gebhart/patrepeval huggingface dataset:
Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions (2000)

We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation.
Leukocyte PI3Kγ and PI3Kδ have temporally distinct roles for leukocyte recruitment in vivo (2007)

Phosphoinositide 3-kinases (PI3Ks) have been considered important in leukocyte motility. PI3Kgamma, the class I(B) PI3K, expressed prominently in leukocytes and also in endothelial cells, mediates leukocyte functional responses induced by chemoattractants. To reveal its role in leukocyte recruitment, we used intravital microscopy to directly visualize leukocyte rolling, adhesion, and emigration in postcapillary venules in PI3Kgamma-deficient (PI3Kgamma(-/-)) mice. We report here that PI3Kgamma deficiency had no significant effects on leukocyte rolling flux or rolling velocity and minor effects on adhesion (30% to 35%) in response to CXC chemokine MIP-2 (CXCL2) or KC (CXCL1). However, leukocyte emigration was severely impaired in PI3Kgamma(-/-) mice in an early (first 90 minutes) response to MIP-2 or KC. Chimeric mice receiving bone marrow transplants revealed that this early response was entirely dependent upon PI3Kgamma in neutrophils but not parenchymal cells (endothelium and others). Identical responses were observed when endogenous chemokine production was induced by TNFalpha; leukocyte emigration was reduced in PI3Kgamma(-/-) mice. More prolonged responses to MIP-2 (for 4 to 5 hours) or TNFalpha (6 to 8 hours) were almost entirely PI3Kgamma independent and largely dependent on PI3Kdelta. Our results reveal that leukocyte emigration response to CXC chemokines is entirely dependent upon PI3Kgamma or PI3Kdelta, but these are nonoverlapping, temporally distinct events in inflamed tissues in vivo.
Inversion variants in the human genome: role in disease and genome architecture (2010)

Significant advances have been made over the past 5 years in mapping and characterizing structural variation in the human genome. Despite this progress, our understanding of inversion variants is still very restricted. While unbalanced variants such as copy number variations can be mapped using array-based approaches, strategies for characterization of inversion variants have been limited and underdeveloped. Traditional cytogenetic approaches have long been able to identify microscopic inversion events, but discovery of submicroscopic events has remained elusive and largely ignored. With the advent of paired-end sequencing approaches, it is now possible to map inversions across the human genome. Based on the paired-end sequencing studies published to date, it is now feasible to make a first map of inversions across the human genome and to use this map to explore the characteristics and distribution of this form of variation. The current map of inversions indicates that many remain to be identified, especially in the smaller size ranges. This review provides an overview of the current knowledge about human inversions and their contribution to human phenotypes. Further characterization of inversions should be considered as an important step towards a deeper understanding of human variation and genome dynamics.
Physicochemical Properties and Tofu Quality of Soybean Cultivar Proto (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysicochemical Properties and Tofu Quality of Soybean Cultivar ProtoChiun-Chuan Roger Wang and Sam Kow-Ching ChangCite this: J. Agric. Food Chem. 1995, 43, 12, 3029–3034Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/jf00060a008https://doi.org/10.1021/jf00060a008research-articleACS PublicationsRequest reuse permissionsArticle Views605Altmetric-Citations35LEARN 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
Inhibition of stimulated meningeal blood flow by a calcitonin gene‐related peptide binding mirror‐image RNA oligonucleotide (2006)

Calcitonin gene-related peptide (CGRP) released from trigeminal afferents is known to play an important role in the control of intracranial blood flow. In a rat preparation with exposed cranial dura mater, periods of electrical stimulation induce increases in meningeal blood flow. These responses are due to arterial vasodilatation mediated in part by the release of CGRP. In this preparation, the effect of a CGRP-binding mirror-image oligonucleotide (Spiegelmer NOX-C89) was examined. Spiegelmer NOX-C89 applied topically at concentrations between 10(-7) and 10(-5) M to the exposed dura mater led to a dose-dependent inhibition of the electrically evoked blood flow increases. The highest dose reduced the mean increases in flow to 56% of the respective control levels. A nonfunctional control Spiegelmer (not binding to CGRP) was ineffective in changing blood flow increases. Intravenous injection of NOX-C89 (5 mg kg(-1)) reduced the evoked blood flow increases to an average of 65.5% of the control. The basal blood flow was not changed by any of the applied substances. In addition, an ex vivo preparation of the hemisected rat skull was used to determine CGRP release from the cranial dura mater caused by antidromic activation of meningeal afferents. In this model, 10(-6) M of NOX-C89 reduced the evoked CGRP release by about 50%. We conclude that increases in meningeal blood flow due to afferent activation can be reduced by sequestering the released CGRP and thus preventing it from activating vascular CGRP receptors. Moreover, the Spiegelmer NOX-C89 may inhibit CGRP release from meningeal afferents. Therefore, the approach to interfere with the CGRP/CGRP receptor system by binding the CGRP may open a new opportunity for the therapy of diseases that are linked to excessive CGRP release such as some forms of primary headaches.
Critical Roles of Glycosaminoglycan Side Chains of Cartilage Proteoglycan (Aggrecan) in Antigen Recognition and Presentation (1998)

Systemic immunization of BALB/c mice with proteoglycan (aggrecan) from fetal human cartilage induces progressive polyarthritis, an experimental disease similar to human rheumatoid arthritis. The development of the disease in this genetically susceptible murine strain is based on cross-reactive immune responses between the immunizing fetal human and mouse self-proteoglycans. One of the cross-reactive and arthritogenic T cell epitopes (92GR/QVRVNSA/IY) is localized in the G1 domain of human/murine proteoglycan. Susceptible BALB/c mice, however, develop arthritis only if both the chondroitin sulfate (CS) and keratan sulfate (KS) side chains of the arthritogenic human proteoglycans are removed. The function of these two glycosaminoglycan side chains is opposite. The presence of a KS side chain in adult proteoglycan inhibits the recognition of arthritogenic T cell epitopes, prevents the development of T cell response, and protects animals from autoimmune arthritis. In contrast, the depletion of the CS side chain generates clusters of CS stubs and provokes a strong B cell response. These carbohydrate-specific B cells are the most important proteoglycan APC. Taken together, proteoglycan-induced progressive polyarthritis is dictated by three major components: genetic background of the BALB/c strain, highly specific T cell response to epitope(s) masked by a KS chain in aging tissue, and the presence of proteoglycan (CS stub)-specific B cells required for sufficient Ag presentation.
Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging (2005)

Mutations in mitochondrial DNA (mtDNA) accumulate in tissues of mammalian species and have been hypothesized to contribute to aging. We show that mice expressing a proofreading-deficient version of the mitochondrial DNA polymerase g (POLG) accumulate mtDNA mutations and display features of accelerated aging. Accumulation of mtDNA mutations was not associated with increased markers of oxidative stress or a defect in cellular proliferation, but was correlated with the induction of apoptotic markers, particularly in tissues characterized by rapid cellular turnover. The levels of apoptotic markers were also found to increase during aging in normal mice. Thus, accumulation of mtDNA mutations that promote apoptosis may be a central mechanism driving mammalian aging.
A Fully Human Antitumor ImmunoRNase Selective for ErbB-2-Positive Carcinomas (2004)

We report the preparation and characterization of a novel, fully human antitumor immunoRNase (IR). The IR, a human RNase and fusion protein made up of a human single chain variable fragment (scFv), is directed to the ErbB-2 receptor and overexpressed in many carcinomas. The anti-ErbB-2 IR, named hERB-hRNase, retains the enzymatic activity of the wild-type enzyme (human pancreatic RNase) and specifically binds to ErbB-2-positive cells with the high affinity (K(d) = 4.5 nm) of the parental scFv. hERB-hRNase behaves as an immunoprotoxin and on internalization by target cells becomes selectively cytotoxic in a dose-dependent manner at nanomolar concentrations. Administered in five doses of 1.5 mg/kg to mice bearing an ErbB-2-positive tumor, hERB-hRNase induced a dramatic reduction in tumor volume. hERB-hRNase is the first fully human antitumor IR produced thus far, with a high potential as a poorly immunogenic human drug devoid of nonspecific toxicity, directed against ErbB-2-positive malignancies.
Comparative Effect of Danazol and a GnRH Agonist on Monocyte Chemotactic Protein‐1 Expression by Endometriotic Cells (2001)

These results put into prominence the capability of danazol to directly inhibit the expression of a potent monocyte chemotactic and activating factor by ectopic endometrial cells shedding more light on the mechanisms underlying the clinical effects of hormonal therapeutic agents used in the treatment of endometriosis.
Advanced Detection Technology for Ion Mobility and Mass Spectrometry (2006)

The development of new technologies and the advancement of existing technical expertise can allow for dramatic improvements to be realized in analytical instrumentation. The development of an integrating solid-state ion detector, designed to have a high sensitivity as well as maintaining a high-level of stability, is described and evaluated. Several versions of the charge-transimpedance amplifier (CTIA) technology were constructed with different operating features. The CTIA-1 is a 32-pixel array detector designed for mass spectrometry. It has the capability to simultaneously detect multiple ion channels with a detection limit less than 100 ions. The CTIA-2 detector features an independent selectable gain for each detection channel. The CTIA-2 is a 4-channel device designed for ion mobility. Further design features were built into the CTIA-5 such as differential noise reduction capabilities.The CTIA-1 technology was evaluated for use in isotope ratio mass spectrometry on a custom-built Mattauch-Herzog mass spectrometer. An evaluation was conducted in terms of the detector sensitivity, stability, accuracy, precision, resolution, and mass bias. The CTIA-2 was tested on a sector mass spectrometer for its response to low ion currents of both positive and negative ions. The detector stability, its accuracy, and its precision were studied.The technique of ion mobility spectrometry is rapidly growing, as it is the main technology used for the detection of explosives at security checkpoints. The need to improve the sensitivity of existing ion mobility instruments has led to the exploration of using the CTIA detector in ion mobility instruments. Improvements in sensitivity of two to three orders of magnitude have been demonstrated using the described CTIA detectors. Additional applications that use ion mobility instruments for the detection of analytes have been presented, the chemical mapping of a halogen-contaminated sand bed, the detection of pesticides, as well as the detection of TNT in drinking water.Results indicate that the CTIA detector technology is well suited for use in both mass spectrometry and ion mobility. The sensitive and stable multi-array CTIA detectors perform well in isotope ratio mass spectrometry. Ion mobility instruments of all types can benefit from the added sensitivity supplied by this technology.
Effects of peroxisome proliferator‐activated receptor‐γ agonists on central nervous system inflammation (2002)

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays a critical role in glucose and lipid metabolism. More recently, PPAR-gamma ligands have been reported to inhibit the expression of proinflammatory molecules by monocytes/macrophages. Of relevance to CNS disease is that PPAR-gamma agonists have been demonstrated to have similar effects on microglia. PPAR-gamma agonists also ameliorate experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. This Mini-Review summarizes the effects of PPAR-gamma agonists in mediating immune responses and the potential of these agonists in the treatment of inflammatory disorders of the CNS.
Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells. (1991)

Antigen-presenting cells (APC) transfected with a construct encoding the hen egg-white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II-restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade.
A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. (1985)

We previously have isolated cDNA clones for several mRNAs that increase in abundance during the differentiation of 3T3 adipocytes but whose physiological role is unknown. We show here that a mRNA that is complementary to one of these clones and encodes a protein of 28 kDa is expressed abundantly in mouse fat pads but not in several other mouse tissues. Sequence analysis of the corresponding cDNA clone indicated that the encoded protein shows 30% overall amino acid homology to several serine proteases including trypsin, chymotrypsin, and elastase. Homology is much higher (64%) between the 28-kDa protein and regions that are strongly conserved among the members of the serine protease family. The derived protein also has key features characteristic of active serine proteases, including the histidine, aspartic acid, and serine residues, which comprise the charge relay system, and a potential cleavage site for activation of the zymogen. Primer extension analysis performed to obtain the sequence of the 5' end of mRNA that encodes the 28-kDa protein indicates that two forms of this mRNA exist and probably arise through alternative splicing. The two mRNAs encode signal sequences that differ by the deletion of one amino acid near the predicted cleavage site of the signal peptide. These results demonstrate that adipocyte differentiation is accompanied by the expression of mRNA encoding a serine protease homologue that can be synthesized with two different signal peptides.
Pulmonary Capillary Endothelium-Bound Angiotensin-Converting Enzyme Activity in Acute Lung Injury (2000)

PCEB-ACE activity decreases early during ALI, correlates with the clinical severity of both the lung injury and the underlying disease, and may be used as a quantifiable marker of underlying pulmonary capillary endothelial dysfunction.
Antibody class switching differs among SJL, C57BL/6 and 129 mice (2007)

Inbred mouse strains used for gene manipulation studies vary in many respects, including immune system function. These differences can interfere with data interpretation unless the mice are well backcrossed. Here, we show that antibody class switching to IgG3 in cultured splenic B cells from Swiss James Lambert (SJL) and 129/Sv mice is 2- to 6-fold less efficient compared with C57BL/6 (B6). Under optimal stimulation conditions, IgA switching is also 2- to 19-fold lower in SJL and 129/Sv B cells. Splenic B cells from SJL mice express higher levels of CD19 and CD21 compared with B6, and their CD21(high)CD23(low) B cells have little CD9 expression, suggesting atypical marginal zone (MZ) B cells. However, sort purification of splenic B cell subsets did not equalize in vitro class switching to IgG3 or IgA between SJL and B6. 129/Sv spleens have a 3-fold greater number of MZ B cells compared with B6, with similar CD9 expression. Poor IgG3 switching by 129/Sv B cells is specific to CD23(high) follicular B cells, whereas similar changes in IgA switching are seen in both CD21(high) and CD23(high) B cell subsets from 129/Sv. Therefore, the functions and phenotypes of mature B cells differ among three common strains of mice.
Structural Analysis of the Sialylated N- and O-Linked Carbohydrate Chains of Recombinant Human Erythropoietin Expressed in Chinese Hamster Ovary Cells. Sialylation Patterns and Branch Location of Dimeric N-acetyllactosamine Units (1995)

The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. The purified sialylated oligosaccharides were analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. Di-, tri-, tri'- and tetraantennary N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. Three different types of alpha 2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), N-glycolylneuraminic acid (2%) and N-acetyl-9-O-acetylneuraminic acid (3%). In the case of partial sialylation, a non-random distribution of the sialic acids over the branches is observed. One or two extra N-acetyllactosamine units, being exclusively located in the branches attached to the alpha 1-6-linked Man residue, can be present in completely or partially sialylated di-, tri'-, and tetraantennary oligosaccharides. Tetraantennary oligosaccharides with N-acetyllactosamine repeats could be digested quantitatively with endo-beta-galactosidase from Bacteroides fragilis, whereas under the same conditions tri' antennary oligosaccharides hardly reacted (< 15%). Using endo-beta-galactosidase from Escherichia freundii, these tri'antennary oligosaccharides could be digested more extensively (> 75%). The O-linked carbohydrate chains were released from the O-glycoprotein by alkaline borohydride treatment, and purified via FPLC on Mono Q and HPLC on Lichrosorb-NH2. Two O-glycans were found, namely, Neu5Ac alpha 2-3Gal beta 1-3GalNAc-ol and Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol.
Role of Surface-Active Phospholipids in Gastric Cytoprotection (1983)

Intragastric administration of a liposomal surfactant suspension markedly reduced acid-induced gastric ulcerogenesis and bleeding in rats. The concentration of surface-active molecules intrinsically present in the gastric mucosa was increased two to six times by administration of 16,16-dimethyl prostaglandin E2. Thus, local accumulation of surface-active phospholipids may be an integral component of the cytoprotective mechanism activated by prostaglandin treatment.
De novo conditioning in trauma-exposed individuals with and without posttraumatic stress disorder. (2000)

Differential conditioning was assessed in 15 medication-free individuals meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for chronic posttraumatic stress disorder (PTSD) and 18 trauma-exposed individuals who never developed PTSD (non-PTSD). Conditioned stimuli (CSs) were colored circles, and the unconditioned stimulus was a "highly annoying" electrical stimulus. Individuals with PTSD had higher resting heart rate (HR) and skin conductance (SC) levels and produced larger SC orienting responses. During conditioning, the PTSD group showed larger differential SC, HR, and electromyogram responses to the reinforced vs. nonreinforced stimuli (CS+ vs. CS-) compared with the non-PTSD group. Only PTSD participants continued to show differential SC responses to CS+ vs. CS- during extinction trials. Results suggest that individuals with PTSD have higher sympathetic nervous system arousal at the time of conditioning and are more conditionable than trauma-exposed individuals without PTSD.
A study of the robustness of pseudorandom binary-array-based surface characterization (1998)

In this paper me report on aspects of the use of color-coded pseudorandom binary arrays (PRBA's) to model three-dimensional scenes. We evaluate the accuracy and the robustness of the pattern recognition phase in the process. Emphasis is on the added value of the use of PRBA's as a tool to make the image processing robust and highly noise insensitive.
Structural and Functional Basis for Therapeutic Modulation of p53 Signaling (2008)

Effective modulation of structural features and/or functional properties of the major tumor suppressor p53 as a wild-type or cancer-associated mutant protein represents a major challenge in drug development for cancer. p53 is an attractive target for therapeutic design because of its involvement as a mediator of growth arrest and apoptosis after exposure to chemoradiotherapy and/or radiotherapy. Although most clinically used cytotoxic agents target stabilization of wild-type p53, there are a number of approaches that hold promise for reactivation of mutant p53. On the other hand, brief blockade of p53 may reduce toxicity from systemic cytotoxic therapy. Screens for restoration of p53 transcriptional responses in p53-deficient cells may provide a functional means to develop anticancer therapeutics. Structure-based modulation continues to hold promise for development of peptides or small molecules capable of modulation of either wild-type or mutant p53 proteins.