gebhart/patrepeval huggingface dataset:
Human Ind1, an Iron-Sulfur Cluster Assembly Factor for Respiratory Complex I (2009)

Respiratory complex I (NADH:ubiquinone oxidoreductase) is a large mitochondrial inner membrane enzyme consisting of 45 subunits and 8 iron-sulfur (Fe/S) clusters. While complex I dysfunction is the most common reason for mitochondrial diseases, the assembly of complex I and its Fe/S cofactors remains elusive. Here, we identify the human mitochondrial P-loop NTPase, designated huInd1, that is critically required for the assembly of complex I. huInd1 can bind an Fe/S cluster via a conserved CXXC motif in a labile fashion. Knockdown of huInd1 in HeLa cells by RNA interference technology led to strong decreases in complex I protein and activity levels, remodeling of respiratory supercomplexes, and alteration of mitochondrial morphology. In addition, huInd1 depletion resulted in massive decreases in several subunits (NDUFS1, NDUFV1, NDUFS3, and NDUFA13) of the peripheral arm of complex I, with the concomitant appearance of a 450-kDa subcomplex representing part of the membrane arm. By a novel radiolabeling technique, the amount of iron associated with complex I was also shown to reflect the dependence of this enzyme on huInd1 for assembly. Together, these data identify huInd1 as a new assembly factor for human respiratory complex I with a possible role in the delivery of one or more Fe/S clusters to complex I subunits.
Application of Vulnerability Discovery Models to Major Operating Systems (2008)

A number of security vulnerabilities have been reported in the Windows, and Linux operating systems. Both the developers, and users of operating systems have to utilize significant resources to evaluate, and mitigate the risk posed by these vulnerabilities. Vulnerabilities are discovered throughout the life of a software system by both the developers, and external testers. Vulnerability discovery models are needed that describe the vulnerability discovery process for determining readiness for release, future resource allocation for patch development, and evaluating the risk of vulnerability exploitation. Here, we analytically describe six models that have been recently proposed, and evaluate those using actual data for four major operating systems. The applicability of the proposed models, and the significance of the parameters involved are examined. The results show that some of the models tend to capture the discovery process better than others.
Incidence and Mortality of Acute Renal Failure in Medicare Beneficiaries, 1992 to 2001 (2006)

This study's objective was to determine the incidence and mortality of acute renal failure (ARF) in Medicare beneficiaries. Data were from hospitalized Medicare beneficiaries (5,403,015 discharges) between 1992 and 2001 from the 5% sample of Medicare claims. For 1992 to 2001, the overall incidence rate of ARF was 23.8 cases per 1000 discharges, with rates increasing by approximately 11% per year. Older age, male gender, and black race were strongly associated (P < 0.0001) with ARF. The overall in-hospital death rate was 4.6% in discharges without ARF, 15.2% in discharges with ARF coded as the principal diagnosis, and 32.6% in discharges with ARF as a secondary diagnosis. In-hospital death rates were 32.9% in discharges with ARF that required renal dialysis and 27.5% in those with ARF that did not require dialysis. Death within 90 d after hospital admission was 13.1% in discharges without ARF, 34.5% in discharges with ARF coded as the principal diagnosis, and 48.6% in discharges with ARF as a secondary diagnosis. Discharges with ARF were more (P < 0.0001) likely to have intensive care and other acute organ dysfunction than those without ARF. For discharges both with and without ARF, rates for death within 90 d after hospital admission showed a declining trend. In conclusion, the incidence rate of ARF in Medicare beneficiaries has been increasing. Those of older age, male gender, and black race are more likely to have ARF. These data show ARF to be a major contributor to morbidity and mortality in hospitalized patients.
Performance evaluation of a reconfiguration-algorithm for memory arrays containing clustered faults (1996)

Reconfiguration of memory arrays using spare rows and columns is useful for yield-enhancement of memories. This paper presents a reconfiguration algorithm (QRCF) for memories that contain clustered faults. QRCF operates in a branch and bound fashion similar to known optimal algorithms that require exponential time. However, QRCF repairs faults in clusters rather than individually. Since many faults are repaired simultaneously, the execution-time of QRCF does not become prohibitive even for large memories containing many faults. The performance of QRCF is evaluated under a probabilistic model for clustered faults in a memory array. For a special case of the fault model, QRCF solves the reconfiguration problem exactly in polynomial time. In the general case, QRCF produces an optimal solution with high probability. The algorithm is also evaluated through simulation. The performance and execution-time of QRCF on arrays containing clustered faults are compared with other approximation algorithms and with an optimal algorithm. The simulation results show that QRCF outperforms previous approximation algorithms by a wide margin and performs nearly as well as the optimal algorithm with an execution-time that is orders of magnitude less.
Brain Anatomical Network and Intelligence (2009)

Intuitively, higher intelligence might be assumed to correspond to more efficient information transfer in the brain, but no direct evidence has been reported from the perspective of brain networks. In this study, we performed extensive analyses to test the hypothesis that individual differences in intelligence are associated with brain structural organization, and in particular that higher scores on intelligence tests are related to greater global efficiency of the brain anatomical network. We constructed binary and weighted brain anatomical networks in each of 79 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Based on their IQ test scores, all subjects were divided into general and high intelligence groups and significantly higher global efficiencies were found in the networks of the latter group. Moreover, we showed significant correlations between IQ scores and network properties across all subjects while controlling for age and gender. Specifically, higher intelligence scores corresponded to a shorter characteristic path length and a higher global efficiency of the networks, indicating a more efficient parallel information transfer in the brain. The results were consistently observed not only in the binary but also in the weighted networks, which together provide convergent evidence for our hypothesis. Our findings suggest that the efficiency of brain structural organization may be an important biological basis for intelligence.
Cytochrome P450 CYP1B1 activity in renal cell carcinoma (2004)

Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has a poor prognosis due to its late presentation and resistance to current anticancer drugs. One mechanism of drug resistance, which is potentially amenable to therapeutic intervention, is based on studies in our laboratory. CYP1B1 is a cytochrome P450 enzyme overexpressed in a variety of malignant tumours. Our studies are now elucidating a functional role for CYP1B1 in drug resistance. Cytochrome P450 reductase (P450R) is required for optimal metabolic activity of CYP1B1. Both CYP1B1 and P450R can catalyse the biotransformation of anticancer drugs at the site of the tumour. In this investigation, we determined the expression of CYP1B1 and P450R in samples of normal kidney and RCC (11 paired normal and tumour and a further 15 tumour samples). The O-deethylation of ethoxyresorufin to resorufin was used to measure CYP1B1 activity in RCC. Cytochrome P450 reductase activity was determined by following the reduction of cytochrome c at 550 nm. The key finding of this study was the presence of active CYP1B1 in 70% of RCC. Coincubation with the CYP1B1 inhibitor alpha-naphthoflavone (10 nM) inhibited this activity. No corresponding CYP1B1 activity was detected in any of the normal tissue examined (n=11). Measurable levels of active P450R were determined in all normal (n=11) and tumour samples (n=26). The presence of detectable CYP1B1, which is capable of metabolising anticancer drugs in tumour cells, highlights a novel target for therapeutic intervention.
<title>Subsurface imaging using the spectral polarization difference technique and NIR illumination</title> (1999)

A subsurface imaging system is utilized to test the ability of the spectral polarization difference imaging technique for deep subsurface imaging in tissues. The illumination of the system is derived from compact class III lasers in the red and NIR spectral region and, alternatively, from a white light source and selection of the appropriate illumination wavelength using band-pass optical filters. The experimental results demonstrate detection and imaging of a high-scattering object located up to 1.5 cm underneath the surface of a host chicken tissue.
Discovering the genetics underlying foetal haemoglobin production in adults (2009)

Sickle cell disease (SCD) and beta thalassaemia, caused by lesions that affect the HBB (beta globin gene), form the most common human genetic disorders world-wide, and represent a major public health problem. Inter-individual variation in foetal haemoglobin (HbF) expression is a known and heritable disease modifier; high HbF levels are correlated with reduced morbidity and mortality in both diseases. This review traces our progress in the understanding of the persistence of HbF in adults as a quantitative trait and the genetic approaches used in teasing out the loci contributing to its variability in normal populations and in patients with haemoglobinopathies. Three major loci -- Xmn1-HBG2 single nucleotide polymorphism, HBS1L-MYB intergenic region on chromosome 6q, and BCL11A -- contribute 20-50% of the trait variance in patients with sickle cell anaemia and healthy European Caucasians. It is likely that the remaining trait variance is due to numerous other loci, many contributing modest effects. Identification of the three major loci has not yet been translated into new therapeutic approaches for HbF reactivation but an immediate application would be an improved prediction of one's ability to produce HbF, which in turn, may improve prediction of disease severity.
Prostacyclin, Atherothrombosis, and Cardiovascular Disease (2007)

Prostacyclin (PGI(2)) is a major product of COX-2 catalyzed metabolism of arachidonic acid in the endothelium. Recent studies have demonstrated that PGI(2) protects against atherothrombosis. The prostacyclin receptor knockout mice exhibit increased atherosclerosis, enhanced thrombosis, and enhanced proliferative response to carotid vascular injury with increased intima to media ratios [1-3]. Moreover, the recent withdrawal of rofecoxib (Vioxx) due to increased cardiovascular events further supports the critical role of prostacyclin in inhibiting atherothrombosis in humans. Such studies have paralleled intense chemical biology studies to develop more stable prostacyclin analogues. Indeed a number of these analogues are currently being successfully used for the treatment of pulmonary hypertension. In this review we will summarize the current literature on some principles of prostacyclin analogue development, our current understanding of the receptor, and recent developments which implicate prostacyclin in atherothrombotic protection. More than 68 million Americans suffer from cardiovascular disease, which causes more deaths, disability and economic loss than any other group of diseases. Further clinical investigations of orally stable prostacyclin analogues for treatment of cardiovascular diseases other than pulmonary hypertension may now be warranted.
ACTIVATION OF IMMEDIATE EARLY GENE, c-fos, AND c-jun IN THE RAT SMALL INTESTINE AFTER ISCHEMIA/REPERFUSION1 (2000)

These results suggest that overexpression of c-fos and c-jun after I/R in the small intestine correlates with programmed cell death and subsequent cellular regeneration.
Inhibition of human immunodeficiency virus type 1 multiplication by antisense and sense RNA expression (1991)

Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4+ lymphocytes and macrophages and causes AIDS in humans. Retroviral vectors allowing neomycin phosphotransferase (npt) gene expression were engineered to express 5' sequences of HIV-1 RNA in the antisense or sense orientation and used to transform the human CD4+ lymphocyte-derived MT4 cell line. Cells expressing antisense or sense RNA to the HIV-1 tat mRNA leader sequence, as part of the 3' untranslated region of the npt mRNA, remained sensitive to HIV-1 infection. In contrast, resistance to HIV-1 infection was observed in cells expressing antisense RNA to the HIV-1 primer-binding site or to the region 5' to the primer-binding site as part of the 3' region of the npt mRNA. Cells expressing the tat mRNA leader sequence in the sense orientation as a precise replacement of the 5' untranslated region of npt mRNA were also resistant to HIV-1. These results indicate that sense and antisense approaches can be used to interfere with HIV-1 multiplication.
Hydrogen peroxide and ferulic acid-mediated oxidative cross-linking of casein catalyzed by horseradish peroxidase and the impacts on emulsifying property and microstructure of acidified gel (2009)

Horseradish peroxidase (HRP, EC 1.11.1.7) was used in this study to catalyze oxidative cross-linking of casein in the presence of hydrogen peroxide and cross-linker ferulic acid. Cross-linking of casein was demonstrated by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and ultraviolet absorbance analysis. Oxidative cross-linked casein mediated by hydrogen peroxide and ferulic acid was prepared at casein concentration of 5% (w/ w), HRP addition of 3 mkat·g-1 proteins, ferulic acid addition of 6 mmol·l-1, 3% (w/w) H2O2 addition of 1 ml, reaction temperature 37°C and reaction time 3 h. Analysis results showed that the emulsifying activity index and emulsifying stability index of cross-linked casein prepared were enhanced compared to that of untreated casein totally. Microstructure of chemical acid-induced gel of cross-linked casein was observed under scanning electron microscopy and appeared to be more compact and uniform than that of casein. Hydrogen peroxide and ferulic acid-mediated oxidative cross-linking of casein catalyzed by horseradish peroxidase might have a beneficial to the emulsifying property or gelation of casein.
The Wt1+/R394W Mouse Displays Glomerulosclerosis and Early-Onset Renal Failure Characteristic of Human Denys-Drash Syndrome (2004)

Renal failure is a frequent and costly complication of many chronic diseases, including diabetes and hypertension. One common feature of renal failure is glomerulosclerosis, the pathobiology of which is unclear. To help elucidate this, we generated a mouse strain carrying the missense mutation Wt1 R394W, which predisposes humans to glomerulosclerosis and early-onset renal failure (Denys-Drash syndrome [DDS]). Kidney development was normal in Wt1(+/R394W) heterozygotes. However, by 4 months of age 100% of male heterozygotes displayed proteinuria and glomerulosclerosis characteristic of DDS patients. This phenotype was observed in an MF1 background but not in a mixed B6/129 background, suggestive of the action of a strain-specific modifying gene(s). WT1 encodes a nuclear transcription factor, and the R394W mutation is known to impair this function. Therefore, to investigate the mechanism of Wt1 R394W-induced renal failure, the expression of genes whose deletion leads to glomerulosclerosis (NPHS1, NPHS2, and CD2AP) was quantitated. In mutant kidneys, NPHS1 and NPHS2 were only moderately downregulated (25 to 30%) at birth but not at 2 or 4 months. Expression of CD2AP was not changed at birth but was significantly upregulated at 2 and 4 months. Podocalyxin was downregulated by 20% in newborn kidneys but not in kidneys at later ages. Two other genes implicated in glomerulosclerosis, TGFB1 and IGF1, were upregulated at 2 months and at 2 and 4 months, respectively. It is not clear whether the significant alterations in gene expression are a cause or a consequence of the disease process. However, the data do suggest that Wt1 R394W-induced glomerulosclerosis may be independent of downregulation of the genes for NPHS1, NPHS2, CD2AP, and podocalyxin and may involve other genes yet to be implicated in renal failure. The Wt1(R394W) mouse recapitulates the pathology and disease progression observed in patients carrying the same mutation, and the mutation is completely penetrant in male animals. Thus, it will be a powerful and biologically relevant model for investigating the pathobiology of the earliest events in glomerulosclerosis.
Experimental Implementation of Fast Quantum Searching (1998)

Using nuclear magnetic resonance techniques with a solution of chloroform molecules we implement Grover's search algorithm for a system with four states. By performing a tomographic reconstruction of the density matrix during the computation good agreement is seen between theory and experiment. This provides the first complete experimental demonstration of loading an initial state into a quantum computer, performing a computation requiring fewer steps than on a classical computer, and then reading out the final state.
Reduced Final Height Outcome in Congenital Adrenal Hyperplasia under Prednisone Treatment: Deceleration of Growth Velocity during Puberty (2007)

Patients with CAH are able to achieve adequate FH with conventional therapy. Total pubertal growth is significantly decreased, and treatment with prednisone results in decreased FH. In addition to biochemical analysis, treatment should be adjusted to normal growth velocity, especially during puberty.
STAT3 Signaling Is Required for Optimal Regression of Large Established Tumors in Mice Treated with Anti-OX40 and TGFβ Receptor Blockade (2015)

In preclinical tumor models, αOX40 therapy is often successful at treating small tumors, but is less effective once the tumors become large. For a tumor immunotherapy to be successful to cure large tumors, it will most likely require not only an agonist to boost effector T-cell function but also inhibitors of T-cell suppression. In this study, we show that combining αOX40 antibodies with an inhibitor of the TGFβ receptor (SM16) synergizes to elicit complete regression of large established MCA205 and CT26 tumors. Evaluation of tumor-infiltrating T cells showed that SM16/αOX40 dual therapy resulted in an increase in proliferating granzyme B(+) CD8 T cells, which produced higher levels of IFNγ, compared with treatment with either agent alone. We also found that the dual treatment increased pSTAT3 expression in both CD4 and CD8 T cells isolated from tumors. Because others have published that STAT3 signaling is detrimental to T-cell function within the tumor microenvironment, we explored whether deletion of STAT3 in OX40-expressing cells would affect this potent combination therapy. Surprisingly, we found that deletion of STAT3 in OX40-expressing cells decreased the efficacy of this combination therapy, showing that the full therapeutic potential of this treatment depends on STAT3 signaling, most likely in the T cells of tumor-bearing mice.
anti-DR antibodies inhibit in vitro production of human rheumatoid factor. (1990)

Anti-MHC class II antibodies have been shown to have a profound effect on the immune system and have been used successfully in the therapy of human and animal autoimmune diseases. In addition, naturally-occurring anti-DR antibodies have been observed in the sera of rheumatoid arthritis (RA) and systemic lupus erythematosus patients. Now, we demonstrate that several monoclonal anti-DR, but not anti-DQ antibodies specifically inhibit the production of rheumatoid factor (RF) in pokeweed-stimulated cultures of peripheral blood mononuclear cells from RA patients. Moreover, partially-purified anti-DR antibodies from RA sera have similar inhibitory effects on in vitro RF synthesis. These results indicate the inhibition of autoantibody production as a possible mechanism operative in immunotherapy using anti-class II antibodies. Furthermore, this data also suggests a protective, beneficial role for the endogenous anti-DR autoantibodies in RA.
Virtualization-aware access control for multitenant filesystems (2014)

In a virtualization environment that serves multiple tenants, storage consolidation at the filesystem level is desirable because it enables data sharing, administration efficiency, and performance optimizations. The scalable deployment of filesystems in such environments is challenging due to intermediate translation layers required for networked file access or identity management. First we present several security requirements in multitenant filesystems. Then we introduce the design of the Dike authorization architecture. It combines native access control with tenant namespace isolation and compatibility to object-based filesystems. We use a public cloud to experimentally evaluate a prototype implementation of Dike that we developed. At several thousand tenants, our prototype incurs limited performance overhead up to 16%, unlike an existing solution whose multitenancy overhead approaches 84% in some cases.
Topical Microbicides to Prevent HIV: Clinical Drug Development Challenges (2008)

Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which has been largely empirically based. Microbicide use occurs in a highly complex environment involving multi-level interactions, behavioral and biochemical, among host, virus, and drug, yet many details of these interactions remain unknown. Fundamental information regarding virus and drug distribution over time in sexually receptive body compartments that is necessary to design a microbicide able to outdistance and outlast the virus is largely absent. Recent efforts have been made to establish a simple conceptual framework for obtaining the knowledge that is likely to inform a more mechanistic, model-based development paradigm. These efforts have also advanced the development of numerous methodological approaches to obtain the knowledge needed to improve microbicide development.
Purification and Characterization of a Keratinolytic Serine Proteinase from Streptomyces albidoflavus (1999)

Streptomyces strain K1-02, which was identified as a strain of Streptomyces albidoflavus, secreted at least six extracellular proteases when it was cultured on feather meal-based medium. The major keratinolytic serine proteinase was purified to homogeneity by a two-step procedure. This enzyme had a molecular weight of 18,000 and was optimally active at pH values ranging from 6 to 9.5 and at temperatures ranging from 40 to 70 degrees C. Its sensitivity to protease inhibitors, its specificity on synthetic substrates, and its remarkably high level of NH2-terminal sequence homology with Streptomyces griseus protease B (SGPB) showed that the new enzyme, designated SAKase, was homologous to SGPB. We tested the activity of SAKase with soluble and fibrous substrates (elastin, keratin, and type I collagen) and found that it was very specific for keratinous substrates compared to SGPB and proteinase K.
Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits (2003)

Systemic transient depletion of monocytes and macrophages, by a single liposomal bisphosphonates injection concurrent with injury, reduces in-stent neointimal formation and arterial stenosis in hypercholesterolemic rabbits.