gebhart/patrepeval huggingface dataset:
Influenza virus targets the mRNA export machinery and the nuclear pore complex (2007)

The NS1 protein of influenza A virus is a major virulence factor that is essential for pathogenesis. NS1 functions to impair innate and adaptive immunity by inhibiting host signal transduction and gene expression, but its mechanisms of action remain to be fully elucidated. We show here that NS1 forms an inhibitory complex with NXF1/TAP, p15/NXT, Rae1/mrnp41, and E1B-AP5, which are key constituents of the mRNA export machinery that interact with both mRNAs and nucleoporins to direct mRNAs through the nuclear pore complex. Increased levels of NXF1, p15, or Rae1 revert the mRNA export blockage induced by NS1. Furthermore, influenza virus down-regulates Nup98, a nucleoporin that is a docking site for mRNA export factors. Reduced expression of these mRNA export factors renders cells highly permissive to influenza virus replication, demonstrating that proper levels of key constituents of the mRNA export machinery protect against influenza virus replication. Because Nup98 and Rae1 are induced by interferons, down-regulation of this pathway is likely a viral strategy to promote viral replication. These findings demonstrate previously undescribed influenza-mediated viral-host interactions and provide insights into potential molecular therapies that may interfere with influenza infection.
A new approach to probing conformational space with molecular mechanics: random incremental pulse search (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new approach to probing conformational space with molecular mechanics: random incremental pulse searchDavid M. Ferguson and Douglas J. RaberCite this: J. Am. Chem. Soc. 1989, 111, 12, 4371–4378Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/ja00194a034https://doi.org/10.1021/ja00194a034research-articleACS PublicationsRequest reuse permissionsArticle Views352Altmetric-Citations176LEARN 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
pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires (2014)

pRESTO is freely available for academic use. The software package and detailed tutorials may be downloaded from http://clip.med.yale.edu/presto.
Secretion of human parathyroid hormone from rat pituitary cells infected with a recombinant retrovirus encoding preproparathyroid hormone. (1984)

In order to study the functions of precursors to secreted proteins, we expressed cloned DNA encoding human preproparathyroid hormone (preproPTH) in rat pituitary cells. We first constructed a recombinant plasmid containing human preproPTH cDNA and retroviral control signals. This recombinant plasmid was transfected into psi-2 cells, a packaging cell line that produces Moloney murine leukemia viral particles containing no retroviral RNA. The transfected psi-2 cells generated helper-free recombinant retrovirus encoding preproPTH, and this recombinant retrovirus was used to infect GH4 rat pituitary cells. Clonal lines of the infected GH4 cells contained copies of the recombinant provirus stably integrated via the long terminal repeats, and the expected RNA transcripts of proviral DNA accumulated in the cytoplasm, although no infectious virus was produced. The infected cells synthesized and processed preproPTH appropriately and secreted PTH in response to thyrotropin-releasing hormone, a secretagogue for GH4 cells. Use of recombinant retrovirus permits the introduction of DNA encoding normal and mutant secreted proteins into a number of cell types specialized for secretion. Analysis of the fate of the resultant proteins will help define the specific molecular interactions involved in transmembrane transport and processing of precursor proteins.
Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12 inhibitor (2020)

CYP2C19 polymorphisms have less impact on vicagrel as compared to clopidogrel. Drug exposure and response to vicagrel in PMs were even higher than to clopidogrel in IMs.
Limbic-cortical dysregulation: a proposed model of depression (1997)

A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.
Membrane 126-kilodalton phosphoglycoprotein associated with human carcinomas identified by a hybridoma antibody to mammary carcinoma cells. (1983)

A large number of hybridomas producing antibodies to the membrane fraction of a human mammary carcinoma cell line have been produced. Among those hybridoma antibodies that bound to exposed surface membrane epitopes on the human mammary carcinoma cell line BT-20, one has been found to bind to all tested breast carcinoma cell lines as well as to a number of other human carcinomas by solid-phase radioimmunoassay. This hybridoma antibody, designated 10-3D2, does not bind to normal mammary epithelium, a variety of control cell lines, or selected normal human tissue homogenates. The 10-3D2 hybridoma antibody identifies by immunoprecipitation a membrane 126-kilodalton protein which is indistinguishable in different tumor cells. It is glycosylated by reference to incorporation of [3H]glucosamine and also is phosphorylated by reference to incorporation of 32P. It is present in a finely granular pattern on the cell surface of mammary carcinoma cells with concentration at the sites of apparent cell-cell contact. This 126-kilodalton phosphoglycoprotein, which we have consistently been unable to identify by immunoprecipitation of intrinsically labeled normal cells, may represent a heretofore unrecognized tumor-associated marker for human mammary carcinomas as well as certain other types of human neoplasms.
The Synthesis and the Exhaustive Methylation of the cis and trans Isomers of 1,2,3,4,4a,5,6,10b-Octahydrophenanthridine and 1,2,3,4,4a,5,6,10b-Octahydrobenzo[f]quinoline1 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis and the Exhaustive Methylation of the cis and trans Isomers of 1,2,3,4,4a,5,6,10b-Octahydrophenanthridine and 1,2,3,4,4a,5,6,10b-Octahydrobenzo[f]quinoline1Tadashi Masamune, Masaji Ohno, Masato Koshi, Shigehiro Ohuchi, and Tsukasa IwadareCite this: J. Org. Chem. 1964, 29, 6, 1419–1424Publication Date (Print):June 1, 1964Publication History Published online1 May 2002Published inissue 1 June 1964https://pubs.acs.org/doi/10.1021/jo01029a038https://doi.org/10.1021/jo01029a038research-articleACS PublicationsRequest reuse permissionsArticle Views182Altmetric-Citations17LEARN 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
Predicting cancer outcomes from histology and genomics using convolutional networks (2018)

Cancer histology reflects underlying molecular processes and disease progression and contains rich phenotypic information that is predictive of patient outcomes. In this study, we show a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how these survival convolutional neural networks (SCNNs) can integrate information from both histology images and genomic biomarkers into a single unified framework to predict time-to-event outcomes and show prediction accuracy that surpasses the current clinical paradigm for predicting the overall survival of patients diagnosed with glioma. We use statistical sampling techniques to address challenges in learning survival from histology images, including tumor heterogeneity and the need for large training cohorts. We also provide insights into the prediction mechanisms of SCNNs, using heat map visualization to show that SCNNs recognize important structures, like microvascular proliferation, that are related to prognosis and that are used by pathologists in grading. These results highlight the emerging role of deep learning in precision medicine and suggest an expanding utility for computational analysis of histology in the future practice of pathology.
Severe Pulmonary Embolism:Pulmonary Artery Clot Load Scores and Cardiovascular Parameters as Predictors of Mortality (2006)

RV/LV ratio and azygos vein diameter are predictors of mortality in patients with severe PE.
Disruption of TgPHIL1 Alters Specific Parameters of Toxoplasma gondii Motility Measured in a Quantitative, Three-Dimensional Live Motility Assay (2014)

T. gondii uses substrate-dependent gliding motility to invade cells of its hosts, egress from these cells at the end of its lytic cycle and disseminate through the host organism during infection. The ability of the parasite to move is therefore critical for its virulence. T. gondii engages in three distinct types of gliding motility on coated two-dimensional surfaces: twirling, circular gliding and helical gliding. We show here that motility in a three-dimensional Matrigel-based environment is strikingly different, in that all parasites move in irregular corkscrew-like trajectories. Methods developed for quantitative analysis of motility parameters along the smoothed trajectories demonstrate a complex but periodic pattern of motility with mean and maximum velocities of 0.58 ± 0.07 µm/s and 2.01 ± 0.17 µm/s, respectively. To test how a change in the parasite's crescent shape might affect trajectory parameters, we compared the motility of Δphil1 parasites, which are shorter and wider than wild type, to the corresponding parental and complemented lines. Although comparable percentages of parasites were moving for all three lines, the Δphil1 mutant exhibited significantly decreased trajectory lengths and mean and maximum velocities compared to the parental parasite line. These effects were either partially or fully restored upon complementation of the Δphil1 mutant. These results show that alterations in morphology may have a significant impact on T. gondii motility in an extracellular matrix-like environment, provide a possible explanation for the decreased fitness of Δphil1 parasites in vivo, and demonstrate the utility of the quantitative three-dimensional assay for studying parasite motility.
Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. (2003)

To identify potential targets for aberrant methylation in pancreatic cancer, we analyzed global changes in gene expression profiles of four pancreatic cancer cell lines after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) and/or the histone deacetylase inhibitor trichostatin A. A substantial number of genes were induced 5-fold or greater by 5Aza-dC alone (631 transcripts), trichostatin A alone (1196 transcripts), and by treatment with both agents (857 transcripts). Four hundred and seventy-five genes were markedly (>5-fold) induced after 5Aza-dC treatment in pancreatic cancer cell lines but not in a nonneoplastic pancreatic epithelial cell line. The methylation status of 11 of these 475 genes was examined in a panel of 42 pancreatic cancers, and all 11 of these genes were aberrantly methylated in pancreatic cancer but rarely, if any, methylated in 10 normal pancreatic ductal epithelia. These genes include UCHL1 (methylated in 100% of 42 pancreatic cancers), NPTX2 (98%), SARP2 (95%), CLDN5 (93%), reprimo (86%), LHX1 (76%), WNT7A (71%), FOXE1 (69%), TJP2 (64%), CDH3 (19%), and ST14 (10%). Three of these 11 genes (NPTX2, SARP2, and CLDN5) were selected for further analysis in a larger panel of specimens, and aberrant methylation of at least one of these three genes was detectable in 100% of 43 primary pancreatic cancers and in 18 of 24 (75%) pancreatic juice samples obtained from patients with pancreatic cancer. Thus, a substantial number of genes are induced by 5Aza-dC treatment of pancreatic cancer cells, and many of them may represent novel targets for aberrant methylation in pancreatic carcinoma.
Bacterial Cytosine Deaminase Mutants Created by Molecular Engineering Show Improved 5-Fluorocytosine–Mediated Cell Killing In vitro and In vivo (2009)

Cytosine deaminase is used in combination with 5-fluorocytosine as an enzyme-prodrug combination for targeted genetic cancer treatment. This approach is limited by inefficient gene delivery and poor prodrug conversion activities. Previously, we reported individual point mutations within the substrate binding pocket of bacterial cytosine deaminase (bCD) that result in marginal improvements in the ability to sensitize cells to 5-fluorocytosine (5FC). Here, we describe an expanded random mutagenesis and selection experiment that yielded enzyme variants, which provide significant improvement in prodrug sensitization. Three of these mutants were evaluated using enzyme kinetic analyses and then assayed in three cancer cell lines for 5FC sensitization, bystander effects, and formation of 5-fluorouracil metabolites. All variants displayed 18- to 19-fold shifts in substrate preference toward 5FC, a significant reduction in IC(50) values and improved bystander effect compared with wild-type bCD. In a xenograft tumor model, the best enzyme mutant was shown to prevent tumor growth at much lower doses of 5FC than is observed when tumor cells express wild-type bCD. Crystallographic analyses of this construct show the basis for improved activity toward 5FC, and also how two different mutagenesis strategies yield closely related but mutually exclusive mutations that each result in a significant alteration of enzyme specificity.
A phase-locked loop for driving vibrating tube densimeters (1989)

A phase-locked loop has been developed for use in driving vibrating tube densimeters. This circuit allows reliable density measurements under high-noise conditions with lower drive power to the vibrating tube. The design and operation of the instrument is discussed.
Arterial Input Function Placement for Accurate CT Perfusion Map Construction in Acute Stroke (2010)

For postprocessing of accurate quantitative CT perfusion maps, laterality of the AIF location is less important than avoiding AIF placement distal to the clot as detected on CT angiography. This pitfall is less severe with deconvolution-based software programs using a delay-insensitive technique than with those using a standard deconvolution method.
Hypoxic mammalian cell radiosensitization by nitric oxide. (1993)

The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell radiosensitizer. Authentic NO gas was nearly as effective as oxygen in radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells using the NO-releasing agent (C2H5)2N[N(O)-NO]- Na+, radiosensitization was also observed with a sensitizer enhancement ratio of 2.4 (1 mM (C2H5)2N[N(O)NO]-Na+). Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell radiosensitization properties of (C2H5)2N[N(O)NO]-Na+, coupled with the vasodilatory effects of NO on tumor vasculature, suggest that such agents open a new avenue of research in radiation oncology.
The Alpher, Bethe and Gamow of IEF, the alpha‐Centaury of electrokinetic methodologies. Part II: Immobilized pH gradients (2007)

The present review (a follow up of Electrophoresis 2006, 27, 923-938 on conventional IEF) highlights the developmental steps of the IPG technology, from a nebulous start limiting the technique to just 1 pH unit intervals up to the description of extended pH gradients, encompassing as much as 8.5 pH units. Although computer algorithms had been developed for optimizing recipes so as to obtain the most precise and most linear pH gradients, it was also realized that nonlinear pH intervals, covering the pH 3-10 range, would be extremely beneficial in 2-D map analysis, since they would follow the pI distribution of proteins in living systems. The synthesis of a number of Immobiline chemicals (the acrylamido weak acids and bases meant to be incorporated into the nascent polyacrylamide chains) is also reported. The review ends with preparative aspects of IPGs, with the introduction of multicompartment electrolyzers with Immobiline membranes.
Conformational characterization of Bombyx mori silk fibroin in the solid state by high-frequency carbon-13 cross polarization-magic angle spinning NMR, x-ray diffraction, and infrared spectroscopy (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational characterization of Bombyx mori silk fibroin in the solid state by high-frequency carbon-13 cross polarization-magic angle spinning NMR, x-ray diffraction, and infrared spectroscopyTetsuo Asakura, Akio Kuzuhara, Ryoko Tabeta, and Hazime SaitoCite this: Macromolecules 1985, 18, 10, 1841–1845Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/ma00152a009https://doi.org/10.1021/ma00152a009research-articleACS PublicationsRequest reuse permissionsArticle Views1710Altmetric-Citations302LEARN 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
Modular Synthesis of Heparan Sulfate Oligosaccharides for Structure−Activity Relationship Studies (2009)

Although hundreds of heparan sulfate binding proteins have been identified and implicated in a myriad of physiological and pathological processes, very little information is known about the ligand requirements for binding and mediating biological activities by these proteins. This difficulty results from a lack of technology for establishing structure-activity relationships, which in turn is due to the structural complexity of natural heparan sulfate (HS) and difficulties of preparing well-defined HS oligosaccharides. To address this deficiency, we developed a modular approach for the parallel combinatorial synthesis of HS oligosaccharides that utilizes a relatively small number of selectively protected disaccharide building blocks, which can easily be converted into glycosyl donors and acceptors. The utility of the modular building blocks has been demonstrated by the preparation of a library of 12 oligosaccharides, which has been employed to probe the structural features of HS for inhibiting the protease, BACE-1. The complex variations in activity with structural changes support the view that important functional information is embedded in HS sequences. Furthermore, the most active derivative provides an attractive lead compound for the preparation of more potent compounds, which may find use as a therapeutic agent for Alzheimer's disease.
Weight loss in obese diabetic and non‐diabetic individuals and long‐term diabetes outcomes – a systematic review (2004)

The aim was to review the evidence for the long-term effects of weight loss on diabetes outcomes in obese people or for those at risk of developing type 2 diabetes. Current evidence is mostly based on short-term studies. This is a systematic review of long-term outcomes of weight loss in studies published between 1966 and 2001. Eleven long-term studies with a follow up of more than 2 years were included. Results show that those with diabetes who lost weight intentionally significantly reduced their mortality risks by 25%. Additionally, weight loss of 9-13 kg was most protective. Patients with the risk of developing diabetes due to either family history of diabetes or impaired glucose tolerance, saw a reduction in this risk. Those with large weight losses achievable with surgical interventions reduced their risk by at least 63%. Metabolic handling of glucose improved in 80% of those already with type 2 diabetes who lost weight. Based on one large study, intentional weight loss in obese patients appears to have a beneficial effect on mortality risk for those with type 2 diabetes. Clearly, further studies are needed to endorse this. The risk of developing diabetes being reduced by weight loss was shown in seven studies. However, the results were from studies with different analytical adjustments and outcome indices, making it difficult to make direct comparisons and should be viewed with caution. More long-term prospective studies need to be conducted with commitment to improving the methodological quality and standardization, in order to accurately assess the long-term effects of weight loss for obese diabetic and non-diabetic individuals.