20 research outputs found

    Hyperbolic structure for a simplified model of dynamical perfect plasticity

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    This paper is devoted to confront two different approaches to the problem of dynam-ical perfect plasticity. Interpreting this model as a constrained boundary value Friedrichs' system enables one to derive admissible hyperbolic boundary conditions. Using variational methods, we show the well-posedness of this problem in a suitable weak measure theoretic setting. Thanks to the property of finite speed propagation, we establish a new regularity result for the solution in short time. Finally, we prove that this variational solution is actually a solution of the hyperbolic formulation in a suitable dissipative/entropic sense, and that a partial converse statement holds under an additional time regularity assumption for the dissipative solutions

    A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion

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    Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS

    Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

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    Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation

    Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

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    Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

    First Hospitality for Educability: An Ethical, Epistemological, and Political Symbiotic Relationship

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    The major aim of the thesis is to inquire into the human problem of the exclusion and marginalization of 'the other' from a philosophical and historical perspective. The problem arises from a modern conceptual paradigm in which 'the other' is not engaged with. The modern paradigm was influenced by the rise of nationalism, imperialism and colonialism, as well as neo-Cartesian philosophy in which the self constructs his or her thinking on a non-relational process with the other since the emphasis is on the self. Traditionally in philosophy, the notion of 'first philosophy' was based on metaphysics (as in the case of Aristotle), or epistemology (as in the case of Descartes). The thesis argues that the problem of exclusion is intrinsically linked to the lack of a first philosophy that is based on a symbiotic relationship between ethics, epistemology and politics. Utilizing and building on the work of Hannah Arendt, Emanuel Levinas, Jacques Derrida, and Zygmunt Bauman the thesis develops an original argument for the centrality of the engagement with 'the other', a conception of 'first philosophy' based on ethics, epistemology and politics, and the formulation of 'first hospitality' for educability. To concretize the development of the philosophical argument developed in the thesis, the historical happening of the Holocaust is utilized as a hermeneutic for modernity through which the construct of 'first hospitality' emerges as an educable response to the problem of exclusion. The thesis ends with concrete and practical implications for education based on the argument of the thesis as well as the critique of the popular discourse in education on inclusion. From a practical perspective, the thesis offers the notion of 'welcoming education' that is based on 'the other' as agent, as a democratic alternative to inclusion.Ph.D

    Fostering Responsible Research with Genome Editing Technologies: a European Perspective

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    International audienceIn this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation
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