gebhart/patrepeval huggingface dataset:
Tetrahydroisoquino [2,1-d][1,4]benzodiazepines. Synthesis and Neuropharmacological Activity (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTetrahydroisoquino [2,1-d][1,4]benzodiazepines. Synthesis and Neuropharmacological ActivityHans Ott, Goetz Hardtmann, Max Denzer, Albert Frey, John Gogerty, George Leslie, and Joseph TrapoldCite this: J. Med. Chem. 1968, 11, 4, 777–787Publication Date (Print):July 1, 1968Publication History Published online26 November 2002Published inissue 1 July 1968https://pubs.acs.org/doi/10.1021/jm00310a610https://doi.org/10.1021/jm00310a610research-articleACS PublicationsRequest reuse permissionsArticle Views233Altmetric-Citations24LEARN 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-Alertsclose Get e-Alerts
Fast skip mode decision with rate-distortion optimization for High Efficiency Video Coding (2014)

In High Efficiency Video Coding (HEVC), the computational complexity has been increased so that an Early SKIP mode decision method is proposed by using coded block flag of an inter prediction unit (PU) to speed up mode decision with BD-bitrate increase. In this paper, we propose a fast SKIP mode decision algorithm to speed up PU mode decision for HEVC in a rate-distortion (RD) optimization sense. It is based on an adaptive linear predictor for PU mode type and available neighboring SKIP mode units on the quad-tree partition structure in HEVC for adaptive RD optimization. Moreover, the proposed method consists of both local (neighboring PUs) and global (previous PUs in current frame) level schemes on each coding unit (CU) level. In this way, it is possible to exploit high correlations between the RD cost of SKIP mode and spatial characteristics of video sequences by using the distribution of SKIP mode and a linear RD cost predictor. Experimental results show that the encoding computational complexity can be reduced by an average of 36 % with threshold RD cost, when compared to that of the HM 12 reference software.
Resistance to Murine Hepatitis Virus Strain 3 Is Dependent on Production of Nitric Oxide (1998)

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.
Clathrin, Adaptors, and Sorting (1990)

CONTENTS INTRODUCTION 15 1 COAT COMPONENTS 153 Clathrin Triskelions and Adaptors ....... 153 Function and Distribution of Adaptors 156 COATED PITS AS MOLECULAR FILTERS ......... ... .. 159 Clathrin-Mediated Endocytosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Clathrin-Mediated Intracellular Sorting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 62 Defective Sorting in Yeast Cells Lacking Clathrin ... 165 Interaction of Receptors with Adaptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 CONCLUSIONS AND PROBLEMS 167
Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues (2002)

Multidrug resistance protein 4 (MRP4/ABCC4) is a member of the MRP subfamily, which in turn is a member of the superfamily of ATP-binding-cassette (ABC) transporters. Within the MRP subfamily, ABCC4,ABCC5 (MRP5), ABCC11 (MRP8) and ABCC12 (MRP9) have similar predicted membrane topologies. All lack the additional transmembrane domain, TMD(0), which is present in the other MRPs. Using cells stably overexpressing ABCC4, this study shows that ABCC4 exports GSH. ABCC4 also facilitates the efflux of cAMP. Depletion of intracellular GSH with DL-buthionine-(S,R)-sulphoximine led to decreased export of cAMP and a corresponding increase in intracellular cAMP was observed. ABCC4 also mediates resistance to purine analogues 9-(2-phosphonylmethoxyethyl)-adenine and 6-thioguanine. This resistance can be reversed by the presence of DL-buthionine-(S,R)-sulphoximine. We conclude that as well as nucleotide and nucleoside analogues, ABCC4 can mediate the export of GSH. In addition, GSH plays an important role in the function of ABCC4. Depletion of intracellular GSH adversely affects the export of cAMP by ABCC4. Resistance to nucleoside analogues is also adversely affected by depletion of cellular GSH.
An overview of flaws in emerging television displays and remedial video processing (2001)

New display principles aim at supreme image quality. The temporal aspects of these devices sometimes remain underexposed in the literature, and the paper presents an overview of new artifacts and possible remedies with signal processing. We discuss typical artifacts due to the unfavourable properties of emerging television displays. We introduce a processing model that eliminates or at least reduces the various artifacts that result from temporal imperfections of CRTs with alternative scanning, liquid crystal displays (LCDs), tiled displays, plasma display panels (PDPs), and colour sequential displays. We conclude that knowledge of the motion in the scene, i.e. motion estimation, is essential to at least partially repair the often unfavourable temporal behaviour of these displays. Such repair is realistic, as these displays have appeared on the market at the moment motion vector estimation has come to maturity for consumer applications.
COSTAR—A computer-based medical information system for ambulatory care (1979)

The storage, retrieval, and communication of information are key features of both the practice of medicine and the administration of health care. This paper describes a COmputer-STored Ambulatory Record (COSTAR) which replaces the traditional document-based patient medical record with a comprehensive, centralized, and integrated information system. COSTAR meets both the medical care and the financial/administrative needs of a variety of different medical practices (whether fee-for-service or prepaid) and can be implemented and operated without on-site programming support. COSTAR has a modular design to facilitate phased implementation, and uses a comprehensive dictionary of terms to standardize and store data. The physician records medical, administrative, and financial information on a single source document (the encounter form); data are input by clerical personnel; information is retrieved via different computer-generated displays and printouts which automatically select and organize the data. The system provides a High-level language which allows the user to access the database from a logical point of view and perform searches or prepare reports without programming support. COSTAR is available on minicomputers using commercially supported software and will be marketed by commercial organizations.
Analysis and Inactivation of vha55, the Gene Encoding the Vacuolar ATPase B-subunit in Drosophila melanogaster Reveals a Larval Lethal Phenotype (1996)

Vacuolar ATPases play major roles in endomembrane and plasma membrane proton transport in eukaryotes. A Drosophila melanogaster cDNA encoding vha55, the 55-kDa vacuolar ATPase (V-ATPase) regulatory B-subunit, was characterized and mapped to 87C2-4 on chromosome 3R. A fly line was identified that carried a single lethal P-element insertion within the coding portion of gene, and its LacZ reporter gene revealed elevated expression in Malpighian tubules, rectum, antennal palps, and oviduct, regions where V-ATPases are believed to play a plasma membrane, rather than an endomembrane, role. The P-element vha55 insertion was shown to be allelic to a known lethal complementation group l(3)SzA (= l(3)87Ca) at 87C, for which many alleles have been described previously. Deletions of the locus have been shown to be larval lethal, whereas point mutations show a range of phenotypes from subvital to embryonic lethal, implying that severe alleles confer a partial dominant negative phenotype. The P-element null allele of vha55 was shown also to suppress ectopic sex combs in Polycomb males, suggesting that transcriptional silencing may be modulated by genes other than those with known homeotic or DNA binding functions.
Molecular analysis of a synthetic tetracycline-binding riboswitch (2005)

Riboswitches are newly discovered regulatory elements that consist solely of RNA, sense their ligand in a preformed binding pocket, and perform a conformational switch in response to ligand binding, resulting in altered gene expression. Regulation by a tetracycline (tc)-binding aptamer when inserted into the 5' untranslated region (UTR) of a reporter gene exhibits all characteristics of a riboswitch. Chemical and enzymatic probing reveals that the aptamer consists of two stems, P1 and P2, which are already present in the absence of tc and form the scaffold of the aptamer. They are separated by a bulge B1-2 and an opposing stem-loop (P3-L3). Tc-dependent changes in the probing pattern only appear in the upper part of the bulge B1-2 (nucleotides 9-13) and the loop L3. Saturating mutagenesis corroborates the involvement of these two regions in regulation. Structural probing of the mutant A55U, which contains a single-nucleotide exchange in loop L3 results in a changed probing pattern of the loop, but also of the opposing bulge B1-2. This denotes that both regions cooperate and form a composite binding pocket. Thus, our model for aptamer-mediated translational regulation is that the ligand-free aptamer has only marginal influence on translational initiation. Tc then leads to an intramolecular connection in a pseudoknot-like manner and turns the aptamer into its inhibitory form. This represents a new mechanism for riboswitch action clearly distinguished from currently known naturally occurring riboswitches, which function by sequestration of the ribosomal binding site, transcriptional attenuation, and ribozyme-mediated degradation.
Brivanib Versus Sorafenib As First-Line Therapy in Patients With Unresectable, Advanced Hepatocellular Carcinoma: Results From the Randomized Phase III BRISK-FL Study (2013)

Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.
Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data (2010)

Genome-wide association analysis of the FHS data detected two new gene regions with genome-wide significance, detected epistatic SNP effects on TC and HDL-C with the significance of suggestive linkage in seven pairs of gene regions, and confirmed some previously reported gene regions associated with TC and HDL-C.
Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density electroencephalogram (2001)

We demonstrate an application of spherical harmonic decomposition to the analysis of the human electroencephalogram (EEG). We implement two methods and discuss issues specific to the analysis of hemispherical, irregularly sampled data. Spatial sampling requirements and performance of the methods are quantified using simulated data. The analysis is applied to experimental EEG data, confirming earlier reports of an approximate frequency-wave-number relationship in some bands.
A synthetic approach to the quassinoids (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA synthetic approach to the quassinoidsClayton H. Heathcock, Cyril Mahaim, Matthew F. Schlecht, and Thanin UtawanitCite this: J. Org. Chem. 1984, 49, 18, 3264–3274Publication Date (Print):September 1, 1984Publication History Published online1 May 2002Published inissue 1 September 1984https://pubs.acs.org/doi/10.1021/jo00192a004https://doi.org/10.1021/jo00192a004research-articleACS PublicationsRequest reuse permissionsArticle Views1232Altmetric-Citations53LEARN 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 Get e-Alerts
Broadly Protective Monoclonal Antibodies against H3 Influenza Viruses following Sequential Immunization with Different Hemagglutinins (2010)

As targets of adaptive immunity, influenza viruses are characterized by the fluidity with which they respond to the selective pressure applied by neutralizing antibodies. This mutability of structural determinants of protective immunity is the obstacle in developing universal influenza vaccines. Towards the development of such vaccines and other immune therapies, our studies are designed to identify regions of influenza viruses that are conserved and that mediate virus neutralization. We have specifically focused on viruses of the H3N2 subtype, which have persisted as a principal source of influenza-related morbidity and mortality in humans since the pandemic of 1968. Three monoclonal antibodies have been identified that are broadly-neutralizing against H3 influenza viruses spanning 40 years. The antibodies react with the hemagglutinin glycoprotein and appear to bind in regions that are refractory to the structural variation required for viral escape from neutralization. The antibodies demonstrate therapeutic efficacy in mice against H3N2 virus infection and have potential for use in the treatment of human influenza disease. By mapping the binding region of one antibody, 12D1, we have identified a continuous region of the hemagglutinin that may act as an immunogen to elicit broadly protective immunity to H3 viruses. The anti-H3 monoclonal antibodies were identified after immunization of mice with the hemagglutinin of four different viruses (A/Hong Kong/1/1968, A/Alabama/1/1981, A/Beijing/47/1992, A/Wyoming/3/2003). This immunization schedule was designed to boost B cells specific for conserved regions of the hemagglutinin from distinct antigenic clusters. Importantly, our antibodies are of naturally occurring specificity rather than selected from cloned libraries, demonstrating that broad-spectrum humoral immunity to influenza viruses can be elicited in vivo.
Intranasal Immunization with CpG Oligodeoxynucleotides as an Adjuvant Dramatically Increases IgA and Protection Against Herpes Simplex Virus-2 in the Genital Tract (2001)

Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HSV and HIV, will likely be dependent on the induction of potent long-lasting mucosal immune responses in the genital tract. Recently, synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs were shown to serve as potent adjuvants for the induction of mucosal immune responses. Here, we show that intranasal immunization with CpG ODN, plus recombinant glycoprotein B (rgB) of HSV-1, results in significantly elevated levels of specific anti-gB IgA Abs in vaginal washes that remained high throughout the estrous cycle. Additionally, dramatically elevated numbers of specific IgA Ab-secreting cells were present and persisted in the genital tract in response to intravaginal (IVAG) HSV-2 challenge. HSV-2-specific CTL were observed at moderate levels in the spleens of CpG or non-CpG ODN-immunized mice. In contrast, strong CTL responses were observed locally in the genital tissues of both groups following IVAG HSV-2 challenge. Interestingly, mice immunized intranasally with rgB plus CpG ODN, but not non-CpG ODN, were significantly protected following IVAG HSV-2 challenge. Measurement of virus in protected CpG-immunized mice revealed a log lower level of replication within the first few days after infection. In conclusion, these results indicate that intranasal immunization with CpG ODN plus protein mediates immunity in the female genital tract capable of protecting against a sexually transmitted pathogen.
Activity-Based Protein Profiling of Oncogene-Driven Changes in Metabolism Reveals Broad Dysregulation of PAFAH1B2 and 1B3 in Cancer (2015)

Targeting dysregulated metabolic pathways is a promising therapeutic strategy for eradicating cancer. Understanding how frequently altered oncogenes regulate metabolic enzyme targets would be useful in identifying both broad-spectrum and targeted metabolic therapies for cancer. Here, we used activity-based protein profiling to identify serine hydrolase activities that were consistently upregulated by various human oncogenes. Through this profiling effort, we found oncogenic regulatory mechanisms for several cancer-relevant serine hydrolases and discovered that platelet activating factor acetylhydrolase 1B2 and 1B3 (PAFAH1B2 and PAFAH1B3) activities were consistently upregulated by several oncogenes, alongside previously discovered cancer-relevant hydrolases fatty acid synthase and monoacylglycerol lipase. While we previously showed that PAFAH1B2 and 1B3 were important in breast cancer, our most recent profiling studies have revealed that these enzymes may be dysregulated broadly across many types of cancers. Here, we find that pharmacological blockade of both enzymes impairs cancer pathogenicity across multiple different types of cancer cells, including breast, ovarian, melanoma, and prostate cancer. We also show that pharmacological blockade of PAFAH1B2 and 1B3 causes unique changes in lipid metabolism, including heightened levels of tumor-suppressing lipids. Our results reveal oncogenic regulatory mechanisms of several cancer-relevant serine hydrolases using activity-based protein profiling, and we show that PAFAH1B2 and 1B3 are important in maintaining cancer pathogenicity across a wide spectrum of cancer types.
The Telobox, a Myb-Related Telomeric DNA Binding Motif Found in Proteins from Yeast, Plants and Human (1996)

The yeast TTAGGG binding factor 1 (Tbf1) was identified and cloned through its ability to interact with vertebrate telomeric repeats in vitro. We show here that a sequence of 60 amino acids located in its C-terminus is critical for DNA binding. This sequence exhibits homologies with Myb repeats and is conserved among five proteins from plants, two of which are known to bind telomeric-related sequences, and two proteins from human, including the telomeric repeat binding factor (TRF) and the predicted C-terminal polypeptide, called orf2, from a yet unknown protein. We demonstrate that the 111 C-terminal residues of TRF and the 64 orf2 residues are able to bind the human telomeric repeats specifically. We propose to call the particular Myb-related motif found in these proteins the 'telobox'. Antibodies directed against the Tbf1 telobox detect two proteins in nuclear and mitotic chromosome extracts from human cell lines. Moreover, both proteins bind specifically to telomeric repeats in vitro. TRF is likely to correspond to one of them. Based on their high affinity for the telomeric repeat, we predict that TRF and orf2 play an important role at human telomeres.
IL-21 Activates Both Innate and Adaptive Immunity to Generate Potent Antitumor Responses that Require Perforin but Are Independent of IFN-γ (2003)

IL-21 is a key factor in the transition between innate and adaptive immune responses. We have used the cytokine gene therapy approach to study the antitumor responses mediated by IL-21 in the B16F1 melanoma and MethA fibrosarcoma tumor models in mice. Retrovirally transduced tumor cells secreting biologically functional IL-21 have growth patterns in vitro similar to that of control green fluorescent protein-transduced cells, but are completely rejected in vivo. We show that IL-21 activates NK and CD8(+) T cells in vivo, thus mediating complete rejection of poorly immunogenic tumors. Rejection of IL-21-secreting tumors requires the presence of cognate IL-21R and does not depend on CD4(+) T cell help. Interestingly, perforin, but not IFN-gamma or other major Th1 and Th2 cytokines (IL-12, IL-4, or IL-10), is required for the IL-21-mediated antitumor response. Moreover, IL-21 results in 50% protection and 70% cure of nonimmunogenic tumors when given before and after tumor challenge, respectively, in C57BL/6 mice. We conclude that IL-21 immunotherapy warrants clinical evaluation as a potential treatment for cancer.
Cytokine profile (IL‐2, IL‐6, IL‐17, IL‐22, and TNF‐α) in vitiligo—New insight into pathogenesis of disease (2018)

Our study shows that cytokines secreted by Th17 cells play an important role in maintenance and spread of vitiligo as they increase in line with extent of disease. Also TNF-α increases in proportion with activity of disease, hence may act as biomarker for identifying patient with aggressive disease.