gebhart/patrepeval huggingface dataset:
Ischemia‐induced changes in glucagon‐like peptide‐1 receptor and neuroprotective effect of its agonist, exendin‐4, in experimental transient cerebral ischemia (2011)

Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damages in the brain. In the present study, ischemia-induced changes in GLP-1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP-1R agonist exendin-4 (EX-4) against ischemic damage was studied. GLP-1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP-1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP-1R protein level was increased again at 10 days after I/R, and GLP-1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX-4 treatment attenuated ischemia-induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose-dependent manner. EX-4 treatment also induced the elevation of GLP-1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP-1R is altered in the ischemic region after an ischemic insult and that EX-4 protects against ischemia-induced neuronal death possibly by increasing GLP-1R expression and attenuating microglial activation against transient cerebral ischemic damage.
Global Indiscriminate Methylation in Cell-Specific Gene Promoters following Reprogramming into Human Induced Pluripotent Stem Cells (2013)

Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells.
ImageNet: a global distributed database for color image storage, and retrieval in medical imaging systems (2003)

The authors describe the overall system design for ImageNet and present a system prototype developed on an Ethernet network in the Computer Engineering Research Laboratory at the University of Arizona. ImageNet is a global distributed color image database and communications system with multiple database nodes and user workstations (WSs). Each database node serves a geographical region with several WS users. The database nodes are interconnected with a fiber optic backbone network. The first prototype of the ImageNet over Ethernet has been successfully implemented. The WS software showed that the user WS software provided the required functionality. One could make data dictionary requests, formulate queries, make single and multiple online as well as offline image transfers, and display images. The WS interface is simple to use, and requires little training for new users. The ImageNet system has applications to global teleradiology and telepathology imaging systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Granulocyte-macrophage colony-stimulating factor regulation in murine T cells and its relation to cyclosporin A. (1988)

The coordinated expression of the hematopoietic growth factors, interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in activated T cells suggests common synthetic pathways. However, cyclosporin A (CsA) appears to differentially effect the synthesis of these two lymphokines. When the supernatants from the concanavalin A-stimulated thymoma EL-4 or the T-cell hybrid 2B4 were assayed on the GM-CSF/IL3-dependent PT-18 and on the IL3-dependent DA-1 cell lines, IL3 activity could not be detected following CsA treatment, but substantial growth activity, which was identified as GM-CSF, was observed on the PT-18 cell line. CsA did not affect the kinetics of GM-CSF release, but inhibited the release of IL3 over a period of 40 h after the cells were stimulated and treated with CsA. In addition, CsA could be added up to 1 h after stimulation of the cells without affecting GM-CSF activity but inhibiting completely the IL3 activity. To substantiate the inability of CsA to inhibit GM-CSF activity, GM-CSF gene expression was evaluated. By Northern analysis GM-CSF mRNA was not inhibited by doses of CsA up to 1 microgram/ml. The data reveal that CsA can dissociate between the production of IL3 and GM-CSF, suggesting that these two CSFs are regulated by different mechanisms.
The AFR-PRELIEVE trial: a prospective, non-randomised, pilot study to assess the Atrial Flow Regulator (AFR) in heart failure patients with either preserved or reduced ejection fraction (2019)

Implantation of the AFR device in heart failure patients is feasible and safe; shunt patency at three months was confirmed in the study. The atrial shunt improved symptoms and surrogate parameters of heart failure in some but not all patients in both the HFpEF and HFrEF groups.
Facile Affinity Maturation of Antibody Variable Domains Using Natural Diversity Mutagenesis (2017)

The identification of mutations that enhance antibody affinity while maintaining high antibody specificity and stability is a time-consuming and laborious process. Here, we report an efficient methodology for systematically and rapidly enhancing the affinity of antibody variable domains while maximizing specificity and stability using novel synthetic antibody libraries. Our approach first uses computational and experimental alanine scanning mutagenesis to identify sites in the complementarity-determining regions (CDRs) that are permissive to mutagenesis while maintaining antigen binding. Next, we mutagenize the most permissive CDR positions using degenerate codons to encode wild-type residues and a small number of the most frequently occurring residues at each CDR position based on natural antibody diversity. This mutagenesis approach results in antibody libraries with variants that have a wide range of numbers of CDR mutations, including antibody domains with single mutations and others with tens of mutations. Finally, we sort the modest size libraries (~10 million variants) displayed on the surface of yeast to identify CDR mutations with the greatest increases in affinity. Importantly, we find that single-domain (V<sub>H</sub>H) antibodies specific for the α-synuclein protein (whose aggregation is associated with Parkinson's disease) with the greatest gains in affinity (>5-fold) have several (four to six) CDR mutations. This finding highlights the importance of sampling combinations of CDR mutations during the first step of affinity maturation to maximize the efficiency of the process. Interestingly, we find that some natural diversity mutations simultaneously enhance all three key antibody properties (affinity, specificity, and stability) while other mutations enhance some of these properties (e.g., increased specificity) and display trade-offs in others (e.g., reduced affinity and/or stability). Computational modeling reveals that improvements in affinity are generally not due to direct interactions involving CDR mutations but rather due to indirect effects that enhance existing interactions and/or promote new interactions between the antigen and wild-type CDR residues. We expect that natural diversity mutagenesis will be useful for efficient affinity maturation of a wide range of antibody fragments and full-length antibodies.
Dendritic Macromers as in Situ Polymerizing Biomaterials for Securing Cataract Incisions (2004)

Dendritic macromers are attractive macromolecules for hydrogel formation since high cross-linking densities at low polymer concentration can be obtained, varied physical properties can be observed based on the macromer structure, and low viscous aqueous solutions can be injected in an in vivo site of irregular shaped to form a well-integrated polymer network. A peptide dendron possessing terminal cysteine residues was synthesized and characterized. When this peptide dendron was mixed with poly(ethylene glycol dialdehyde) in aqueous solution at pH = 7.4, a hydrogel spontaneously formed as a consequence of thiazolidine linkages between the macromers. Such in situ polymerized hydrogels are of interest for tissue engineering and wound-repair applications. To evaluate the potential use of this hydrogel sealant in ophthalmic surgeries, a 3-mm clear corneal incision (i.e., the wounds created during a typical cataract surgery) was successfully sealed.
Differential Effects of Costimulatory Pathway Modulation on Corneal Allograft Survival (2006)

Augmented ligation of the PD-1 negative costimulatory molecule significantly prolongs corneal allograft survival. However, in contrast to findings in other allograft models, signaling through the positive costimulatory molecule ICOS appears to be less important in allogeneic rejection of cornea.
Signal transduction in the interferon system. (1998)

Interferons (IFNs) comprise a family of secreted proteins that function as important biologic response modifiers in vertebrates. Interferons are produced in response to viral and other microbial infections, they bind to specific receptors on the surface of target cells, and they induce rapid activation of gene transcription. Interferon-stimulated genes modulate many biologic effects of IFNs. Characterization of the molecular mechanisms of IFN-induced gene activation led to the discovery of two distinct families of proteins, known as the Janus family kinases (Jaks) and the signal transducers and activators of transcription (Stats). These signaling proteins transduce intracellular signals from IFN receptors to the nucleus and activate transcription of IFN-stimulated genes. Subsequent studies have shown that many cytokines, hormones, and growth factors signal their target cells through the Jak-Stat signal transduction pathway. Significant molecular cross-talk between Jaks and Stats recruited to IFN receptors in response to IFN-alpha stimulation and other signaling pathways may be involved in the etiology of some of the side effects associated with IFN-alpha therapy.
Hemostatic markers in acute transient ischemic attacks. (1994)

These findings suggest that after acute reversible cerebral ischemia, there is early transient activation of thrombogenesis and ongoing fibrinolysis.
Analysis of Reactive Oxygen Species Generating Systems in Rat Epididymal Spermatozoa1 (2001)

Epididymal sperm maturation culminates in the acquisition of functional competence by testicular spermatozoa. The expression of this functional state is dependent upon a redox-regulated, cAMP-mediated signal transduction cascade that controls the tyrosine phosphorylation status of the spermatozoa during capacitation. Analysis of superoxide anion (O2(-.)) generation by rat epididymal spermatozoa has revealed a two-component process involving electron leakage from the sperm mitochondria at complexes I and II and a plasma membrane NAD(P)H oxidoreductase. Following incubation in a glucose-, lactate-, and pyruvate-free medium (-GLP), O2(-.) generation was suppressed by 86% and 96% in caput and cauda spermatozoa, respectively. The addition of lactate, malate, or succinate to spermatozoa incubated in medium -GLP stimulated O2(-.) generation. This increase could be blocked by rotenone and oligomycin (R/O) in the presence of malate or lactate but not succinate. Stimulation with all three substrates, as well as spontaneous O2(-.) production in +GLP medium, was blocked by the flavoprotein inhibitor, diphenylene iodonium. Diphenylene iodonium, but not R/O, suppressed NAD(P)H-induced lucigenin-dependent chemiluminescence. This NAD(P)H-dependent enzyme resided in the sperm plasma membrane and its activity was regulated by zinc and uncharacterized cytosolic factors. Reverse transcription-polymerase chain reaction analysis indicated that the sperm NAD(P)H oxidoreductase complex is quite distinct from the equivalent leukocyte system.
Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility (2004)

Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum. We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function. Gapds(-/-) males were infertile and had profound defects in sperm motility, exhibiting sluggish movement without forward progression. Although mitochondrial oxygen consumption was unchanged, sperm from Gapds(-/-) mice had ATP levels that were only 10.4% of those in sperm from WT mice. These results imply that most of the energy required for sperm motility is generated by glycolysis rather than oxidative phosphorylation. Furthermore, the critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility.
Shedding of Kidney Injury Molecule-1, a Putative Adhesion Protein Involved in Renal Regeneration (2002)

KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury. The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins. Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions. In this study, we report that the KIM-1b transcript is expressed predominantly in adult human kidney. We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein. We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage. A monoclonal antibody that binds at or close to the proteolytic site can partially block the shedding of KIM-1. Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase. We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer.
A Salmonella typhimurium strain genetically engineered to secrete effectively a bioactive human interleukin (hIL)-6 via the Escherichia coli hemolysin secretion apparatus (1998)

Human interleukin-6 (hIL-6) cDNA was genetically fused with the Escherichia coli hemolysin secretorial signal (hlyAS) sequence in a plasmid vector. Recombinant E. coli XL-1 Blue and attenuated Salmonella typhimurium secreted a 30 kDa hIL-6-HlyAS fusion protein, with an additional form of higher apparent molecular mass produced by S. typhimurium. In S. typhimurium cultures hIL-6-HlyAS concentrations entered a plateau at 500 to 600 ng ml−1 culture supernatant. In contrast to E. coli XL-1 Blue, in S. typhimurium culture supernatants hIL-6-HlyAS was accumulated faster reaching three-fold higher maximal concentrations. The cell proliferating activity of hIL-6-HlyAS fusion protein(s) was equivalent to that of mature recombinant hIL-6. Furthermore, hIL-6-secreting S. typhimurium were less invasive than the attenuated control strain. Therefore, the bulky hemolysin secretorial peptide at the C-terminus of the fusion protein does not markably affect hIL-6 activity, suggesting that the hemolysin secretion apparatus provides an excellent system to study immunomodulatory effects of in situ synthesized IL-6 in Salmonella vaccine strains.
Effect of different coloured luminous surrounds on LED discomfort glare perception (2013)

Recently, there has been increased interest in energy-efficient lighting as energy resources become higher in demand. Anecdotal evidence suggests that certain populations believe light-emitting diodes (LED) produce more glare than traditional technologies. This may be due to a number of factors such as spectral power distribution (SPD), source luminance, or beam intensity distribution. A study was conducted to assess the effect of different SPDs on the perception of discomfort glare from an LED source. For the range of conditions evaluated, the presence of any luminous surround significantly reduced the perception of discomfort glare from the LED array. The blue luminous surround reduced discomfort glare perception significantly less than the white or the yellow luminous surrounds. The implications for solid-state lighting systems are discussed.
Identification of a Binding Site on the Type II Activin Receptor for Activin and Inhibin (2000)

Type II activin receptors (ActRII and ActRIIB) are single-transmembrane domain serine/threonine kinase receptors that bind activin to initiate the signaling and cellular responses triggered by this hormone. Inhibin also binds type II activin receptors and antagonizes many activin effects. Here we describe alanine scanning mutagenesis of the ActRII extracellular domain. We identify a cluster of three hydrophobic residues (Phe(42), Trp(60), and Phe(83)) that, when individually mutated to alanine in the context of the full-length receptor, cause the disruption of activin and inhibin binding to ActRII. Each of the alanine-substituted ActRII mutants retaining activin binding maintains the ability to form cross-linked complexes with activin and supports activin cross-linking to the type I activin receptor ALK4. Unlike wild-type ActRII, the three mutants unable to bind activin do not cause an increase in activin signaling when transiently expressed in a corticotroph cell line. Together, our results implicate these residues in forming a critical binding surface on ActRII required for functional interactions with both activin and inhibin. This first identification of a transforming growth factor-beta family member binding site may provide a general basis for characterizing binding sites for other members of the superfamily.
Predicting Structural and Optical Properties of Hollow-Core Photonic Bandgap Fibers from Second Stage Preforms (2013)

We propose a simple theory based on mass conservation that allows accurate prediction of guidance properties in hollow-core photonic bandgap fibers (HC-PBGF) from knowledge of the second stage preforms from which the fibers are drawn.
Genomic Analysis of Gene Expression in C. elegans (2000)

Until now, genome-wide transcriptional profiling has been limited to single-cell organisms. The nematode Caenorhabditis elegans is a well-characterized metazoan in which the expression of all genes can be monitored by oligonucleotide arrays. We used such arrays to quantitate the expression of C. elegans genes throughout the development of this organism. The results provide an estimate of the number of expressed genes in the nematode, reveal relations between gene function and gene expression that can guide analysis of uncharacterized worm genes, and demonstrate a shift in expression from evolutionarily conserved genes to worm-specific genes over the course of development.
Ecdysone-controlled expression of transgenes (2002)

Inducible expression systems show great potential for use in human gene therapy and systems based on insect ecdysone receptors are particularly promising candidates. This article describes such systems and reviews actual and potential uses of ecdysone-controlled transgenes in vitro and in vivo. The ligand specificity of ecdysone receptor-based systems is considered, along with the safety and efficacy of the ecdysteroid and non-steroidal compounds used to activate them.
Some 9-Aza-alloxazines (1949)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome 9-Aza-alloxazinesJ. Benjamin. ZieglerCite this: J. Am. Chem. Soc. 1949, 71, 5, 1891–1893Publication Date (Print):May 1, 1949Publication History Published online1 May 2002Published inissue 1 May 1949https://pubs.acs.org/doi/10.1021/ja01173a532https://doi.org/10.1021/ja01173a532research-articleACS PublicationsRequest reuse permissionsArticle Views115Altmetric-Citations11LEARN 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
Designing meningitis vaccines. (2000)

Conjugate polysaccharide vaccines are a recent intervention to combat the relative inability of young children to mount an effective immune response against encapsulated bacteria, especially Haemophilus influenzae (Hib), Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp). These organisms cause the majority of community acquired septicaemia and meningitis in UK children. Their capsular polysaccharides, important virulence factors in evading phagocytosis, are poorly immunogenic in young children compared to adults. Conjugation, by covalent linking, of the polysaccharide to an immunogenic protein, has been demonstrated for each of these organisms to produce good antibody response to the polysaccharide. Conjugate Hib vaccines have proven effective in reducing Hib meningitis and invasive disease in the countries that have introduced them. Pneumococcal conjugate vaccines have proven effective in preventing invasive disease caused by serotypes contained in the vaccines. Efficacy studies are awaited for meningococcal conjugate vaccines.
Glycoside Hydrolases and Glycosyltransferases. Families, Modules, and Implications for Genomics (2000)

One of the first insights into the modular nature of carbohydrate-active enzymes was provided by the dissection of a plant cell wall-degrading enzyme into two functional modules ([van Tilbeurgh et al., 1986][1]). The general architecture deduced for this protein featured two independent globular