gebhart/patrepeval huggingface dataset:
Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis (2005)

Atorvastatin had no statistically significant effect on the composite primary end point of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with diabetes receiving hemodialysis.
Cloning of a Phosphatidic Acid-preferring Phospholipase A1 from Bovine Testis (1998)

We report the molecular cloning and expression of a phosphatidic acid-preferring phospholipase A1 from bovine testis. The open reading frame encoded an 875-amino acid protein with a calculated molecular mass of 97,576 daltons and a pI of 5.61. The sequence included a region similar to a lipase consensus sequence containing the putative active site serine and also included a potential, coiled-coil-forming region. Expression of the open reading frame in COS1 cells resulted in a 20-44-fold increase in phosphatidic acid phospholipase A1 activity over that of control cells. Mutation of the putative active site serine (amino acid 540) demonstrated that it was essential for this increase in enzyme activity. Northern blot analysis revealed at least five different messages with the highest overall message levels in mature testis, but detectable message in all tissues examined. Two possible alternately spliced regions in the open reading frame also were identified. Finally, a search of the data base identified six related proteins: a potential counterpart of the phospholipase A1 in Caenorhabditis elegans, two putative lipases in yeast, and three proteins separately encoded by the Drosophila retinal degeneration B gene and its mouse and human homologues.
Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease (1997)

We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hIgG1-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgG1-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgG1-CD4 did not synergize therapeutically with the panlymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.
The orthopoxvirus type I IFN binding protein is essential for virulence and an effective target for vaccination (2008)

Nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. Orthopoxviruses (OPVs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ECTV; an agent of mousepox), encode immune response modifiers (IRMs) that can increase virulence by decreasing the host immune response. We show that one of these IRMs, the type I interferon (IFN) binding protein (bp) of ECTV, is essential for ECTV virulence and is a natural target of the antibody response. More strikingly, we demonstrate that immunization with recombinant type I IFN bp protects mice from lethal mousepox. Collectively, our experiments have important implications for our understanding of the role of IRMs in OPV virulence and of type I IFNs in OPV infections. Furthermore, our work provides proof of concept that effective antiviral vaccines can be made to prevent disease by targeting virulence factors as an alternative to the traditional approach that attempts to prevent infection by virus neutralization.
The up‐regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1α (2008)

While it is well established that stroke and cerebral hypoperfusion are both significant risk factors for Alzheimer's disease, the molecular link between ischemia and amyloid precursor protein processing has only been recently established. Specifically, hypoxia significantly increases beta-site APP cleaving enzyme (BACE1) gene transcription through the over-expression of hypoxia inducible factor 1alpha, resulting in increased BACE1 secretase activity and amyloid-beta production. In this study, we significantly extend these findings both in vitro, in differentiated SK-N-BE neuroblastoma cells, and in vivo, in rats subjected to cerebral ischemia, showing that hypoxia up-regulates BACE1 expression through a biphasic mechanism. The early post-hypoxic up-regulation of BACE1 depends on the production of reactive oxygen species mediated by the sudden interruption of the mitochondrial electron transport chain, while the later expression of BACE1 is caused by hypoxia inducible factor 1alpha activation. The involvement of reactive oxygen species released by mitochondria in the BACE1 up-regulation was confirmed by the complete protection exerted by complex I inhibitors such as rotenone and diphenyl-phenylen iodonium. Moreover, the oxidative stress-mediated up-regulation of BACE1 is mediated by c-jun N terminal kinase pathway as demonstrated by the protection exerted by the silencing of c-jun N-terminal kinase isoforms 1 and 2. Our study strengthens the hypothesis that oxidative stress is a basic common mechanism of amyloid-beta accumulation.
The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase (2009)

Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs. In this study, we characterized the pharmacological chaperone 1-deoxynojirimycin (DNJ) on 76 different mutant forms of GAA identified in Pompe disease. DNJ significantly increased enzyme activity and protein levels for 16 different GAA mutants in patient-derived fibroblasts and in transiently transfected COS-7 cells. Additionally, DNJ increased the processing of these GAA mutants to their mature lysosomal forms, suggesting facilitated trafficking through the secretory pathway. Immunofluorescence microscopy studies showed increased colocalization of GAA with the lysosomal marker LAMP2 after incubation with DNJ, confirming increased lysosomal trafficking. Lastly, a GAA structural model was constructed based on the related eukaryotic glucosidase maltase-glucoamylase. The mutated residues identified in responsive forms of GAA are located throughout most of the structural domains, with half of these residues located in two short regions within the catalytic domain. Taken together, these data support further evaluation of DNJ as a potential treatment for Pompe disease in patients that express responsive forms of GAA.
Designing PCR Primer for DNA Methylation Mapping (2007)

DNA methylation is an epigenetic mechanism of gene regulation, and aberrant methylation has been associated with various types of diseases, especially cancers. Detection of DNA methylation has thus become an important approach for studying gene regulation and has potential diagnostic application. Bisulfite-conversion-based PCR methods, such as bisulfite-sequencing PCR (BSP) and methylation-specific PCR (MSP), remain the most commonly used techniques for methylation detection. Primer design for this type of PCR is challenging because of the extreme DNA sequence composition after bisulfite modification and the special constraints on the primers and their location on the DNA template. To facilitate methylation detection, a primer design program called MethPrimer has been developed specifically for bisulfite-conversion-based PCR. MethPrimer accepts a DNA sequence as input, performs a digital bisulfite conversion of the input sequence, and then picks primers on the converted sequence. Results of primer selection are delivered through a Web browser in text and graphic views. This chapter discusses the process of using MethPrimer to design BSP and MSP primers.
Mutation ofwaaC, Encoding Heptosyltransferase I inCampylobacter jejuni81-176, Affects the Structure of both Lipooligosaccharide and Capsular Carbohydrate (2006)

Campylobacter jejuni 81-176 lipooligosaccharide (LOS) is composed of two covalently linked domains: lipid A, a hydrophobic anchor, and a nonrepeating core oligosaccharide, consisting of an inner and outer core region. We report the isolation and characterization of the deepest rough C. jejuni 81-176 mutant by insertional mutagenesis into the waaC gene, encoding heptosyltransferase I that catalyzes the transfer of the first L-glycero-D-manno-heptose residue to 3-deoxy-D-manno-octulosonic residue (Kdo)-lipid A. Tricine gel electrophoresis, followed by silver staining, showed that site-specific mutation in the waaC gene resulted in the expression of a severely truncated LOS compared to wild-type strain 81-176. Gas-liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy showed that the waaC LOS species lacked all sugars distal to Kdo-lipid A. Parallel structural studies of the capsular polysaccharides of the wild-type strain 81-176 and waaC mutant revealed loss of the 3-O-methyl group in the waaC mutant. Complementation of the C. jejuni mutant by insertion of the wild-type C. jejuni waaC gene into a chromosomal locus resulted in LOS and capsular structures identical to those expressed in the parent strain. We also report here the presence of O-methyl phosphoramidate in wild-type strain 81-176 capsular polysaccharide.
Identification of Dehalobacter reductive dehalogenases that catalyse dechlorination of chloroform, 1,1,1-trichloroethane and 1,1-dichloroethane (2013)

Two novel reductive dehalogenases (RDases) that are highly similar to each other but catalyse distinct dechlorination reactions were identified from Dehalobacter-containing mixed cultures. These two RDases were partially purified from crude protein extracts of anaerobic dechlorinating enrichment cultures using blue native polyacrylamide gel electrophoresis. Gel slices were assayed for dechlorinating activity, and associated proteins were identified using liquid chromatography tandem mass spectrometry with the metagenome of the parent culture as the reference database. The two RDases identified, annotated as CfrA and DcrA, share an amino acid identity of 95.2 per cent, but use different substrates: CfrA dechlorinates chloroform (CF) and 1,1,1-trichloroethane (1,1,1-TCA), but not 1,1-dichloroethane; DcrA dechlorinates 1,1-dichloroethane, but not CF or 1,1,1-TCA. These two novel RDases share no more than 40 per cent amino acid identity to any other known or putative RDases, but both have a twin-arginine motif and two iron-sulfur binding motifs conserved in most RDases. Peptides specific to two putative membrane anchor proteins, annotated as CfrB and DcrB, were also detected in gel slices.
Probing Steric and Hydrophobic Effects on Enzyme-Substrate Interactions by Protein Engineering (1986)

Steric and hydrophobic effects on substrate specificity were probed by protein engineering of subtilisin. Subtilisin has broad peptidase specificity and contains a large hydrophobic substrate binding cleft. A conserved glycine (Gly(166)), located at the bottom of the substrate binding left, was replaced by 12 nonionic amino acids by the cassette mutagenesis method. Mutant enzymes showed large changes in specificity toward substrates of increasing size and hydrophobicity. In general, the catalytic efficiency (k(cat)/K(m)) toward small hydrophobic substrates was increased (up to 16 times) by hydrophobic substitutions at position 166 in the binding cleft. Exceeding the optimal binding volume of the cleft ( approximately 160 A(3)), by enlarging either the substrate side chain or the side chain at position 166, evoked precipitous drops in catalytic efficiency (k(cat)/K(m)) (up to 5000 times) as a result of steric hindrance.
Synthetic Integrin-binding Peptides Promote Adhesion and Proliferation of Human Periodontal Ligament Cells in vitro (1998)

Periodontal ligament (PDL) cells have been shown to express several integrins (alphav, alpha5, beta1, beta3) that use RGD (arginine-glycine-aspartic Acid)-dependent mechanisms for the recognition and binding of their ligands. The objective of this study was to evaluate the effects of certain integrin-binding cyclic and linear synthetic RGD-containing peptides on PDL cells' adhesion, proliferation, and de novo protein synthesis in vitro. Fifth passages of normal human PDL cells established from teeth extracted from patients (ages 12 to 14) for orthodontic reasons were used for all experiments. Synthetic peptides containing the EPRGDNYR sequence in two different spatial conformations (linear and cyclic) were covalently attached to bovine serum albumin (BSA). Type I collagen, EPRGDNYR-BSA conjugates, 1:1 mixtures of type I collagen and conjugates, as well as BSA (a negative control) were coated on bacteriological plastic and evaluated for their attachment-promoting activities. In addition, the effects of these substrates on cell proliferation were evaluated by [3H]thymidine incorporation by the PDL cells. For attachment and spreading, the cyclic forms of EPRGDNYR-BSA conjugate and type I collagen were most potent, followed by linear EPRGDNYR-BSA conjugate. The effects of all collagen/conjugate mixtures were equivalent to that of type I collagen except for the collagen/linear EPRGDNYR-BSA mixture, which was less potent. The cyclic EPRGDNYR-BSA conjugate was the most effective substrate to stimulate cell proliferation, and it was followed in potency by the linear peptide-BSA conjugate. Collagen alone did not stimulate [3H]thymidine incorporation above the control level. Mixtures of collagen with all of the conjugates showed stimulatory effects similar to that of the cyclic peptide-BSA conjugate. No significant differences in de novo protein synthesis were detected. These results suggest that the synthetic RGD-containing peptides attached to a carrier are potent ligands for the human PDL cells, and that they could provide a basis for the development of new strategies aimed at the regeneration of the periodontium.
Hemophilia A (1985)

To understand the molecular basis of hemophilia A and to provide heterozygote detection and prenatal diagnosis by DNA analysis, we used cloned factor VIII:C DNA fragments to study 10 affected families. In four of these families, inhibitors of factor VIII:C had developed in affected persons. In one such family a deletion of approximately 80 kb within the factor VIII:C gene was identified. Carriers of the deletion were identified through detection of an abnormal DNA fragment located at the deletion end points. In another family a single nucleotide change in the coding region of the factor VIII:C gene produced a nonsense codon leading to premature termination of factor VIII:C synthesis. Carrier detection was performed in eight female members of this four-generation family. In a third family a small change in the size of a restriction-endonuclease fragment correlated with the presence of the mutant gene, and in the other seven families the molecular defect has not yet been identified. In addition, we used two common polymorphic sites in the factor VIII:C gene to differentiate the normal from the defective gene in four of six obligate female carriers from families with patients in whom inhibitors did not develop. Carrier detection was possible in other members of these families. These data suggest that DNA analysis of the factor VIII:C gene provides an accurate method of carrier detection and, potentially, of prenatal diagnosis in at least 50 per cent of the pedigrees affected by hemophilia A.
In Situ Gas-Phase Hydrosilylation of Plasma-Synthesized Silicon Nanocrystals (2011)

Surface passivation of semiconductor nanocrystals (NCs) is critical in enabling their utilization in novel optoelectronic devices, solar cells, and biological and chemical sensors. Compared to the extensively used liquid-phase NC synthesis and passivation techniques, gas-phase routes provide the unique opportunity for in situ passivation of semiconductor NCs. Herein, we present a method for in situ gas-phase organic functionalization of plasma-synthesized, H-terminated silicon (Si) NCs. Using real-time in situ attenuated total reflection Fourier transform IR spectroscopy, we have studied the surface reactions during hydrosilylation of Si NCs at 160 °C. First, we show that, during gas-phase hydrosilylation of Si NCs using styrene (1-alkene) and acetylene (alkyne), the reaction pathways of the alkenes and alkynes chemisorbing onto surface SiH(x) (x = 1-3) species are different. Second, utilizing this difference in reactivity, we demonstrate a novel pathway to enhance the surface ligand passivation of Si NCs via in situ gas-phase hydrosilylation using the combination of a short-chain alkyne (acetylene) and a long-chain 1-alkene (styrene). The quality of surface passivation is further validated through IR and photoluminescence measurements of Si NCs exposed to air.
The approximation power of moving least-squares (1998)

A general method for near-best approximations to functionals on <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-struck upper R Superscript d"> <mml:semantics> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="double-struck">R</mml:mi> </mml:mrow> <mml:mi>d</mml:mi> </mml:msup> <mml:annotation encoding="application/x-tex">\mathbb {R}^d</mml:annotation> </mml:semantics> </mml:math> </inline-formula>, using scattered-data information is discussed. The method is actually the moving least-squares method, presented by the Backus-Gilbert approach. It is shown that the method works very well for interpolation, smoothing and derivatives’ approximations. For the interpolation problem this approach gives Mclain’s method. The method is near-best in the sense that the local error is bounded in terms of the error of a local best polynomial approximation. The interpolation approximation in <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-struck upper R Superscript d"> <mml:semantics> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="double-struck">R</mml:mi> </mml:mrow> <mml:mi>d</mml:mi> </mml:msup> <mml:annotation encoding="application/x-tex">\mathbb {R}^d</mml:annotation> </mml:semantics> </mml:math> </inline-formula> is shown to be a <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper C Superscript normal infinity"> <mml:semantics> <mml:msup> <mml:mi>C</mml:mi> <mml:mi mathvariant="normal">∞</mml:mi> </mml:msup> <mml:annotation encoding="application/x-tex">C^\infty</mml:annotation> </mml:semantics> </mml:math> </inline-formula> function, and an approximation order result is proven for quasi-uniform sets of data points.
Regiocontrolled Iodoaminocyclization Reaction of an Ambident Nucleophile Mediated by Basic Metallic Reagent (1997)

A new and general method of iodine-mediated cyclization reactions of allyl or homoallyl carbamates, ureas, and amides was found to give N-cyclized products as single regioisomers. The present reaction proceeded in good yield through regiocontrol (N-cyclization > O-cyclization) and the increase in the reactivity of an ambident nucleophile by a basic metallic reagent. The N-cyclization selectivity was remarkably affected by the additive employed. The iodoaminocyclization reaction of the homoallyl carbamates and ureas with a chiral center at the homoallylic position was found to proceed with high 1,3-cis- and 1,3-trans-selectivity, respectively.
Dopamine in Schizophrenia (1996)

The DA hypothesis of schizophrenia is one of the oldest biological hypotheses of schizophrenia with many revised versions. However, it is unlikely that any single neurotransmitter hypothesis is able to explain the biological basis of such a highly heterogenous disorder as schizophrenia in a satisfactory way. Rather, it is evident that the biological vulnerability factors and the 'acute neurophysiology' of schizophrenic symptoms involve a complex set of imbalances of aberrant connections in neuronal circuits in the brain. Dopamine is likely to be one of the transmitter substances involved, as evidenced by recent neuroimaging studies in neuroleptic-naive schizophrenia. Regardless of whether the DA hypothesis of schizophrenia is true or not, the DA hypothesis of neuroleptic drug action still has a relatively solid basis. The DA D2 receptor blockade remains the best characterized clinically useful mechanism of drug action to alleviate psychotic symptoms. The ongoing and future work on the precise role of DA in schizophrenia should focus on first-episode/admission neuroleptic-naive schizophrenic patients. Such studies represent the best opportunity of finding out specific changes in the dopaminergic pathways and relating them in a meaningful way to various dimensions of psychopathology seen in schizophrenic patients.
The physics of amorphous-silicon thin-film transistors (1989)

The basic physics underlying the operation and key performance issues of amorphous-silicon thin-film transistors (TFTs) are discussed. The static transistor characteristics are determined by the localized electronic states that occur in the bandgap of the amorphous silicon. The deep states, mostly consisting of Si dangling bonds, determine the threshold voltage, and the conduction band-tail states determine the field-effect mobility. The finite capture and emission times of the deep localized states lead to a dynamic transistor characteristic that can be described by a time-dependent threshold voltage. The transistors also show longer time threshold voltage shifts due to two other distinct mechanisms: charge trapping in the silicon nitride gate insulator and metastable dangling bond state creation in the amorphous silicon. These two mechanisms show characteristically different bias, temperature, and time dependencies of the threshold voltage shift. Illumination of a TFT causes the generation of electron-hole pairs in the space-charge region leading to a steady-state equal flux of electrons and holes and a reduction in the band-bending. In most applications, the photosensitivity should be minimized. The uniformity of large arrays of transistors for display applications is excellent, with variations in the threshold voltage of 0.5-1.0 V.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>