gebhart/patrepeval huggingface dataset:
Integrated analysis of copy number and loss of heterozygosity in primary breast carcinomas using high-density SNP array (2011)

Breast cancer is a heterogeneous disease, marked by extensive chromosomal aberrations. In this study, we aimed to explicate the underlying chromosomal copy number (CN) alterations and loss of heterozygosity (LOH) implicated in a cohort of Malaysian hospital-based primary breast carcinoma samples using a single nucleotide polymorphism (SNP) array platform. The analysis was conducted by hybridizing the extracted DNA of 70 primary breast carcinomas and 37 normal peripheral blood samples to the Affymetrix 250K Sty SNP arrays. Locus-specific CN aberrations and LOH were statistically summarized using the binary segmentation algorithm and hidden Markov model. Selected genes from the SNP array analysis were also validated using quantitative real-time PCR. The merging of CN and LOH data fabricated distinctive integrated alteration profiles, which were comprised of finely demarcated minimal sites of aberrations. The most prevalent gains (≥ 30%) were detected at the 8q arm: 8q23.1, 8q23.3, 8q24.11, 8q24.13, 8q24.21, 8q24.22, 8q24.23 and 8q24.3, whilst the most ubiquitous losses (≥ 20%) were noted at the 8p12, 8p21.1, 8p21.2, 8p21.1-p21.2, 8p21.3, 8p22, 8p23.1, 8p23.1‑p23.2, 8p23.3, 17p11.2, 17p12, 17p11.2-p12, 17p13.1 and 17p13.2 regions. Copy-neutral LOH was characterized as the most prevailing LOH event, in which the most frequent distributions (≥ 30%) were revealed at 3p21.31, 5q33.2, 12q24.12, 12q24.12‑q24.13 and 14q23.1. These findings offer compre-hensive genome-wide views on breast cancer genomic changes, where the most recurrent gain, loss and copy-neutral LOH events were harboured within the 8q24.21, 8p21.1 and 14q23.1 loci, respectively. This will facilitate the uncovering of true driver genes pertinent to breast cancer biology and the develop-ment of prospective therapeutics.
Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types. (1991)

To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp 160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.
Inheritance of susceptibility to experimental autoimmune encephalomyelitis (1996)

Experimental autoimmune encephalomyelitis is a disease of the central nervous system that can be readily induced in a variety of species by immunization with myelin proteins. It is one of the most commonly studied models of cell-mediated autoimmune disease and consequently has been important in the elucidation of many immunological functions in vivo. Nevertheless, very little is understood about the genetic and environmental factors that control the disease. Several groups have begun undertaking systematic genetic analyses in mice to identify loci that associate with increased susceptibility to disease. In this review, we will summarize the work that has been done to understand the genetic predisposition that makes certain inbred animals susceptible to disease and others resistant, and we will discuss some of the difficulties in the genetic analysis that have arisen due to the complexities of this disease model.
Processing of yellow fever virus polyprotein: role of cellular proteases in maturation of the structural proteins (1989)

The yellow fever virus (YFV) cDNA segment coding for the part of the precursor polyprotein generating the structural proteins C (capsid), prM (precursor to the membrane protein M), and E (envelope) was expressed in vitro by using the T7 promoter-polymerase transcription system coupled to translation in rabbit reticulocyte lysates. A polypeptide of the expected molecular weight was observed to accumulate in the assay and was processed into proteins C, prM, and E only when dog pancreas microsomal membranes were added to the translation system. Proteins prM and E were translocated inside the endoplasmic reticulum, where prM underwent glycosylation. Regions essential for translocation of these proteins were localized to the 18- and 15-amino-acid C-terminal hydrophobic regions of proteins C and prM, respectively. Translocation of protein prM appeared to be less efficient than that of protein E. Maturation of these proteins followed different kinetics, indicating that the prM signal is probably cleaved off more slowly. A polypeptide composed of proteins C and prM, similar to the NVx polypeptide described in yellow fever virus-infected cells, was also produced in the in vitro system in the presence of membranes. No mature protein M was detected, suggesting that the cleavage of prM to M is a late processing event mediated by a protease different from endoplasmic reticulum signalases.
In Principle Method for Noninvasive Determination of the Fetal Genome (2010)

Abstract We illustrate the concept of noninvasive determination of the fetal genome by shotgun sequencing maternal plasma. The approach is based on molecular counting of alleles in maternal cell-free DNA: the inheritance of paternal haplotypes can be determined by counting paternal specific alleles present on each of the paternal haplotypes; the inheritance of maternal haplotypes can be revealed by counting the alleles on each maternal haplotype and determining the relative representation of the two maternal haplotypes. The concept was experimentally proven by sequencing a synthetic mixture of genomic DNA samples from a child and her mother, whose whole-genome haplotypes (defined by ~800,000 SNPs), together with those of the father, were previously determined. Light sequencing (0.25x) of such sample containing ~16% child’s DNA enabled the inheritance of parental haplotypes to be correctly resolved over most part of the genome, and partially resolved when prior knowledge of paternal whole-genome haplotypes is absent. Translating this approach to maternal plasma DNA samples, together with increased sequencing depth and phase knowledge of additional numbers of parental SNPs, should enable clinically practical sequencing of the fetal genome.
Pig kidney Na+,K+‐ATPase (1986)

cDNAs complementary to pig kidney mRNAs coding for alpha- and beta-subunits of Na+,K+-ATPase were cloned and sequenced. Selective tryptic hydrolysis of the alpha-subunit within the membrane-bound enzyme and tryptic hydrolysis of the immobilized isolated beta-subunit were also performed. The mature alpha- and beta-subunits contain 1016 and 302 amino acid residues, respectively. Structural data on the peptides from extramembrane regions of the alpha-subunit and on glycopeptides of the beta-subunit underlie a model for the transmembrane arrangement of Na+,K+-ATPase polypeptide chains.
The CD28-B7 costimulatory pathway and its role in autoimmune disease (1997)

The activation of naive CD4+ T cells requires two discrete signals: a signal delivered by the T cell receptor following recognition of antigen and an accessory signal transduced when costimulatory receptors interact with their ligands. Particularly important in the development of an immune response to foreign antigens is the T cell molecule CD28, which delivers a potent costimulus when engaged by ligands, B7-1 and B7-2, on antigen-presenting cells. It is interesting that blockade of B7 molecules, which disrupts interactions with CD28 and prevents delivery of the CD28 costimulus, also alters the immune responses to self antigens and prevents the development of clinical disease in murine models of systemic and organ-specific autoimmunity. Herein we review the roles of CD28 and its B7 ligands in the pathogenesis of autoimmunity, discuss efforts to treat animal models of autoimmunity by modifying the CD28 signal, and consider the mechanisms by which manipulation of the CD28 signal alters the course of experimental autoimmune disease.
Novel HBT with reduced thermal impedance (1995)

Heterojunction bipolar transistors have been fabricated using a novel process in which the majority of the front side of the chip is metallized to serve as the groundplane. The completed chip is assembled inverted so that the emitters are next to the heat sink; base and collector are contacted using through-wafer vias and microstrip lines on the back side of the chip. These devices show a 50% reduction in thermal impedance compared to conventionally fabricated devices and have achieved power densities of 10 W/mm of emitter length. Such devices are expected to have substantially lower emitter inductance as well, which may lead to improved gain at higher frequencies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Differential distribution of TRP Ca2+ channel isoforms in mouse brain. (1998)

Mammalian homologues of the Drosophila TRP proteins, which are essential for light-activated, phosphatidyl-inositide (PI)-dependent Ca2+ conductance in Drosophila photoreceptors, were molecularly identified, to investigate receptor-activated Ca2+ influx in the mammalian nervous system. Two cloned mouse TRP homologues, TRP3 and TRP4, structurally related to the voltage-dependent Na+ channel, were expressed predominantly in the brain, where a sharp contrast in the distribution of the RNA transcripts for TRP isoforms was demonstrated by in situ hybridization analysis. TRP3 mRNA was concentrated in cerebellar Purkinje cells and sparsely localized in the cerebellar granule layer, pontine nuclei, and thalamus, whereas TRP4 mRNA was abundantly expressed in hippocampal CA1 pyramidal neurons, dentate gyrus granule cells, and cerebral cortical neurons, and in the septal nuclei and the mitral layer of olfactory bulb. The distinct spatial patterns of TRP isoforms implicate that neurons are highly heterogeneous in receptor-activated Ca2+ influx responsible for the second phase of PI-mediated rise in intracellular Ca2+.
Low-power CMOS implantable nerve signal analog processing circuit (2002)

We describe a low-voltage low-power CMOS nerve signal analog processing circuit for biomedical applications. It is dedicated to an implantable bladder controller. After amplifying the nerve signal with low-noise high-CMRR instrumentation amplifier, it is rectified and bin-integrated (RBI) with a low-power CMOS analog processing circuit. This circuit is based on switched capacitor technique. Using techniques to reduce operational amplifier requirements ensures low-power consumption. The circuit has been designed in CMOS 0.35 /spl mu/m technology. The simulation results of the main parts of the proposed analog circuit are presented. At a supply voltage of 2.2 V the power dissipation is 700 /spl mu/W.
Analysis and control of hysteresis in PD/SOI CMOS (2003)

A new methodology to characterize and analyze hysteresis in PD/SOI CMOS inverter-based circuits, including its true worst case, is defined, and new insight into the underlying physics is provided. The methodology is used to explore novel device/circuit designs for controlling hysteresis as the PD/SOI CMOS technology is scaled to <100 nm.
The photovoltaic response in poly(p-phenylene vinylene) thin-film devices (1994)

We report measurements of the photovoltaic effect in diode structures formed with thin films (100 nm) of the conjugated polymer poly(p-phenylene vinylene), PPV, sandwiched between electrodes of indium/tin oxide, ITO, and either aluminium, magnesium or calcium. Under illumination incident through the ITO contact, large open-circuit voltages were measured, which saturated at approximately 1.2 V for Al and Mg devices, and approximately 1.7 V for Ca devices. Quantum efficiencies (short-circuit current/incident photon flux) of order 1% were measured at low intensities (0.1 mW cm-2). The spectral response of the photocurrent demonstrates that photon absorption near the electron-collecting electrode optimizes the photocurrent, indicating that device performance is limited by low electron mobilities in the bulk PPV. The photocurrent exhibits a weak temperature dependence, with an activation energy that is a function of the electric field in the polymer. We have used these measurements to estimate an exciton binding energy in PPV of approximately 0.4 eV.
Endothelial function studies in pulmonary vascular disease: Determination of angiotensin converting enzyme activity in humans (Review) (2002)

Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme. The majority of ACE has been found on the pulmonary capillary endothelium (PCE). Pulmonary capillary endothelium-bound (PCEB)-ACE has been extensively studied by means of indicator dilution techniques in animals and man. We have recently developed and applied methodologies for assaying pulmonary capillary endothelium-bound (PCEB) angiotensin convertin enzyme (ACE) activity in man. This article provides a summary of our studies in human subjects utilizing similar methodology. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 μCi or 2 nmol), was injected as a bolus into the subclavian vein of patients and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage. To investigate the PCE in this manner we tested the hypothesis that PCEB-ACE is depressed in patients diagnosed with acute lung injury and estimated interaction of an ACE inhibitor (enalaprilat) with PCE in human subjects. An inverse correlation was found between the pulmonary endothelium-bound ACE activity (v) and the lung injury score (r=0.379; p<0.01). Similarly, an inverse correlation was found between the pulmonary capillary perfusion index (CPI) and the lung injury score (r=0.284, p<0.05). PCEB-ACE activity in the group of patients with mild lung injury was significantly different from the group of control patients (0.44±0.048 vs. 1.15±0.05; p<0.01). Trace amounts (1.5 μg/kg) of enalaprilat had no significant effect on mean arterial pressure (91±6 vs. 84±7 vs. 88±6 mmHg for T1, T2 and T3, respectively), but significantly decreased PCEB-ACE activities. When normalized to pre-drug (T1) activity levels, enalaprilat inhibited PCEB and SE ACE activity at T2 by 74±6 and 68±6%, respectively. PCEB-ACE measurements can be used in clinical practice for estimating PCE functions and can provide new insight into the physiology of the pulmonary circulation.
Humanin Is a Novel Neuroprotective Agent Against Stroke (2006)

Our results demonstrate that HNG protects against cerebral ischemia/reperfusion injury in mice. HNG offers neuroprotection in vivo at least in part by inhibiting ERK activation. These findings suggest a potential therapeutic role for HNG in the treatment of stroke.
Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. (1994)

BCL-2 is a 26-kDa integral membrane protein that represses apoptosis by an unknown mechanism. Recent findings indicate that Ca2+ release from the endoplasmic reticulum (ER) mediates apoptosis in mouse lymphoma cells. In view of growing evidence that BCL-2 localizes to the ER, as well as mitochondria and the perinuclear membrane, we investigated the possibility that BCL-2 represses apoptosis by regulating Ca2+ fluxes through the ER membrane. A cDNA encoding BCL-2 was introduced into WEHI7.2 cells and two subclones, W.Hb12 and W.Hb13, which express high and low levels of BCL-2 mRNA and protein, respectively, were isolated. WEHI7.2 cells underwent apoptosis in response to treatment with the glucocorticoid hormone dexamethasone, whereas W.Hb12 and W.Hb13 cells were protected from apoptosis, revealing a direct relationship between the level of BCL-2 expression and the degree of protection. Significantly, BCL-2 also blocked induction of apoptosis by thapsigargin (TG), a highly specific inhibitor of the ER-associated Ca2+ pump. TG completely inhibited ER Ca2+ pumping in both WEHI7.2 and W.Hb12 cells, but the release of Ca2+ into the cytosol after inhibition of ER Ca2+ pumping was significantly less in W.Hb12 cells than in WEHI7.2 cells, indicating that BCL-2 reduces Ca2+ efflux through the ER membrane. By reducing ER Ca2+ efflux, BCL-2 interfered with a signal for "capacitative" entry of extracellular Ca2+, preventing a sustained increase of cytosolic Ca2+ in TG-treated cells. These findings suggest that BCL-2 either directly or indirectly regulates the flux of Ca2+ across the ER membrane, thereby abrogating Ca2+ signaling of apoptosis.
RAID organization and performance (2003)

A disk array architecture that generalizes the RAID (redundant arrays of inexpensive disks) level V data organization while providing excellent storage utilization, response times, and fault tolerance is discussed. A key feature of the approach is that reliability groups can contain several check data disks beyond the single parity disk. RAID response times for fault-free and failure recovery operations are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily (1991)

The structures of two vaccinia virus genes (B15R and B18R) from near the right inverted terminal repeat are described. These genes encode proteins of 36.5K and 40.7K, respectively, which have an N-terminal hydrophobic sequence, possible sites for attachment of N-linked carbohydrate and a short string of hydrophobic residues near the C terminus. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons established that the two gene products are related to each other (20% identity) and to the immunoglobulin (Ig) superfamily. Intriguingly, the nearest homologues of these proteins in the SWISS-PROT (version 14) database are the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. The product of one of these genes is known to be expressed on the cell surface early during infection and immunity directed against it confer resistance to virus infection without directly neutralizing virus infectivity. We propose a novel method for virus immune evasion in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6 and prevent these cytokines reaching their natural receptors. In consequence the inflammatory response would be diminished and virus replication enhanced.
Rational Design of Micro-RNA-like Bifunctional siRNAs Targeting HIV and the HIV Coreceptor CCR5 (2010)

Small-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are distinguished by their modes of action. SiRNAs serve as guides for sequence-specific cleavage of complementary mRNAs and the targets can be in coding or noncoding regions of the target transcripts. MiRNAs inhibit translation via partially complementary base-pairing to 3' untranslated regions (UTRs) and are generally ineffective when targeting coding regions of a transcript. In this study, we deliberately designed siRNAs that simultaneously direct cleavage and translational suppression of HIV RNAs, or cleavage of the mRNA encoding the HIV coreceptor CCR5 and suppression of translation of HIV. These bifunctional siRNAs trigger inhibition of HIV infection and replication in cell culture. The design principles have wide applications throughout the genome, as about 90% of genes harbor sites that make the design of bifunctional siRNAs possible.
Do NSAIDs exert their colon cancer chemoprevention activities through the inhibition of mucosal prostaglandin synthetase? (1995)

Nonsteroidal antiinflammatory drugs (NSAIDs) have considerable potential as chemopreventive agents for colorectal cancer. Recent case-control drug surveillance and large cohort studies found that patients with regular aspirin use had a reduced incidence of colorectal cancer and/or decreased death rate from this disease. Several different NSAIDs reduce formation of both colon adenomatous polyps (the precursor lesion of colon cancer) and cancers in experimental animals given known carcinogens. Perhaps most convincing are reports that the NSAID sulindac promotes regression and inhibits recurrence of adenomatous colon polyps in patients with adenomatous polyposis coli. The best characterized pharmacologic effect of the NSAIDs is their reduction of prostaglandin synthesis by inhibiting prostaglandin synthetase PGE2, which catalyzes the formation of prostaglandin precursors from arachidonic acid. Several lines of evidence are contrary to the concept that inhibition of prostaglandin synthesis is central to the NSAIDs' chemopreventive effects. Relatively high levels of prostaglandins have been reported to inhibit tumor cell growth both in vivo and in vitro, and to inhibit differentiation in some tumor cell lines. We evaluated comparative chemopreventive effects on colon tumor formation in an azoxymethane (AOM)-induced colon carcinogenesis rat model using the NSAIDs piroxicam, sulindac, and sulindac sulfone, a metabolite of sulindac which lacks the anti-prostaglandin synthetase activity typically associated with NSAID-induced gastrointestinal toxicities. The results demonstrate that sulindac sulfone, a compound lacking anti-prostaglandin synthetase activity, inhibits AOM-induced colon cancer in rats. Substantial dose-dependent reductions in both tumor burden and tumor multiplicity were observed in the sulindac sulfone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Label‐Free Impedance Biosensors: Opportunities and Challenges (2007)

Impedance biosensors are a class of electrical biosensors that show promise for point-of-care and other applications due to low cost, ease of miniaturization, and label-free operation. Unlabeled DNA and protein targets can be detected by monitoring changes in surface impedance when a target molecule binds to an immobilized probe. The affinity capture step leads to challenges shared by all label-free affinity biosensors; these challenges are discussed along with others unique to impedance readout. Various possible mechanisms for impedance change upon target binding are discussed. We critically summarize accomplishments of past label-free impedance biosensors and identify areas for future research.