gebhart/patrepeval huggingface dataset:
Hypercoagulability in Heart Failure (1997)

Thromboembolism is an important complication in patients with heart failure. A variety of factors associated with heart failure predispose to thrombosis. These include vascular pathology, increased coagulability, and impaired flow. The focus of this review is to summarize data on platelet function and coagulation indices in heart failure. Several studies have shown that patients with heart failure have increased plasma concentrations of beta-thromboglobulin, a marker of platelet activation. Increased plasma concentrations of fibrinopeptide A and thrombin activation have also been demonstrated. In addition, plasma concentrations of endothelial procoagulants, von Willebrand factor, fibrinolytic products, and D-dimer are also increased during heart failure. If platelet activation and hypercoagulability are a surrogate for clinical events, treatment with antiplatelet or anticoagulant therapy can potentially reduce thromboembolism and mortality in heart failure.
Insulin glargine in the treatment of type 1 and type 2 diabetes (2006)

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time-action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.
Effects of Neuropeptide Y on Appetite (1999)

Neuropeptide Y (NPY) is a polypeptide containing 36 amino acids. Circulating NPY originates predominantly from the sympatho-adrenomedullary nervous system. It has a vasoconstrictive and mitogenic effect on blood vessels and seems to be involved in blood pressure regulation and angiogenesis. NPY is a potent orexigenic agent and is presumed to play a leading role in the regulation of eating behavior. Stimulation of the NPY-ergic arcuate - paraventricular nucleus (ARC-PVN) pathway by exercise, fasting, energy loss (glucosuria) is followed by increased appetite and food intake and increased parasympathetic activity, but suppression of sympathetic activity and energy expenditure. The end result of this process is an increase of energy stores. Activity of the NPY-ergic ARC-PVN pathway is suppressed by leptin - a polypeptide produced by adipocytes. Although functioning of an NPY-leptin feedback was found in rodents, it seems likely that also in man the NPY-leptin axis is involved in the regulation of food intake and energy expenditure.
Lithium compound treatment and psoriasis (1979)

Observations were made of 12 cases of psoriasis that developed and three cases of psoriasis that became exacerbated during treatment with lithium compounds. Only two patients had a family history of psoriasis, and results of a search for increased frequencies of the histocompatibility antigens seen in psoriasis vulgaris were negative. The clinical features were identical to severe psoriasis vulgaris and the diagnosis was confirmed by histologic examination performed in six cases. However, the skin changes disappeared or returned to pretreatment level after withdrawal of lithium compounds. A positive provocation test result was obtained in two cases, the secondary latency time being shorter than the primary. We suggest that the psoriasis was induced or exacerbated by lithium compounds. (<i>Arch Dermatol</i>115:1185-1187, 1979)
Molecular analysis of blood vessel formation and disease (1997)

Blood vessels affect the quality of life in many ways. They provide an essential nutritive function during growth and repair of tissues but, on the other hand, can become affected by disorders or trauma, resulting in bleeding, thrombosis, arterial stenosis, and atherosclerosis. Three molecular systems, the vascular endothelial growth factor (VEGF) system, the plasminogen system, and the coagulation system, have been implicated in the formation and pathobiology of blood vessels. This review focuses on the role of these systems in these processes. Recent gene-targeting studies have identified VEGF as a potent modulator of the formation of endothelial cell-lined channels. Somewhat unanticipated, the initiator of coagulation is not only involved in the control of hemostasis but also in the maturation of a muscular wall around the endothelium. With different murine models of cardiovascular disease, a pleiotropic role of the plasminogen system was elucidated in thrombosis, in arterial neointima formation after vascular wound healing and allograft transplantation, in atherosclerosis, and in the formation of atherosclerotic aneurysms. Surprisingly, tissue-type plasminogen activator is also involved in brain damage after ischemic or neurotoxic insults. The insights from these gene-targeting studies have formed the basis for designing gene therapy strategies for restenosis and thrombosis, which have been successfully tested in these knockout models.
The impact-acceleration model of head injury: Injury severity predicts motor and cognitive performance after trauma (1999)

This study examines neuropsychological dysfunction after varying severities of the Impact Acceleration Model of diffuse traumatic brain injury. Adult rats (340 g-400 g) were divided into five groups, and exposed to varying degrees of Impact Acceleration Injury (1 m, 2 m, 2.1 m/500 g and second insult). After injury, animals were allowed to recover; acute neurological reflexes, beam walk score, beam balance score, inclined plane score, and Morris Water Maze score were then assessed at multiple time points. Injury of all severities caused significant motor and cognitive deficits. With milder injuries these effects were transient; however, with more severe injuries no recovery in function was seen. The addition of hypoxia and hypotension made a moderate injury worse than a severe injury. The acute neurological reflexes, the beam balance test and the inclined plane test distinguished between the more severely injured groups, but were affected less by mild injury. The beam walk test was sensitive to mild injury, but appeared unable to distinguish between the severe groups. The Morris Water Maze was sensitive for all injury groups, but appeared to adopt a different response profile with secondary insult. This study has for the first time characterized the degree of motor and cognitive deficits in rodents exposed to differing severities of Impact Acceleration Injury. These data confirm that the tests considered, and the Injury Model used, provide a useful system for the consideration of potential therapies which might ameliorate neuropsychological deficits in diffuse brain injury.
Investigations of a siloxane-based polymer electrolyte employing carbon-13, silicon-29, lithium-7, and sodium-23 solid-state NMR spectroscopy (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInvestigations of a siloxane-based polymer electrolyte employing carbon-13, silicon-29, lithium-7, and sodium-23 solid-state NMR spectroscopyR. Spindler and D. F. ShriverCite this: J. Am. Chem. Soc. 1988, 110, 10, 3036–3043Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/ja00218a006https://doi.org/10.1021/ja00218a006research-articleACS PublicationsRequest reuse permissionsArticle Views375Altmetric-Citations83LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. (1998)

We tested the hypothesis that endothelial nitric oxide synthase (eNOS) modulates angiogenesis in two animal models in which therapeutic angiogenesis has been characterized as a compensatory response to tissue ischemia. We first administered L-arginine, previously shown to augment endogenous production of NO, to normal rabbits with operatively induced hindlimb ischemia. Angiogenesis in the ischemic hindlimb was significantly improved by dietary supplementation with L-arginine, compared to placebo-treated controls; angiographically evident vascularity in the ischemic limb, hemodynamic indices of limb perfusion, capillary density, and vasomotor reactivity in the collateral vessel-dependent ischemic limb were all improved by oral L-arginine supplementation. A murine model of operatively induced hindlimb ischemia was used to investigate the impact of targeted disruption of the gene encoding for ENOS on angiogenesis. Angiogenesis in the ischemic hindlimb was significantly impaired in eNOS-/- mice versus wild-type controls evaluated by either laser Doppler flow analysis or capillary density measurement. Impaired angiogenesis in eNOS-/- mice was not improved by administration of vascular endothelial growth factor (VEGF), suggesting that eNOS acts downstream from VEGF. Thus, (a) eNOS is a downstream mediator for in vivo angiogenesis, and (b) promoting eNOS activity by L-arginine supplementation accelerates in vivo angiogenesis. These findings suggest that defective endothelial NO synthesis may limit angiogenesis in patients with endothelial dysfunction related to atherosclerosis, and that oral L-arginine supplementation constitutes a potential therapeutic strategy for accelerating angiogenesis in patients with advanced vascular obstruction.
What's new in the literature: An update of new research since the original WHS diabetic foot ulcer guidelines in 2006 (2014)

The objective of the paper was to update the diabetic foot ulcer guidelines that were previously published in 2006. We performed a key word search using MEDLINE and Cochrane reviews for publication between January 2006 and January 2012. Articles that fit the inclusion criteria were reviewed and the previous guidelines were updated.
Hepatocyte Nuclear Factor 1α Plays a Critical Role in PCSK9 Gene Transcription and Regulation by the Natural Hypocholesterolemic Compound Berberine (2009)

PCSK9 is a natural inhibitor of LDL receptor (LDLR) that binds the extracellular domain of LDLR and triggers its intracellular degradation. PCSK9 and LDLR are coordinately regulated at the transcriptional level by sterols through their promoter-imbedded sterol response elements (SRE) and co-induced by statins. Identification of regulatory networks modulating PCSK9 transcription is important for developing selective repressors of PCSK9 to improve statin efficacy by prolonging the up-regulation of LDLR. Interestingly, the plant-derived hypocholesterolemic compound berberine (BBR) up-regulates LDLR expression while down-regulating PCSK9. In our investigations to define mechanisms underlying the transcriptional suppression of PCSK9 by BBR in HepG2 cells, we have identified a highly conserved hepatocyte nuclear factor 1 (HNF1) binding site residing 28 bp upstream from SRE as a critical sequence motif for PCSK9 transcription and its regulation by BBR. Mutation of the HNF1 site reduced PCSK9 promoter activity >90%. A battery of functional assays identified HNF1alpha as the predominant trans-activator for PCSK9 gene working through this sequence motif. We further provide evidence suggesting that HNF1 site works cooperatively with SRE as HNF1 mutation significantly attenuated the activity of nuclear SREBP2 to transactivate PCSK9 promoter. Finally, we show that a coordinate modest reduction of HNF1alpha and nuclear SREBP2 by BBR led to a strong suppression of PCSK9 transcription through these two critical regulatory sequences. This is the first described example of SREBP pairing with HNF1 to control an important regulatory pathway in cholesterol homeostasis. This work also provides a mechanism for how BBR suppresses PCSK9 transcription.
발레 실기수업 전후의 신체성분 변화특성 (2003)

본 연구는 바가노바 메소드 레벨 3 수준의 여중생 발레 전공자 16명을 임의추출하여 120분간의 실기수업후 체성분 변화를 측정 분석하였다. 신체성분은 Bio Space(Korea)에서 제작한 InBody 3.0을 이용하였으며, 통계적 검증을 통하여 다음과 같은 결론을 얻었다. 첫째, 체중, 체지방, 체지방율, 비만도는 유의한 수준으로 감소하였고, 체지방, 복부비만 등의 감소는 유의한 수준이 아니었다. 둘째, 체수분량에서 오른다리 수분량 왼다리 수분량, 부종지수 등은 수업후에 증가하였으나 유의하지 않았고, 체수분량, 세포내액, 세포외액, 오른팔 수분량, 왼팔 수분량, 몸통 수분량 등은 수업후에 감소하였으나 유의하지 않았다. 셋째, 기초 대사량은 수업전보다 수업후에 감소하였으나 유의하지 않았다. 넷째, 구조변인에서 신체질량은 유의하게 감소하였고, 근육량, 단백질 등의 감소는 유의하지 않았다. 또한, 근육형태, 상하균형, 상체 좌우균형, 하체 좌우균형 등은 유의하게 변화하지 않았다. 다섯째, 체격변인에서 신장은 전혀 변화가 없었고, 허벅지 둘레와 허리둘레 변인은 유의하게 감소시켰다. 그러나 모든 변인에서 수업전과 후의 상관계수가 유의한 것으로 나타났고, 이는 감소 또는 증가경향이 일정한 것을 알 수 있었다. 본 연구를 실시한 후에 제언하고자 하는 것은 첫째, 여고생이나 남자 무용수의 발레실기 수업전후의 신체성분의 변화에 대한 연구가 이루어졌으면 하는 것과 둘째, 신체성분과 무용 수행력간의 관계를 규명할 것을 제언한다.
Effective medium models for the optical properties of inhomogeneous materials (1981)

The Maxwell Garnett and Bruggeman effective medium theories are derived for the average dielectric permeability of heterogeneous materials from a unified theoretical approach. It starts by specifying two random unit cells which represent different microstructures. Requiring that these cells should not be detectable by electromagnetic radiation when embedded in an effective medium, we show from an extended optical theorem that the forward scattering amplitude must vanish. Setting the leading term in the expansion series of this quantity equal to zero yields the effective medium theories pertaining to the two microstructures. The remaining terms provide estimates of the accuracy of the approximations. This approach is then used in numerical computations for Co-AI(2)O(3) cermets.
Hydrogen Fluoride/Tetrahydrofuran as a Fluorinating Medium. A General Synthesis of 1,1,1,2-Tetrafluoro-2-alkenes (1987)

A general and simple two step synthesis of 1,1,1,2-tetrafluoro-2-alkenes is presented. The key step is the rearrangement-conversion of 1,1,2-trifluoro-1-alken-3-ols under the influence of hydrogen fluoride/tetrahydrofuran (5:1) as a fluorinating medium.
The personal side of genomics (2007)

Innovations in DNA sequencing and genotyping are opening doors for personal genomics. Nathan Blow explores these technological advances and their implications.
Issues in the design and use of a distributed file system (1980)

This paper discusses an independent file facility, one that is not embedded in an operating system. The distributed file system (DFS) is so named because it is implemented on a cooperating set of server computers connected by a communications, network, which together create the illusion of a single, logical system for the creation, deletion, and random accessing of data. Access to the DFS can only be accomplished over the network; a computer (or, more precisely, a program running on one) that uses the DFS is called a client . This paper describes the division of responsibility between servers and clients. The basic tool for maintaining data consistency in these situations is the atomic property of transactions, which protects clients from system malfunctions and from the competing activities of other clients. Several cooperating clients may share a transaction. The DFS provides an unconventional locking mechanism between transactions that supports client caches and eliminates a novel form of deadly embrace. We have implemented and put into service a system based on these concepts.
Mechanism of inhibition of papain by chicken egg white cystatin (1989)

N-terminally truncated forms of chicken egg white cystatin and its cyanogen bromide fragments were isolated and assayed for inhibition of papain. Truncated forms beginning with Gly-9 and Ala-10 had a 5000-fold lower affinity for papain than the two isoelectric forms (pI = 6.5 and 5.6) of the full-length inhibitor (Ki = 6 pM and 7 pM) or a truncated form beginning with Leu-7 (Ki = 6 pM), indicating the outstanding importance of one or two residues preceding conserved Gly-9 for binding. A weak inhibition of papain (Ki = 900 nM) was exhibited by the intermediate cyanogen bromide fragment (residues 30-89) containing the chicken cystatin QLVSG variation of the QVVAG segment which is conserved in almost all members of the cystatin superfamily. The obtained affinity data provide independent evidence for the validity of the proposed docking model of a chicken cystatin-papain complex [(1988) EMBO J. 7, 2593-2599].
The Spring Nucleus: A Microkernel for Objects (1993)

The Spring system is a distributed operating system that supports a distributed, object-oriented application framework. Each individual Spring system is based around a microkernel known as the nucleus, which is structured to support fast cross-address-space object invocations. This paper discusses the design rationale for the nucleus&amp;apos;s IPC facilities and how they fit into the overall Spring programming model. We then describe how the internal structure of the nucleus is organized to support fast crossaddress -space calls, including some specific details and performance information on the current implementation. 1. Introduction Currently there is considerable interest in both industry and academia in structuring operating systems as sets of cooperating services rather than as single monolithic programs. This trend is driven by two main motivations. First, there is a belief that it will be easier (and faster) to develop and modify OS components if they are required to be cleanly isolate...
Prediction of Liver Injury Induced by Chemicals in Human With a Multiparametric Assay on Isolated Mouse Liver Mitochondria (2012)

Drug-induced liver injury (DILI) in humans is difficult to predict using classical in vitro cytotoxicity screening and regulatory animal studies. This explains why numerous compounds are stopped during clinical trials or withdrawn from the market due to hepatotoxicity. Thus, it is important to improve early prediction of DILI in human. In this study, we hypothesized that this goal could be achieved by investigating drug-induced mitochondrial dysfunction as this toxic effect is a major mechanism of DILI. To this end, we developed a high-throughput screening platform using isolated mouse liver mitochondria. Our broad spectrum multiparametric assay was designed to detect the global mitochondrial membrane permeabilization (swelling), inner membrane permeabilization (transmembrane potential), outer membrane permeabilization (cytochrome c release), and alteration of mitochondrial respiration driven by succinate or malate/glutamate. A pool of 124 chemicals (mainly drugs) was selected, including 87 with documented DILI and 37 without reported clinical hepatotoxicity. Our screening assay revealed an excellent sensitivity for clinical outcome of DILI (94 or 92% depending on cutoff) and a high positive predictive value (89 or 82%). A highly significant relationship between drug-induced mitochondrial toxicity and DILI occurrence in patients was calculated (p < 0.001). Moreover, this multiparametric assay allowed identifying several compounds for which mitochondrial toxicity had never been described before and even helped to clarify mechanisms with some drugs already known to be mitochondriotoxic. Investigation of drug-induced loss of mitochondrial integrity and function with this multiparametric assay should be considered for integration into basic screening processes at early stage to select drug candidates with lower risk of DILI in human. This assay is also a valuable tool for assessing the mitochondrial toxicity profile and investigating the mechanism of action of new compounds and marketed compounds.
Identification of C3b-binding regions on herpes simplex virus type 2 glycoprotein C (1990)

Glycoprotein C from herpes simplex viruses types 1 and 2 (gC-1 and gC-2) acts as a receptor for the C3b fragment of the third component of complement. Our goal is to identify domains on gC involved in C3b receptor activity. Here, we used in-frame linker-insertion mutagenesis of the cloned gene for gC-2 to identify regions of the protein involved in C3b binding. We constructed 41 mutants of gC-2, each having a single, double, or triple insertion of four amino acids at sites spread across the protein. A transient transfection assay was used to characterize the expressed mutant proteins. All of the proteins were expressed on the transfected cell surface, exhibited processing of N-linked oligosaccharides, and bound one or more monoclonal antibodies recognizing distinct antigenic sites on native gC-2. This suggested that each of the mutant proteins was folded into a native structure and that a loss of C3b binding by any of the mutants could be attributed to the disruption of a specific functional domain. When the panel of insertion mutants was assayed for C3b receptor activity, we identified three distinct regions that are important for C3b binding, since an insertion within those regions abolished C3b receptor activity. Region I was located between amino acids 102 and 107, region II was located between residues 222 and 279, and region III was located between residues 307 and 379. In addition, region III has some structural features similar to a conserved motif found in complement receptor 1, the human C3b receptor. Finally, blocking experiments indicated that gC-1 and gC-2 bind to similar locations on the C3b molecule.
LKB1 and AMP‐activated protein kinase control of mTOR signalling and growth (2009)

The AMP-activated serine/threonine protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes that is activated under conditions of low intracellular ATP following stresses such as nutrient deprivation or hypoxia. In the past 5 years, work from a large number of laboratories has revealed that one of the major downstream signalling pathways regulated by AMPK is the mammalian target-of-rapamycin [mammalian target of rapamycin (mTOR) pathway]. Interestingly, like AMPK, the mTOR serine/threonine kinase plays key roles not only in growth control and cell proliferation but also in metabolism. Recent work has revealed that across eukaryotes mTOR orthologues are found in two biochemically distinct complexes and only one of those complexes (mTORC1 in mammals) is acutely sensitive to rapamycin and regulated by nutrients and AMPK. Many details of the molecular mechanism by which AMPK inhibits mTORC1 signalling have also been decoded in the past 5 years. AMPK directly phosphorylates at least two proteins to induce rapid suppression of mTORC1 activity, the TSC2 tumour suppressor and the critical mTORC1 binding subunit raptor. Here we explore the molecular connections between AMPK and mTOR signalling pathways and examine the physiological processes in which AMPK regulation of mTOR is critical for growth or metabolic control. The functional conservation of AMPK and TOR in all eukaryotes, and the sequence conservation around the AMPK phosphorylation sites in raptor across all eukaryotes examined suggest that this represents a fundamental cell growth module connecting nutrient status to the cell growth machinery. These findings have broad implications for the control of cell growth by nutrients in a number of cellular and organismal contexts.