gebhart/patrepeval huggingface dataset:
Research Findings (2009)

AbstractThis chapter presents the research findings of this study. In particular, the author presents and discusses the results of the hypotheses derived from the study model. The chapter contains five main sections. In the first section, Model Specification, the key elements and concepts which underlie the Structural Equation Modeling methodology are explained in more detail. In the second section, The Baseline Model, the author explores the relations between the observed and unobserved variables individually. The following section, The Extended Model, expands the baseline model by simultaneously analyzing the relations between observed and unobserved variables. The fourth section, The Complex Model, determines the most important relationships between the model's determinants from different perspectives. The various sections' analysis and findings will be summarized and reflected in the chapter's final part, Implications.KeywordsBaseline ModelGrowth StrategyRecovery StageRestructuring ProcessTotal Indirect EffectThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Chronic AT1 receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival (1999)

In this model, losartan did not improve survival compared to placebo and quinapril and, if anything, increased mortality. Our results suggest that AT1 receptor antagonists and ACE inhibitors are not necessarily equivalent or interchangeable in terms of their effects on cardiac hypertrophy and survival in selected progressive heart failure models.
Multidimensional Graphing in Two-Dimensional Spaces (1989)

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Analysis of Translational Activity of Extracts Derived from Oocytes and Eggs of Xenopus laevis (2003)

Over the years, cell-free translation systems have been prepared from a wide variety of cell types. These vary considerably with respect to translational efficiency, both in translating the endogenous cellular mRNA and in utilizing added mRNAs. For studies focused on the properties or translation products of particular mRNA species, the majority of workers employ the efficient and well-characterized cell-free systems derived from the rabbit reticulocyte lysate or the wheat germ embryo, and commercial preparations of both of these are now available (although at extremely high unit cost!). In contrast, the spur for the development of translation systems from other cells and organisms is usually the wish to elucidate mechanisms controlling translation in that particular cell type. In general the efficiency of translation in cell-free extracts derived from nonerythroid animal cells rarely approaches that of the reticulocyte lysate and, in some cases, is lower by orders of magnitude. The precise reason for this is not clear, but one factor could be that reticulocytes lyse easily if suspended in water; thus no disruptive homogenization steps are required for the preparation of the lysate (see Note 7).
Structural and Functional Characteristics of the B-domain-deleted Recombinant Factor VIII Protein, r-VIII SQ (2001)

Recombinant factor VIII SQ (r-VIII SQ), ReFacto, is a recombinant factor VIII product similar to the smallest active factor VIII protein found in plasma-derived factor VIII (p-VIII) concentrates. The protein comprises two polypeptide chains of 80 and 90 kDa and lacks the major part of the heavily glycosylated B-domain i.e. amino acids Gln744 to Ser1637. r-VIII SQ retains six potential glycosylation sites for N-linked oligosaccharides at asparagine residues 41, 239, 582, 1685, 1810 and 2118. We describe a thorough comparison of the characteristics of r-VIII SQ with those of p-VIII. The primary and secondary structures of r-VIII SQ were in good agreement with that of B-domain-deleted p-VIII (p-VIII-LMW) as shown by SDS-PAGE, Western blotting with antifactor VIII antibodies, tryptic mapping, amino acid sequence analysis and circular dichroism spectroscopy. A few divergences also existed. Thus r-VIII SQ was shown to contain a small amount of the single chain primary translation product of 170 kDa and also the product specific sequence of 14 amino acids, the SQ-link, in the C-terminal end of the 90 kDa chain. It was shown that r-VIII SQ had a high specific activity of about 14,000 IU VIII:C/mg as determined by use of a chromogenic substrate assay. The r-VIII SQ protein was comparable to p-VIII forms with a retained B-domain, in terms of potency measured by a chromogenic substrate or a two-stage clotting assay, in interactions with thrombin, and with activated protein C (APC) in combination with Protein S. The ability of r-VIII SQ to participate as a cofactor in factor Xa generation in a mixture of factors IXa and X, phospholipid and calcium was in conformity with that of p-VIII. Furthermore r-VIII SQ had a good binding capacity for phospholipid vesicles and von Willebrand factor (vWF) as shown in gel filtration studies. The same kinetics in binding to von Willebrand factor was found for r-VIII SQ and p-VIII as determined by real-time biospecific interaction analysis (BIA) with use of the BIAcore instrument. The apparent association rate constant was 4 x 10(6) M(-1)s(-1). Two dissociation rate constants were found, 1 X 10(-2)s(-1) and 4 x 10(-4)s(-1). The results extend the present knowledge that the factor VIII B-domain is dispensable for the factor VIII cofactor function in hemostasis.
Isolation and initial characterization of multiple species of T-lymphocyte subset cDNA clones. (1987)

A modified differential screening procedure was applied to analyze cDNA libraries of cloned helper T lymphocytes (Th) and cytolytic T lymphocytes (CTL). Negative and positive differential screening and RNA blot analysis were used to identify cDNA clones that were expressed preferentially in Th or CTL. Seven clones corresponded to previously described T-cell genes, and 16 additional types of cDNA clones were isolated, 9 from Th and 7 from CTL. Of these, 3 were expressed in both Th and CTL, 7 were expressed in only Th, and 6 only in CTL. These clones were analyzed for induction after stimulation by interleukin 2 or Con A or after stimulation of the T-cell antigen receptor (TCR). Three different patterns of expression were seen: induction only by Con A, induction by Con A and interleukin 2, and induction by Con A and TCR stimulation. The approach is potentially useful for analyzing paths of T-cell differentiation and detecting cDNA clones encoding unrecognized cytokines.
Modulational Instability Induced by Cavity Boundary Conditions in a Normally Dispersive Optical Fiber (1997)

We study experimentally the role played by cavity boundary conditions in the onset of modulational instability in nonlinear and dispersive waves. This study is performed by means of an externally driven optical cavity made of a single-mode silica fiber. Spectral measurements of the intracavity field allow us to identify modulational instability in the presence of normal dispersion. This finding demonstrates that cavity boundary conditions fundamentally alter the physical mechanisms which are at the origin of modulational instability.
Age Changes and Sex Differences in Serum Dehydroepiandrosterone Sulfate Concentrations throughout Adulthood (1984)

In a cross-sectional study, serum dehydroepiandrosterone sulfate (DS) concentrations were measured in 981 men and 481 women, aged 11-89, yr. The resulting data were asymetrically distributed and were normalized by logarithmic transformation and analyzed by 5-yr age grouping (e.g. 15-19 yr, 20-24 yr, etc.). The DS concentration peaked at age 20-24 yr in men (logarithmic mean, 3470 ng/ml) and at age 15-19 yr in women (log mean, 2470 ng/ml). Mean values then declined steadily in both sexes (log mean at greater than 70 yr of age, 670 ng/ml in men and 450 ng/ml in women) and were significantly higher in men than women at ages from 20-69 yr. Analysis of 517 randomly selected sera (from women) which had been stored frozen for 10-15 yr gave results indistinguishable from values obtained from fresh specimens. In a supplementary study, a longitudinal analysis of weekly specimens from 4 normal men, aged 36-59 yr, revealed individual variability (mean coefficient of variation, 19%) and failed to demonstrate any monthly, seasonal, or annual rhythmicity. Based on the above analyses, a table of normal serum DS ranges for adult men and women is presented for use as a clinical reference.
Structures of human constitutive nitric oxide synthases (2014)

Mammals produce three isoforms of nitric oxide synthase (NOS): neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The overproduction of NO by nNOS is associated with a number of neurodegenerative disorders; therefore, a desirable therapeutic goal is the design of drugs that target nNOS but not the other isoforms. Crystallography, coupled with computational approaches and medicinal chemistry, has played a critical role in developing highly selective nNOS inhibitors that exhibit exceptional neuroprotective properties. For historic reasons, crystallography has focused on rat nNOS and bovine eNOS because these were available in high quality; thus, their structures have been used in structure-activity-relationship studies. Although these constitutive NOSs share more than 90% sequence identity across mammalian species for each NOS isoform, inhibitor-binding studies revealed that subtle differences near the heme active site in the same NOS isoform across species still impact enzyme-inhibitor interactions. Therefore, structures of the human constitutive NOSs are indispensible. Here, the first structure of human neuronal NOS at 2.03 Å resolution is reported and a different crystal form of human endothelial NOS is reported at 1.73 Å resolution.
Influence of the scattering phase function on light transport measurements in turbid media performed with small source–detector separations (1996)

Many methods of optical tissue diagnosis require that measurements be performed with small source-detector separations in a backscatter geometry. Monte Carlo simulations are used to demonstrate that for these situations light transport depends on the exact form of the angular scattering probability distribution, P(theta). Simulations performed with different forms of P(theta) with the same value of ?cos theta? result in the collection of significantly different fractions of the incident photons, particularly when small-numerical-aperture delivery and collection fibers are employed. More photons are collected for the distribution that has a higher probability of scattering events with theta > 125 degrees . For the clinically relevant optical parameters employed here, the differences in light collection are >60%.
Expression of the synthetic gene of an artificial DDT-binding polypeptide in Escherichia coli (1987)

This paper reports the expression of an artificial functional polypeptide in bacteria. The gene of a designed 24-residue DDT-binding polypeptide (DBP) was inserted between the BamHI and PstI cleavage sites of plasmid pUR291. The hybrid plasmid, pUR291-DBP, was cloned in Escherichia coli JM109. After induction by isopropyl-beta-D-thiogalactopyranoside a fusion protein was expressed in which DBP was linked to the COOH-terminus of beta-galactosidase. DBP, which is stable to trypsin, was obtained by tryptic digestion of the fusion protein and subsequent fractionation of the tryptic peptides by reversed-phase h.p.l.c. Recombinant and chemically synthesized DBP showed identical chromatographic properties, amino acid composition, and chymotryptic digestion patterns. Both the beta-galactosidase-DBP fusion and isolated recombinant DBP bound DDT. The fusion protein was 25 times as potent as the designed 24-residue DBP in activating a cytochrome P-450 model system using equimolar catalytic amounts of the two proteins.
Overlay error due to lens coma and asymmetric illumination dependence on pattern features (1998)

Coma aberration of projection optics and asymmetric illumination degrade a resist profile symmetricity and enhanced a placement error which depend on pattern size, density and feature. Relative displacements between 2.0 micrometer isolated lines and sub-micron periodic lines are measured to characterize the coma aberration and the illumination telecentricity. A conventional overlay inspection tool and bars-in-bars marks are used for this evaluation. It is difficult to measure the placement error of periodic patterns because their inner patterns have a different placement error from their both ends. The differences in line- width between both ends of periodic lines are caused by the differences in placement errors between their inner and their both ends patterns. The measurement marks for periodic lines are fabricated by the double exposure of two marks. When the resist patterns are imaged by the interference of only three diffracted beams, the coma aberration of Zernike's polynomials can be calculated by the simple expressions from the measurement results. We derived the condition of coherency (sigma) and pattern pitch P which satisfy the imaging of only three diffracted beams. The coma aberration is estimated to be 0.12 wavelength at maximum for the exposure system we applied. In this method, the focus is not so important for the accurate measurement because the measurement data remain constant at any foci. It takes only one hour to estimate the coma aberration completely including a sample making (sample making: 0.5 h, measurement/evaluation: 0.5 h). The relative pattern shifts between large patterns and fine patterns could be usually caused by not only coma aberration but also illumination optics. The telecentricity of the illumination optics is also discussed in this paper.
Apolipoprotein-mediated Plasma Membrane Microsolubilization (1999)

Lipid-free apolipoprotein (apo) A-I contributes to the reverse transport of cholesterol from the periphery to the liver by solubilizing plasma membrane phospholipid and cholesterol. The features of the apolipoprotein required for this process are not understood and are addressed in the current study. Membrane microsolubilization of human fibroblasts is not specific for apo A-I; unlipidated apos A-II, C, and E incubated with the fibroblast monolayers at a saturating concentration of 50 micrograms/ml are all able to release cholesterol and phospholipid similarly. To determine the properties of the apolipoprotein that drive the process, apo A-I peptides spanning the entire sequence of the protein were utilized; the peptides correspond to the 11- and 22-residue amphipathic alpha-helical segments, as well as adjacent combinations of the helices. Of the 20 helical peptides examined, only peptides representing the N-and C-terminal portions of the protein had the ability to solubilize phospholipid and cholesterol. Cholesterol efflux to the most effective peptides, 44-65 and 209-241, was approximately 50 and 70%, respectively, of that to intact apo A-I. Deletion mutants of apo E and apo A-I were constructed that have reduced lipid binding affinities as compared with the intact molecule. The proteins, apo A-I (Delta222-243), apo A-I (Delta190-243), apo E3 (Delta192-299) and apo E4 (Delta192-299) all exhibited a decreased ability to remove cellular cholesterol and phospholipid. These decreases correlated with the reduced ability of these proteins to penetrate into a phospholipid monomolecular film. Overall, the results indicate that insertion of amphipathic alpha-helices between the plasma membrane phospholipid molecules is a required step in the mechanism of apolipoprotein-mediated cellular lipid efflux. Therefore the lipid binding ability of the apolipoprotein is critical for efficient membrane microsolubilization.
Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors (2019)

Proteases are a major enzyme group playing important roles in a wide variety of biological processes in life forms ranging from viruses to mammalians. The aberrant activity of proteases can lead to various diseases; consequently, host proteases have been the focus of intense investigation as potential therapeutic targets. A wide range of viruses encode proteases which play an essential role in viral replication and, therefore, constitute attractive targets for the development of antiviral therapeutics. There are numerous examples of successful drug development targeting cellular and viral proteases, including antivirals against human immunodeficiency virus and hepatitis C virus. Most FDA-approved antiviral agents are peptidomimetics and macrocyclic compounds that interact with the active site of a targeted protease. Norovirus proteases are cysteine proteases that contain a chymotrypsin-like fold in their 3D structures. This review focuses on our group's efforts related to the development of norovirus protease inhibitors as potential anti-norovirus therapeutics. These protease inhibitors are rationally designed transition-state inhibitors encompassing dipeptidyl, tripeptidyl and macrocyclic compounds. Highly effective inhibitors validated in X-ray co-crystallization, enzyme and cell-based assays, as well as an animal model, were generated by launching an optimization campaign utilizing the initial hit compounds. A prodrug approach was also explored to improve the pharmacokinetics (PK) of the identified inhibitors.
Effects of calcium antagonists on the electrical alternans of the ST segment and on associated mechanical alternans during acute coronary occlusion in dogs. (1983)

Effects of calcium antagonists on the ST alternans and associated mechanical alternans during acute coronary occlusion were examined in anesthetized dogs. The heart rate was fixed by atrial pacing. The intravenous administration of 0.2 mg/kg verapamil attenuated the ST alternans as did 0.5 mg/kg diltiazem. Although these drugs significantly attenuated TQ depression during occlusion, the attenuation was observed after a longer period of occlusion and when the degree of TQ depression was comparable to that during the control occlusion. Nifedipine, 0.03 mg/kg, slightly attenuated the ST alternans, but 0.5 mg/kg dipyridamole had no effect. These results support the idea that slow inward currents are involved in the ST alternans. On the other hand, the mechanical alternans was attenuated in six of 11 dogs. It is probable that factors other than the electrical alternans may also contribute to the mechanical alternans.
Vitamin E and Cardiovascular Disease (2010)

The objective of this article is to review the role of vitamin E in cardiovascular disease. We begin by describing the general characteristics and metabolism of vitamin E and the pathogenesis of atherosclerosis as it relates to oxidation. We also discuss key in vitro studies, animal studies, observational studies, and clinical trials regarding the potentially cardioprotective effect of vitamin E. Lastly, we outline the current recommendations regarding vitamin E in the prevention and treatment of cardiovascular disease as stated by the American Heart Association. Vitamin E is a fat-soluble antioxidant vitamin and alpha-tocopherol is its most naturally abundant and active form. Oxidation is a key step in atherogenesis. Oxidized low-density lipoprotein stimulates endothelial cells to produce inflammatory markers, is involved in foam cell formation, has cytotoxic effects on endothelial cells, inhibits the motility of tissue macrophages, and inhibits nitric oxide-induced vasodilatation. Vitamin E has been shown to increase oxidative resistance in vitro and prevent atherosclerotic plaque formation in mouse models. Consumption of foods rich in vitamin E has been associated with lower risk of coronary heart disease in middle-aged to older men and women. Clinical studies at large have not demonstrated a benefit of vitamin E in the primary and secondary prevention of cardiovascular disease. Vitamin E supplementation might be associated with an increase in total mortality, heart failure, and hemorrhagic stroke. The American Heart Association does not support the use of vitamin E supplements to prevent cardiovascular disease, but does recommend the consumption of foods abundant in antioxidant vitamins and other nutrients.
Interleukin 2 deficiency is a common feature of autoimmune mice. (1981)

IL 2 production was studied in autoimmune mice to assess the role of this lymphokine in the pathogenesis of murine lupus. Spleen and lymph node cells from autoimmune-susceptible mice show an age-dependent loss in the ability to produce functional IL 2. This defect correlates with disease expression and is most severe in MLR/Mp-Ipr/Ipr mice. MLR/Mp-Ipr/Ipr thymocytes gradually lose responsiveness to IL 2 with age. These results suggest that the immunoregulatory abnormalities of autoimmune mice may be due in part to IL 2 deficiency.
Differences in expression of oncogenes and tumor suppressor genes in different sites of head and neck squamous cell. (1999)

These results show that the expression of a number of proteins is not identical in the three major localizations of HNSCC and indicate the different tumor biology of cancers originating from different sites in the Head and Neck. It is therefore not justified to consider the different localizations as one entity. Moreover, these differences may have clinical and prognostic relevance.
The ‘yellow brick road’ to branched complex N-glycans (1991)

Journal Article The 'yellow brick road' to branched complex N-glycans Get access Harry Schachter Harry Schachter Research Institute, Hospital for Sick Children, and Department of Biochemistry, University of TorontoToronto, Ontario, M5G 1X8, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Glycobiology, Volume 1, Issue 5, November 1991, Pages 453–461, https://doi.org/10.1093/glycob/1.5.453 Published: 01 November 1991 Article history Received: 02 August 1991 Accepted: 30 August 1991 Published: 01 November 1991
Fusion with an RNA binding domain to confer target RNA specificity to an RNase: design and engineering of Tat-RNase H that specifically recognizes and cleaves HIV-1 RNA in vitro (1996)

A target RNA/DNA-specific nuclease could be constructed if a specific RNA/DNA binding domain allowing target RNA/DNA recognition was fused to a (deoxy)ribonucleolytic domain allowing target RNA/ DNA cleavage. The design and construction of such a chimeric enzyme could be of value for both basic research involving structure-function relationships and applied research requiring inactivation of harmful RNA/DNA molecules of cellular or pathogenic origin. The feasibility of this designer nuclease approach for inactivating specific RNA/DNA molecules was assessed using human immunodeficiency virus type-1 (HIV-1) RNA as a model. Trans-activator of transcription (Tat) protein is one of the key regulatory proteins encoded by HIV-1. It binds to the trans-activation-responsive (TAR) RNA element located within the 5' non-coding region of HIV-1 RNAs. The TAR RNA binding domain of this protein was fused to the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT). RNase H by itself lacks an RNA binding domain. The chimeric Tat-RNase H protein was shown to specifically recognize and cleave HIV-1 TAR RNA in vitro. Cleavage was abolished by mutations in the Tat binding region within the TAR RNA, indicating that it is specific to HIV-1 TAR RNA.
Neural Control of the Kidney (2003)

This article provides a chronological perspective on the development of knowledge concerning the neural control of renal function and is divided into three parts: the past, the present, and the future.