Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in vivo: evidence that thrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis.

We examined the effect of a specific thrombin inhibitor, Ro 46-6240, alone and combined with an antagonist of the platelet GP IIb/IIIa, Ro44-9883, on the response to tissue-type plasminogen activator in a canine model of thrombolysis. Platelet activity was determined by measuring the excretion of 2,3-dinorthromboxane (TX)B2, an enzymatic metabolite of TXA2. Ro 46-6240 administered before tissue-type plasminogen activator induced a dose-dependent prolongation of the activated partial thromboplastin time and prothrombin time. The time to reperfusion decreased dose-dependently (P < .01) to 10 +/- 6 min vs. 52 +/- 5 min in controls. Ro 46-6240 also prevented reocclusion, which occurred in every case in control experiments. Urinary excretion of 2,3-dinor-TXB2 increased from 3 +/- 1 to 37 +/- 9 ng/mg creatinine in controls after reperfusion. This increase was reduced in a dose-dependent fashion by Ro 46-6240, such that at the highest dose, urinary 2,3-dinor-TXB2 after reperfusion was 5.6 +/- 1 ng/mg creatinine. Similar functional and biochemical effects were seen when a subthreshold dose of Ro 46-6240 was combined with Ro 44-9883. At the dose used, Ro 44-9883 alone abolished platelet aggregation ex vivo but failed to modify the response to tissue-type plasminogen activator or the excretion of 2,3-dinor-TXB2 after reperfusion (51 +/- 6 ng/mg creatinine, n = 3). However, the combination of Ro 44-9883 and Ro 46-6240 reduced the time to reperfusion (40 +/- 8 vs. 68 +/- 15 min; n = 7, P < .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5 +/- 1 ng/mg creatinine, n = 4). These findings suggest that thrombin mediates platelet activation during coronary thrombolysis. The increased platelet activity results in platelet aggregation and a subsequent increase in TXA2 formation.
The Roles of Peripheral Participants and Brokers: Within and Beyond Communities of Practices

The objective of our chapter is to gain a better understanding of learning trajectories connecting external and internal communities of practices. To do so we studied four internal communities of practice by actors belonging to a same external community. We realized semi-directive interviews in these communities supplemented by direct observation of meetings. Our results give a new perspective on participation to communities of practice. We describe how young members act as boundary spanners between the communities and the practice in their organization while more senior members act as unique facilitators with a balance between boundary spanning and buffering. We describe in detail the personal characteristics of these senior members.
The prevalence of narcolepsy among Chinese in Hong Kong

Narcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500‐fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical‐polysomnographic‐HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep‐wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010–0.117%). All available narcoleptic subjects were HLA DRB1‐1501 positive and 50% were DQB1‐0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross‐ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.
An effective solution to reduce motion artefact in new generation reflectance pulse oximeter

This paper presents a non-invasive and wearable optical technique to monitor physiological assessment by means of photoplethysmography (PPG). The study aims to research into an effective way to capture human critical physiological parameters, i.e. oxygen saturation (SaO2%), heart rate, respiration rate through a well contracted and wearable patch probe together with a real-time and secure wireless communication functionalities. The work presents the first step of this research; an automatic noise cancellation method using a 3-axes MEMS accelerometer to recover signals corrupted by body movement as one of the biggest sources of motion artefacts. These kinds of motion artefacts could be reduced by an appropriate electronic design and development for self-cancellation noise and stability of the sensor. The signals from the acceleration and the PPG sensor are highly correlated thus the desire PPG signals retrieved with reduced motion artefacts. The preliminary results from the bench tests and the laboratory setup demonstrate that the goal of the high performance wearable PPG is viable and feasible.
The Effects of Trust-Assuring Arguments on Consumer Trust in Internet Stores: Application of Toulmin's Model of Argumentation

The difficulty Internet stores face in developing consumer trust is an ongoing impediment to the proliferation of Internet shopping. In order to develop consumer trust, many e-commerce strategies and Website features have been proposed in the IS discipline. Trust-assuring arguments are one proposed feature and refer to a statement or statements offering support for a claim made by an Internet store to address trust related issues. Although trust-assuring arguments are often found in Internet stores, to date little research has examined the effects of the arguments in building consumer trust. To fill the gap, this paper examines the effects of trustassuring arguments on consumer trust in Internet stores.
Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease.

OBJECTIVE To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease. DESIGN Case-control study of men with and without prostate disease who were participants in a prospective aging study. SETTING Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging. PATIENTS Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer. OUTCOME MEASURES Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease. RESULTS Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer greater than BPH greater than control; P less than .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 micrograms/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively. CONCLUSIONS The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.
The Adaptive Water Governance Project: Assessing Law, Resilience and Governance in Regional Socio-Ecological Water Systems Facing a Changing Climate

The article will summarize the findings of the Adaptive Water Governance Project, an interdisciplinary project bringing together legal and resilience scholars. The AWG project explores means to link ecological resilience and the law and policy governing the process of water management in complex, multi-jurisdictional water basins. The project focuses on assessing resilience to climate change in six North American water basins which provide examples of heavily regulated and developed social-ecological system. A common goal that informs the work of the AWG team is to meet the challenge of posing solutions in recognition of the fact that we do not write on a clean slate. Rather than propose a new form of governance, we focus on bridging existing governance to proposed approaches asking how we might get there from here. The perspective legal scholars bring to the study of resilience and adaptive governance is the recognition that legal systems, while establishing boundaries and fostering a primary goal of economic and social stability, nevertheless are inherently adaptable and have throughout history responded to new challenges. The AWG Project asks four questions on the role of law in adaptive governance. (1) What is the role of law in setting boundaries by identifying approaching thresholds or tipping points in the system? (2) What is the role of law in creating either a disturbance or window of opportunity in which adaptive forms of governance may emerge? (3) What is the role of law in presenting barriers to adaptive forms of governance? (4) What is the role of law in facilitating adaptive forms of governance? Our basin assessments reveal the role of law in: establishing boundaries, that once crossed, signal approaching thresholds; in creating conditions for establishment of rights that alter expectations sufficiently to open a window to new and sometimes collaborative approaches to water governance; in providing an avenue for the development of new process tools to facilitate emergence of adaptive forms of governance; and in presenting barriers to adaptation as a result of rigid and fragmented authority.
Dynamic Interactions of Ntr1-Ntr2 with Prp43 and with U5 Govern the Recruitment of Prp43 To Mediate Spliceosome Disassembly

ABSTRACT The Saccharomyces cerevisiae splicing factors Ntr1 (also known as Spp382) and Ntr2 form a stable complex and can further associate with DExD/H-box RNA helicase Prp43 to form a functional complex, termed the NTR complex, which catalyzes spliceosome disassembly. We show that Prp43 interacts with Ntr1-Ntr2 in a dynamic manner. The Ntr1-Ntr2 complex can also bind to the spliceosome first, before recruiting Prp43 to catalyze disassembly. Binding of Ntr1-Ntr2 or Prp43 does not require ATP, but disassembly of the spliceosome requires hydrolysis of ATP. The NTR complex also dynamically interacts with U5 snRNP. Ntr2 interacts with U5 component Brr2 and is essential for both interactions of NTR with U5 and with the spliceosome. Ntr2 alone can also bind to U5 and to the spliceosome, suggesting a role of Ntr2 in mediating the binding of NTR to the spliceosome through its interaction with U5. Our results demonstrate that dynamic interactions of NTR with U5, through the interaction of Ntr2 with Brr2, and interactions of Ntr1 and Prp43 govern the recruitment of Prp43 to the spliceosome to mediate spliceosome disassembly.
Careful with Composition: Limitations of the Indifferentiability Framework

Random oracle model (ROM) is an idealized model, where all participating parties have access to a public random oracle. This oracle answers all queries, specified by a key, by generating and outputting a truly random value from its output domain. Whenever a query with the same key is repeated, it answers with the same value. Pseudocode for such random oracle is shown in Figure 1(above). The random oracle model was introduced by Bellare and Rogaway [4] to connect cryptographic theory and practice. As a result, a lot of practical, in-use cryptographic schemes are proven secure in ROM and for many of them, ROM proofs are the only ones known.
Regulatory roles of adiponectin receptor 1 and 2 in sheep preadipocytes during adipocyte differentiation

Abstract Adipose tissue has long been considered as an energy storage organ. Adipokines, produced by and secreted from adipose tissues, play an important role in regulating fat accumulation, energy balance, and glucose metabolism. Adiponectin receptors (AdipoR1 and AdipoR2) are expressed in various sheep tissues, including adipose tissue. However, the role of adiponectin receptor-mediated signalling has never been investigated in sheep adipose tissue. In this study, sheep preadipocytes were ultimately differentiated into typical adipocytes in vitro 7 days after differentiation. The expression levels of LPL (lipoprotein lipase), HSL (Hormone-sensitive lipase), FAS (fatty acid synthase), and PPARα/PPARγ (peroxisome proliferator-activated receptor alpha/gamma) were significantly changed in the sheep preadipocytes during differentiation for 7 days. After induction of preadipocyte differentiation, lipid accumulation increased significantly in the transfected preadipocytes of AdipoR1-siRNA1 but decreased in the AdipoR1-overexpression (AdipoR1-GFP) preadipocytes. In addition, the expression of HSL and PPARγ was significantly changed in preadipocytes by transfected with AdipoR1-siRNA1 or AdipoR1-GFP. However, the lipid accumulation and adipogenic gene expression were not significantly changed in preadipocytes by transfected with AdipoR2-siRNA2 and AdipoR2-GFP. Taken together, these results indicate that AdipoR1 could regulate sheep adipose metabolism via regulating HSL and PPARγ expression during adipocyte differentiation. Highlights We first established an in vitro culture system for sheep preadipocytes derived from the paraspinal muscle adipose. Sheep preadipocytes were ultimately differentiated into typical adipocytes after induction and differentiation. Both suppression and overexpression of adiponectin receptor 1 expression affect lipid accumulation and adipocyte metabolism during adipocyte differentiation.
MEDIATION MODELS OF PREGNANCY DESIRES AND UNPLANNED PREGNANCY IN YOUNG, UNMARRIED WOMEN

Summary This paper examines the proposition that sexual and contraceptive behaviours mediate the relationship between the pregnancy desires of young, unmarried women and their having an unplanned pregnancy. The sample consisted of 854 18- to 19-year-old women living in Michigan, USA. First, the positive and negative pregnancy desires of these women were measured, as were the women’s perceptions of the positive and negative desires of their sexual partners. Then the extent to which these four types of desires, as well as several types of interactions between them, prospectively predicted the occurrence of subsequent pregnancies were tested with logistic regression analyses, initially alone and then after the addition of several types of sexual and contraceptive mediator variables. The results demonstrated that four of the ten significant motivational predictors became non-significant following the introduction of the contraceptive mediator variables and that the predictive strength of the other six significant motivational predictors was substantially reduced by their introduction. A number of factors that may account for only a partial mediational effect in some models are discussed.
Confounded by sequencing depth in association studies of rare alleles

Next‐generation DNA sequencing technologies are facilitating large‐scale association studies of rare genetic variants. The depth of the sequence read coverage is an important experimental variable in the next‐generation technologies and it is a major determinant of the quality of genotype calls generated from sequence data. When case and control samples are sequenced separately or in different proportions across batches, they are unlikely to be matched on sequencing read depth and a differential misclassification of genotypes can result, causing confounding and an increased false‐positive rate. Data from Pilot Study 3 of the 1000 Genomes project was used to demonstrate that a difference between the mean sequencing read depth of case and control samples can result in false‐positive association for rare and uncommon variants, even when the mean coverage depth exceeds 30× in both groups. The degree of the confounding and inflation in the false‐positive rate depended on the extent to which the mean depth was different in the case and control groups. A logistic regression model was used to test for association between case‐control status and the cumulative number of alleles in a collapsed set of rare and uncommon variants. Including each individual's mean sequence read depth across the variant sites in the logistic regression model nearly eliminated the confounding effect and the inflated false‐positive rate. Furthermore, accounting for the potential error by modeling the probability of the heterozygote genotype calls in the regression analysis had a relatively minor but beneficial effect on the statistical results. Genet. Epidemiol. 35: 261‐268, 2011. © 2011 Wiley‐Liss, Inc.
Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma

Purpose: Malignant peripheral nerve sheath tumors (MPNST) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have used a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma. Experimental Design: Whole-exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n = 3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was used for functional analysis. Results: There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with nonsynonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Finally, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo. Conclusions: Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study. Clin Cancer Res; 21(18); 4201–11. ©2015 AACR.
The Headache Profile of Idiopathic Intracranial Hypertension

The headache profile of idiopathic intracranial hypertension (IIH, pseudotumour cerebri) has not previously been prospectively studied. We administered a questionnaire to 63 cases at the time of diagnosis. Fifty-eight of the cases had headache and 93% of those with headache reported it to be their most severe ever. Patients characteristically noted a pulsatile headache of gradually increasing intensity that had awakened them. Daily headache occurred in 74% of those reporting headache. Pain in a nerve root distribution or retro-ocular pain with eye movement, uncommon with other headache disorders, help to differentiate this headache syndrome.
One Single In-frame AUG Codon Is Responsible for a Diversity of Subcellular Localizations of Glutaredoxin 2 in Saccharomyces cerevisiae*

Glutaredoxins belong to a family of small proteins with glutathione-dependent disulfide oxidoreductase activity involved in cellular defense against oxidative stress. The product of the yeast GRX2 gene is a protein that is localized both in the cytosol and mitochondria. To throw light onto the mechanism responsible for the dual subcellular distribution of Grx2 we analyzed mutant constructs containing different targeting information. By altering amino acid residues around the two in-frame translation initiation start sites of the GRX2 gene, we could demonstrate that the cytosolic isoform of Grx2 was synthesized from the second AUG, lacking an N-terminal extension. Translation from the first AUG resulted in a long isoform carrying a mitochondrial targeting presequence. The mitochondrial targeting properties of the presequence and the influence of the mature part of Grx2 were analyzed by the characterization of the import kinetics of specific fusion proteins. Import of the mitochondrial isoform is relatively inefficient and results in the accumulation of a substantial amount of unprocessed form in the mitochondrial outer membrane. Substitution of Met35, the second translation start site, to Val resulted in an exclusive targeting to the mitochondrial matrix. Our results show that a plethora of Grx2 subcellular localizations could spread its antioxidant functions all over the cell, but one single Ala to Gly mutation converts Grx2 into a typical protein of the mitochondrial matrix.