gebhart/patrepeval huggingface dataset:
Comparative genomics of the neglected human malaria parasite Plasmodium vivax (2008)

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
Monoamine Oxidase Activity and Monoamine Metabolism in Brains of Parkinsonian Patients Treated with l‐Deprenyl (1986)

Monoamine oxidase (MAO) type A and type B were measured using kynuramine, 3,4-dihydroxyphenylethylamine (dopamine, DA), and 5-hydroxytryptamine (5-HT, serotonin) in 20 brain areas. The highest activities were found in the striatum (caudate nucleus, putamen, globus pallidus, and substantia nigra), hypothalamus, and c-mammilare. The ratio of DA to 5-HT deamination varied in the different regions, being in favor of DA in the striatum. With kynuramine as the substrate IC50 values of a number of inhibitors indicated that l-deprenyl was far more potent an inhibitor of human brain MAO than clorgyline or harmaline. N-Desmethylpropargylindane hydrochloride (AGN 1135) was also shown to have MAO-B inhibitory selectivity similar to that of l-deprenyl. Brains obtained at autopsy from l-deprenyl-treated Parkinsonian patients showed that, whereas MAO-B was fully inhibited by the therapeutic doses of l-deprenyl, substantial MAO-A activity was still evident. These results are matched by the significant increases of DA noted in caudate nucleus, globus pallidus, putamen, and substantia nigra and the unaltered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the same regions. These data indicate that the therapeutic actions of l-deprenyl may lie in its selective inhibition of MAO-B resulting in increased brain levels of DA formed from L-dihydroxyphenylacetic acid (L-DOPA).
Virion incorporation of envelope glycoproteins with long but not short cytoplasmic tails is blocked by specific, single amino acid substitutions in the human immunodeficiency virus type 1 matrix (1995)

Incorporation of envelope glycoproteins into a budding retrovirus is an essential step in the formation of an infectious virus particle. By using site-directed mutagenesis, we identified specific amino acid residues in the matrix domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein that are critical to the incorporation of HIV-1 envelope glycoproteins into virus particles. Pseudotyping analyses were used to demonstrate that two heterologous envelope glycoproteins with short cytoplasmic tails (the envelope of the amphotropic murine leukemia virus and a naturally truncated HIV-2 envelope) are efficiently incorporated into HIV-1 particles bearing the matrix mutations. Furthermore, deletion of the cytoplasmic tail of HIV-1 transmembrane envelope glycoprotein gp41 from 150 to 7 or 47 residues reversed the incorporation block imposed by the matrix mutations. These results suggest the existence of a specific functional interaction between the HIV-1 matrix and the gp41 cytoplasmic tail.
Simvastatin Inhibits Growth Factor Expression and Modulates Profibrogenic Markers in Lung Fibroblasts (2005)

Simvastatin is best known for its antilipidemic action and use in cardiovascular disease due to its inhibition of 3-hydroxy-3-methylglutaryl CoenzymeA (HMG CoA) reductase, a key enzyme in the cholesterol synthesis pathway. Inhibition of biological precursors in this pathway also enables pleiotrophic immunomodulatory and anti-inflammatory capabilities, including modulation of growth factor expression. Connective tissue growth factor (CTGF) and persistent myofibroblast formation are major determinants of the aggressive fibrotic disease, idiopathic pulmonary fibrosis (IPF). In this study we used human lung fibroblasts derived from healthy and IPF lungs to examine Simvastatin effects on CTGF gene and protein expression, analyzed by RT-PCR and ELISA, respectively. Simvastatin significantly inhibited (P < 0.05) CTGF gene and protein expression, overriding the induction by transforming growth factor-beta1, a known potent inducer of CTGF. Such Simvastatin suppressor action on growth factor interaction was reflected functionally on recognized phenotypes of fibrosis. alpha-smooth muscle actin expression was downregulated and collagen gel contraction reduced by 4.94- and 7.58-fold in IMR90 and HIPF lung fibroblasts, respectively, when preconditioned with 10 microM Simvastatin compared with transforming growth factor-beta1 treatment alone after 24 h. Our data suggest that Simvastatin can modify critical determinants of the profibrogenic machinery responsible for the aggressive clinical profile of IPF, and potentially prevents adverse lung parenchymal remodeling associated with persistent myofibroblast formation.
Effectiveness of Electrolyzed Oxidized Water Irrigation in a Burn-Wound Infection Model (2000)

Irrigation and disinfection with EOW may become useful in preventing burn-wound sepsis.
The DESIRE study – psoriasis patients’ satisfaction with topical treatment using a fixed combination of calcipotriol and betamethasone dipropionate in daily clinical practice (2009)

Daivobet (Dovobet) is a fixed combination ointment of calcipotriol and betamethasone dipropionate. The real-life clinical use of calcipotriol/betamethasone dipropionate treatment was assessed in this multi-centre, single-group, non-interventional study. Patients with psoriasis vulgaris who had a recent calcipotriol/betamethasone dipropionate prescription prior to the study start evaluated their satisfaction with the treatment after a 4-week course and after repeated courses for up to 6 months. Of the 1224 patients enrolled, 81.5% completed the 6-month study period. Approximately 75% of the patients were satisfied/very satisfied after one calcipotriol/betamethasone dipropionate treatment course and the satisfaction was high regardless of initial disease severity. Repeated calcipotriol/betamethasone dipropionate courses were prescribed for 22.9% of the patients and treatment satisfaction remained high (about 80%). The majority (60%) of the patients were willing to provide co-payments for calcipotriol/betamethasone dipropionate within their national health insurance system.
StatCache: A probabilistic approach to efficient and accurate data locality analysis (2004)

The widening memory gap reduces performance of applications with poor data locality. Therefore, there is a need for methods to analyze data locality and help application optimization. In this paper we present StatCache, a novel sampling-based method for performing data-locality analysis on realistic workloads. StatCache is based on a probabilistic model of the cache, rather than a functional cache simulator. It uses statistics from a single run to accurately estimate miss ratios of fully-associative caches of arbitrary sizes and generate working-set graphs. We evaluate StatCache using the SPEC CPU2000 benchmarks and show that StatCache gives accurate results with a sampling rate as low as 10/sup -4/. We also provide a proof-of-concept implementation, and discuss potentially very fast implementation alternatives.
A New Method for Investigating the Sampling Technique of Fine Needle Aspiration Biopsy (1990)

An automatic sampler of fine needle aspiration biopsy for cytology (FNAC) is presented in order to study the technical performance of FNAC in vitro. The effects of the following sampling technique variables on specimen size and quality can be independently and quantitatively studied: suction force, duration and rate of increase of suction; count, frequency, amplitude and angle between the needle strokes; length, diameter, content and tip configuration of the needle; and target tissue. The efficacy of the sampler was compared with a manual method. It was demonstrated that the poor reproducibility of manual FNAC, combined with inaccuracy in following instructions regarding changes in sampling technique, render the manual system unsuitable for quantitative studies. The clumsiness of the manual system may be responsible for contradictory recommendations on how FNAC should be carried out. With the new in vitro sampler FNAC sampling can be studied under fully controlled conditions.
Four-cell stage mouse blastomeres have different developmental properties (2005)

Blastomeres of the early mouse embryo are thought to be equivalent in their developmental properties at least until the eight-cell stage. However, the experiments that have led to this conclusion could not have taken into account either the spatial origin of individual blastomeres or the spatial allocation and fate of their progeny. We have therefore readdressed this issue having defined cell lineages in mouse embryos undergoing different patterns of cleavage in their second division cycle. This has enabled us to identify a major group of embryos in which we can predict not only the spatial origin of each given four-cell blastomeres, but also which region of the blastocyst is most likely to be occupied by its progeny. We show that a pattern of second cleavage divisions in which a meridional division is followed by one that is equatorial or oblique allows us to identify blastomeres that differ in their fate and in their developmental properties both from each other and from their cousins. We find that one of these four-cell stage blastomeres that inherits some vegetal membrane marked in the previous cleavage cycle tends to contribute to mural trophectoderm. The progeny of its sister tend to donate cells to part of the ICM lining the blastocyst cavity and its associated trophectoderm. Chimaeras made entirely of these equatorially or obliquely derived blastomeres show developmental abnormalities in both late preimplantation and early postimplantation development. By contrast, chimaeras made from four-cell stage blastomeres from early meridional divisions develop normally. The developmental defects of chimaeras made from the most vegetal blastomeres that result from later second cleavages are the most severe and following transplantation into foster mothers they fail to develop to term. However, when such individual four-cell blastomeres are surrounded by blastomeres from random positions, they are able to contribute to all embryonic lineages. In conclusion, this study shows that while all four-cell blastomeres can have full developmental potential, they differ in their individual developmental properties according to their origin in the embryo from as early as the four-cell stage.
High Speed Reprojection And Its Applications (1988)

Reprojection is the process by which projections are produced from an image such that, if these projections are filtered and backprojected, they yield the original image. Because of the computational expense of reprojection, algorithms that employ this process have never been widely used. A method is presented that enables an unmodified backprojector to be used as a reprojector. Because backprojectors are designed to exploit the parallelism in the backprojection algorithm, the time required to obtain reprojections is significantly reduced. Another method, based on the Fourier Slice Theorem, is presented that enables a general purpose array processor to be used as a high speed reprojector. It is also shown that the parameters of the reprojection algorithm can be adjusted to decrease significantly the time required to perform an application that uses reprojection. Finally, two applications of reprojection in computed tomography are discussed.
Antineoplastic Agents. 443. Synthesis of the Cancer Cell Growth Inhibitor Hydroxyphenstatin and Its Sodium Diphosphate Prodrug (2000)

A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineoplastic activity, and the benzophenone derivative of combretastatin A-1 was therefore synthesized. The benzophenone, designated hydroxyphenstatin (6a), was synthesized by coupling of a protected bromobenzene and a benzaldehyde to give the benzhydrol with subsequent oxidation to the ketone. Hydroxyphenstatin was converted to the sodium phosphate prodrug (6e) by a dibenzyl phosphite phosphorylation and subsequent benzyl cleavage (6a --> 6d --> 6e). While hydroxyphenstatin (6a) was a potent inhibitor of tubulin polymerization with activity comparable to that of combretastatin A-1 (3a), the phosphorylated derivative (6e) was inactive.
Gene-targeted B-deficient mice reveal a critical role for B cells in the CD4 T cell response (1995)

The role of B cells in promoting T cell responses is still controversial. In this study, we use JHD mice which have a targeted mutation in the JH gene and are thus rendered deficient in B cells to address this issue. We show here that immunization of JHD mice with soluble antigen fails to prime CD4 T cells, for either clonal expansion or delivery of immunological help for antibody responses. This lack of CD4 T cell priming in JHD mice corresponds to a 3- to 9-fold lower co-stimulatory activity of antigen-presenting cells (APC) from the JHD mice, as measured by anti-CD3-induced proliferative responses of CD4 T cells. This in turn is due to a defect of APC from JHD mice in response to T cell-mediated induction of co-stimulatory activity. As the development of macrophages and dendritic cells is unaffected in the JHD mice, our results demonstrate that B cells play a critical role in CD4 T cell priming, possibly by delivering a critical co-stimulatory activity for clonal expansion of CD4 T cells.
Association Between Optimism and Serum Antioxidants in the Midlife in the United States Study (2012)

Optimism was associated with greater carotenoid concentrations, and this association was partially explained by diet and smoking status. The direction of effects cannot be conclusively determined. Effects may be bidirectional given that optimists are likely to engage in health behaviors associated with more serum antioxidants, and more serum antioxidants are likely associated with better physical health that enhances optimism.
Single-Ion Li+, Na+, and Mg2+ Solid Electrolytes Supported by a Mesoporous Anionic Cu–Azolate Metal–Organic Framework (2017)

A novel Cu(II)-azolate metal-organic framework (MOF) with tubular pores undergoes a reversible single crystal to single crystal transition between neutral and anionic phases upon reaction with stoichiometric amounts of halide or pseudohalide salts. The stoichiometric transformation between the two phases allows loading of record amounts of charge-balancing Li<sup>+</sup>, Na<sup>+</sup>, and Mg<sup>2+</sup> ions for MOFs. Whereas the halide/pseudohalide anions are bound to the metal centers and thus stationary, the cations move freely within the one-dimensional pores, giving rise to single-ion solid electrolytes. The respective Li<sup>+</sup>-, Na<sup>+</sup>-, and Mg<sup>2+</sup>-loaded materials exhibit high ionic conductivity values of 4.4 × 10<sup>-5</sup>, 1.8 × 10<sup>-5</sup>, and 8.8 × 10<sup>-7</sup> S/cm. With addition of LiBF<sub>4</sub>, the Li<sup>+</sup> conductivity improves to 4.8 × 10<sup>-4</sup> S/cm. These are the highest values yet observed for MOF solid electrolytes.
Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack (1995)

In this study, changes in plasma levels of calcitonin gene-related peptide (CGRP) and substance P (SP) during a spontaneous-like cluster headache attack provoked by nitroglycerin were evaluated. Peptide variations after spontaneous or sumatriptan-induced remission were also assessed. Blood was collected from the external jugular vein homolateral to the pain side of 30 male cluster headache patients; 18 men were in an active and 12 in a remission one. Plasma levels of CGRP and SP were determined using sensitive radioimmunoassays for each peptide. CGRP-like immunoreactivity (CGRP-LI) was found to be augmented in patients in an active period and became elevated further at the peak of the provoked attack. A complete reversal occurred both after spontaneous and sumatriptan-induced remission. On the contrary, nitroglycerin neither provoked a cluster headache attack nor altered CGRP-LI in the patients in a remission period. The augmented levels of CGRP-LI measured before and after nitroglycerin administration, when the provoked attack reached the maximum intensity, suggest an activation of the trigeminovascular system during the active period of cluster headache. Moreover, the clinical and biochemical actions showed by sumatriptan stress the involvement of serotonin in cluster headache mechanisms.
Methane emissions from cattle (1995)

Increasing atmospheric concentrations of methane have led scientists to examine its sources of origin. Ruminant livestock can produce 250 to 500 L of methane per day. This level of production results in estimates of the contribution by cattle to global warming that may occur in the next 50 to 100 yr to be a little less than 2%. Many factors influence methane emissions from cattle and include the following: level of feed intake, type of carbohydrate in the diet, feed processing, addition of lipids or ionophores to the diet, and alterations in the ruminal microflora. Manipulation of these factors can reduce methane emissions from cattle. Many techniques exist to quantify methane emissions from individual or groups of animals. Enclosure techniques are precise but require trained animals and may limit animal movement. Isotopic and nonisotopic tracer techniques may also be used effectively. Prediction equations based on fermentation balance or feed characteristics have been used to estimate methane production. These equations are useful, but the assumptions and conditions that must be met for each equation limit their ability to accurately predict methane production. Methane production from groups of animals can be measured by mass balance, micrometeorological, or tracer methods. These techniques can measure methane emissions from animals in either indoor or outdoor enclosures. Use of these techniques and knowledge of the factors that impact methane production can result in the development of mitigation strategies to reduce methane losses by cattle. Implementation of these strategies should result in enhanced animal productivity and decreased contributions by cattle to the atmospheric methane budget.
A positive genetic selection for disrupting protein–protein interactions: Identification of CREB mutations that prevent association with the coactivator CBP (1996)

The Escherichia coli tet-repressor (TetR) operator system was used to develop a variation of the yeast two-hybrid assay in which disruptions of protein-protein interactions can be identified by a positive selection. This assay, designated the "split-hybrid system," contains a two-component reporter. The first component contains LexA binding sites upstream of the TetR gene and the second contains TetR operator binding sites upstream of HIS3. Interaction of one protein fused to the LexA DNA binding domain with a second protein fused to the VP16 activation domain results in TetR expression. TetR subsequently binds to the tet operators, blocking the expression of HIS3 and preventing yeast growth in media lacking histidine. The utility of the split-hybrid system was analyzed by examining the phosphorylation-dependent interaction of CREB and its coactivator CREB binding protein (CBP). CREB and CBP associate through an interaction that depends upon CREB phosphorylation at Ser-133. Mutation of this phosphorylation site prevents yeast growth in the standard two-hybrid assay but allows growth in the split-hybrid strains. The split-hybrid system was used to identify other CREB mutations that disrupt its association with CBP. These mutations localized around the site of CREB phosphorylation, indicating that only a small portion of the CREB activation domain is required for CBP interaction. The yeast split-hybrid system should be useful in identifying mutations, proteins, peptides, and drugs that disrupt protein-protein interactions.
Structural and Genetic Characterization of the Shigella boydii Type 10 and Type 6 O Antigens (2005)

Comparison of the O antigens of Shigella boydii types 10 and 6 by chemical analysis and nuclear magnetic resonance spectroscopy showed that their structures are similar, with the only difference being the presence or absence of d-ribofuranose, which is the immunodominant sugar in S. boydii type 10. In S. boydii type 6, a residue previously reported as alpha-d-GlcpA, was shown to be beta-d-GlcpA as in S. boydii type 10. S. boydii types 10 and 6 are reported not to cross-react serologically, and the role of d-ribofuranose in the specificity of S. boydii was confirmed by making a mutant of type 10 that lacked d-ribofuranose. However, S. boydii type 11, which has a d-ribofuranose but with different linkage does show cross-reaction with type 10. The O-antigen gene loci of S. boydii types 10 and 6 were shown to be virtually identical except that orf8 (wbaM), which was confirmed as the ribofuranosyltransferase gene, is interrupted by IS629 in type 6. Therefore, it is proposed that the O-antigen gene cluster of S. boydii type 6 was derived from type 10 by an IS element insertion.
The phage RNA polymerases are related to DNA polymerases and reverse transcriptases (1993)

The single subunit DNA-dependent RNA polymerase (RNAP) that is encoded by bacteriophage T7 is the prototype of a class of relatively simple RNAPs that includes the RNAPs of the related phages T3 and SP6, as well as the mitochondrial RNAPs. The T7 enzyme has been crystallized, and recent genetic and biochemical analyses have facilitated an interpretation of this structure. A growing body of evidence suggests that the phage-like RNAPs are related to other nucleotide polymerases such as DNA polymerases, RNA-dependent RNA polymerases, and reverse transcriptases. In this work, we review information concerning the structure and function of T7 RNAP, and evidence in support of its assignment to a broader class of nucleotide polymerases.
Reductive Phosphine-Mediated Ligation of Nitroxyl (HNO) (2009)

Nitroxyl (HNO) demonstrates a unique chemical and biological profile compared to nitric oxide (NO). Phosphorus NMR studies reveal that HNO reacts with triarylphosphines to give the corresponding phosphine oxide and aza-ylide. In the presence of a properly situated electrophilic ester, the aza-ylide undergoes a Staudinger ligation to yield an amide with the nitrogen atom being derived from HNO. These results define new HNO reactivity and provide the basis of new HNO detection methods.