gebhart/patrepeval huggingface dataset:
Salvianolic acid B attenuates MMP‐2 and MMP‐9 expression in vivo in apolipoprotein‐E‐deficient mouse aorta and in vitro in LPS‐treated human aortic smooth muscle cells (2006)

Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a Chinese medicinal herb, is believed to have multiple therapeutic and preventive against human vascular diseases, including atherosclerosis and restenosis. To elucidate the underlying cellular mechanisms, we produced hypercholesterolemia by feeding apo-E-deficient mice a 0.15% cholesterol diet and inflammation in human aortic smooth muscle cells (HASMCs) with the endotoxin lipopolysaccharide (LPS), focusing on the metallopreteinases MMP-2 and MMP-9, the relevant signal transduction pathways and the effects of Sal B. Immunohistochemical analyses indicated apo-E-deficient mice fed a 0.15% cholesterol diet for 12 weeks exhibited thickened intima and elevated levels of MMP-2 and MMP-9 in aortic sections, both of which were attenuated by 0.3% Sal B dietary supplement. Western blotting and zymography analyses indicated that unstimulated HASMCs exhibited basal levels of protein and activity levels for MMP-2 and barely detectable levels for MMP-9, both of which were markedly upregulated by LPS, which also induced cell migration. Sal B significantly attenuated upregulations of both MMPs as well as the LPS-induced cell migration through the inactivation of MMP-2 and MMP-9 protein synthesis as well as the downregulation of the extracellular-signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). These results demonstrate that Sal B has anti-migration properties on smooth muscle cells and may explain its anti-atherosclerotic properties. This novel mechanism of action of Sal B, in addition to its previously reported inhibition of LDL oxidation, may help explain its efficacy in the treatment of atherosclerosis.
The Role of ADAM 15 in Glomerular Mesangial Cell Migration (2002)

Mesangial cells (MC) occupy the core of the renal glomerulus and are surrounded by a mesangial matrix. In certain diseases, MC migrate through this matrix into the pericapillary space. The mechanisms involved, however, are poorly understood. Members of the ADAM (A Disintegrin And Metalloproteinase) family of membrane proteins have the potential to be key modulators of cell-matrix interactions through the activities of their constituent domains. We have studied the possible role of ADAM 15 in human (H) MC migration in vitro. HMC ADAM 15 was expressed at low levels in serum-free medium but was increased during migration. Antibodies to the individual domains of ADAM 15 and the incorporation of antisense ADAM 15, (but not control oligonucleotide) inhibited this migration. Furthermore, inhibition of migration by the broad spectrum metalloproteinase inhibitor BB3103, demonstrated that metalloproteinase activity was essential for migration. ADAM 15, extracted from HMC membranes, was an active metalloproteinase, which degraded both type IV collagen and gelatin prepared from fibrillar collagen. Activity was inhibited by EDTA but not by phenylmethylsulfonyl fluoride. This is the first report of the potential of ADAM 15 for involvement in the restructuring of the mesangial matrix and in the migration of MC in disease.
Neutrophil Extracellular Traps Kill Bacteria (2004)

Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
Photocontrol of Neural Activity: Biophysical Mechanisms and Performance in Vivo (2008)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPhotocontrol of Neural Activity: Biophysical Mechanisms and Performance in VivoLucas Sjulson† and Gero Miesenböck*‡View Author Information Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, and Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, United Kingdom* To whom correspondence should be addressed. E-mail: [email protected]†Yale University School of Medicine.‡University of Oxford.Cite this: Chem. Rev. 2008, 108, 5, 1588–1602Publication Date (Web):May 1, 2008Publication History Received11 February 2008Published online1 May 2008Published inissue 1 May 2008https://pubs.acs.org/doi/10.1021/cr078221bhttps://doi.org/10.1021/cr078221breview-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views2275Altmetric-Citations56LEARN 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 SUBJECTS:Genetics,Light,Peptides and proteins,Receptors,Sensor probes Get e-Alerts
A proposal of a new system for the examination of passing to higher education: the example of theology faculty (2012)

Yükseköğretime geçiş sınavı, yükseköğretim kurumlarında eğitim almak isteyen öğrenciler için büyük önem taşır. Dolayısıyla bu sınav, öğrencilerin kendilerini geliştirmelerini sağlamak için çok önemli bir fırsattır ve bu fırsatın en iyi şekilde değerlendirilmesi gerekmektedir. Bu yazıda, öğrencilerin geçmiş bilgilerini korumak, en azından bir yabancı dil öğrenmelerini sağlamak ve analitik düşünce seviyelerini yükseltmek için sınavın nasıl kullanılabileceğine dair yeni bir öneri getirilecek ve bunu ilahiyat fakültesi örneği üzerinden anlatıp genel bir öneride bulunulacaktır.
Triglycerides and HDL Cholesterol (2009)

Diabetes carries a high risk of atherosclerosis, and cardiovascular disease, especially coronary heart disease (CHD) and stroke, is by far the leading cause of death among patients with type 2 diabetes. Although statins reduce the risk of major vascular events by about one-fifth per millimole per liter reduction in LDL cholesterol, with similar proportional reductions in major coronary events, stroke, and the need for coronary revascularization, the residual risk remains high. In the Scandinavian Simvastatin Survival Study (4S) (1), although the relative risk reduction in diabetic patients was larger than in nondiabetic patients, simvastatin-treated diabetic patients were still at higher risk of death than the placebo-treated nondiabetic patients. Multifactorial intervention reduces the risk even further, but significant danger remains. Current guidelines call for an aggressive treatment strategy to reduce LDL cholesterol, blood pressure, and glucose levels in diabetic patients, but data concerning the management of high triglyceride (TG) levels and low HDL cholesterol levels remains inconclusive. This article reviews the data concerning diabetic dyslipidemia and its management.

The cluster of lipid abnormalities associated with type 2 diabetes is defined by a high concentration of TG and small dense LDL and a low concentration of HDL cholesterol. Plasma LDL cholesterol levels are generally normal. Insulin resistance is believed to contribute to this atherogenic dyslipidemia by increasing the hepatic secretion of VLDL and other apolipoprotein (apo)B-containing lipoprotein particles, as a result of increased free fatty acid flux to the liver (2,3). This may also be the result of a diminished suppressive effect of insulin on apoB secretion, either at the level of the regulation of apoB degradation, or inhibition of microsomal TG transfer protein activity (4). Through the action of cholesterol ester transfer protein, TGs are transferred from VLDL to HDL, creating TG-rich HDL particles, which are hydrolyzed by hepatic …
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin (2000)

Hemagglutinin (HA) is the receptor-binding and membrane fusion glycoprotein of influenza virus and the target for infectivity-neutralizing antibodies. The structures of three conformations of the ectodomain of the 1968 Hong Kong influenza virus HA have been determined by X-ray crystallography: the single-chain precursor, HA0; the metastable neutral-pH conformation found on virus, and the fusion pH-induced conformation. These structures provide a framework for designing and interpreting the results of experiments on the activity of HA in receptor binding, the generation of emerging and reemerging epidemics, and membrane fusion during viral entry. Structures of HA in complex with sialic acid receptor analogs, together with binding experiments, provide details of these low-affinity interactions in terms of the sialic acid substituents recognized and the HA residues involved in recognition. Neutralizing antibody-binding sites surround the receptor-binding pocket on the membrane-distal surface of HA, and the structures of the complexes between neutralizing monoclonal Fabs and HA indicate possible neutralization mechanisms. Cleavage of the biosynthetic precursor HA0 at a prominent loop in its structure primes HA for subsequent activation of membrane fusion at endosomal pH (Figure 1). Priming involves insertion of the fusion peptide into a charged pocket in the precursor; activation requires its extrusion towards the fusion target membrane, as the N terminus of a newly formed trimeric coiled coil, and repositioning of the C-terminal membrane anchor near the fusion peptide at the same end of a rod-shaped molecule. Comparison of this new HA conformation, which has been formed for membrane fusion, with the structures determined for other virus fusion glycoproteins suggests that these molecules are all in the fusion-activated conformation and that the juxtaposition of the membrane anchor and fusion peptide, a recurring feature, is involved in the fusion mechanism. Extension of these comparisons to the soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) protein complex of vesicle fusion allows a similar conclusion.
Maximum likelihood multiple projection schemes for hidden Markov models (1999)

In many complex pattern recognition tasks the choice of a \\good&amp;quot; feature space in which to model the data varies depending on the signal content. Multiple feature subspaces can be used, for example phone dependent subspaces in speech recognition. Handling multiple subspaces whilst still maintaining meaningful likelihood comparisons between classes is a complex problem. This paper views this multiple projection problem in a maximum likelihood framework. Two forms of multiple projection schemes are described in terms of tying a standard semi-tied covariance matrix system. The rst results in model complexity control over the dimensions, whilst selecting the appropriate feature space for that complexity. The second may be viewed as a simultaneous projection and optimisation of a set of semi-tied transforms. These two schemes are compared on a large vocabulary task. Varying the complexity over the dimension was found to slightly increase speed and reduce model size without degrading the pe...
Tumor necrosis factor‐α stimulation of calcitonin gene‐related peptide expression and secretion from rat trigeminal ganglion neurons (2005)

Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-alpha caused a coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.
PPARγSignaling Mediates the Evolution, Development, Homeostasis, and Repair of the Lung (2012)

Epithelial-mesenchymal interactions mediated by soluble growth factors determine the evolution of vertebrate lung physiology, including development, homeostasis, and repair. The final common pathway for all of these positively adaptive properties of the lung is the expression of epithelial parathyroid-hormone-related protein, and its binding to its receptor on the mesenchyme, inducing PPARγ expression by lipofibroblasts. Lipofibroblasts then produce leptin, which binds to alveolar type II cells, stimulating their production of surfactant, which is necessary for both evolutionary and physiologic adaptation to atmospheric oxygen from fish to man. A wide variety of molecular insults disrupt such highly evolved physiologic cell-cell interactions, ranging from overdistention to oxidants, infection, and nicotine, all of which predictably cause loss of mesenchymal peroxisome-proliferator-activated receptor gamma (PPARγ) expression and the transdifferentiation of lipofibroblasts to myofibroblasts, the signature cell type for lung fibrosis. By exploiting such deep cell-molecular functional homologies as targets for leveraging lung homeostasis, we have discovered that we can effectively prevent and/or reverse the deleterious effects of these pathogenic agents, demonstrating the utility of evolutionary biology for the prevention and treatment of chronic lung disease. By understanding mechanisms of health and disease as an evolutionary continuum rather than as dissociated processes, we can evolve predictive medicine.
Nonopsonic phagocytosis of Pseudomonas aeruginosa requires facilitated transport of d -glucose by macrophages. (1995)

Pseudomonas aeruginosa is the predominant respiratory tract pathogen in patients with cystic fibrosis (CF), and its resistance to phagocytosis may contribute to its virulence. P. aeruginosa ingestion by macrophages occurs only in the presence of D-glucose or D-mannose, sugars present in low concentrations in the endobronchial space. Here we show that only isolates of P. aeruginosa and not other bacterial species were ingested by murine macrophages in a glucose-dependent manner. Glucose transport inhibitors blocked both [3H]-2-deoxy-glucose (2dG) uptake and phagocytosis of P. aeruginosa. P. aeruginosa pretreated with 2dG or 5-thio-D-glucose (5TG) was efficiently ingested. Macrophages pretreated with 2dG or 5TG were able to bind but unable to ingest P. aeruginosa in the presence of glucose; however, they efficiently ingested zymosan or IgG-coated sheep erythrocytes. Macrophages produced lactate only from glucose or mannose. The facilitative glucose transporter GLUT1 mRNA transcript was detected by PCR in preparations from purified macrophages. The nucleotide sequence of the PCR product was identical to that published for murine GLUT1. GLUT1 protein was detected with anti-GLUT1-peptide polyclonal Abs. We conclude that glucose exerts its effect on the macrophage, not on the bacterium, in the glucose-dependent nonopsonic phagocytosis of P. aeruginosa and that glucose transport via GLUT1 by the macrophages is required to trigger ingestion. The unique glucose dependency for phagocytosis of P. aeruginosa by macrophages may contribute to the pathogenicity of this bacterial species in CF patients.
Severe impairment in liver insulin signaling fails to alter hepatic insulin action in conscious mice (2005)

Insulin exerts its potent effects on hepatic glucose fluxes via direct and indirect mechanisms. Whereas a liver-specific insulin receptor (IR) knockout (LIRKO) mouse exhibits glucose intolerance as well as insulin resistance, it is unclear whether a more acute decrease in the expression of hepatic IR would be sufficient to induce hepatic insulin resistance. Here we report that the downregulation of hepatic IR expression by up to 95% does not modify hepatic insulin action. The i.p. administration (2 injections over 1 week) of an antisense oligodeoxynucleotide (ASO) directed to reduce insulin expression downregulated hepatic IR expression in C57BL6J mice. A high dose of IR-ASO decreased IR protein approximately 95%, while a control-ASO failed to modify IR expression. At this dose, the IR-ASO also decreased IR expression in adipose tissue but did not significantly decrease IR expression in hypothalamus or skeletal muscle. Insulin action was assessed with insulin clamp studies in conscious mice. The rate of glucose infusion during the clamp studies was comparable in control-ASO– and IR-ASO–treated mice. Importantly, the depletion of liver IR protein markedly impaired downstream insulin signaling in the liver, but it failed to modify the rate of glucose production. Thus, near ablation of liver IR does not alter insulin action on glucose production.
Charge flow during metal-insulator contact (1992)

The electrification of polymethyl methacrylate films is studied by scanning force microscopy. Charged areas generated by contact electrification are always found to be larger than those generated by corona discharge, and are surprisingly much larger than the area of contact. After each single contact made with the metal tip on the insulator charge was transferred, the sign of which was arbitrary. It is argued that charge already flows and spreads into the insulator at the time of metal-insulator contact.
A CERTAIN CLASS OF ANALYTIC FUNCTIONS DEFINED BY RUSCHEWEYH DERIVATIVES (1999)

This paper deals with a class H(A,B,) of analytic functions and we obtain coefficient estimates and related results.
Circulating tumor cells (2013)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
MUC1/sec-Expressing Tumors Are Rejected In Vivo by a T Cell-Dependent Mechanism and Secrete High Levels of CCL2 (2004)

MUC1/sec is a secreted form of the glycoprotein mucin 1 (MUC1). To characterize the role that MUC1 and MUC1/sec have in tumor progression, these genes were expressed in DA-3 mammary tumor cells. DA-3 cells and DA-3 cells expressing the transmembrane MUC1 gene (DA-3/TM) grow with similar kinetics in BALB/c mice. Surprisingly, DA-3 cells expressing and secreting MUC1/sec (DA-3/sec) fail to form tumors in vivo. The mechanism of rejection was evaluated using mice deficient in constituents of the immune system. All mice lacking IFN-gamma, NK, NKT, or macrophages formed DA-3/sec tumors that regressed shortly after implantation. However, progressively growing DA-3/sec tumors developed in mice devoid of T lymphocytes. The importance of T lymphocytes in the rejection of DA-3/sec tumors was further supported by detection of DA-3-specific CTL in mice challenged with the DA-3/sec tumor. Recruitment of appropriate APC and effector cells is an important first step in the tumor clearance. Indeed, DA-3/sec cells or cell supernatants recruited 3-4 times as many macrophages as DA-3/TM cells in vivo, suggesting that a secreted chemotactic product is produced from DA-3/sec cells. RNA and protein analysis of DA-3/sec cells revealed that several genes are up-regulated by MUC1/sec expression, including MCP-1 (CCL-2). These results suggest DA-3/sec cells are capable of recruiting immune cells, and that rejection of DA-3/sec tumors, although aided by cells of the innate immune response, is ultimately due to T cell-mediated events.
Characterization of a human RPD3 ortholog, HDAC3 (1998)

Histone acetylation levels in cells result from a dynamic equilibrium between competing histone acetylases and deacetylases. Changes in histone acetylation levels occur during both transcriptional activation and silencing. Cloning of the cDNA for a human histone deacetylase (HDAC1) has shown that it represents a human ortholog of the yeast transcriptional regulator RPD3. We have screened the expressed sequence tag database (National Center for Biotechnology Information) with the yeast RPD3 sequence and identified a human ortholog of RPD3, HDAC3. This cDNA encodes a protein of 428 amino acids with 58% sequence identity with HDAC1p. By using a specific polyclonal antiserum recognizing the C-terminal domain of HDAC3p and Western blotting, we detected a single approximately 49-kDa band in several tumor cell lines. HDAC3p is expressed predominantly in the nuclear compartment. Immunoprecipitation experiments with either an antiserum against HDAC3p or an anti-FLAG antiserum and a flagged HDAC3 cDNA showed that HDAc3p exhibits deacetylase activity both on free histones and on purified nucleosomes. This deacetylase activity is inhibited by trichostatin, trapoxin, and butyrate in vitro to the same degree as the deacetylase activity associated to HDAC1p. These observations identify another member of a growing family of human HDAC genes.