gebhart/patrepeval huggingface dataset:
Evidence for unique association signals in SLE at the CD28–CTLA4–ICOS locus in a family-based study (2006)

CD28, CTLA4 (cytotoxic T lymphocyte-associated protein 4) and ICOS (inducible T cell co-stimulator) are good candidate genes for systemic lupus erythematosus (SLE) because of their role in regulating T cell activation. CTLA4 inhibits CD28-mediated T cell activation. CTLA4 is expressed on CD4+ and CD8+ activated T cells, and also B cells, but CD28 and ICOS are largely restricted to T cells. An interval encompassing the CD28-CTLA4-ICOS locus on chromosome 2q33 was linked to lupus in two genome-wide linkage scans. This large family-based association study in 532 UK SLE families represents the first high-density genetic screen of 80 SNPs at this locus. There are seven haplotype blocks across the locus. In CTLA4, the strongest signal comes from two variants, located 2.1 kb downstream from the 3'-UTR. These polymorphisms, rs231726 (SNP 43) and rs231726 (SNP 44), are in complete linkage disequilibrium (LD) (r(2)=1) and are associated with SLE P=0.0008 (GH) and P=0.01 (family-based association test). There is also a signal in the distal 3' flanking region of CTLA4/ICOS promoter (P=0.003). There was no confirmation of published associations for SLE in the promoter or coding region of CTLA4. These SLE risk alleles are more distal than those identified in Graves' disease and are in LD with Graves' disease protective alleles identified in both of these regions of CTLA4 (Ueda et al. 2003). These factors suggest an SLE-specific pattern of association. The functional consequences of the associated polymorphisms are likely to influence CTLA4 expression, although it is possible that genetically modulated ICOS expression is involved in SLE susceptibility.
S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury (2012)

As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) ( n =138 subjects) and serum ( n =80 subjects) samples across a 6-day time course. Long-bone fracture, Injury Severity Score (ISS), and isolated head injury status were variables used to assess extracerebral sources of S100b in serum. After TBI, CSF and serum S100b levels were increased over healthy controls across the first 6 days post-TBI ( p ≤0.005 and p ≤0.031). Though CSF and serum levels were highly correlated during early time points post-TBI, this association diminished over time. Bivariate analysis showed that subjects who had temporal CSF profiles with higher S100b concentrations had higher acute mortality ( p <0.001) and worse Glasgow Outcome Scale (GOS; p =0.002) and Disability Rating Scale (DRS) scores ( p =0.039) 6 months post-injury. Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores ( p =0.032), temporal serum profiles were associated with acute mortality ( p =0.015). High CSF S100b levels were observed in women ( p =0.022) and older subjects ( p =0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.
Ordering method for reducing state space in compositional verification (2003)

Proposes an efficient ordering method for solving the state explosion problem in compositional verification of discrete event systems. A system to be verified is specified by untimed DEVS (discrete event system specification) formalism. The size of the intermediate state space during the compositional verification is dependent on the sequence of composing system components. Application of this method to some classical verification problems has shown that the size of the intermediate state space during composition is markedly reduced.
A Surgical Model for Normotensive Chronic Renal Failure in the Growing Piglet (1992)

Studying the effects of chronic uremia in children has been hindered by the lack of a suitable large mammalian animal model with normotensive renal failure. We performed nephrectomy with simultaneous contralateral partial nephrectomy using a stapling device and absorbable staples in 22 domestic piglets. Up to 93% of the total renal mass could be excised by this method. A chronic uremic state was reproducibly developed and correlated with the percentage of renal mass excised. There were no associated postoperative complications with the stapled partial nephrectomy. Pigs with moderate renal failure had a significant decrease in growth compared to those with mild renal failure, which represents the successful development of a normotensive large mammalian animal model that could be used to study the effects of chronic renal failure and hyperfiltration during a state of rapid growth. In addition, this study confirms the successful use of a stapling device to perform partial nephrectomy.
Traces of bacterial lipopolysaccharide suppress IFN-gamma-induced nitric oxide synthase gene expression in primary mouse macrophages. (1993)

A nitric oxide synthase (iNOS) inducible by cytokines and microbial products contributes to the cytotoxic and antimicrobial activity of mouse macrophages. Bacterial LPS interacts synergistically with IFN-gamma to induce iNOS when both stimuli are added together. In contrast, we show here that pre-exposure of peritoneal macrophages to low concentrations of LPS suppresses the induction of iNOS when IFN-gamma is added subsequently. Suppression required pretreatment with LPS for at least 8 h and was optimal with LPS concentrations in the range of 50 to 200 pg/ml. Suppression was exerted by smooth and rough forms of LPS from Escherichia coli and by lipid A from Salmonella minnesota, but not by a biologically inactive lipid A from Rhodobacter sphaeorides. Suppression of nitrite accumulation and iNOS enzyme activity by prior exposure of macrophages to LPS could be explained by their markedly decreased content of iNOS protein, as revealed by immunoblot with monospecific anti-iNOS IgG. Messenger RNA for iNOS was affected in a biphasic manner by pretreatment with LPS. Five hours after addition of IFN-gamma, iNOS mRNA levels were unaltered or even enhanced by pretreatment with LPS, but by 24 to 48 h, expression of iNOS mRNA was inhibited strongly enough to account for the reduced levels of iNOS protein. Suppression by LPS did not appear to be mediated by endogenous prostaglandins, transforming growth factor-beta, or TNF-alpha, even though pretreatment with exogenous TNF-alpha was also suppressive. These findings suggest that preactivation of pathways normally contributing to synergistic induction of iNOS may deplete macrophages of factors needed for its expression. Regulation of iNOS in vivo may depend on the relative tempo with which the inflammatory and immune responses evolve.
Development of Diagnostic Fragment Ion Library for Glycated Peptides of Human Serum Albumin: Targeted Quantification in Prediabetic, Diabetic, and Microalbuminuria Plasma by Parallel Reaction Monitoring, SWATH, and MSE (2015)

Human serum albumin is one of the most abundant plasma proteins that readily undergoes glycation, thus glycated albumin has been suggested as an additional marker for monitoring glycemic status. Hitherto, only Amadori-modified peptides of albumin were quantified. In this study, we report the construction of fragment ion library for Amadori-modified lysine (AML), N(ε)-(carboxymethyl)lysine (CML)-, and N(ε)-(carboxyethyl)lysine (CEL)-modified peptides of the corresponding synthetically modified albumin using high resolution accurate mass spectrometry (HR/AM). The glycated peptides were manually inspected and validated for their modification. Further, the fragment ion library was used for quantification of glycated peptides of albumin in the context of diabetes. Targeted Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH) analysis in pooled plasma samples of control, prediabetes, diabetes, and microalbuminuria, has led to identification and quantification of 13 glycated peptides comprised of four AML, seven CML, and two CEL modifications, representing nine lysine sites of albumin. Five lysine sites namely K549, K438, K490, K88, and K375, were observed to be highly sensitive for glycation modification as their respective m/z showed maximum fold change and had both AML and CML modifications. Thus, peptides involving these lysine sites could be potential novel markers to assess the degree of glycation in diabetes.
Permeable Membrane Experiment (1993)

<div class="htmlview paragraph">The purpose of the Permeable Membrane Experiment is to gather flight data on three areas of membrane performance that are influenced by the presence of gravity. These areas are: (1) liquid/gas phase separation, (2) gas bubble interference with diffusion through porous membranes and (3) wetting characteristics of hydrophilic membrane surfaces. These data are important in understanding the behavior of membrane/liquid/gas interfaces where surface tension forces predominate. The data will be compared with 1-g data already obtained and with predicted microgravity behavior. The data will be used to develop designs for phase separation and plant nutrient delivery systems and will be available to the life support community for use in developing technologies which employ membranes.</div> <div class="htmlview paragraph">A conceptual design has been developed to conduct three membrane experiments, in sequence, aboard a single Complex Autonomous Payload (CAP) carrier to be carried in the Shuttle Orbiter payload bay. One experiment is conducted for each of the three membrane performance areas under study. These experiments are discussed in this paper.</div>
Establishment of a clinically correlated human pericardial fluid bank: Evaluation of intrapericardial diagnostic potential (1999)

The development of a clinically correlated human pericardial fluid bank and database is described. A unique feature of this registry is the availability of a large number of pericardial fluid samples for testing with respect to multiple factors and for correlation with angiographic findings and clinical syndromes expressed by the patients. The collection of data at the present time comprises frozen pericardial fluid samples obtained from patients who have undergone cardiac surgery; and historical, clinical, and laboratory data obtained from the patient records. Nearly 400 samples have been stored and analyzed thus far, with sample entry continuing. This registry is designed to evaluate the local factors that play a role in mediating or reflecting myocardial or coronary responses. Pathophysiologic processes of particular interest include restenosis, plaque ruptures, and angiogenesis. Study of the pericardial fluid bank should lead to enhanced understanding of molecular mechanisms, as well as to the explanation for the reasons underlying interpatient variability in these processes. It is further anticipated that this information might provide a foundation for the diagnostic use of pericardial fluid to individualize therapies targeting angiogenesis or plaque physiology.
A Flexible Multi-Volume Shader Framework for Arbitrarily Intersecting Multi-Resolution Datasets (2007)

We present a powerful framework for 3D-texture-based rendering of multiple arbitrarily intersecting volumetric datasets. Each volume is represented by a multi-resolution octree-based structure and we use out-of-core techniques to support extremely large volumes. Users define a set of convex polyhedral volume lenses, which may be associated with one or more volumetric datasets. The volumes or the lenses can be interactively moved around while the region inside each lens is rendered using interactively defined multi-volume shaders. Our rendering pipeline splits each lens into multiple convex regions such that each region is homogenous and contains a fixed number of volumes. Each such region is further split by the brick boundaries of the associated octree representations. The resulting puzzle of lens fragments is sorted in front-to-back or back-to-front order using a combination of a view-dependent octree traversal and a GPU-based depth peeling technique. Our current implementation uses slice-based volume rendering and allows interactive roaming through multiple intersecting multi-gigabyte volumes.
Autonomic Workload and Resources Management of Cloud Computing Services (2014)

The power consumption of data centers and cloud systems have increased almost three times between 2007 and 2012. Over-provisioning techniques are typically used for meeting the peak workloads. In this paper we present an autonomic power and performance management method for cloud systems in order to dynamically match the application requirements with "just-enough" system resources at runtime that lead to significant power reduction while meeting the quality of service requirements of the cloud applications. Our solution offers the following capabilities: 1) real-time monitoring of the cloud resources and workload behavior running on virtual machines (VMs), 2) determine the current operating point of both workloads and the VMs running these workloads, 3) characterize workload behavior and predict the next operating point for the VMs, 4) dynamically manage the VM resources (scaling up and down the number of cores, CPU frequency, and memory amount) at run time, and 5) assign available cloud resources that can guarantee optimal power consumption without sacrificing the QoS requirements of cloud workloads. We validate the performance of our approach using the RUBiS benchmark, an auction model emulating eBay transactions that generates a wide range of workloads (such as browsing and bidding with different number of clients). Our experimental results show that our approach can lead to reduction in power consumption up to 87% when compared to the static resource allocation strategy, 72% compared to adaptive frequency scaling strategy and 66% compared to a similar multi-resource management strategy.
A Role for Collagen IV Cross-links in Conferring Immune Privilege to the Goodpasture Autoantigen (2008)

The detailed structural basis for the cryptic nature (crypticity) of a B cell epitope harbored by an autoantigen is unknown. Because the immune system may be ignorant of the existence of such "cryptic" epitopes, their exposure could be an important feature in autoimmunity. Here we investigated the structural basis for the crypticity of the epitopes of the Goodpasture autoantigen, the alpha3alpha4alpha5 noncollagenous-1 (NC1) hexamer, a globular domain that connects two triple-helical molecules of the alpha3alpha4alpha5 collagen IV network. The NC1 hexamer occurs in two isoforms as follows: the M-isoform composed of monomer subunits in which the epitopes are accessible to autoantibodies, and the D-isoform composed of both monomer and dimer subunits in which the epitopes are cryptic. The D-isoform was characterized with respect to quaternary structure, as revealed by mass spectrometry of dimer subunits, homology modeling, and molecular dynamics simulation. The results revealed that the D-isoform contains two kinds of cross-links as follows: S-hydroxylysyl-methionine and S-lysyl-methionine cross-links, which stabilize the alpha3alpha5-heterodimers and alpha4alpha4-homodimers, respectively. Construction and analysis of a three-dimensional model of the D-isoform of the alpha3alpha4alpha5 NC1 hexamer revealed that crypticity is a consequence of the following: (a) sequestration of key residues between neighboring subunits that are stabilized by domain-swapping interactions, and (b) by cross-linking of subunits at the trimer-trimer interface, which stabilizes the structural integrity of the NC1 hexamer and protects against binding of autoantibodies. The sequestrated epitopes and cross-linked subunits represent a novel structural mechanism for conferring immune privilege at the level of quaternary structure. Perturbation of the quaternary structure may be a key factor in the etiology of Goodpasture disease.
Assessing attention deficit hyperactivity disorder via quantitative electroencephalography: An initial validation study. (1999)

Spectral analysis of the electrophysiological output at a single, midline prefrontal location (the vertex) was conducted in 482 individuals, ages 6-30 years old, to test the hypothesis that cortical slowing in the prefrontal region can serve as a basis for differentiating patients with attention deficit hyperactivity disorder (ADHD) from nonclinical control groups. Participants were classified into 3 groups (ADHD, inattentive; ADHD, combined; and control) on the basis of the results of a standardized clinical interview, behavioral rating scales, and a continuous performance test. Quantitative electroencephalographic (QEEG) findings indicated significant maturational effects in cortical arousal in the prefrontal cortex as well as evidence of cortical slowing in both ADHD groups, regardless of age or sex. Sensitivity of the QEEG-derived attentional index was 86%; specificity was 98%. These findings constituted a positive initial test of a QEEG-based neurometric test for use in the assessment of ADHD.
Selectivity and resistance to poisons of commercial hydrogen sensors (2015)

The resistance of several models of catalytic, workfunction-based metal-oxide-semiconductor and electrochemical hydrogen sensors to chemical contaminants such as SO2, H2S, NO2 and hexamethyldisiloxane (HMDS) has been investigated. These sensor platforms are among the most commonly used for the detection of hydrogen. The evaluation protocols were based on the methods recommended in the ISO 26142:2010 standard. Permanent alteration of the sensor response to the target analyte (H2) following exposure to potential poisons at the concentrations specified in ISO 26142 was rarely observed. Although a shift in the baseline response was often observed during exposure to the potential poisons, only in a few cases did this shift persist after removal of the contaminants. Overall, the resistance of the sensors to poisoning was good. However, a change in sensitivity to hydrogen was observed in the electrochemical platform after exposure to NO2 and for a catalytic sensor during exposure to SO2. The siloxane resistance test prescribed in ISO 26142, based on exposure to 10 ppm HMDS, may possibly not properly reflect sensor robustness to siloxanes. Further evaluation of the resistance of sensors to other Si-based contaminants and other exposure profiles (e.g., concentration, exposure times) is needed.
Pharmacokinetics and bioavailability of percutaneous ibuprofen. (1995)

The absorption, pharmacokinetics and bioavailability of ibuprofen (CAS 15687-27-1) were investigated for an ibuprofen gel preparation (ibugel) for percutaneous application, and compared to a standard oral ibuprofen tablet preparation. The monocentric, randomised, 2-way cross-over study with 7-day wash-out period was performed on 18 healthy female volunteers with an average age of 26.3 +/- 4.8 years (range: 20-38 years), average weight 60.4 +/- 7.6 kg, and average height 164.7 +/- 5.9 cm. Blood samples were taken from the volunteers before administration of the tablet or gel, and periodically during 24 h after administration. The ibuprofen content in these samples was determined using a validated HPLC method. Main pharmacokinetic parameters derived from individual plasma concentration-time courses included: Cmax, tmax, AUCO-->24, AUCO-->infinity, MRTO-->infinity, t1/2 and Frel. For percutaneous application of 500 mg ibuprofen (10 g 5% gel on the back, area of 20 x 20 cm) with occlusion for 2 h, a Cmax of 7.1 +/- 4.4 micrograms/ml (95% confidence interval (CI): 5.0-9.1) was obtained at 2.4 +/- 0.8 h (95% CI: 2.0-2.8). For oral administration of 400 mg, Cmax was 36.7 +/- 7.5 micrograms/ml (95% CI: 33.2-40.1) at 1.1 +/- 0.8 h (95% CI: 0.7-1.5). The (dose-corrected) relative bioavailability of the topical ibuprofen was found to be 22 +/- 12% (95% CI: 14-30%) of that after oral administration. The plasma elimination half-life was 2.5 +/- 1.4 h (95% CI: 1.9-3.2) for topical administration, and 1.8 +/- 0.5 h (95% CI: 1.6-2.1) after oral administration (not significant, p > 0.05). The surprisingly high levels of ibuprofen found in the plasma after percutaneous application are still below the threshold where systemic side effects might be expected (10 micrograms/ml). The high peak plasma concentration and relative bioavailability of percutaneous ibuprofen are likely due to the galenical formation of the gel preparation, which contains isopropyl alcohol and propylene glycol as co-solvents and is adjusted to pH 5, and to the use of occlusion.
Real-Time PCR Assay Targets the 23S-5S Spacer for Direct Detection and Differentiation of <i>Legionella</i> spp. and <i>Legionella pneumophila</i> (2003)

ABSTRACT A real-time PCR for the ABI Prism 7000 system targeting the 23S-5S spacer of Legionella spp. was developed. Simultaneous detection and differentiation of Legionella spp. and Legionella pneumophila within 90 min and without post-PCR melting-curve analysis was achieved using two TaqMan probes. In sputum samples from 23 controls and 17 patients with legionellosis, defined by positive culture, urinary antigen testing, or seroconversion, 94% sensitivity and 100% specificity were observed.
Sampling rate conversion systems using a new generalized form of the discrete Fourier transform (1995)

A recursive factorization of the polynomial 1-z/sup N/ leads to an efficient algorithm for the computation of the discrete Fourier transform (DFT) and the cyclic convolution. The paper introduces a new recursive polynomial factorization of the polynomial when N is highly composite. The factorization is used to define a generalized form of the DFT and to derive an efficient algorithm for the computation. The generalized form of the DFT is shown to be closely related to the polyphase decomposition of a sequence, and is applied for the design of sampling rate conversion systems, it gives not only alternative derivations for the polyphase interpolation and the polyphase decimation by an integer factor, but also a new sampling rate conversion system by a rational factor, which is more efficient than the known rational polyphase implementation when the filter length is large.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Defining schizophrenia: Operational criteria (1993)

The use of operational criteria to define the syndrome of schizophrenia has dramatically improved the reliability of diagnosis. However, none of the many different operational definitions for schizophrenia has proven superior validity and it is therefore suggested that a polydiagnostic appproach is adopted until the aetiology of schizophrenia is determined and consequently most valid definition known. The operational criteria checklist for psychotic illness (OPCRIT) facilitates such a polydiagnostic approach and the paper goes on to describe the use of OPCRIT on various data sets of psychotic subjects to explore three further questions. The first of these considers the relationship between different definitions. The second question relates to which other psychotic disorders and personality types might be included within a broader schizophrenia spectrum and the third question considered relates to the different sub-types of disorder found in schizophrenia and whether these are aetiologically separate or merely quantitative differences.