220 research outputs found

    Verifying Monadic Second-Order Properties of Graph Programs

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    The core challenge in a Hoare- or Dijkstra-style proof system for graph programs is in defining a weakest liberal precondition construction with respect to a rule and a postcondition. Previous work addressing this has focused on assertion languages for first-order properties, which are unable to express important global properties of graphs such as acyclicity, connectedness, or existence of paths. In this paper, we extend the nested graph conditions of Habel, Pennemann, and Rensink to make them equivalently expressive to monadic second-order logic on graphs. We present a weakest liberal precondition construction for these assertions, and demonstrate its use in verifying non-local correctness specifications of graph programs in the sense of Habel et al.Comment: Extended version of a paper to appear at ICGT 201

    Hierarchical Graph Transformation

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    If systems are specified by graph transformation, large graphs should be structured in order to be comprehensible. In this paper, we present an approach for the rule-based transformation of hierarchically structured (hyper)graphs. In these graphs, distinguished hyperedges contain graphs that can be hierarchical again. Our framework extends the well-known double-pushout approach from at to hierarchical graphs. In particular, we show how pushouts and pushout complements of hierarchical graphs and graph morphisms can be constructed recursively. Moreover, we make rules more expressive by introducing variables which allow to copy and to remove hierarchical subgraphs in a single rule application

    ‘Don’t just travel’: thinking poetically on the way to professional knowledge

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    This paper describes how the medium of ‘found poetry’ is incorporated into a doctoral programme for nurses, educators and allied health and social care professionals at the start of their various doctoral journeys. It advocates a narrative practice approach to issues of researcher identity and reflexivity. ‘Finding’ the poems begins with the creation of collages as representational anchors for students to talk about themselves, their professional practice, their hopes and expectations of the doctoral experience, and their research ideas. (Re)presenting their transcribed talk as poetry involves culling and playing with words, phrases and segments, making changes in spacing, lines and rhythm to arrive at an evocative distillation (Butler-Kisber, 2002). This process enables each person to bring stories and/or fragments of experience into critical engagement with others. Poetic thinking functions pedagogically, helping students find a critical voice to enliven and hone their reflexive writing in relation to their doctoral experience and their research positioning. Arts-based methods of inquiry are an ongoing topic of interest in research communities. Found poetry is a useful starting point to explore creative means by which research participants can recount their stories, and equally, by which researchers can witness and disseminate what they have to tell.self funde

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

    Labelled Graph Rewriting Meets Social Networks

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    International audienceThe intense development of computing techniques and the increasing volumes of produced data raise many modelling and analysis challenges. There is a need to represent and analyse information that is: complex –due to the presence of massive and highly heterogeneous data–, dynamic –due to interactions, time, external and internal evolutions–, connected and distributed in networks. We argue in this work that relevant concepts to address these challenges are provided by three ingredients: labelled graphs to represent networks of data or objects; rewrite rules to deal with concurrent local transformations; strategies to express control versus autonomy and to focus on points of interests. To illustrate the use of these concepts, we choose to focus our interest on social networks analysis, and more precisely in this paper on random network generation. Labelled graph strategic rewriting provides a formalism in which different models can be generated and compared. Conversely, the study of social networks, with their size and complexity, stimulates the search for structure and efficiency in graph rewriting. It also motivated the design of new or more general kinds of graphs, rules and strategies (for instance, to define positions in graphs), which are illustrated here. This opens the way to further theoretical and practical questions for the rewriting community

    Multisite clinical validation of isothermal amplification-based SARS-CoV-2 detection assays using different sampling strategies

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    Isothermal amplification-based tests have been introduced as rapid, low-cost, and simple alternatives to real-time reverse transcriptase PCR (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. The clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP coronavirus disease of 2019 [COVID-19] detection test and OptiGene COVID-19 direct plus RT-loop-mediated isothermal amplification [LAMP] test) was compared with that of clinical RT-PCR assays using different sampling strategies. A total of 1,378 participants were tested across 4 study sites. Compared with standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic site from which the sample was collected. Sensitivity for nasopharyngeal sampling was 65.4% (range across study sites, 52.8% to 79.8%), for midturbinate was 88.2%, for saliva was 55.1% (range across study sites, 42.9% to 77.8%), and for anterior nares was 66.7% (range across study sites, 63.6% to 76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall, 82.7%) and those with a higher viral load (overall, 92.4% for cycle threshold [CT] of #25). Sensitivity and specificity of the OptiGene direct plus RT-LAMP test, which was conducted at a single study site, were 25.5% and 100%, respectively. The Atila iAMP COVID test with midturbinate sampling is a rapid, low-cost assay for detecting SARS-CoV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-CoV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption. IMPORTANCE Numerous SARS-CoV-2 detection assays have been developed and introduced into the market under emergency use authorizations (EUAs). EUAs are granted primarily based on small studies of analytic sensitivity and specificity with limited clinical validations. A thorough clinical performance evaluation of SARS-CoV-2 assays is important to understand the strengths, limitations, and specific applications of these assays. In this first large-scale multicentric study, we evaluated the clinical performance and operational characteristics of two isothermal amplification-based SARS-CoV-2 tests, namely, (i) iAMP COVID-19 detection test (Atila BioSystems, USA) and (ii) COVID-19 direct plus RT-LAMP test (OptiGene Ltd., UK), compared with those of clinical RT-PCR tests using different sampling strategies (i.e., nasopharyngeal, self-sampled anterior nares, self-sampled midturbinate, and saliva). An important specific use for these isothermal amplification-based, rapid, low-cost, and easy-to-perform SARS-CoV-2 assays is to allow for a safer return to preventive clinical encounters, such as cancer screening, particularly in low- and middle-income countries that have low SARS-CoV-2 vaccination rates

    LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease

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    Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate particularly late stages of human disease. Thus, there is a need for an animal model that can be used for investigating the factors that potentiate the inflammatory response within NASH. We have previously shown that 7-day high-fat-high-cholesterol (HFC) feeding induces steatosis and inflammation in both APOE2ki and Ldlr(-/-) mice. However, it is not known whether the early inflammatory response observed in these mice will sustain over time and lead to liver damage. We hypothesized that the inflammatory response in both models is sufficient to induce liver damage over time.APOE2ki and Ldlr(-/-) mice were fed a chow or HFC diet for 3 months. C57Bl6/J mice were used as control.Surprisingly, hepatic inflammation was abolished in APOE2ki mice, while it was sustained in Ldlr(-/-) mice. In addition, increased apoptosis and hepatic fibrosis was only demonstrated in Ldlr(-/-) mice. Finally, bone-marrow-derived-macrophages of Ldlr(-/-) mice showed an increased inflammatory response after oxidized LDL (oxLDL) loading compared to APOE2ki mice.Ldlr(-/-) mice, but not APOE2ki mice, developed sustained hepatic inflammation and liver damage upon long term HFC feeding due to increased sensitivity for oxLDL uptake. Therefore, the Ldlr(-/-) mice are a promising physiological model particularly vulnerable for investigating the onset of hepatic inflammation in non-alcoholic steatohepatitis
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