gebhart/patrepeval huggingface dataset:
In Vivo Complex Formation of Oxidized α 1 -Antitrypsin and LDL (2001)

An inactivated form of alpha(1)-antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T-oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehyde- or 4-hydroxy-2-nonenal-modified AT, but neither normal active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) was isolated from human plasma LDL by affinity column with an OxAT-4 antibody-coated carrier. AT-LDL was degraded 4 times more effectively by mouse peritoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesions of the coronary artery, but distribution of it was not completely identical to that of macrophages. In situ hybridization revealed AT expression by macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macrophages, then attached to LDL in the intimal layer of the arterial wall. Although AT-LDL that escapes into the blood stream can be cleared by hepatocytes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherogenesis.
The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins (1991)

Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures.
Drug Therapy for Idiopathic Male Infertility: Rationale Versus Evidence (2006)

Drug therapy for idiopathic male infertility is at best empirical. There is no clear benefit of using any medication in these patients. Moreover, androgens should not be used because they may actually suppress spermatogenesis.
Improved Alignment Models for Statistical Machine Translation (1999)

In this paper, we describe improved alignment models for statistical machine translation. The statistical translation approach uses two types of information: a translation model and a language model. The language model used is a bigram or general m-gram model. The translation model is decomposed into a lexical and an alignment model. We describe two different approaches for statistical translation and present experimental results. The first approach is based on dependencies between single words, the second approach explicitly takes shallow phrase structures into account, using two different alignment levels: a phrase level alignment between phrases and a word level alignment between single words. We present results using the Verbmobil task (German-English, 6000word vocabulary) which is a limited-domain spoken-language task. The experimental tests were performed on both the text transcription and the speech recognizer output. 1 Statistical Machine Translation The goal of machine trans...
CCN2 (CTGF) Gene Polymorphism Is a Novel Prognostic Risk Factor for Cardiovascular Outcomes in Hemodialysis Patients (2010)

We demonstrate for the first time that CCN2 gene polymorphism is a prognostic risk factor for CV morbidity and mortality in HD patients. These data may have important implications for better understanding the link between accelerated atherosclerosis and increased mortality in HD population.
Oxygen Radicals and the Disease Process (1998)

Free radicals and human disease - trick or treat? oxygen free radical involvement in cerebral ischemia/reperfusion injury oxygen radicals and ageing free radicals in rheumatoid arthritis - redox regulation of gene transcription and proteolytic tissue destruction implication of reactive oxygen metabolites in inflammatory bowel disease interleukin-1, neutrophils and oxidants in acute lung injury free radicals and critical care medicine human immunodeficiency virus-1 tat protein and oxidant/antioxidant balance role of reactive oxygen species in multistage carcinogenesis.
Dynamic register promotion of stack variables (2011)

Dynamic Binary Translation (DBT) has been widely used in various applications. Although new architectures and micro-architectures often create performance opportunities for programmers and compilers, such performance opportunities may not be exploited by legacy executables. For example, the additional general-purpose and XMM registers in the Intel64 architecture do not benefit the IA-32 binaries. In this paper, we designed and developed a DBT system to dynamically promote stack variables in the source binaries to the additional registers of the target architecture. One of the most challenging problems is how to deal with the possible but rare memory aliases between promoted stack variables and other implicit memory references. We devised a runtime alias detection approach based on the page protection mechanism in Linux and a novel stack switching method to catch memory aliases at run-time. This approach is much less expensive than traditional approaches like inserting address checking instructions. On an Intel64 platform, our DBT system with speculative stack variable promotion has sped up several SPEC CPU2006 benchmarks in IA-32 code, with the largest performance gain over 45%.
Direct detection of hepatitis C virus (HCV) RNA from whole blood, and comparison with HCV RNA in plasma and peripheral blood mononuclear cells (1995)

Hepatitis C virus (HCV) requires reverse transcriptase-polymerase chain reaction (RT-PCR) or branched DNA signal amplification assays to be detected in patient samples. Although conventional methods of RNA isolation are employed for samples of serum, plasma, and peripheral blood mononuclear cells (PBMCs), whole blood is generally considered an unsuitable source of RNA because of abundant RNases and polymerase inhibitors. Using a cationic surfactant, Catrimox-14, we adapted a procedure for RNA isolation from whole blood, plasma, and PBMCs that yields RNA template suitable for HCV RT-PCR. RNA isolation required less than 2 hr, and HCV sequences were easily detected in sample volumes of 50 microliters whole blood or plasma, and in less than 1 x 10(4) PBMC. Following the addition of blood to Catrimox, HCV RNA was stable in the mixture when incubated for at least 7 days at room temperature prior to RNA extraction. Comparison of whole blood HCV RNA and plasma HCV RNA from individuals with chronic hepatitis suggests that HDV RNA can be more reliably detected in whole blood. Three of 15 HCV antibody positive patients (20%) had HCV RNA present in whole blood but simultaneously obtained plasma samples were negative. Two of the HCV antibody negative individuals with chronic hepatitis contained HCV RNA in whole blood, yet one of these patient's plasma was negative for viral RNA. The Catrimox-14 method of RNA purification is useful for detecting HCV RNA in whole blood and blood subfractions, and provides a practical method of measuring plasma and PBMC HCV RNA from clinical specimens.
Measurable Residual Disease at Induction Redefines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk Without NPM1 Mutations (2018)

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD-. Patients without high-risk factors, including Flt3 internal tandem duplication wt/- NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD-; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD-, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD- (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.
Partitioned register file for TTAs (1995)

A practical implementation of high performance instruction level parallel architectures is constrained by the difficulty to build a large monolithic multi-ported register file (RF). A solution is to partition the RF into smaller RFs while keeping the total number of registers and ports equal. This paper applies RF partitioning to transport triggered architectures (TTAs); these architectures are of the VLIW type. One may expect that partitioning increases the number of executed cycles because it constrains the number of ports per RF. It is shown that these performance losses are small; e.g. partitioning an RF with 24 registers and four read and four write ports into four RFs with 6 registers and one read and one write port gives a performance loss of only 5.8%. Partitioned RFs consume less area than monolithic RFs with the same number of ports and registers. Experiments show that, if the area saved by partitioning is spent on extra registers, partitioning does, on average, not reduce the performance; it may even result in a small performance gain.
Characterization and Expression Analysis of Mesenchymal Stem Cells from Human Bone Marrow and Adipose Tissue (2004)

Human mesenchymal stem cells (MSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. This differentiation potential makes MSC excellent candidates for cell-based tissue engineering. In this study, we have examined phenotypes and gene expression profile of the human adipose tissue-derived stromal cells (ATSC) in the undifferentiated states, and compared with that of bone marrow stromal cells (BMSC). ATSC were enzymatically released from adipose tissues from adult human donors and were expanded in monolayer with serial passages at confluence. BMSC were harvested from the metaphysis of adult human femur. Flowcytometric analysis showed that ATSC have a marker expression that is similar to that of BMSC. ATSC expressed CD29, CD44, CD90, CD105 and were absent for HLA-DR and c-kit expression. Under appropriate culture conditions, MSC were induced to differentiate to the osteoblast, adipocyte, and chondrogenic lineages. ATSC were superior to BMSC in respect to maintenance of proliferating ability, and microarray analysis of gene expression revealed differentially expressed genes between ATSC and BMSC. The proliferating ability and differentiation potential of ATSC were variable according to the culture condition. The similarities of the phenotypes and the gene expression profiles between ATSC and BMSC could have broad implications for human tissue engineering.
The NO/cGMP pathway inhibits Rap1 activation in human platelets via cGMP-dependent protein kinase I (2005)

The NO/cGMP signalling pathway strongly inhibits agonist-induced platelet aggregation. However, the molecular mechanisms involved are not completely defined. We have studied NO/cGMP effects on the activity of Rap 1, an abundant guanine-nucleotidebinding protein in platelets. Rap 1-GTP levels were reduced by NO-donors and activators of NO-sensitive soluble guanylyl cyclase. Four lines of evidence suggest that NO/cGMP effects are mediated by cGMP-dependent protein kinase (cGKI): (i) Rap 1 inhibition correlated with cGKI activity as measured by the phosphorylation state of VASP, an established substrate of cGKI, (ii) 8-pCPT-cGMP, a membrane permeable cGMP-analog and activator of cGKI, completely blocked Rap1 activation, (iii) Rp-8pCPT-cGMPS, a cGKI inhibitor, reversed NO effects and (iv) expression of cGKI in cGKI-deficient megakaryocytes inhibited Rap1 activation. NO/cGMP/cGKI effects were independent of the type of stimulus used for Rap1 activation. Thrombin-,ADP- and collagen-induced formation of Rap 1-GTP in platelets as well as turbulence-induced Rap 1 activation in megakaryocytes were inhibited. Furthermore, cGKI inhibited ADP-induced Rap 1 activation induced by the Galpha(i)-coupled P2Y12 receptor alone, i.e. independently of effects on Ca2+-signalling. From these studies we conclude that NO/cGMP inhibit Rap 1 activation in human platelets and that this effect is mediated by cGKI. Since Rap1 controls the function of integrin alpha(IIb)beta3, we propose that Rap 1 inhibition might play a central role in the anti-aggregatory actions of NO/cGMP.
HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors (2010)

Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV-) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV - participants from the pre-CART era (1988-1995; N = 857) and CART era (2000-2007; N = 937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.
Phenazine Compounds in Fluorescent Pseudomonas Spp. Biosynthesis and Regulation (2006)

The phenazines include upward of 50 pigmented, heterocyclic nitrogen-containing secondary metabolites synthesized by some strains of fluorescent Pseudomonas spp. and a few other bacterial genera. The antibiotic properties of these compounds have been known for over 150 years, but advances within the past two decades have provided significant new insights into the genetics, biochemistry, and regulation of phenazine synthesis, as well as the mode of action and functional roles of these compounds in the environment. This new knowledge reveals conservation of biosynthetic enzymes across genera but raises questions about conserved biosynthetic mechanisms, and sets the stage for improving the performance of phenazine producers used as biological control agents for soilborne plant pathogens.
The Elusive Role of the Potential Factor X Cation-binding Exosite-1 in Substrate and Inhibitor Interactions (2004)

A number of studies suggest that blood-clotting factor X (FX) uses secondary site(s) to interact (as a substrate) with its activators. Numerous pieces of evidence also imply that, within prothrombinase (as an enzyme), activated FX (FXa) uses exosite(s) for cofactor Va and/or prothrombin recognition. Similarly, FXa exosite(s) seem to govern interaction with inhibitors. An obvious difference between FXa and thrombin resides within a region called exosite-1: positively charged in thrombin and clearly of opposite polarity in FXa. To investigate the role of this potential cation-binding exosite, we prepared a series of mutants within loops 34-40 and 70-80 of FX. Overall, the mutations induced relatively subtle, non-synergistic modulation. The potential exosite was dispensable for FX activation and is unlikely to constitute a critical region for factor Va binding, albeit it is clearly important for prothrombin activation. Our data also implicate loop 34-40 of FXa in the interaction with the tissue factor pathway inhibitor, in prevention of plasminogen activator inhibitor-1 binding, and in tempering inhibition by heparin-activated antithrombin. Compared with FX, mutants with reduced electrostatic potential potentiated thrombin production in FX-depleted plasma, whereas mutants with inverted electrostatic potential impeded clotting. Despite the definite consequences observed, disruption of the potential cation-binding exosite of FX had rather weak effects, far from what would be expected if this region was as crucial as in thrombin.
The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. (1981)

Disseminated intravascular coagulation (DIC) is a common occurrence during clinical sepsis and can be induced in the experimental host by LPS. Fibrin deposition in the hepatic microcirculation has been observed within 30 min of i.v. injection of LPS. Because mononuclear phagocytes have been shown to produce a PCA after exposure to LPS, we have examined the ability of a homogeneous population of explanted hepatic macrophages to express PCA. Addition of as little as 10 ng/ml of LPS stimulated a 15- to 20-fold increase in PCA over control culture levels within 7 1/2 hr post-treatment. The PCA was found to be membrane-associated, with approximately 90 to 95% of the total PCA present in the cellular lysates, and more than 85% was inhibited by pretreatment of the cells with the diazonium salt of sulfanilic acid, an inhibitor of ecto-enzymes. In contrast to tissue thromboplastin produced by other M phi populations, the H-M phi PCA was found to be markedly sensitive both to heat inactivation at 56 degrees C and to inhibition by 1 mM DFP. Additionally, assays involving both a 1-stage coagulation test as well as an enzyme assay with a Factor Xa-specific substrate (using normal and deficient human plasmas) demonstrated that the H-M phi PCA appears to activate Factor X directly. Unlike tissue thromboplastin, the H-M phi PCA is non-dependent of Factor VII activation. These studies: 1) demonstrate the LPS induces a unique PCA in the H-M phi, and 2) support a role for the H-M phi in the initiation of DIC in endotoxemic shock.
The Role of Implant Surface Characteristics in the Healing of Bone (1996)

The surface of an implant determines its ultimate ability to integrate into the surrounding tissue. The composite effect of surface energy, composition, roughness, and topography plays a major role during the initial phases of the biological response to the implant, such as protein adsorption and cellular adherence, as well as during the later and more chronic phases of the response. For bone, the successful incorporation (and hence rigid fixation) of an alloplastic material within the surrounding bony bed is called osteointegration. The exact surface characteristics necessary for optimal osteointegration, however, remain to be elucidated. This review will focus on how surface characteristics, such as composition and roughness, affect cellular response to an implant material. Data from two different culture systems suggest that these characteristics play a significant role in the recruitment and maturation of cells along relevant differentiation pathways. In the case of osteointegration, if the implant surface is inappropriate or less than optimal, cells will be unable to produce the appropriate complement of autocrine and paracrine factors required for adequate stimulation of osteogenesis at the implant site. In contrast, if the surface is appropriate, cells at the implant surface will stimulate interactions between cells at the surface and those in distal tissues. This, in turn, will initiate a timely sequence of events which include cell proliferation, differentiation, matrix synthesis, and local factor production, thereby resulting in the successful incorporation of the implant into the surrounding bony tissue.