2,291 research outputs found

    An Analysis of Mechanisms Underlying the Antifibrinolytic Properties of Radiographic Contrast Agents

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    Background: Radiographic contrast agents inhibit fibrinolysis, although by poorly defined pathways. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47998/1/11239_2004_Article_397950.pd

    Induction of Heme Oxygenase-1 Expression Inhibits Platelet-Dependent Thrombosis

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    Heme oxygenase-1 (HO-1) plays a key role in protecting tissue from oxidative stress. Although some studies implicate HO-1 in modulating thrombosis after vascular injury, the impact of HO-1 on the rate of clot formation in vivo is poorly defined. This study examined the potential function of HO-1 in regulating platelet-dependent arterial thrombosis. Platelet-rich thrombi were induced in C57BL/6J mice by applying 10% ferric chloride to the exposed carotid artery. Mean occlusion time of wild-type mice (n = 10) was 14.6 ± 1.0 min versus 12.9 ± 0.6 min for HO-1-/- mice (n = 11, p = 0.17). However, after challenge with hemin, mean occlusion time was significantly longer in wild-type mice (16.3 ± 1.2 min, n = 15) than HO-1-/- mice (12.0 ± 1.0 min, n = 9; p = 0.021). Hemin administration induced an approximately twofold increase in oxidative stress, measured as plasma thiobarbituric acid reactive substances. Immunohistochemical analysis revealed that hemin induced a robust increase in HO-1 expression within the carotid arterial wall. Ex vivo blood clotting within a collagen-coated perfusion chamber was studied to determine whether the accelerated thrombosis observed in HO-1-/- mice was contributed to by effects on the blood itself. Under basal conditions, mean clot formation during perfusion of blood over collagen did not differ between wild-type mice and HO-1-/- mice. However, after hemin challenge, mean clot formation was significantly increased in HO-1-/- mice compared with wild-type controls. These results suggest that, under basal conditions, HO-1 does not exert a significant effect on platelet-dependent clot formation in vivo. However, under conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1. Enhanced HO-1 expression in response to oxidative stress may represent an adaptive response mechanism to down-regulate platelet activation under prothrombotic conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63386/1/1523086041361677.pd

    No sex scandals please, we're French: French attitudes towards politicians' public and private conduct

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    The notion of distinct ‘public’ and ‘private’ spheres underpins much normative and practical engagement with political misconduct. What is less clear is whether citizens draw distinctions between misdemeanours in the ‘public’ and ‘private’ spheres, and whether they judge these in systematically different ways. This paper explores attitudes to political misconduct in France. French citizens are often said to be particularly relaxed about politicians’ private affairs, but there has been little empirical evidence for this proposition. Drawing on original survey data, this paper demonstrates clearly that French citizens draw a sharp distinction between politicians’ public and private transgressions, and are more tolerant of the latter

    Control of dephasing in spin qubits during coherent transport in silicon

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    One of the key pathways towards scalability of spin-based quantum computing systems lies in achieving long-range interactions between electrons and increasing their inter-connectivity. Coherent spin transport is one of the most promising strategies to achieve this architectural advantage. Experimental results have previously demonstrated high fidelity transportation of spin qubits between two quantum dots in silicon and identified possible sources of error. In this theoretical study, we investigate these errors and analyze the impact of tunnel coupling, magnetic field and spin-orbit effects on the spin transfer process. The interplay between these effects gives rise to double dot configurations that include regimes of enhanced decoherence that should be avoided for quantum information processing. These conclusions permit us to extrapolate previous experimental conclusions and rationalize the future design of large scale quantum processors.Comment: 18 pages, 9 figure

    Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

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    Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade. Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis. All statistical tests were two-sided ones. Results: OMm and OM (both with likelihood ratio statistic [LRS] P Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions. Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.</p
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