gebhart/patrepeval huggingface dataset:
S108 Genome-wide association study in chronic thromboembolic pulmonary hypertension reveals new insights into aetiology (2017)

<h3>Introduction</h3> Chronic thromboembolic pulmonary hypertension (CTEPH) is an infrequent but important complication of acute pulmonary embolism (PE). Thrombophilias and non-O blood groups are genetic risk factors for venous thromboembolism (VTE), however they are not independently associated with CTEPH. Identifying genetic risk factors for CTEPH would provide important insights into pathobiology and might allow risk-stratification following PE. We undertook a genome-wide association study (GWAS) in CTEPH to identify novel disease loci. <h3>Methods</h3> To date, 1457 Caucasian CTEPH patients were enrolled from 10 European and US Centres and compared to 1536 healthy Caucasian controls from the Wellcome Trust Case Control Consortium. Genotyping was performed using the HumanOmniExpressExome-8 array. Quality control criteria and statistical analysis are summarised in figure 1. <h3>Results</h3> 1250 CTEPH cases, 1492 controls and 7 million single-nucleotide polymorphisms (SNPs) were included after quality control exclusions. Two loci, in chromosomes 4 and 9 were significantly associated with CTEPH (figure 1). The lead SNP in chr9 (rs532436, OR=2.38, p=4.6x10<sup>-32</sup>) is highly correlated with the tagging SNP for the A1 blood group (rs507666, R<sup>2</sup>=0.99). Reconstructing genetic ABO groups confirmed an over-representation of the A1A1 group in CTEPH compared to controls (7% vs. 2.9%, OR 4.5). Additionally, there were 11 significant SNPs in the chr9 <i>ADAMTS13</i> gene locus that is moderately correlated with <i>ABO</i> (R<sup>2</sup>=0.33). The lead SNP in chr4 (rs13130318, OR=1.4, p=5.6x10<sup>-8</sup>) is highly correlated with a missense variant in <i>FGG</i> (rs6050, R<sup>2</sup>=0.89) associated with decreased fibrinogen protein and increased resistance to fibrinolysis in CTEPH. There were no associations at the <i>F5</i> locus, which is highly significant in VTE. <h3>Conclusions</h3> We report the first GWAS in CTEPH, identifying at least 2 genetic loci associated with the disease. The <i>ABO</i> association is driven by the A1 blood group and represents the largest population attributable genetic risk factor for CTEPH, which is higher than previously reported for VTE. The potential <i>ADAMTS13</i> association is a plausible biological candidate, and further work will establish whether it is independent from <i>ABO</i>. The lack of associations with other loci found in VTE suggests that <i>ABO</i> might have a pathobiological role in CTEPH in addition to its contribution to VTE.
A genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics (2018)

Abstract Biomechanical cues dynamically control major cellular processes but whether genetic variants actively participate in mechano-sensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies have identified chromosome 1p32.2 as one of the most strongly associated loci with CAD/IS; however, the causal mechanism related to this locus remains unknown. Employing statistical analyses, ATAC-seq, and H3K27ac/H3K4me2 ChIP-Seq in human aortic endothelium (HAEC), our results demonstrate that rs17114036, a common noncoding polymorphism at the 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR/Cas9-based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional flow by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays further demonstrate that CAD/IS protective allele at rs17114036 in PLPP3 intron 5 confers an increased endothelial enhancer activity. ChIPPCR and luciferase assays show that CAD/IS protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2, which increases the enhancer activity under unidirectional flow. These results demonstrate for the first time that a human single-nucleotide polymorphism contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechano-sensing mechanisms. Significance Statement Biomechanical stimuli control major cellular functions and play critical roles in the pathogenesis of diverse human diseases. Although recent studies have implicated genetic variation in regulating key biological processes, whether human genetic variants contribute to the cellular mechano-sensing mechanisms remains unclear. This study provides the first line of evidence supporting an underappreciated role of genetic predisposition in cellular mechanotransduction mechanisms. Employing epigenomic profiling, genome-editing, and latest human genetics approaches, our data demonstrate that rs17114036, a common noncoding polymorphism implicated in coronary artery disease and ischemic stroke by genome-wide association studies, dynamically regulates endothelial responses to blood flow (hemodynamics) related to atherosclerosis via regulation of an intronic enhancer. The results provide new molecular insights linking disease-associated genetic variants to cellular mechanobiology.
Challenges and Opportunities in Developing Novel Drugs for TB (2011)

Mycobacterium tuberculosis is a difficult pathogen to combat and the first-line drugs currently in use are 40-60 years old. The need for new TB drugs is urgent, but the time to identify, develop and ultimately advance new drug regimens onto the market has been excruciatingly slow. On the other hand, the drugs currently in clinical development, and the recent gains in knowledge of the pathogen and the disease itself give us hope for finding new drug targets and new drug leads. In this article we highlight the unique biology of the pathogen and several possible ways to identify new TB chemical leads. The Global Alliance for TB Drug Development (TB Alliance) is a not-for-profit organization whose mission is to accelerate the discovery and development of new TB drugs. The organization carries out research and development in collaboration with many academic laboratories and pharmaceutical companies around the world. In this perspective we will focus on the early discovery phases of drug development and try to provide snapshots of both the current status and future prospects.
Role of lipopolysaccharide and related cytokines in Helicobacter pylori infection. (1997)

Helicobacter pylori is a gram-negative bacterium which accounts for the development of chronic gastritis and peptic ulcer in man. In this review, emphasis has been laid on the role of lipopolysaccharide (LPS) of the H. pylori cellular wall in the pathogenesis of gastroduodenal disease. H. pylori LPS exhibits a reduced endotoxic potency in terms of pyrogenicity, lethality, toxicity, mitogenicity, cytokine (CK) release and chromogenic limulus amebocyte lysate assay. This low biological activity of the LPS could be ascribed to the underacylation and underphosphorylation pattern of the lipid A backbone. However, also LPS core structures seem to contribute to the biological activity of the molecule. Despite this low immunological potential, an array of proinflammatory CKs are produced both in vitro and in vivo following stimulation of mucosal cells with H. pylori organisms. It is likely that LPS plays a major role in triggering interleukin (IL)-8, IL-1 and tumor necrosis factor-alpha production from both epithelial cells and macrophages. Finally, the lower immune response elicited by H. pylori LPS in comparison with other enterobacterial LPS may represent an escape mechanism from the host immunosurveillance exerted by this bacterium, thus allowing its survival and persistence in the gastric niche.
ESTERIFICATION OF CREATINE (1922)

Many of the amino-acids resulting from hydrolysis of proteins have been esterified by treatment with absolute alcohol and dry hydrogen chloride.The amino-acid, usually amphoteric in reaction because of the simultaneous presence of an amino and a carboxyl group, becomes strongly basic when the carboxyl is esterified, and the amino group readily adds an equivalent of mineral acid to form a stable crystalline salt.Fractional distillation in vacua of these basic esters constitutes Fischer's well known method of separating certain of the amino-acids present in the acid hydrolysate of proteins.From glycine, or aminoacetic acid, the simplest of the aminoacids, the hydrochloride of the ethyl ester is readily obtained in large crystals.Creatine, or methylguanidine-acetic acid, may be regarded as a substituted glycine.The conversion of creatine into creatinine by loss of water is readily effected by treatment with mineral acid.It was significant, therefore, to find that treatment of creatine with absolute alcohol and dry hydrogen chloride, a condition ideal for the removal of water, resulted not in the ring closure but rather in esterification of the carboxyl group.Esters were readily obtained in this way with methyl, ethyl, and n-butyl alcohols.Since no esters of creatine are described in the literature, the following derivatives may be of interest.Creatine Methyl Ester Hydrochloride.-10 gm. of creatine, previously dried at loo", were suspended in 100 cc. of absolute methyl alcohol and dry hydrogen chloride was passed in.In a short time
Approach and Its Applications by Chaotic (1999)

characteristics. We propose a way, called trajectory par-allel measurement (TPM), based on the chaotic approachto distinguish determinism and randomness in a timeseries, and apply this to a chaotic time series with ran-dom noise, summarizing the results of practical appliea-tion in diagnosing automatic transmission.
Synthesis and Structural Characterization of the First Organically Templated Vanadyl(IV) Arsenato- and Phosphato-oxalates: (C4H12N2)[VO(C2O4)HXO4] (X = As, P) (1999)

Two novel piperazinium vanadyl(IV) compounds, (C4H12N2)[VO(C2O4)HAsO4] (1) and (C4H12N2)[VO(C2O4)HPO4] (2), have been prepared under mild hydrothermal conditions and structurally characterized by single-crystal X-ray diffraction, thermogravimetric analysis, and magnetic susceptibility. They adopt a one-dimensional structure in which ladder-like chains are constituted by the three-connected V and three-connected X (X = As for 1 and P for 2) centers. Within the infinite chains the oxalate group coordinates to each of the V centers as a bidentate ligand. They are the first inorganic/organic mixed-anion materials prepared in the vanadium arsenate and vanadium phosphate systems. Crystal data for 1: orthorhombic, P212121, a = 6.5595(1) Å, b = 12.4689(1) Å, c = 14.6363(1) Å, Z = 4. Crystal data for 2: as above, except a = 6.4022(4) Å, b = 12.4735(8) Å, c = 14.653(1) Å. Acccording to the results of TG analysis, both compounds are thermally stable to ca. 250 °C. Our magnetic study revealed that exchange coupling occurred between the nearest VO2+ centers along the infinite (-V-O-X-O)2 chains. Good fits of the magnetic susceptibility data were obtained by using the Bonner and Fisher S = 1/2 linear chain model.
Investigating commercially relevant packaging solutions to improve storage stability of mechanically filleted Atlantic mackerel (Scomber scombrus) produced under industrial conditions (2020)

Abstract This study investigated the efficacy of three commercially relevant packaging methods (vacuum with water glazing VAC-G; vacuum with seawater VAC-S; shatter-layer packaging SL) to improve frozen storage stability of mechanically filleted Atlantic mackerel at − 25 °C, in comparison to water glazing alone (GL) and storage as whole unglazed, block frozen fish. Besides proximate composition and pH of raw material, quality changes were analysed by free fatty acid content (FFA), water holding capacity (WHC), cooking yield, lipid oxidation (lipid hydroperoxides, PV; non-protein bound thiobarbituric acid reactive substances, TBARS) and sensory profiles of cooked samples after 3.5, 8, 10 and 12 months of frozen storage. Vacuum-packaging was effective in mitigating the PV and TBARS as well as rancid odour and flavour. The inclusion of seawater in VAC-S altered the sensory textural attributes of the mackerel fillet to be more juicy, tender and soft and increased the attribute of salty flavour in the sample. SL delayed rancid odour and flavour by 2 months compared to GL. Processing of mackerel under industrial conditions, including filleting, handling, double-freezing and glazing accelerated the formation of FFA as well as losses of WHC and cooking yield in the fillet regardless the packaging methods.
Crosslinked Poly(Methyl Vinyl Ether-Co-Maleic Anhydride) as Topical Vehicles for Hydrophilic and Lipophilic Drugs (2003)

Poly(methyl vinyl ether-co-maleic anhydride) crosslinked with ethylene glycol (GZ-ET), 1,4-butanediol (GZ-BUT), 1,6-exandiol (GZ-EX), 1,8-octanediol (GZ-OCT), 1,10-decanediol (GZ-DEC) or 1,12-dodecanediol (GZ-DOD) was prepared and employed as a supporting material for aqueous topical gels containing pyridoxine hydrochloride (PYCL) chosen as a hydrophilic model molecule or for O/A emulsion containing beta-carotene chosen as a hydrophobic model molecule. We analyzed the effect of the nature of the crosslinker on the permeation of hydrophilic and lipophilic vitamins through porcine skin by in vitro permeation studies. The vehicles formed by crosslinked poly(methyl vinyl ether-co-maleic anhydride) showed enhanced vitamins permeation with respect to the same vehicles formed by noncrosslinked poly(methyl vinyl ether-co-maleic anhydride) (GZ). The decrease in the crosslinker acyl chain length provides vehicles accelerating the drug permeability through the skin.
On the antiviral activity of diffusomycin (oxazolomycin). (1992)

The effect of the beta-lactone antibiotic diffusomycin (oxazolomycin) was investigated against vaccinia (Lister), herpes simplex type 1 (Kupka), influenza A (WSN; H1N1), and Coxsackie A9 viruses. Diffusomycin reduced significantly the plaque formation of enveloped DNA and RNA viruses by more than 90% in the range of the maximally tolerated dose. As could be shown with vaccinia virus, the antiviral action was not caused by virucidal effect on virions or by interaction with virus adsorption and penetration. In one-step growth cycle assays diffusomycin prevented the replication of herpes simplex type 1, vaccinia and influenza A viruses in a dose-dependent manner. The replication of influenza A viruses was blocked immediately after addition of the compound during zero to six hr p.i. Partial reversibility of the antiviral action was established by washing off the antibiotic from chicken embryo cells (CEC) infected with influenza A virus. Finally, replication of Coxsackie A9 virus was not inhibited by diffusomycin. Electron-optical studies revealed a reduced synthesis of HSV-1 nucleocapsids in dependence on the concentration of the compound.
Intermediaries personalize information streams (2000)

article Free AccessIntermediaries personalize information streams Authors: Paul Maglio IBM Almaden Research Center, San Jose, CA IBM Almaden Research Center, San Jose, CAView Profile , Rob Barrett IBM Almaden Research Center, San Jose, CA IBM Almaden Research Center, San Jose, CAView Profile Authors Info & Claims Communications of the ACMVolume 43Issue 8Aug. 2000 pp 96–101https://doi.org/10.1145/345124.345158Published:01 August 2000Publication History 71citation2,505DownloadsMetricsTotal Citations71Total Downloads2,505Last 12 Months68Last 6 weeks6 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteView all FormatsPDF
Composition and properties of egg white (2017)

Eggs are the most economical and abundant source of high-quality dietary protein, and are noteworthy for both their nutritional and functional properties. This chapter provides detailed information about the structure, chemical composition and functionality of egg white. Section 2 reviews the structure of egg white, and Section3 offers an overview of the proteins in egg white. Sections 4–9 then provide a detailed review of nine important proteins. Finally, Section 10 covers carbohydrates, minerals and vitamins as minor components of egg white.
Flexible auto-refresh (2015)

DRAM cells require periodic refreshing to preserve data. In JEDEC DDRx devices, a refresh operation is performed via an auto-refresh command, which refreshes multiple rows in multiple banks simultaneously. The internal implementation of auto-refresh is completely opaque outside the DRAM --- all the memory controller can do is to instruct the DRAM to refresh itself --- the DRAM handles all else, in particular determining which rows in which banks are to be refreshed. This is in conflict with a large body of research on reducing the refresh overhead, in which the memory controller needs fine-grained control over which regions of the memory are refreshed. For example, prior works exploit the fact that a subset of DRAM rows can be refreshed at a slower rate than other rows due to access rate or retention period variations. However, such row-granularity approaches cannot use the standard auto-refresh command, which refreshes an entire batch of rows at once and does not permit skipping of rows. Consequently, prior schemes are forced to use explicit sequences of activate (ACT) and precharge (PRE) operations to mimic row-level refreshing. The drawback is that, compared to using JEDEC's auto-refresh mechanism, using explicit ACT and PRE commands is inefficient, both in terms of performance and power.
High-frequency performance of lattice-strained heterojunction GaInAs/GaAs bipolar transistors (1986)

The performance of bipolar devices and circuits in the novel lattice-strained GaInAs/GaAs materials system show an improving trend with increased In composition in the base. An fT of 8 GHz has been measured using an 8 μm emitter stripe width and 8% In. A small-signal model is presented.
MonoGRNet: A Geometric Reasoning Network for Monocular 3D Object Localization (2018)

Detecting and localizing objects in the real 3D space, which plays a crucial role in scene understanding, is particularly challenging given only a single RGB image due to the geometric information loss during imagery projection. We propose MonoGRNet for the amodal 3D object detection from a monocular RGB image via geometric reasoning in both the observed 2D projection and the unobserved depth dimension. MonoGRNet is a single, unified network composed of four task-specific subnetworks, responsible for 2D object detection, instance depth estimation (IDE), 3D localization and local corner regression. Unlike the pixel-level depth estimation that needs per-pixel annotations, we propose a novel IDE method that directly predicts the depth of the targeting 3D bounding box's center using sparse supervision. The 3D localization is further achieved by estimating the position in the horizontal and vertical dimensions. Finally, MonoGRNet is jointly learned by optimizing the locations and poses of the 3D bounding boxes in the global context. We demonstrate that MonoGRNet achieves state-of-the-art performance on challenging datasets.
Abstract CN06-01: Induction of oral cavity cancer in rats by (S)-N'-nitrosonornicotine, a constituent of smokeless tobacco (2012)

Abstract Smokeless tobacco products such as moist oral snuff are being promoted by the tobacco industry with a half billion dollars per year in advertising. It is likely that the prevalence of smokeless tobacco use will continue to increase in the U.S. Smokeless tobacco products are widely used in other parts of the world and are considered by the International Agency for Research on Cancer as causes of cancer of the oral cavity, esophagus and pancreas in humans. However, no previous study has reported the presence of a strong oral cavity carcinogen in these products. N'-Nitrosonornicotine (NNN) occurs in significant amounts in smokeless tobacco products, generally being found at levels of 1 - 10 μg/g tobacco. Since NNN has a chiral center, it exists as (S)- and (R)- enantiomers. (S)-NNN is the major enantiomer in smokeless tobacco products. While racemic NNN (a 50:50 mixture of (S)- and (R)-NNN) has been previously shown to cause esophageal tumors in rats, the carcinogenicity of the individual enantiomers has not been reported. Based on our published metabolism and DNA binding studies of (S)-NNN, we hypothesized that it might be a more powerful carcinogen than (R)-NNN and, furthermore, that it might cause oral cancer. Groups of 24 male F-344 rats were treated with either (S)-NNN (15 ppm), (R)-NNN (15 ppm), or racemic NNN (30 ppm) in the drinking water for 15-20 months. Necropsy of 20 rats treated with (S)-NNN demonstrated a 100% incidence of oral cavity tumors. More than 60 oral cavity tumors were observed, including benign and malignant tumors of the buccal mucosa, soft and hard palate, tongue, and pharynx. All rats also had esophageal tumors. (R)-NNN was significantly less carcinogenic than (S)-NNN. Racemic NNN also induced a high incidence of oral cavity and esophageal tumors. The results of this study demonstrate for the first time the presence of a strong oral cavity carcinogen in smokeless tobacco. (S)-NNN is a prime target for elimination from these products as a positive step toward cancer prevention. Citation Format: Stephen S. Hecht, Sandra James-Yi, Gerard O'Sullivan, Irina Stepanov, Mingyao Wang, Fekadu Kassie, Steven Carmella, Pramod Upadhyaya, Silvia Balbo. Induction of oral cavity cancer in rats by (S)-N'-nitrosonornicotine, a constituent of smokeless tobacco. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN06-01.
Observer Based Detection of Sensor Faults in Wind Turbines (2009)

An observer based scheme is proposed to detect sensor faults in wind turbines. In the example used for the proposed scheme the wind turbine drive train is considered. A model of the drive train is used to design the observer, and in this model the wind speed is an important input, however, if an unknown input observer the fault detection scheme can be non dependent on the actual wind speed. The scheme is validated on data from a more advanced and detailed simulation model. The proposed scheme detects the sensor faults a few samples after the beginning of the faults.