gebhart/patrepeval huggingface dataset:
Human immunodeficiency virus type 1 integrase: effects of mutations on viral ability to integrate, direct viral gene expression from unintegrated viral DNA templates, and sustain viral propagation in primary cells (1995)

Integrase is the only viral protein necessary for integration of retroviral DNA into chromosomal DNA of the host cell. Biochemical analysis of human immunodeficiency virus type 1 (HIV-1) integrase with purified protein and synthetic DNA substrates has revealed extensive information regarding the mechanism of action of the enzyme, as well as identification of critical residues and functional domains. Since in vitro reactions are carried out in the absence of other viral proteins and they analyze strand transfer of only one end of the donor substrate, they do not define completely the process of integration as it occurs during the course of viral infection. In an effort to further understand the role of integrase during viral infection, we initially constructed a panel of 24 HIV-1 mutants with specific alanine substitutions throughout the integrase coding region and analyzed them in a human T-cell line infection. Of these mutant viruses, 12 were capable of sustained viral replication, 11 were replication defective, and 1 was temperature sensitive for viral growth. The replication defective viruses express and correctly process the integrase and Gag proteins. Using this panel of mutants and an additional set of 18 mutant viruses, we identified nine amino acids which, when replaced with alanine, destroy integrase activity. Although none of the replication-defective mutants are able to integrate into the host genome, a subset of them with alterations in the catalytic triad are capable of Tat-mediated transactivation of an indicator gene linked to the viral long terminal repeat promoter. We present evidence that integration of the HIV-1 provirus is essential not only for productive infection of T cells but also for virus passage in both cultured peripheral blood lymphocytes and macrophage cells.
Type I Interferon in the Pathogenesis of Lupus (2014)

Investigations of patients with systemic lupus erythematosus have applied insights from studies of the innate immune response to define IFN-I, with IFN-α as the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I-signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFN-I-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained antivirus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients.
Live-Cell Analysis of a Green Fluorescent Protein-Tagged Herpes Simplex Virus Infection (1999)

Many stages of the herpes simplex virus maturation pathway have not yet been defined. In particular, little is known about the assembly of the virion tegument compartment and its subsequent incorporation into maturing virus particles. Here we describe the construction of a herpes simplex virus type 1 (HSV-1) recombinant in which we have replaced the gene encoding a major tegument protein, VP22, with a gene expressing a green fluorescent protein (GFP)-VP22 fusion protein (GFP-22). We show that this virus has growth properties identical to those of the parental virus and that newly synthesized GFP-22 is detectable in live cells as early as 3 h postinfection. Moreover, we show that GFP-22 is incorporated into the HSV-1 virion as efficiently as VP22, resulting in particles which are visible by fluorescence microscopy. Consequently, we have used time lapse confocal microscopy to monitor GFP-22 in live-cell infection, and we present time lapse animations of GFP-22 localization throughout the virus life cycle. These animations demonstrate that GFP-22 is present in a diffuse cytoplasmic location when it is initially expressed but evolves into particulate material which travels through an exclusively cytoplasmic pathway to the cell periphery. In this way, we have for the first time visualized the trafficking of a herpesvirus structural component within live, infected cells.
Virtual Screening for β-Secretase (BACE1) Inhibitors Reveals the Importance of Protonation States at Asp32 and Asp228 (2005)

A comparative virtual screen for beta-secretase (BACE1) inhibitors using different docking methods (FlexX and FlexX-Pharm), scoring functions (Dock, Gold, Chem, PMF, FlexX), protonation states (default and calculated), and protein conformations (apo and ligand bound) has been performed. Apo and ligand bound conformations of BACE1 were both found to be suitable for virtual screening. Assigning calculated protonation states to catalytic Asp32 and Asp228 residues resulted in significant improvement of enrichment factors as calculated at 1% of the ranked database. Using 1FKN we obtained no enrichment by FlexX/D-Score that was improved to 36 when considering calculated protonation states. We also show that combining calculated protonation states with pharmacophore constraints using FlexX-Pharm/D-Score improved enrichment further to 41. Enrichments reported in this study suggest our screening protocol will be effective in the virtual screening of large compound libraries for BACE1 inhibitors.
Pharmacological evidence that calcitonin gene-related peptide is implicated in cerebral autoregulation (1994)

In anesthetized rats, we examined the possibility that calcitonin gene-related peptide (CGRP, a neuropeptide) released in response to transient hypotension may contribute to the reflex autoregulation of cerebral blood flow. Changes in pial arterial diameter (mean 33.0 +/- 1.1 microns) with changes in systemic arterial blood pressure (mean 101.9 +/- 2.7 mmHg) were observed directly through a closed cranial window. In capsaicin-treated rats (depletor of CGRP and substance P, 50 nmol capsaicin injected intracisternally 24 h before experiment), vasodilatation, which was evoked on transient hypotension, and vasoconstriction on reverse of hypotension were markedly attenuated or almost abolished. When changes in pial arterial diameter were plotted as a function of changes in blood pressure, the slopes of regression lines for vasodilatation and vasoconstriction were markedly reduced after capsaicin treatment. Similar reductions were evidenced under suffusion of CGRP antibody serum (1:1,000) and after CGRP receptor desensitization but not after substance P receptor desensitization. Pretreatment with glibenclamide, a K(+)-channel antagonist, also caused severe alterations in the autoregulatory vasomotor responses to hypotension and its reverse. Suffusion with mock cerebrospinal fluid, containing either CGRP or cromakalim, a K(+)-channel opener, dilated the pial artery in a concentration-dependent manner, and their effects were antagonized by glibenclamide. Substance P produced a vasodilatation, which was unaffected by glibenclamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Material design of hole transport materials capable of thick-film formation in organic light emitting diodes (2007)

In this study, the authors show an empirical guideline for designing hole transport materials (HTMs) that suppress rises in driving voltage even with a few hundred nanometer thick film in the organic light emitting diodes (OLEDs). In a device structure of indium tin oxide (110nm)/hole transport layer (HTL) (Xnm)∕4,4′-N,N′-bis[N-(1-naphthyl)-N-phenyl-amino]biphenyl (10nm)/tris-(8-hydroxyquinoline)aluminum (Alq3) (50nm)∕MgAg (100nm)∕Ag (10nm), the authors compared electroluminescence characteristics of the OLEDs having a thin-film HTL (X=50nm) and a thick-film HTL (X=300nm) using 13 kinds of HTMs. They observed a closed correlation between suppression of the driving voltage and the HTMs’ thermal characteristics. Highly thermally stable HTMs resulted in a small increase in the driving voltage.
STRUCTURE AND ACTIVITIES OF GROUP II INTRONS (1995)

Group II introns are found in eubacteria and eubacterial-derived, organellar genomes. They have ribozymic activities, by which they direct and catalyze the splicing of the exons flanking them. This chapter reviews the secondary structure and known tertiary interactions of the ribozymic component of group II introns in relation to the problems of specifying splice sites and building a catalytic core. We pay special attention to the relationship between the transesterification and hydrolytic modes of initiating splicing and the stereospecificities of these reactions. A number of group II introns encode proteins of the reverse transcriptase family; the activity of these proteins enables the host introns to change genomic locations by mechanisms that are only beginning to be deciphered. Finally, we briefly discuss multipartite and post-transcriptionally edited group II introns, together with the intron microcosm of Euglena gracilis chloroplasts and the possible relationships between group II and spliceosome-catalyzed splicing processes.
Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene (1994)

We describe the cloning of the mouse HGMP01A gene that encodes a melanocortin receptor functionally distinct from the adrenal cortex corticotropin (adrenocorticotrophic hormone; ACTH) receptor and the melanocyte-stimulating hormone (MSH) receptor expressed in melanoma. The gene encodes a protein of 323 amino acids with a calculated molecular mass of 35,800 Da, displaying potential sites for N-linked glycosylation and phosphorylation by protein kinase C. An RNAase protection assay detected weak expression in the brain, but not in adrenal gland, skin, or any of the other tissues tested. Stable CHO cell lines expressing over 100,000 receptors per cell were generated. The recombinant receptor binds iodinated [Nle4,D-Phe7]alpha-MSH (NDP-MSH) with an apparent Kd of 700 pM. Displacement of the ligand by a variety of pro-opiomelanocortin-derived peptides revealed a pharmacological profile distinct from that of the classical ACTH and MSH receptors. NDP-MSH was the most powerful competitor (IC50 1.4 nM), followed by gamma-MSH (IC50 7 nM). alpha-MSH, beta-MSH and ACTH-(1-39) were significantly less potent, with IC50 values of 30, 19 and 21 nM respectively. ACTH-(4-10) was poorly active (IC50 2.4 microM), while corticotropin-like intermediate lobe peptide (CLIP) and beta-endorphin were totally ineffective. The recombinant receptor was found to stimulate adenylate cyclase. The potency order of the agonists in this assay was consistent with that of the binding displacement assays. This receptor represents the orthologue of the human melanocortin 3 receptor reported recently. The growing family of melanocortin receptors constitute the molecular basis for the variety of actions of melanocortins that have been described over the years. The availability of functionally expressed receptors from the melanocortin family will allow the development of a specific pharmacology, and a better understanding of the function of the pro-opiomelanocortin-derived peptides.
Innate immune recognition: mechanisms and pathways (2000)

The innate immune system is an evolutionarily ancient form of host defense found in most multicellular organisms. Inducible responses of the innate immune system are triggered upon pathogen recognition by a set of pattern recognition receptors. These receptors recognize conserved molecular patterns shared by large groups of microorganisms. Recognition of these patterns allows the innate immune system not only to detect the presence of an infectious microbe, but also to determine the type of the infecting pathogen. Pattern recognition receptors activate conserved host defense signaling pathways that control the expression of a variety of immune response genes.
The Circulatory Effects of Intravenous Phentolamine in Man (1965)

Circulatory observations have been made on six normal subjects and six hypertensive patients before and after the acute intravenous injection of 5 mg. of phentolamine. The drug caused a prompt reduction in systemic vascular resistance which resulted in a rapid fall in systemic blood pressure in spite of an increase in heart rate and cardiac output. Evidence is presented that the predominant vascular activity of the drug is to cause a direct relaxation of vascular smooth muscle, an effect far more potent than its antagonism of circulating catecholamines or its very much weaker sympathetic-blocking action. This direct depressor effect on vascular smooth muscle unaccompanied by any but slight sympathetic blocking activities endows the drug with theoretically ideal antihypertensive properties. Phentolamine caused a transient but significant reduction in oxygen uptake in the majority of individuals. It is suggested that this may be due to a direct inhibition of cellular oxidative mechanisms. An appraisal of the circulatory activities of the drug with particular regard to its use as a diagnostic test for pheochromocytoma leads to serious doubts, not only with regard to the precision with which the results of such tests can be interpreted, but also to the validity of the use of the drug as a reliable screening test for excessive circulating catecholamines.
Adenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphate (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdenosine 5'-phosphorothioate. A nucleotide analog that is a substrate, competitive inhibitor, or regulator of some enzymes that interact with adenosine 5'-phosphateAndrew Walter. Murray and Maurice R. AtkinsonCite this: Biochemistry 1968, 7, 11, 4023–4029Publication Date (Print):November 1, 1968Publication History Published online1 May 2002Published inissue 1 November 1968https://pubs.acs.org/doi/10.1021/bi00851a032https://doi.org/10.1021/bi00851a032research-articleACS PublicationsRequest reuse permissionsArticle Views439Altmetric-Citations98LEARN 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
The herpes simplex virus type 1 alpha protein ICP27 can act as a trans-repressor or a trans-activator in combination with ICP4 and ICP0 (1988)

The herpes simplex virus type 1 (HSV-1) alpha proteins ICP4, ICP0, and ICP27 are trans-acting proteins which affect HSV-1 gene expression. To investigate potential interactions between these alpha products and to determine the specificity of action of the alpha proteins in combination with each other compared with their activities individually, we performed a series of transient-expression assays. In these assays we used plasmids containing the alpha genes encoding ICP4, ICP0, and ICP27 either singly or in combination as effectors and HSV-1 genes of different kinetic classes and heterologous genes as targets. The HSV-1 targets consisted of promoter-regulatory domains from alpha (ICP0 and ICP27), beta (thymidine kinase and alkaline exonuclease), beta-gamma (glycoprotein D, glycoprotein B, and VP5), and gamma (glycoprotein C) genes, each fused to the chloramphenicol acetyltransferase (CAT) gene. The heterologous target genes consisted of the simian virus 40 early promoter with enhancer and the Rous sarcoma virus long terminal repeat promoter and enhancer each fused to the CAT gene. Target promoter activity was measured by the assay of CAT activity in extracts of transfected cells and by Northern (RNA) blot hybridization of CAT mRNA. The results of these experiments showed that ICP4 activated only HSV-1 target genes, whereas ICP0 activated all of the targets and ICP27 had little effect on any of the targets. ICP4 and ICP0 had a synergistic effect when inducing HSV-1 targets, but they did not have this effect on the heterologous targets pSV2-CAT or pRSV-CAT. In fact, lower levels of CAT activity and CAT mRNA were found in the presence of both effectors than with ICP0 alone. Most interestingly, although the effector plasmid containing the ICP27 gene had little effect on its own, two different and marked effects depending on the target were observed when ICP27 was combined with ICP4 or ICP0 or both. A trans-repression of the induction seen with ICP4 and ICP0 was found when ICP27 was present in the transfections with pSV2-CAT, pRSV-CAT, pICP0-CAT, pICP27-CAT, pTK-CAT, pgD-CAT, pgB-CAT, and pgC-CAT. This resulted in CAT activity levels which were similar to or lower than the basal level of expression of the target genes in the absence of effector plasmids. This trans-repression occurred over a wide range of concentrations of input ICP27 plasmid. In contrast to this repressive effect of ICP27, a trans-activation was seen when ICP4, ICP0, and ICP27 plasmids were combined in transfections with pAE-CAT and pVP5-CAT as targets. This trans-activation also occurred over a 10-fold range of input ICP27 plasmid. These results suggest that ICP27 can facilitate both down
Female physiology during exercise (1990)

Physiological responses and adaptations of women to exercise are influenced by her genetically determined morphological and functional characteristics, and by her level of physical fitness. Physiological responses of women during submaximal and maximal exercise differ quantitatively from those of men but adaptations to training are qualitatively similar in both. Studies demonstrate that differences between the sexes in performance of athletic events that require high aerobic or anaerobic capacity are due, to a large extent, to differences in body structure and composition: the average woman is smaller and lighter and has less muscle mass than the average man. These characteristics influence physiologic responses of the musculoskeletal, cardiovascular and respiratory systems during exercise. This article describes physiological responses of women during exercise in relation to her sex related morphological characteristics, and the adaptations that occur with physical training.
Simultaneous HDS of DBT and 4,6-DMDBT over single-pot Ti-SBA-15-NiMo catalysts: influence of Si/Ti ratio on the structural properties, dispersion and catalytic activity (2017)

Influence of Si/Ti ratios on structural properties and HDS activity of DBT and DMDBT is investigated. New structural HDS catalyst is formed with TiO<sub>2</sub> phases predominates at Si/Ti = 1. DDS rate is enhanced by Ti addition while HYD rate remain almost constant.
High-resolution surface plasmon resonance sensor based on linewidth-optimized nanohole array transmittance (2006)

A high spectral resolution, 2D nanohole-array-based surface plasmon resonance sensor that operates at normal or near normal incidence--facilitating high spatial resolution imaging--is presented. The angular and spectral transmittance of the structure is modified from a Fano type to a pure Lorentzian line shape with a parallel and orthogonal polarizer-analyzer pair. This change leads to a linewidth narrowing that maximizes the sensor resolution, which we show to be of O(10(-5)) refractive index units (RIU). We estimate the potential of this system of O(10(-6)) RIU under optimal conditions.
Manipulating Corynebacteria, from Individual Genes to Chromosomes (2005)

Corynebacterium glutamicum is an industrial organism with a long history of use for the production of various fine chemicals. The C. glutamicum -mediated production of l-glutamic acid by fermentation was one of the very first industrial processes of the biotechnology era. This fermentation
Metalenses at visible wavelengths: Diffraction-limited focusing and subwavelength resolution imaging (2016)

Subwavelength resolution imaging requires high numerical aperture (NA) lenses, which are bulky and expensive. Metasurfaces allow the miniaturization of conventional refractive optics into planar structures. We show that high-aspect-ratio titanium dioxide metasurfaces can be fabricated and designed as metalenses with NA = 0.8. Diffraction-limited focusing is demonstrated at wavelengths of 405, 532, and 660 nm with corresponding efficiencies of 86, 73, and 66%. The metalenses can resolve nanoscale features separated by subwavelength distances and provide magnification as high as 170×, with image qualities comparable to a state-of-the-art commercial objective. Our results firmly establish that metalenses can have widespread applications in laser-based microscopy, imaging, and spectroscopy.
Agents that reduce work and information overload (1994)

article Free Access Share on Agents that reduce work and information overload Author: Pattie Maes MIT Media Lab., Cambridge, MA MIT Media Lab., Cambridge, MAView Profile Authors Info & Claims Communications of the ACMVolume 37Issue 7July 1994 pp 30–40https://doi.org/10.1145/176789.176792Published:01 July 1994Publication History 26citation8,051DownloadsMetricsTotal Citations26Total Downloads8,051Last 12 Months137Last 6 weeks19 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Tetranucleotide repeat polymorphism in the apolipoprotein B gene (1990)

Journal Article Tetranucleotide repeat polymorphism in the apolipoprotein B gene Get access Giovanni Zuliani, Giovanni Zuliani Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines BoulevardDallas, TX 75235, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen H. Hobbs Helen H. Hobbs Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines BoulevardDallas, TX 75235, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 14, 25 July 1990, Page 4299, https://doi.org/10.1093/nar/18.14.4299 Published: 25 July 1990
Transmembrane grasshopper Semaphorin I promotes axon outgrowth in vivo (1997)

Members of the Semaphorin family of glycoproteins play an important role in axonal pathfinding by functioning as inhibitory guidance cues. Here we provide evidence that a transmembrane form of Semaphorin (Semaphorin I), which is expressed by bands of epithelial cells in the developing grasshopper limb bud, functions as an attractive/permissive cue for the growth cones of the subgenual organ. In addition, we demonstrate that Semaphorin I is needed for initial axonal outgrowth from the subgenual organ. These results are consistent with an alternative function for a transmembrane form of Semaphorin and may explain the previously reported arrest of the proximal extension of the subgenual organ growth cones in the absence of the Ti1 pioneer pathway.