gebhart/patrepeval huggingface dataset:
Recombinant von Willebrand Factor-Insight into Structure and Function through Infusion Studies in Animals with Severe von Willebrand Disease (2002)

We used a canine and a murine model of von Willebrand disease (vWD) to study the in vivo effects of recombinant von Willebrand factor (vWF). Two preparations were used: (1) a fully processed mature vWF; this was achieved by coexpression of furin. (2) A preparation containing unprocessed pro-vWF, the propeptide still covalently linked to mature vWF. Both preparations induced an increase in canine and murine factor VIII:C (FVIII), which was sustained even when vWF antigen had been removed from the circulation. vWF multimers were analyzed in the plasma samples after infusion using ultra high-resolution 3% agarose gels to allow the separation of homoforms and heteroforms of the vWF polymers. Administration of pro-vWF to dogs with severe vWD resulted in the removal of the propeptide and maturation of vWF in the circulation, indicating that the propeptide cleavage from unprocessed vWF can occur extracellularly. This suggests that the vWF propeptide, besides being derived from the Weibel-Palade bodies of endothelial cells after stimulation, can also be cleaved by pro-vWF in plasma. Using a murine model of vWD, the involvement of the low-density lipoprotein receptor-related protein (LRP) in the clearance of FVIII was established. The low levels of FVIII observed in the absence of vWF are due to an enhanced clearance of FVIII by binding to LRP and removal from the circulation through endocytosis. Administration of the receptor-associated protein (RAP) as a recombinant fusion protein to vWF knockout mice significantly improved the in vivo recovery of recombinant FVIII and the survival time of otherwise rapidly cleared FVIII.
Standardization and the Group Lasso Penalty (2011)

We re-examine the original Group Lasso paper of Yuan and Lin (2007). The form of penalty in that paper seems to be designed for problems with uncorrelated features, but the statistical community has adopted it for general problems with correlated features. We show that for this general situation, a Group Lasso with a different choice of penalty matrix is generally more effective. We give insight into this formulation and show that it is intimately related to the uniformly most powerful invariant test for inclusion of a group. We demonstrate the efficacy of this method- the "standardized Group Lasso"- over the usual group lasso on real and simulated data sets. We also extend this to the Ridged Group Lasso to provide within group regularization as needed. We discuss a simple algorithm based on group-wise coordinate descent to fit both this standardized Group Lasso and Ridged Group Lasso.
Various applications of TALEN- and CRISPR/Cas9-mediated homologous recombination to modify the Drosophila genome (2014)

Modifying the genomes of many organisms is becoming as easy as manipulating DNA in test tubes, which is made possible by two recently developed techniques based on either the customizable DNA binding protein, TALEN, or the CRISPR/Cas9 system. Here, we describe a series of efficient applications derived from these two technologies, in combination with various homologous donor DNA plasmids, to manipulate the Drosophila genome: (1) to precisely generate genomic deletions; (2) to make genomic replacement of a DNA fragment at single nucleotide resolution; and (3) to generate precise insertions to tag target proteins for tracing their endogenous expressions. For more convenient genomic manipulations, we established an easy-to-screen platform by knocking in a white marker through homologous recombination. Further, we provided a strategy to remove the unwanted duplications generated during the "ends-in" recombination process. Our results also indicate that TALEN and CRISPR/Cas9 had comparable efficiency in mediating genomic modifications through HDR (homology-directed repair); either TALEN or the CRISPR/Cas9 system could efficiently mediate in vivo replacement of DNA fragments of up to 5&emsp14;kb in Drosophila, providing an ideal genetic tool for functional annotations of the Drosophila genome.
EDITORIAL: THE STRUCTURAL ADJUSTMENT OF STRUCTURAL ADJUSTMENT: SUB-SAHARAN AFRICA 1980-1993 (1994)

Summary Two major problems confront an outsider seeking to understand, or a newcomer seeking to participate in structural adjustment: first it has a deceptively familiar terminology in which familiar words have specialized (and changing) meanings and second, structural adjustment in SSA has been radically adjusted over the past decade. The two major sections of this editorial seek to provide guides to the terminology and to how the “lessons of experience” have altered the substance, time horizons and presentation of structural adjustment. They also pose some of major present gaps or unresolved problem area. Resumé Les gens de l'extérieur qui cherchent à comprendre l'ajustement structurel, ainsi que les nouveaux?venus qui cherchent à y participer, s'affrontent à deux problèmes cruciaux: d'abord, l'ajustement structurel possède son propre vocabulaire, qui semblerait apparemment familier mais qui est, pour autant, décepteur en raison du fait que ses termes familiers sont revêtus de significations à la fois spécialisées et changeantes; et deuxièmement, l'ajustement structurel en Afrique sous?saharienne a lui?même subi un ajustement radical au cours de la dernière décennie. Les deux sections majeures du présent éditorial cherchent à servir de guides de la terminologie et de démontrer dans quelle manière les “leçons de l'expérience” ont modifié le contenu, les horizons temporels, et la présentation de l'ajustement structurel. Ces sections cherchent aussi à révéler quelques?unes des principales lacunes à l'heure actuelle, ainsi que certains des domaines problématiques qu'il reste à solutionner. Resumen El neófito que trata de entender o participar en el ajuste estructural se enfrenta a dos problemas fundamentales: en primer lugar, éste tiene una terminología falsamente familiar en la cual las palabras conocidas adquieren significados especializados (y cambiantes); en segundo lugar el ajuste estructural en el Africa sub?Sahariana ha sido radicalmente ‘ajustado’ en el curso de la última década. Las dos secciones principales de este editorial procuran proveer guías a la terminología y al modo en que las ‘lecciones de experiencia’ han alterado la esencia, los límites de tiempo y la presentación del ajuste estructural. Estas secciones tambien exponen algunas de las principales lagunas de conocimiento o áreas problemáticas aún sin resolver.
Dysphagia in the elderly: management and nutritional considerations (2012)

Dysphagia is a prevalent difficulty among aging adults. Though increasing age facilitates subtle physiologic changes in swallow function, age-related diseases are significant factors in the presence and severity of dysphagia. Among elderly diseases and health complications, stroke and dementia reflect high rates of dysphagia. In both conditions, dysphagia is associated with nutritional deficits and increased risk of pneumonia. Recent efforts have suggested that elderly community dwellers are also at risk for dysphagia and associated deficits in nutritional status and increased pneumonia risk. Swallowing rehabilitation is an effective approach to increase safe oral intake in these populations and recent research has demonstrated extended benefits related to improved nutritional status and reduced pneumonia rates. In this manuscript, we review data describing age related changes in swallowing and discuss the relationship of dysphagia in patients following stroke, those with dementia, and in community dwelling elderly. Subsequently, we review basic approaches to dysphagia intervention including both compensatory and rehabilitative approaches. We conclude with a discussion on the positive impact of swallowing rehabilitation on malnutrition and pneumonia in elderly who either present with dysphagia or are at risk for dysphagia.
Parametric Amplification Using Low-Frequency Pumping (1958)

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Heat shock factor 1 and heat shock proteins: Critical partners in protection against acute cell injury (2002)

OBJECTIVE: Life-threatening conditions cause severe changes in the organization and conformation of macromolecules, creating urgent requirements for protein repair to ensure survival. As molecular chaperones, heat shock proteins (HSP) that have specialized functions in protein folding are now well established to restore homeostasis in cells and organisms. Augmentation of HSP synthesis is tightly regulated by stress-inducible heat shock factors (HSF), which are part of a transcriptional signaling cascade with both positive (e.g., HSP) and negative (e.g., proinflammatory cytokines) properties. In this review, we discuss the biological roles and mechanisms of HSP-mediated protection in pathophysiologic conditions (ischemia, sepsis, and preeclampsia) and the regulation for stress-dependent HSP synthesis and speculate about future applications for harnessing HSF and HSP partners as cytoprotective agents. DATA SOURCES: Reactive oxygen species are major pathogenic factors in cell death pathways (e.g., necrosis, apoptosis), in part, because of proteotoxic effects. In intact organisms, forced overexpression of HSP per se affords effective counterbalance against ischemia challenges (e.g., heart and brain) and systemic conditions (e.g., sepsis). Besides stressful conditions, gene-targeting studies have uncovered new functions for heat shock transcription factors (e.g., maintenance of intrauterine pregnancy) in mammals. In parallel, pharmacologic studies using small molecules are paving the way for future prospects to exploit the beneficial properties of HSP, albeit an important but presently elusive goal. CONCLUSIONS: Together, HSF and HSP partners are attractive targets in therapeutic strategies designed to stimulate endogenous protective mechanisms against deleterious consequences of oxidative stress. With further technological advances, it is anticipated that the spotlight on HSP, alone or in combination with other stress response pathways, could, ultimately, reduce injury and accelerate functional recovery of susceptible organs in living organisms including humans.
Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. (1996)

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (approximately 10% of CD3+ cells, especially of CD4+ cells); (b) NTx on day 3 eliminates CD25+ T cells from the periphery for several days; inoculation immediately after NTx of CD25+ splenic T cells from syngeneic non-Tx adult mice prevents autoimmune development, whereas inoculation of CD25- T cells even at a larger dose does not; and furthermore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25+ cell-depleted spleen cell suspensions from older, even 1-yr-old, nu/+ mice. The CD25- populations from neonates or adults are also similar in the profile of cytokine formation. These results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25+ T cells that sustain potentially pathogenic self-reactive T cells in a CD25- dormant state; the thymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transiently, eliminate/reduce the autoimmune-preventive CD25+ T cells, thereby leading to activation of the self-reactive T cells that have been produced before NTx.
Recognition of Proline‐Rich Motifs by Protein–Protein‐Interaction Domains (2005)

Protein-protein interactions are essential in every aspect of cellular activity. Multiprotein complexes form and dissociate constantly in a specifically tuned manner, often by conserved mechanisms. Protein domains that bind proline-rich motifs (PRMs) are frequently involved in signaling events. The unique properties of proline provide a mechanism for highly discriminatory recognition without requiring high affinities. We present herein a detailed, quantitative assessment of the structural features that define the interfaces between PRM-binding domains and their target PRMs, and investigate the specificity of PRM recognition. Together with the analysis of peptide-library screens, this approach has allowed the identification of several highly conserved key interactions found in all complexes of PRM-binding domains. The inhibition of protein-protein interactions by using small-molecule agents is very challenging. Therefore, it is important to first pinpoint the critical interactions that must be considered in the design of inhibitors of PRM-binding domains.
An Analysis on the Schemes for Detecting and Preventing ARP Cache Poisoning Attacks (2007)

The address resolution protocol (ARP) is used by computers to map network addresses (IP) to physical addresses (MAC). The protocol has proved to work well under regular circumstances, but it was not designed to cope with malicious hosts. By performing ARP cache poisoning or ARP spoofing attacks, an intruder can impersonate another host (man-in-the-middle attack) and gain access to sensitive information. Several schemes to mitigate, detect and prevent these attacks have been proposed, but each has its limitations. In this paper we analyze each of these schemes, identify their strengths and weaknesses, and propose guidelines for the design of an alternative and (arguably) better solution to the problem of ARP cache poisoning.
교실 수업용 가이거-뮬러 튜브의 제작과 염화칼륨(KCl)에서 방출되는 베타 및 감마선 측정 탐구 (2012)

고등학교와 대학교 학생들이 탐구실험에 활용할 수 있는 가이거-뮬러 튜브를 간단한 튜브의 부품들을 이용하여 제작하는 과정을 자세히 서술하였다. 베타와 감마선을 방출하는 방사선 시료는 생활 주변에서 쉽게 구할 수 있는 염화칼륨(KCl)을 이용하였다. 베타와 감마선의 전기적 신호 측정에 필요한 전자회로와 LabVIEW 프로그램도 제작하였다. 결과적으로 이 연구에서 제작한 가이거-뮬러 튜브로 염화칼륨에서 방출되는 베타와 감마선을 측정하였다.
Enhanced alpha 1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes. Relation to the expression of pertussis toxin-sensitive G protein and alpha 1-adrenergic receptors. (1990)

The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced alpha 1-adrenergic receptor-mediated rise in cytosolic calcium, whether a pertussis toxin-sensitive G protein is involved in coupling the alpha 1-adrenergic receptor to changes in intracellular calcium and whether enhanced alpha 1 responsiveness is associated with an increase in the level of expression of the alpha 1-adrenergic receptor or in the pertussis toxin-sensitive G protein or proteins. To test the hypothesis that the cardiomyopathic state is associated with a greater alpha 1-receptor-mediated rise in cytosolic calcium, we studied the effect of phenylephrine (in the presence of propranolol) on time-averaged cytosolic calcium concentration ([Ca2+]i) in isolated cardiac myocytes from cardiomyopathic and age-matched control hamsters. Phenylephrine caused a greater increase both in time-averaged [Ca2+]i (an increase of 48 +/- 8% versus 12 +/- 3%, p less than 0.01) and in contractility (+181 +/- 22% versus +35 +/- 9%, p less than 0.01) in cardiomyopathic than in normal cardiac myocytes. Exposure to pertussis toxin (200 ng/ml for 3 hours) attenuated the alpha 1-adrenergic receptor-mediated increase in contractility and time-averaged [Ca2+]i in both cardiomyopathic and normal cells. The level of pertussis toxin-sensitive G protein, as determined by pertussis toxin-mediated [32P]ADP-ribosylation, was 1.6-fold higher in cardiomyopathic versus normal hamster hearts. The density of alpha 1-adrenergic receptors, as measured by the antagonist radioligand [3H]prazosin and the affinity of the receptor for agonist and antagonist were similar in myopathic and normal heart membranes. Thus, in cardiac myocytes from hamsters, the alpha 1-adrenergic receptor-mediated effects on [Ca2+]i and contractility appear to be mediated by a pertussis toxin-sensitive G protein or proteins. In myocytes from cardiomyopathic hamsters, these alpha 1-adrenergic effects were increased in magnitude, as was the level of pertussis toxin-sensitive G protein, but there was no measurable alteration in the density or ligand binding properties of alpha 1-adrenergic receptors.
Homogeneous liposome lysis assay for determination of anti-streptolysin O antibody titer in serum (1988)

We developed a liposome lysis assay for determining anti-streptolysin O antibodies (ASO) in human sera involving the use of carboxyfluorescein-entrapped multilamellar liposomes. This assay system was based on the inhibition of streptolysin O-induced liposome lysis by ASO. Briefly, after incubation of a given amount of streptolysin O with ASO for 30 min at 37 degrees C, carboxyfluorescein-entrapped liposomes composed of egg yolk phosphatidylcholine and cholesterol in a molar ratio of 1:1 were added to the mixture to determine the residual streptolysin O activity. Liposome lysis, detected as carboxyfluorescein release from the liposomes, was inversely proportional to the ASO titer. The results of within-run and between-run precision studies indicated that the liposome lysis assay is accurate and gives reproducible data. Bilirubin, hemoglobin, and triglycerides did not interfere with the liposome lysis assay. The ASO titers of 100 patient sera, evaluated by our new method and the Rantz-Randall method, showed good correlation.
Modulation of epothilone analog production through media design (2002)

Recently, the epothilone polyketide synthase (PKS) was successfully introduced into a heterologous production host for the large-scale production of epothilone D. We have found that at least three other epothilones can also be produced as the major fermentation product of this recombinant strain by supplementation of specific substrates to the production media. Addition of acetate or propionate to the media results in modulation of the epothilone D:C ratio, whereas addition of L-serine with either acetate or propionate yields epothilone H(1) or H(2) as the major product. This strategy permits production of at least four novel epothilones by culturing a single host with a genetically modified epothilone PKS in various media.
Capillary pumps for autonomous capillary systems (2006)

Autonomous capillary systems (CSs), where liquids are displaced by means of capillarity, are efficient, fast and convenient platforms for many bioanalytical applications. The proper functioning of these microfluidic devices requires displacing accurate volumes of liquids with precise flow rates. In this work, we show how to design capillary pumps for controlling the flow properties of CSs. The capillary pumps comprise microstructures of various shapes with dimensions from 15-250 microm, which are positioned in the capillary pumps to encode a desired capillary pressure. The capillary pumps are designed to have a small flow resistance and are preceded by a constricted microchannel, which acts as a flow resistance. Therefore, both the capillary pump and the flow resistance define the flow rate in the CS, and flow rates from 0.2-3.7 nL s(-1) were achieved. The placement and the shape of the microstructures in the capillary pumps are used to tailor the filling front of liquids in the capillary pumps to obtain a reliable filling behaviour and to minimize the risk of entrapping air. The filling front can, for example, be oriented vertically or tilted to the main axis of the capillary pump. We also show how capillary pumps having different hydrodynamic properties can be connected to program a sequence of slow and fast flow rates in a CS.
Dual Porosity, Dual Permeability Formulation for Fractured Reser- voir Simulation (1996)

This study reviews key physical mechanisms and calculation methods for modelling of fluid flow in North Sea fractured reservoirs. The main matrixfracture fluid exchange mechanisms described are gravity drainage, capillary imbibition and molecular diffusion. Important issues such as capillary continuity between matrix blocks, reinfiltration of fluids from higher to lower blocks and effect of block shape on flow processes are also addressed. Simulation studies of water-flooding in fractured reservoirs are reported for the purpose of identifying the effects of gravity and capillary forces on oil recovery. Included are studies of effects of capillary continuity and degree of wetting. The results show that for intermediately wetted systems, such as the Ekofisk reservoir, capillary continuity has a major effect on oil recovery. Laboratory processes involving high pressure gas injection in fractured systems have been studied by compositional simulation. The results show that changes in interfacial tension caused by diffusion, may have dramatic effects on oil recovery. Computational aspects of fluid exchange processes are discussed, including conventional dual porosity formulation, use of matrix-fracture transfer functions, and detailed numerical calculation. The only solution to more representative modelling of flow in fractured reservoirs is more detailed calculations. A multiple grid concept is proposed which may drastically increase the detail of the simulation.
Conditioned Avoidance Response in the Development of New Antipsychotics (2009)

Schizophrenia presents with positive/psychotic, negative and cognitive symptoms. Positive symptoms seems due to a dopamine mesolimbic overreactivity, while negative/cognitive symptoms may conversely be due to mesocortical hypo-dopaminergia. Traditional dopamine D2 receptor blocking antipsychotics (e.g. haloperidol) are effective against psychotic/positive symptoms, but less so against negative/cognitive symptoms. Some D2 receptor blockage, however, seems necessary for efficacy against psychotic symptoms. Therefore, current antipsychotic drug improvement strategies include modest D2 receptor blockage, or partial D2 stimulation, combined with adjunct pharmacological properties that may enhance: i) D2 blockage efficacy; and ii) cognitive functioning. There are also strategies with no direct D2 blockage. Clinical activity is often tested in animal screening tests (so called animal models). The screening test conditioned avoidance response in rats has shown particular sensitivity, with high predictive validity, for detection of drug antipsychotic activity. The present review assessed the significance, accuracy and use of the conditioned avoidance response test as a screening tool in current antipsychotic drug development. It was found that: i) the conditioned avoidance response test holds a strong position, is frequently used in current antipsychotic drug development, and is commonly considered a reliable screening tool, with high predictive validity, for the detection of potential antipsychotic activity; ii) in current antipsychotic drug development, the conditioned avoidance response test is able to detect pharmacological properties contributing to antipsychotic activity in the presence of sub-therapeutic D2 receptor blockade, as well as detecting antipsychotic activity of compounds having no direct D2 blocking properties.