gebhart/patrepeval huggingface dataset:
A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: Application to Mycobacterium tuberculosis (2003)

We describe a postgenomic in silico approach for identifying genes that are likely to be essential and estimate their proportion in haploid genomes. With the knowledge of all sites eligible for mutagenesis and an experimentally determined partial list of nonessential genes from genome mutagenesis, a Bayesian statistical method provides reasonable predictions of essential genes with a subsaturation level of random mutagenesis. For mutagenesis, a transposon such as Himar1 is suitable as it inserts randomly into TA sites. All of the possible insertion sites may be determined a priori from the genome sequence and with this information, data on experimentally hit TA sites may be used to predict the proportion of genes that cannot be mutated. As a model, we used the Mycobacterium tuberculosis genome. Using the Himar1 transposon, we created a genetically defined collection of 1,425 insertion mutants. Based on our Bayesian statistical analysis using Markov chain Monte Carlo and the observed frequencies of transposon insertions in all of the genes, we estimated that the M. tuberculosis genome contains 35% (95% confidence interval, 28%-41%) essential genes. This analysis further revealed seven functional groups with high probabilities of being enriched in essential genes. The PE-PGRS (Pro-Glu polymorphic GC-rich repetitive sequence) family of genes, which are unique to mycobacteria, the polyketide/nonribosomal peptide synthase family, and mycolic and fatty acid biosynthesis gene families were disproportionately enriched in essential genes. At subsaturation levels of mutagenesis with a random transposon such as Himar1, this approach permits a statistical prediction of both the proportion and identities of essential genes of sequenced genomes.
Dexmedetomidine for the treatment of postanesthesia shivering in children (2006)

This study demonstrates the efficacy of dexmedetomidine in the treatment of postanesthesia shivering.
Purification of Growth Hormone-Releasing Factor (1965)

Growth hormone (GH)-releasing activity of ovine hypothalamic extracts was evaluated by an in vivo assay. The extracts were injected iv into male rats and their pituitaries were removed 30 min later. The decrease in hypophysial GH activity in the pituitaries of these rats was estimated by the tibial epiphysial cartilage test devised by Greenspan and Li. A significant decrease in GH content was taken as evidence of GH-releasing activity. Gel filtration on Sephadex G-25 separated fractions with significant GH-releasing activity at a dose of 70-80 μg of peptide. The active material was further purified by chromatography on carboxymethylcellulose (CMC). The GH-releasing factor (GH-RF) was eluted from the column by application of ammonium acetate buffers of increasing pH and ionic strength. The highly purified GH-RF was active at a dose of 2-4 μg of peptide as determined by the Folin-Lowry reaction. It appears to be a basic polypeptide with a molecular weight of 1800-2200 on the basis of its mobility on Sephadex. (Endocrinology77: 932, 1965)
Thrombolysis in peripheral arterial graft occlusion. (1993)

Acute thrombosis of arterial bypass grafts in the lower extremities poses a significant risk for limb loss. Graft salvage in patients affected by this complication remains a challenge. The vascular surgeon must consider the spectrum of treatment options (thrombolysis, thrombectomy, graft replacement) in managing acute graft thrombosis. Oral anticoagulants should be considered in patients with low-flow polytetrafluoroethylene (PTFE) grafts and after successful thrombolysis, with or without revision. The role of thrombolytic therapy for occluded vein grafts is less clear, but successful lysis is likely in patients who present within 48 hours of graft thrombosis and the etiology includes a correctable graft stenosis.
Bivalent role of the phosphatidylinositol-3-kinase (PI3K) during influenza virus infection and host cell defence (2006)

Infections with influenza A viruses result in the activation of a variety of intracellular signalling pathways. Recent findings suggest that in response to double-stranded RNA (dsRNA), which is commonly used as a mimic for accumulating viral RNA, the phosphatidylinositol-3-kinase (PI3K) is activated and mediates activation of the transcription factor interferon regulatory factor 3 (IRF-3). Thus, we investigated the function of PI3K during influenza virus infection. The pathway was activated upon infection and consistent with earlier findings using dsRNA, inhibition of PI3K itself or block of signalling by the PI3K product, the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), results in misphosphorylation and impaired dimerization of IRF-3 as well as reduced IRF-3-dependent promoter activity. This would imply an antiviral function of the kinase in influenza virus-infected cells. However, upon inhibition of PI3K, titers of progeny virus were reduced rather than enhanced. This was coincident with a strong decrease of viral protein accumulation that was not due to a block of protein synthesis or inhibition of the viral polymerase complex. Immunofluorescence studies revealed that PI3K rather appears to regulate a very early step during viral entry. Thus PI3K is a perfect example of a seemingly antiviral signalling component that is misused by the virus to support effective replication.
Voiced/Unvoiced/Mixed excitation classification of speech (1982)

Methods for performing voiced/unvoiced/mixed excitation classification of speech are explored. The decision-making process is viewed as a pattern recognition problem. Three aspects of the task are examined: classifier type, decision structure, and feature selection. A variety of different approaches are compared. A classifier is obtained which, in limited tests, achieves 95 percent classification accuracy on speaker dependent tests (with 82.7 percent correct identification of mixed excitation frames), and 94 percent accuracy on speaker independent tests (with 77.6 percent correct identification of mixed excitation frames). The classifier uses a binary decision tree structure, in which a speech segment is first classified as predominantly voiced or predominantly unvoiced, then tested to determine if the excitation for the segment is mixed or not. Each decision is made using a Bayes classifier. The feature selection procedure identified a set of 14 features to make the voiced/unvoiced/mixed excitation classification.
Calcium‐Based Lewis Acid Catalysts (2013)

Recently, Lewis acidic calcium salts bearing weakly coordinating anions such as Ca(NTf₂)₂, Ca(OTf)₂, CaF₂ and Ca[OCH(CF₃)₂]₂ have been discovered as catalysts for the transformation of alcohols, olefins and carbonyl compounds. High stability towards air and moisture, selectivity and high reactivity under mild reaction conditions render these catalysts a sustainable and mild alternative to transition metals, rare-earth metals or strong Brønsted acids.
Angiogenesis and Cancer Control: From Concept to Therapeutic Trial (1999)

BACKGROUND: There is extraordinary interest in developing angiosuppressive agents for cancer treatment. Several new agents appear promising for the treatment of a variety of human cancers. Current concepts and new agents in clinical trials are the focus of this article. In particular, the introduction of a new treatment for human brain tumors is presented in detail, using an antiangiogenic agent, penicillamine, and depletion of an obligatory cofactor of angiogenesis, copper. METHODS: The explosive increase in literature on antiangiogenesis is reviewed using computerized search, findings presented at the recent national cancer and angiogenesis meetings. A specific protocol, NABTT 97-04, "Penicillamine and Copper Reduction for Newly Diagnosed Glioblastoma," is presented as an example of angiotherapeutic drug discovery. RESULTS: A number of promising molecular approaches are being introduced to suppress tumor angiogenesis. Major categories of angiogenesis antagonists include protease inhibitors, direct inhibitors of endothelial cell proliferation and migration, suppression of angiogenic growth factors, inhibition of endothelial-specific integrin/ survival signaling, chelators of copper, and inhibitors with specific other mechanisms. The preliminary results of early trials offer a glimpse into how antiangiogenesis therapy will be integrated into future care of the patient with cancer. CONCLUSIONS: Thirty-five antiangiogenesis therapies are currently being evaluated in clinical trials. As we learn more about the fundamental mechanisms of angiogenesis, eg, the role of copper in growth factor activation, effective methods of cancer control will be implemented.
Properties of Engineered Poly-3-Hydroxyalkanoates Produced in Recombinant Escherichia coli Strains (2000)

To prepare medium-chain-length poly-3-hydroxyalkanoates (PHAs) with altered physical properties, we generated recombinant Escherichia coli strains that synthesized PHAs with altered monomer compositions. Experiments with different substrates (fatty acids with different chain lengths) or different E. coli hosts failed to produce PHAs with altered physical properties. Therefore, we engineered a new potential PHA synthetic pathway, in which ketoacyl-coenzyme A (CoA) intermediates derived from the beta-oxidation cycle are accumulated and led to the PHA polymerase precursor R-3-hydroxyalkanoates in E. coli hosts. By introducing the poly-3-hydroxybutyrate acetoacetyl-CoA reductase (PhbB) from Ralstonia eutropha and blocking the ketoacyl-CoA degradation step of the beta-oxidation, the ketoacyl-CoA intermediate was accumulated and reduced to the PHA precursor. Introduction of the phbB gene not only caused significant changes in the monomer composition but also caused changes of the physical properties of the PHA, such as increase of polymer size and loss of the melting point. The present study demonstrates that pathway engineering can be a useful approach for producing PHAs with engineered physical properties.
Prognostic Impact of Bim, Puma, and Noxa Expression in Human Colon Carcinomas (2008)

The proapoptotic BH3-only proteins Bim and Puma can provide prognostic information for stage II and III colon cancer patients receiving 5-fluorouracil-based adjuvant chemotherapy. Furthermore, our results support BH3-only proteins as molecular targets of novel anticancer drugs.
Filtercake Cleanup in Open-Hole Gravel-Packed Completions: A Necessity or a Myth? (2000)

Abstract Offshore reservoirs requiring sand control pose a major completion challenge because of extremely high cost and risk involved in remedial treatments, particularly in sub-sea completion and/or deep-water environments. It is therefore of utmost importance to ensure sand control without sacrificing flow conformance, recoverable reserves and well deliverability throughout the expected life of the completion. A major trend in these environments is towards open-hole, horizontal, gravel-packed completions. Although gravel packing stabilizes the wellbore, it can also entrap the filter-cake formed by the reservoir drilling fluid, potentially resulting in high drawdown requirements (flow initiation pressures) and/or low production rates (retained permeabilities). The cleanup procedures in the industry have varied significantly from no cleanup at all to complicated two-stage breaker treatments involving post-completion coiled tubing intervention, with no guidelines existing in the literature. In this paper, we present experimental results and field cases involving filter-cake flow-back through gravel packs with and without cleanup. Effects of various parameters, including gravel size (40/60, 20/40, and 12/20), formation permeability, drill-solids type (clays, quartz) and concentration, and the type of cleanup fluid have been investigated. Flow initiation pressure and retained permeabilities during flow back are reported as a function of these parameters. The experimental results show that the flow initiation pressure is a strong function of gravel size and the type of drill solids. It is concluded that, in clean (low-to-no clay content) formations of large grains and high permeabilities (~ several darcies) requiring large gravel sizes (e.g., 12/20), an enzyme or an oxidizer treatment is sufficient based on laboratory results and productivity predictions. This conclusion is also supported by several field applications as shown. In lower permeability (~ 100–250 md) formations of small sand sizes requiring smaller gravel (e.g., 40/60) elimination of both the fluid loss control agent (starch) and bridging agent (CaCO3) is necessary based on high flow initiation pressures and low retained permeabilities. In intermediate permeability (~ 500–800 md) formations of medium size sand-grains typically requiring 20/40 gravel, the results depend strongly on the type of drill solids: in clean formations (no clays in drilling fluid), an enzyme or an oxidizer treatment is sufficient, while in dirty formations removal of both CaCO3 and starch is necessary. These results are also supported by field case histories presented in the paper.
Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids (1993)

We have previously presented a precursor-product stable isotopic technique for measuring in vivo the fraction of very low-density lipoprotein-fatty acids (VLDL-FA) derived from de novo lipogenesis (fractional DNL). Here, we propose a technique for converting fractional DNL into absolute rates of DNL and describe its explicit underlying assumptions. The technique combines the fractional DNL method with a modification of the method of S. Klein, V. R. Young, G. L. A. Blackburn, B. R. Bistrain, and R. R. Wolfe (J. Clin. Invest. 78: 928-933, 1986), for estimating hepatic reesterification of free fatty acids (FFA). Infusions of [1,2,3,4-13C]palmitate and [1-13C]acetate are performed concurrently with indirect calorimetry in human subjects. Fractional DNL (based on mass isotopomer distribution analysis of VLDL-FA), the rate of appearance of plasma FFA (Ra of FFA), and net fat oxidation in the whole body are measured. Equations from the hepatic reesterification model, modified to include the contribution from DNL, allow calculation of absolute DNL (= fractional DNL x [Ra of FFA - net whole body fat oxidation], when respiratory quotient < 1.0). Sample results from human subjects with different dietary energy intakes are presented, with calculations of absolute DNL, absolute reesterification, and absolute fat oxidation rates. The assumptions of this technique (in particular, that all fat oxidized is derived at steady state from circulating FFA and that DNL and reesterification of FFA both occur exclusively in liver) are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
Tacrolimus and Cyclosporine a Inhibit Allostimulatory Capacity and Cytokine Production of Human Myeloid Dendritic Cells (2001)

Myeloid dendritic cells (DCs) are pivotal in the recognition of alloantigens and, therefore, in the induction of allograft rejection. Induction of alloreactive T cell proliferation by myeloid DCs depends on the maturation of DCs, the expression of costimulatory molecules, and the cytokine environment. This study investigated the effects of tacrolimus and cyclosporine A (CsA) on DC maturation and allostimulatory capacity. Myeloid DCs were propagated from normal blood monocytes with interleukin (IL) 4 and GM-CSF for 7 days in the presence or absence of tacrolimus (FK506; 10 nM) or CsA (1 microg/mL). Exposure of DCs during maturation to tacrolimus or CsA resulted in no significant change in the expression of DC phenotypic markers, including CD80, CD86, and HLA Class I and II antigens determined by flow cytometry. T cell proliferation in one-way, mixed-leukocyte reaction experiments revealed a decreased allostimulatory capacity of DCs that matured in the presence of tacrolimus or CsA compared with untreated controls (P<0.02). Production of inflammatory cytokines, tumor necrosis factor alpha (P<0.04) and IL-12 (P<0.04) in response to lipopolysaccharide (1 microg/mL) or staphylococcal enterotoxin B (1 microg/mL) induction was significantly reduced in DCs exposed to tacrolimus or CsA during maturation. In contrast, production of the immuninhibitory cytokine IL-10 was not decreased in tacrolimus- or CsA-treated DCs. These results suggest that tacrolimus and CsA inhibit the allostimulatory capacity of in vitro-generated myeloid DCs without significant effects on DC phenotypic maturation. Decreased production of IL-12 and tumor necrosis factor alpha, but not of IL-10, is likely to contribute to the impaired accessory-cell function of tacrolimus- and CsA-treated DCs. Thus, tacrolimus and CsA can inhibit recognition of alloantigens by decreasing the accessory-cell capacity of monocyte-derived myeloid DCs.
Comparative studies of chitinases A and B from Serratia marcescens (1996)

Serratia marcescens produces several chitinolytic enzymes, including chitinase A (ChiA) and chitinase B (ChiB). In this study, ChiB was purified to homogeneity using a newly developed protocol based on hydrophobic interaction chromatography. Subsequently, characteristics of ChiB and of the hitherto only partly characterized ChiA were determined and compared. Pure ChiA and ChiB shared several characteristics such as a broad pH optimum around pH 5.0-6.0, and a temperature optimum between 50 and 60 degrees C. Both enzymes were fairly stable, with half-lives of more than 10 d at 37 degrees C, pH 6.1. Analyses of the degradation of various N-acetylglucosamine oligomers, fluorogenic substrates and colloidal chitin showed that both enzymes cleave chitobiose [(GlcNAc)2] from (GlcNAc)n and thus possess an exo-N,N'-diacetylchitobiohydrolase activity. Both enzymes were also capable of producing monomers from longer (GlcNAc)n substrates, indicating that they also have an endochitinase (ChiA) or exo-N,N',N"-triacetylchitotriohydrolase (ChiB) activity. Kinetic analyses with 4-methylumbelliferyl-beta-D-N,N'-diacetylchitobioside, an analogue of (GlcNAc)3, showed cooperative kinetics for ChiA, whereas for ChiB normal hyperbolic kinetics were observed. ChiA had a higher specific activity towards chitin than ChiB and synergistic effects on the chitin degradation rate were observed upon combining the two enzymes. These results, together with the results of sequence comparisons and previous studies of the cellular localization of the two chitinases in S. marcescens indicate possible roles for ChiA and ChiB in chitin breakdown.
Infectious Bronchitis Virus in Testicles and Venereal Transmission (2011)

Even though males represent only 8%-12% of the birds of a breeder flock, their role in infectious bronchitis virus (IBV) dissemination is largely unknown. We first assessed the effect of IBV replication in the chicken testes. Ten-week-old males were inoculated with Arkansas (Ark) or Massachusetts (Mass) IBV virulent strains. Seven days postinoculation (DPI) IBV RNA was detected in testicles of 100% of M41- and in 96% of Ark-infected males. Marginal nonsynonymous variation was detected in spike (S) gene of the predominant population of IBV replicating in the testes compared to the S gene of the predominant population of viruses prior to inoculation. IBV M41 and Ark were detected in spermatogonia and Sertoli cells of testicles of infected roosters by immunofluorescence, without evident histopathological changes. We next assessed venereal transmission of IBV by artificially inseminating 54-wk-old hens either with semen from IBV-infected roosters or with IBV suspended in naïve semen. IBV RNA was detected in the trachea of all hens inseminated with IBV-spiked semen and in 50% of hens inseminated with semen from IBV-infected males. The egg internal and external quality was negatively affected in hens inseminated with semen containing IBV. These results provide experimental evidence for IBV venereal transmission.
Random projection in dimensionality reduction (2001)

Random projections have recently emerged as a powerful method for dimensionality reduction. Theoretical results indicate that the method preserves distances quite nicely; however, empirical results are sparse. We present experimental results on using random projection as a dimensionality reduction tool in a number of cases, where the high dimensionality of the data would otherwise lead to burden-some computations. Our application areas are the processing of both noisy and noiseless images, and information retrieval in text documents. We show that projecting the data onto a random lower-dimensional subspace yields results comparable to conventional dimensionality reduction methods such as principal component analysis: the similarity of data vectors is preserved well under random projection. However, using random projections is computationally significantly less expensive than using, e.g., principal component analysis. We also show experimentally that using a sparse random matrix gives additional computational savings in random projection.
A Slow Clearing, Fibrin-Specific, PAI-1 Resistant Variant of t-PA (T103N, KHRR 296-299 AAAA) (1993)

Site directed mutagenesis was used to construct a t-PA variant that contains an additional glycosylation site in the first kringle domain (T103N) combined with a tetra-alanine substitution in the protease domain (KHRR 296-299 AAAA). This combination variant has a plasma clearance rate that is 4.5-fold slower in rats and 5.4-fold slower in rabbits than t-PA. It is also less than one tenth as active as t-PA towards plasminogen in the presence of fibrinogen, and has approximately twice the normal activity in the presence of fibrin. It shows substantial resistance to the fast acting inhibitor, plasminogen activator inhibitor-1 (PAI-1), requiring a 10-fold greater molar excess of PAI-1 to reduce its activity by 50%, compared to t-PA. This is the result of a reduction of nearly 100-fold in the second order rate constant for PAI-1 inactivation. These results show that it is possible to combine mutations in different domains of t-PA to construct a variant which is simultaneously slower clearing, less reactive towards plasminogen in the absence of a fibrin clot, and resistant to inactivation by PAI-1.
Functionalization of Methacrylate Polymers with Thiooximes: A Robust Postpolymerization Modification Reaction and a Method for the Preparation of H2S-Releasing Polymers (2014)

The effectiveness of thiooxime formation as a postpolymerization modification reaction was evaluated. To this end, methacrylate polymers bearing pendant aldehyde functionality were prepared via reversible addition–fragmentation chain transfer (RAFT) polymerization of 2-(4-formylbenzoyloxy)ethyl methacrylate. Polymer side-chain derivatizations with tert-butylhydrazide, O-benzylhydroxylamine, and S-aroylthiohydroxylamine (SATHA) were shown to be quantitative, forming the corresponding hydrazone, oxime, and thiooxime, respectively. This work represents the first example of thiooxime formation on polymers, achieving high conversions under mild conditions. In response to thiol functionality, S-aroylthiooximes decomposed to release H2S: an endogenous signaling gas with significant therapeutic potential. H2S release from the resulting thiooxime-functionalized polymers was observed in the presence of cysteine and glutathione; moreover, degradation kinetics could be controlled by tuning the electronics at the para position of the corresponding SATHA-derived ring. In addition to generating polymers capable of controlled H2S release, this methodology also enables thiol-triggered degradation of pendant functionalities at neutral pH.