gebhart/patrepeval huggingface dataset:
Assembly of the Dystrophin-Associated Protein Complex Does Not Require the Dystrophin Cooh-Terminal Domain (2000)

Dystrophin is a multidomain protein that links the actin cytoskeleton to laminin in the extracellular matrix through the dystrophin associated protein (DAP) complex. The COOH-terminal domain of dystrophin binds to two components of the DAP complex, syntrophin and dystrobrevin. To understand the role of syntrophin and dystrobrevin, we previously generated a series of transgenic mouse lines expressing dystrophins with deletions throughout the COOH-terminal domain. Each of these mice had normal muscle function and displayed normal localization of syntrophin and dystrobrevin. Since syntrophin and dystrobrevin bind to each other as well as to dystrophin, we have now generated a transgenic mouse deleted for the entire dystrophin COOH-terminal domain. Unexpectedly, this truncated dystrophin supported normal muscle function and assembly of the DAP complex. These results demonstrate that syntrophin and dystrobrevin functionally associate with the DAP complex in the absence of a direct link to dystrophin. We also observed that the DAP complexes in these different transgenic mouse strains were not identical. Instead, the DAP complexes contained varying ratios of syntrophin and dystrobrevin isoforms. These results suggest that alternative splicing of the dystrophin gene, which naturally generates COOH-terminal deletions in dystrophin, may function to regulate the isoform composition of the DAP complex.
Tumor Necrosis Factor-α Induces Skeletal Muscle Insulin Resistance in Healthy Human Subjects via Inhibition of Akt Substrate 160 Phosphorylation (2005)

Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-alpha (TNF-alpha) concentrations have been implicated in the development of insulin resistance, but direct evidence in humans is lacking. Here, we demonstrate that TNF-alpha infusion in healthy humans induces insulin resistance in skeletal muscle, without effect on endogenous glucose production, as estimated by a combined euglycemic insulin clamp and stable isotope tracer method. TNF-alpha directly impairs glucose uptake and metabolism by altering insulin signal transduction. TNF-alpha infusion increases phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, and c-Jun NH(2)-terminal kinase, concomitant with increased serine and reduced tyrosine phosphorylation of insulin receptor substrate-1. These signaling effects are associated with impaired phosphorylation of Akt substrate 160, the most proximal step identified in the canonical insulin signaling cascade regulating GLUT4 translocation and glucose uptake. Thus, excessive concentrations of TNF-alpha negatively regulate insulin signaling and whole-body glucose uptake in humans. Our results provide a molecular link between low-grade systemic inflammation and the metabolic syndrome.
[Induction of cell cycle arrest in bladder cancer RT4 cells by capsaicin]. (2010)

Capsaicin induces the cell cycle arrest of bladder cancer RT4 cells G(0)/G(1) phase and growth inhibition via TRPV1 receptor by modulating the expression of P53, P21 and CDK2.
Using In Vitro Immunomodulatory Properties of Lactic Acid Bacteria for Selection of Probiotics against Salmonella Infection in Broiler Chicks (2016)

Poultry is known to be a major reservoir of Salmonella. The use of lactic acid bacteria has become one of successful strategies to control Salmonella in poultry. The purpose of this study was to select lactic acid bacteria strains by their in vitro immunomodulatory properties for potential use as probiotics against Salmonella infection in broiler chicks. Among 101 isolated lactic acid bacteria strains, 13 strains effectively survived under acidic (pH 2.5) and bile salt (ranging from 0.1% to 1.0%) conditions, effectively inhibited growth of 6 pathogens, and adhered to Caco-2 cells. However, their in vitro immunomodulatory activities differed significantly. Finally, three strains with higher in vitro immunomodulatory properties (Lactobacillus plantarum PZ01, Lactobacillus salivarius JM32 and Pediococcus acidilactici JH231) and three strains with lower in vitro immunomodulatory activities (Enterococcus faecium JS11, Lactobacillus salivarius JK22 and Lactobacillus salivarius JM2A1) were compared for their inhibitory effects on Salmonella adhesion and invasion to Caco-2 cells in vitro and their antimicrobial effects in vivo. The former three strains inhibited Salmonella adhesion and invasion to Caco-2 cells in vitro, reduced the number of Salmonella in intestinal content, spleen and liver, reduced the levels of lipopolysaccharide-induced TNF-α factor (LITAF), IL-1β, IL-6 and IL-12 in serum and increased the level of IL-10 in serum during a challenge study in vivo more efficiently than the latter three strains. These results suggest that in vitro immunomodulatory activities could be used as additional parameters to select more effective probiotics as feed supplements for poultry.
Inhibition of thiaminase I from Bacillus thiaminolyticus. Evidence supporting a covalent 1,6-dihydropyrimidinyl-enzyme intermediate (1987)

Thiaminase I from Bacillus thiaminolyticus strain Matsukawa et Misawa is completely and irreversibly inhibited by treatment with 4-amino-6-chloro-2-methylpyrimidine. Inhibition is a time-dependent first-order process, exhibiting a half-time of 4 h at an inhibitor concentration of 5 mM. A specific active-site-directed inactivation is supported by protection of the enzymatic activity in the presence of the substrates thiamin and quinoline as well as by the observation that a stoichiometric amount of inorganic chloride is released during inactivation. 4-Amino-5-(anilinomethyl)-6-chloro-2-methylpyrimidine, which resembles the structure of the product of base exchange of thiamin with aniline, inactivates thiaminase approximately 2 orders of magnitude faster. Inactivation is again complete and irreversible and is a time-dependent first-order process, in this case exhibiting saturation at low inhibitor concentrations (KI = 96 microM). Enzyme inactivation can be explained as the result of displacement of chloride from the chloropyrimidine by a nucleophile at the enzyme active site. The inactivation suggests that the Zoltewicz-Kauffman model of bisulfite-catalyzed thiamin cleavage [Zoltewicz, J. A., & Kauffman, G. M. (1977) J. Am. Chem. Soc. 99, 3134-3142], which calls for the reversible nucleophilic addition of catalyst across the 1,6 double bond of thiamin's pyrimidine ring, may be applicable to thiaminase as well.
Towards Automatic Learning of Procedures from Web Instructional Videos (2017)

The potential for agents, whether embodied or software, to learn by observing other agents performing procedures involving objects and actions is rich. Current research on automatic procedure learning heavily relies on action labels or video subtitles, even during the evaluation phase, which makes them infeasible in real-world scenarios. This leads to our question: can the human-consensus structure of a procedure be learned from a large set of long, unconstrained videos (e.g., instructional videos from YouTube) with only visual evidence? To answer this question, we introduce the problem of procedure segmentation--to segment a video procedure into category-independent procedure segments. Given that no large-scale dataset is available for this problem, we collect a large-scale procedure segmentation dataset with procedure segments temporally localized and described; we use cooking videos and name the dataset YouCook2. We propose a segment-level recurrent network for generating procedure segments by modeling the dependencies across segments. The generated segments can be used as pre-processing for other tasks, such as dense video captioning and event parsing. We show in our experiments that the proposed model outperforms competitive baselines in procedure segmentation.
QMEAN server for protein model quality estimation (2009)

Model quality estimation is an essential component of protein structure prediction, since ultimately the accuracy of a model determines its usefulness for specific applications. Usually, in the course of protein structure prediction a set of alternative models is produced, from which subsequently the most accurate model has to be selected. The QMEAN server provides access to two scoring functions successfully tested at the eighth round of the community-wide blind test experiment CASP. The user can choose between the composite scoring function QMEAN, which derives a quality estimate on the basis of the geometrical analysis of single models, and the clustering-based scoring function QMEANclust which calculates a global and local quality estimate based on a weighted all-against-all comparison of the models from the ensemble provided by the user. The web server performs a ranking of the input models and highlights potentially problematic regions for each model. The QMEAN server is available at http://swissmodel.expasy.org/qmean.
Macroporous hydrogel membranes for a hybrid artificial pancreas. II. Biocompatibility (1983)

A histological evaluation of the biocompatibility of a new porous hydrogel membrane made of 2-hydroxyethyl methacrylate (2-HEMA) was performed. Isolated membranes and diffusion chambers made of this material and filled with rabbit pancreas were implanted in diabetic rats for periods of up to 8 1/2 months. Histologic evaluation showed that this polymer elicits minimal tissue reaction within the first 7 weeks but some increase in granulation tissue and fibrosis thereafter. A component of this tissue reaction is neovascularization, and many blood vessels were noted immediately adjacent to the membrane's surface. Calcification of the membrane was also progressive but could be minimized by formulations resulting in the incorporation of acid groups throughout the hydrogel and on its surface. Diffusion chambers made of this new material show promise for use in a "hybrid" artificial pancreas for the treatment of diabetes.
Construction of a Human Immunodeficiency Virus Type 1 (HIV-1) Library Containing Random Combinations of Amino Acid Substitutions in the HIV-1 Protease due to Resistance by Protease Inhibitors (2002)

Human immunodeficiency virus type 1 (HIV-1) heterogeneity contributes to the emergence of drug-resistant virus, escape from host defense systems, and/or conversion of the cellular tropism. To establish an in vitro system to address a heterogeneous virus population, we constructed a library of HIV-1 molecular clones containing a set of random combinations of zero to 11 amino acid substitutions associated with resistance to protease inhibitors by the HIV-1 protease. The complexity (2.1 x 10(5)) of the HIV-1 library pNG-PRL was large enough to cover all of the possible combinations of zero to 11 amino acid substitutions (a total of 4,096 substitutions possible). The T-cell line MT-2 was infected with the HIV-1 library, and resistant viruses were selected after treatment by the protease inhibitor ritonavir (0.03 to 0.30 microM). The viruses that contained three to eight amino acid substitutions could be selected within 2 weeks. These results demonstrate that this HIV-1 library could serve as an alternative in vitro system to analyze the emergence of drug resistance and to evaluate the antiviral activity of novel compounds against multidrug-resistant viruses.
Biofunctionalization of Gold Nanoparticles (2007)

Abstract The sections in this article are Introduction General Synthetic Routes Direct Synthesis of Ligand‐protected Au NPs Strongly Ionic Ligand‐protected Au NPs Weakly Ionic Ligand‐protected Au NPs Au NPs Protected with Neutral Ligands Ligand Exchange Reaction Preparative‐scale Synthesis and Solution‐phase Characterization of DNA ‐directed Nanoparticle Assemblies Bifunctional Proteins for Programmable Assembly of Nanoparticles Strategies for Eliminating Nonspecific Interactions and Enabling Specific Binding with Biomolecules Biological Applications Nucleic Acids Proteins Cells and Virus Acknowledgments
Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma (2006)

In this study, we identified a possible mechanism as the basis of the association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7 were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7 and EGFR overexpression correlated with short survival in EGFR-positive GBM patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the progression of EGFR-overexpressed GBM.
Biofilm Formation: A Clinically Relevant Microbiological Process (2001)

Microorganisms universally attach to surfaces and produce extracellular polysaccharides, resulting in the formation of a biofilm. Biofilms pose a serious problem for public health because of the increased resistance of biofilm-associated organisms to antimicrobial agents and the potential for these organisms to cause infections in patients with indwelling medical devices. An appreciation of the role of biofilms in infection should enhance the clinical decision-making process.
Electrochemically directed synthesis of oligonucleotides for DNA microarray fabrication (2005)

We demonstrate a new method for making oligonucleotide microarrays by synthesis in situ. The method uses conventional DNA synthesis chemistry with an electrochemical deblocking step. Acid is delivered to specific regions on a glass slide, thus allowing nucleotide addition only at chosen sites. The acid is produced by electrochemical oxidation controlled by an array of independent microelectrodes. Deblocking is complete in a few seconds, when competing side-product reactions are minimal. We demonstrate the successful synthesis of 17mers and discrimination of single base pair mismatched hybrids. Features generated in this study are 40 mum wide, with sharply defined edges. The synthetic technique may be applicable to fabrication of other molecular arrays.
High dose Intravenous Gammaglobulins in Autoimmune Disorders: Mode of action and Therapeutic Uses (1989)

Gammaglobulins administered intramuscularly have been used for more than 40 years to treat antibody deficiency states. In the last decade intravenous preparations were developed. They do not aggregate and contain IgG molecules with intact recognition and effector functions. These compounds are safe and only minor side effects were reported even when high doses were given. While studying their effect when given in high doses to hypogammaglobulinemic patients, an accidental finding was observed regarding their beneficial effect in idiopathic thrombocytopenic purpura (ITP). This observation led to many studies looking at the effect of high dose gammaglobulin in several other autoimmune diseases. While the effect in acute ITP is well established, there are encouraging reports in respect to the effect of intravenous gammaglobulin in many other disorders, but no final conclusion can be drawn due to the small numbers of cases studied. The mechanism by which intravenous gammaglobulin exerts its function is still unclear. It may work through the Fc receptor in the reticuloendothelial system, as an immunoregulator agent or interact in the idiotype-antiidiotype network. Intravenous gammaglobulin seems to be an important therapeutic tool in a large number of autoimmune disorders of various etiologies.
Reduction of Reactive Oxygen Species Prevents Hypoxia-induced CREB Depletion in Pulmonary Artery Smooth Muscle Cells (2011)

Hypoxia-induced pulmonary arterial hypertension (PAH) is a deadly disease characterized by progressive remodeling and persistent vasoconstriction of the pulmonary arterial system. Remodeling of the pulmonary artery (PA) involves smooth muscle cell (SMC) proliferation, hypertrophy, migration, and elevated extracellular matrix (ECM) production elicited by mitogens and oxidants produced in response to hypoxic insult. We previously reported that the transcription factor cAMP response element binding protein (CREB) is depleted in medial PA SMCs in remodeled, hypertensive vessels in rats or calves exposed to chronic hypoxia. In culture, CREB loss can be induced in PA SMCs by exogenous oxidants or platelet-derived growth factor. Forced depletion of CREB with small interfering RNA (siRNA) in PA SMCs is sufficient to induce their proliferation, hypertrophy, migration, dedifferentiation, and ECM production. This suggests that oxidant and/or mitogen-induced loss of CREB in medial SMCs is, in part, responsible for PA thickening. Here, we tested whether oxidant scavengers could prevent the loss of CREB in PA SMCs and inhibit SMC proliferation, migration, and ECM production using in vitro and in vivo models. Exposure of PA SMCs to hypoxia induced hydrogen peroxide (H2O2) production and loss of CREB. Treatment of SMCs with exogenous H2O2 or a second oxidant, Sin-1, elicited CREB depletion under normoxic conditions. Exogenous H2O2 also induced SMC proliferation, migration, and increased elastin levels as did forced depletion of CREB. In vivo, hypoxia-induced thickening of the PA wall was suppressed by the superoxide dismutase mimetic, Tempol, which also prevented the loss of CREB in medial SMCs. Tempol also reduced hypoxia-induced SMC proliferation and elastin deposition in the PA. The data indicate that CREB levels in the arterial wall are regulated in part by oxidants produced in response to hypoxia and that CREB plays a crucial role in regulating SMC phenotype and PA remodeling.
rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants (2007)

IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.
Activation of Receptor for Advanced Glycation End Products (1999)

Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules and engages diverse ligands relevant to distinct pathological processes. One class of RAGE ligands includes glycoxidation products, termed advanced glycation end products, which occur in diabetes, at sites of oxidant stress in tissues, and in renal failure and amyloidoses. RAGE also functions as a signal transduction receptor for amyloid beta peptide, known to accumulate in Alzheimer disease in both affected brain parenchyma and cerebral vasculature. Interaction of RAGE with these ligands enhances receptor expression and initiates a positive feedback loop whereby receptor occupancy triggers increased RAGE expression, thereby perpetuating another wave of cellular activation. Sustained expression of RAGE by critical target cells, including endothelium, smooth muscle cells, mononuclear phagocytes, and neurons, in proximity to these ligands, sets the stage for chronic cellular activation and tissue damage. In a model of accelerated atherosclerosis associated with diabetes in genetically manipulated mice, blockade of cell surface RAGE by infusion of a soluble, truncated form of the receptor completely suppressed enhanced formation of vascular lesions. Amelioration of atherosclerosis in these diabetic/atherosclerotic animals by soluble RAGE occurred in the absence of changes in plasma lipids or glycemia, emphasizing the contribution of a lipid- and glycemia-independent mechanism(s) to atherogenesis, which we postulate to be interaction of RAGE with its ligands. Future studies using mice in which RAGE expression has been genetically manipulated and with selective low molecular weight RAGE inhibitors will be required to definitively assign a critical role for RAGE activation in diabetic vasculopathy. However, sustained receptor expression in a microenvironment with a plethora of ligand makes possible prolonged receptor stimulation, suggesting that interaction of cellular RAGE with its ligands could be a factor contributing to a range of important chronic disorders.
DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies (2015)

Active smoking is a major preventable public health problem and an established critical factor for epigenetic modification. In this systematic review, we identified 17 studies addressing the association of active smoking exposure with methylation modifications in blood DNA, including 14 recent epigenome-wide association studies (EWASs) and 3 gene-specific methylation studies (GSMSs) on the gene regions identified by EWASs. Overall, 1460 smoking-associated CpG sites were identified in the EWASs, of which 62 sites were detected in multiple (≥3) studies. The three most frequently reported CpG sites (genes) in whole blood samples were cg05575921 (AHRR), cg03636183 (F2RL3), and cg19859270 (GPR15), followed by other loci within intergenic regions 2q37.1 and 6p21.33. These significant smoking-related genes were further assessed by specific methylation assays in three GSMSs and reflected not only current but also lifetime or long-term exposure to active smoking. In conclusion, this review summarizes the evidences for the use of blood DNA methylation patterns as biomarkers of smoking exposure for research and clinical practice. In particular, it provides a reservoir for constructing a smoking exposure index score which could be used to more precisely quantify long-term smoking exposure and evaluate the risks of smoking-induced diseases.
Reducing the overhead for quantum computation when noise is biased (2015)

We analyze a model for fault-tolerant quantum computation with low overhead suitable for situations where the noise is biased. The basis for this scheme is a gadget for the fault-tolerant preparation of magic states that enable universal fault-tolerant quantum computation using only Clifford gates that preserve the noise bias. We analyze the distillation of $|T\ensuremath{\rangle}$-type magic states using this gadget at the physical level, followed by concatenation with the 15-qubit quantum Reed-Muller code, and comparing our results with standard constructions. In the regime where the noise bias (rate of Pauli $Z$ errors relative to other single-qubit errors) is greater than a factor of 10, our scheme has lower overhead across a broad range of relevant noise rates.
Single-step purification of shuttle vectors from yeast for high frequency back-transformation intoE. coli (1990)

Journal Article Single-step purification of shuttle vectors from yeast for high frequency back-transformation into E. coli Get access Alister C. Ward Alister C. Ward CSIRO Division of Biomolecular Engineering, 343 Royal Parade, Parkville and Russell Grimwade School of Biochemistry, University of MelbourneParkville, Victoria 3052, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 17, 11 September 1990, Page 5319, https://doi.org/10.1093/nar/18.17.5319 Published: 11 September 1990 Article history Received: 19 July 1990 Published: 11 September 1990
The packer filter: an efficient mechanism for user-level network code (1987)

Code to implement network protocols can be either inside the kernel of an operating system or in user-level processes. Kernel-resident code is hard to develop, debug, and maintain, but user-level implementations typically incur significant overhead and perform poorly.