mediated by transfected PACE as well as the endogenous CHO cell propeptide processing enzyme. Pulse-chase labeling indicated that PACE processed profactor IX late within the secretory pathway, although a secreted soluble mutant PACE was also capable of processing profactor IX in the conditioned medium. The results implicate PACE as a candidate for the enzyme that processes profactor IX in vivo.
Generalizing data to provide anonymity when disclosing information (abstract) (1998)

No abstract available.
Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML (2013)

Mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are frequently found in glioma, acute myeloid leukemia (AML), melanoma, thyroid cancer, and chondrosarcoma patients. Mutant IDH produces 2-hydroxyglutarate (2HG), which induces histone- and DNA-hypermethylation through inhibition of epigenetic regulators. We investigated the role of mutant IDH1 using the mouse transplantation assay. Mutant IDH1 alone did not transform hematopoietic cells during 5 months of observation. However, mutant IDH1 greatly accelerated onset of myeloproliferative disease-like myeloid leukemia in mice in cooperation with HoxA9 with a mean latency of 83 days compared with cells expressing HoxA9 and wild-type IDH1 or a control vector (167 and 210 days, respectively, P = .001). Mutant IDH1 accelerated cell-cycle transition through repression of cyclin-dependent kinase inhibitors Cdkn2a and Cdkn2b, and activated mitogen-activated protein kinase signaling. By computational screening, we identified an inhibitor of mutant IDH1, which inhibited mutant IDH1 cells and lowered 2HG levels in vitro, and efficiently blocked colony formation of AML cells from IDH1-mutated patients but not of normal CD34(+) bone marrow cells. These data demonstrate that mutant IDH1 has oncogenic activity in vivo and suggest that it is a promising therapeutic target in human AML cells.
Platinum drugs in the treatment of non-small-cell lung cancer (2002)

The use of chemotherapy is considered standard therapy in patients with locally advanced non-small-cell lung cancer that cannot be treated with radiotherapy and in those with metastatic non-small-cell lung cancer and good performance status. This approach is also accepted in patients with earlier stage disease, when combined with radiotherapy in those with non-resectable locally advanced disease, or in the preoperative setting. Randomised clinical studies and meta-analyses of the literature have confirmed the beneficial survival effect of platinum-based chemotherapy. Cisplatin and carboplatin have been successfully used with other drugs in a wide variety of well-established two-drug combinations while three-drug combinations are still under investigation. Cisplatin and carboplatin use is limited by toxicity and inherent resistance. These considerations have prompted research into new platinum agents, such as the trinuclear platinum agent BBR3464, the platinum complex ZD0473 and oxaliplatin. These compounds could be developed in combination with agents such as paclitaxel, gemcitabine or vinorelbine in patients with advanced and/or refractory solid tumours.
Isolation and Characterization of a GDP/GTP Exchange Protein Specific for the Rab3 Subfamily Small G Proteins (1997)

The Rab small G protein family, consisting of nearly 30 members, is implicated in intracellular vesicle trafficking. They cycle between the GDP-bound inactive and GTP-bound active forms, and the former is converted to the latter by the action of a GDP/GTP exchange protein (GEP). No GEP specific for each Rab family member or Rab subfamily has been isolated. Here we purified a GEP from rat brain with lipid-modified Rab3A as a substrate. The purified protein was specifically active on Rab3A, Rab3C, and Rab3D of the Rab3 subfamily. Of these subfamily members, Rab3A and Rab3C are implicated in Ca2+-dependent exocytosis, particularly in neurotransmitter release. This GEP (Rab3 GEP) was active on the lipid-modified form, but not on the lipid-unmodified form. Rab3 GEP showed a minimum molecular mass of about 200 kDa on SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a rat brain cDNA library and determined its primary structure. The isolated cDNA encoded a protein with a Mr of 177,982 and 1,602 amino acids, which showed no homology to any known protein. The recombinant protein exhibited GEP activity toward Rab3A, Rab3C, and Rab3D. Northern blot and Western blot analyses indicated that Rab3 GEP was expressed in all the rat tissues examined with the highest expression in brain.
Glycerate kinase of the hyperthermophilic archaeon Thermoproteus tenax: new insights into the phylogenetic distribution and physiological role of members of the three different glycerate kinase classes (2007)

A re-evaluation of available genome sequence information as well as biochemical and phylogenetic studies revealed the presence of the branched ED pathway as common route for sugar degradation in Archaea that utilize the ED pathway. Detailed analyses including phylogenetic studies demonstrate the presence of three distinct glycerate kinase classes in extant organisms that share no common origin. The affiliation of characterized glycerate kinases with the different enzyme classes as well as their physiological/cellular function reveals no association with particular pathways but a separate phylogenetic distribution. This work highlights the diversity and complexity of the central carbohydrate metabolism. The data also support a key function of the conversion of glycerate to 2- or 3-phosphoglycerate via glycerate kinase in funneling various substrates into the common EMP pathway for catabolic and anabolic purposes.
Detection of antibodies to Mycobacterium tuberculosis plasma membrane antigen by enzyme-linked immunosorbent assay (1986)

Antibody activity against Mycobacterium tuberculosis of sera from an area with a high prevalence of tuberculosis was measured by enzyme-linked immunosorbent assay (ELISA) with a plasma-membrane extract from M. tuberculosis strain H37RV. All sera from relapsed tuberculosis patients and 82.5% of sera from new untreated cases gave positive results. The seronegative group of tuberculosis patients gave positive results by direct microscopy and culture. No clear correlation between antibody and delayed hypersensitivity or extent of disease was observed. Chemotherapy was associated with a higher antibody response. Specificity of the test with healthy control subjects from the high prevalence area was 85%. Negative results were obtained with 145 sera from presumed healthy European subjects and with seven sera from BCG-vaccinated subjects.
Passive Diagnosis for Wireless Sensor Networks (2009)

Network diagnosis, an essential research topic for traditional networking systems, has not received much attention for wireless sensor networks (WSNs). Existing sensor debugging tools like sympathy or EmStar rely heavily on an add-in protocol that generates and reports a large amount of status information from individual sensor nodes, introducing network overhead to the resource constrained and usually traffic-sensitive sensor network. We report our initial attempt at providing a lightweight network diagnosis mechanism for sensor networks. We further propose PAD, a probabilistic diagnosis approach for inferring the root causes of abnormal phenomena. PAD employs a packet marking scheme for efficiently constructing and dynamically maintaining the inference model. Our approach does not incur additional traffic overhead for collecting desired information. Instead, we introduce a probabilistic inference model that encodes internal dependencies among different network elements for online diagnosis of an operational sensor network system. Such a model is capable of additively reasoning root causes based on passively observed symptoms. We implement the PAD prototype in our sea monitoring sensor network test-bed. We also examine the efficiency and scalability of this design through extensive trace-driven simulations.
Matricellular Hevin Regulates Decorin Production and Collagen Assembly (2006)

Matricellular proteins such as SPARC, thrombospondin 1 and 2, and tenascin C and X subserve important functions in extracellular matrix synthesis and cellular adhesion to extracellular matrix. By virtue of its reported interaction with collagen I and deadhesive activity on cells, we hypothesized that hevin, a member of the SPARC gene family, regulates dermal extracellular matrix and collagen fibril formation. We present evidence for an altered collagen matrix and levels of the proteoglycan decorin in the normal dermis and dermal wound bed of hevin-null mice. The dermal elastic modulus was also enhanced in hevin-null animals. The levels of decorin protein secreted by hevin-null dermal fibroblasts were increased by exogenous hevin in vitro, data indicating that hevin might regulate both decorin and collagen fibrillogenesis. We also report a decorin-independent function for hevin in collagen fibrillogenesis. In vitro fibrillogenesis assays indicated that hevin enhanced fibril formation kinetics. Furthermore, cell adhesion assays indicated that cells adhered differently to collagen fibrils formed in the presence of hevin. Our observations support the capacity of hevin to modulate the structure of dermal extracellular matrix, specifically by its regulation of decorin levels and collagen fibril assembly.
The Reconstruct Therapy Research in Anterior Cruciate Ligament Injury of Knees (2010)

Knee joint the biggest and the most complicated joint.It is hurt more and easily in doing sports.The Anterior Cruciate Ligament is hurt more familiar and serious.We shoud learn the data of epidemiology of injury,functional anatomy、hurt of occurrence rate、diagnosis and treatmen、the function reconstruction of treatment and complication in order to learn the present study on ACL injury.
An integrin antagonist (MK‐0429) decreases proteinuria and renal fibrosis in the ZSF1 rat diabetic nephropathy model (2017)

Multiple integrins have been implicated in modulating renal function. Modulation of integrin function can lead to pathophysiological processes associated with diabetic nephropathy such as alterations in the glomerular filtration barrier and kidney fibrosis. The complexity of these pathophysiological changes implies that multiple integrin subtypes might need to be targeted to ameliorate the progression of renal disease. To address this hypothesis, we investigated the effects of MK-0429, a compound that was originally developed as an αvβ3 inhibitor for the treatment of osteoporosis, on renal function and fibrosis. We demonstrated that MK-0429 is an equipotent pan-inhibitor of multiple av integrins. MK-0429 dose-dependently inhibited podocyte motility and also suppressed TGF-β-induced fibrosis marker gene expression in kidney fibroblasts. Moreover, in the obese ZSF1 rat model of diabetic nephropathy, chronic treatment with MK-0429 resulted in significant reduction in proteinuria, kidney fibrosis, and collagen accumulation. In summary, our results suggest that inhibition of multiple integrin subtypes might lead to meaningful impact on proteinuria and renal fibrosis in diabetic nephropathy.
Dexmedetomidine Infusion for the Management of Opioid-Induced Hyperalgesia (2010)

The cases presented provide support for the clinical utility of alpha-2 agonists during opioid dose reduction in patients with OIH as well suggesting that they may contribute to the recovery of normal nociceptive and antinociceptive responses.
Molecular Cloning of a Gene Selectively Induced by Gamma Interferon from Human Macrophage Cell Line U937 (1989)

A cDNA clone encoding a gamma interferon (IFN-gamma)-inducible mRNA in human cells of the macrophage lineage was isolated and characterized. The corresponding gene, gamma.1, was selectively induced by IFN-gamma, responding a hundredfold better to IFN-gamma than to IFN-alpha. The induction was rapid and transient, with maximal mRNA accumulation at about 3 h and decline to the basal level after 48 h. Transcriptional activation could be detected as early as 5 min after IFN-gamma stimulation and accounted entirely for the mRNA accumulation. The induction of gamma.1 by IFN-gamma was cell-type restricted, being seen only in macrophages and endothelial cells. In addition, phorbol ester-induced differentiation of promyelocytic HL-60 cells and promonocytic THP-1 cells rendered the gamma.1 gene inducible by IFN-gamma. The 1.0-kilobase gamma.1 cDNA sequence encoded a small predicted polypeptide of 38 amino acids and had a conserved sequence associated with rapidly turning over mRNAs. In vitro translation of the gamma.1 transcript yielded a 4,000-dalton polypeptide.
Chemistry and structure of modified uridines in the anticodon, wobble position of transfer RNA are determined by thiolation (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry and structure of modified uridines in the anticodon, wobble position of transfer RNA are determined by thiolationHanna Sierzputowska-Gracz, Elzbieta Sochacka, Andrzej Malkiewicz, Kenneth Kuo, Charles W. Gehrke, and Paul F. AgrisCite this: J. Am. Chem. Soc. 1987, 109, 23, 7171–7177Publication Date (Print):November 1, 1987Publication History Published online1 May 2002Published inissue 1 November 1987https://doi.org/10.1021/ja00257a044RIGHTS & PERMISSIONSArticle Views564Altmetric-Citations102LEARN 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 InReddit PDF (2 MB) Get e-Alerts Get e-Alerts
An Efficient Micro-Stimulator Array Using Unitary-Size DAC With Adiabatic Baseband Scheme (2006)

This paper presents novel approaches for higher-resolution, higher output gain, better-linearity, and less-power-consumption micro-stimulator array. To achieve higher output gain for more ideal stimulus current without extra cascode stage, a gain-boosting design is adopted. To achieve higher-resolution and better linearity, a continuous pulse-width modulation-based conversion architecture has been proposed. To overcome extra power consumption of the baseband control logic, the energy recovery scheme is also applied. A monolithic circuitry of this efficient stimulator array has been realized by using TSMC 0.18- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">μ</i> m 1P6M standard CMOS technology and the experimental results show improvement over the prior approaches.