18 research outputs found

    Critical behaviour of combinatorial search algorithms, and the unitary-propagation universality class

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    The probability P(alpha, N) that search algorithms for random Satisfiability problems successfully find a solution is studied as a function of the ratio alpha of constraints per variable and the number N of variables. P is shown to be finite if alpha lies below an algorithm--dependent threshold alpha\_A, and exponentially small in N above. The critical behaviour is universal for all algorithms based on the widely-used unitary propagation rule: P[ (1 + epsilon) alpha\_A, N] ~ exp[-N^(1/6) Phi(epsilon N^(1/3)) ]. Exponents are related to the critical behaviour of random graphs, and the scaling function Phi is exactly calculated through a mapping onto a diffusion-and-death problem.Comment: 7 pages; 3 figure

    Tetracycline Inducible Gene Manipulation in Serotonergic Neurons

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    The serotonergic (5-HT) neuronal system has important and diverse physiological functions throughout development and adulthood. Its dysregulation during development or later in adulthood has been implicated in many neuropsychiatric disorders. Transgenic animal models designed to study the contribution of serotonergic susceptibility genes to a pathological phenotype should ideally allow to study candidate gene overexpression or gene knockout selectively in serotonergic neurons at any desired time during life. For this purpose, conditional expression systems such as the tet-system are preferable. Here, we generated a transactivator (tTA) mouse line (TPH2-tTA) that allows temporal and spatial control of tetracycline (Ptet) controlled transgene expression as well as gene deletion in 5-HT neurons. The tTA cDNA was inserted into a 196 kb PAC containing a genomic mouse Tph2 fragment (177 kb) by homologous recombination in E. coli. For functional analysis of Ptet-controlled transgene expression, TPH2-tTA mice were crossed to a Ptet-regulated lacZ reporter line (Ptet-nLacZ). In adult double-transgenic TPH2-tTA/Ptet-nLacZ mice, TPH2-tTA founder line L62-20 showed strong serotonergic β-galactosidase expression which could be completely suppressed with doxycycline (Dox). Furthermore, Ptet-regulated gene expression could be reversibly activated or inactivated when Dox was either withdrawn or added to the system. For functional analysis of Ptet-controlled, Cre-mediated gene deletion, TPH2-tTA mice (L62-20) were crossed to double transgenic Ptet-Cre/R26R reporter mice to generate TPH2-tTA/Ptet-Cre/R26R mice. Without Dox, 5-HT specific recombination started at E12.5. With permanent Dox administration, Ptet-controlled Cre-mediated recombination was absent. Dox withdrawal either postnatally or during adulthood induced efficient recombination in serotonergic neurons of all raphe nuclei, respectively. In the enteric nervous system, recombination could not be detected. We generated a transgenic mouse tTA line (TPH2-tTA) which allows both inducible and reversible transgene expression and inducible Cre-mediated gene deletion selectively in 5-HT neurons throughout life. This will allow precise delineation of serotonergic gene functions during development and adulthood

    L’intelligence artificielle dans les structures d’urgences : place de la formation et de la garantie humaine

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    International audienceThe research on artificial intelligence (AI) applied to emergency medicine and its daily use in emergency departments has significantly increased in recent years. AI should be considered as a tool to assist in the diagnosis and therapeutic management of patients and to improve the organization of the emergency departments, particularly considering contextual constraints from several aspects. AI has not only advantages (reproducibility, speed) but also risks (error, loss of critical thinking). Like the General Data Protection Regulation, especially for health, the European Commission has published a draft regulation called “AI Act” for the design, development, and use of AI algorithms. It wishes to impose, among other things, a human guarantee, in other words, human supervision to ensure the safety of patients, caregivers, and institutions. The establishment of a multiprofessional human guarantee college aiming to guarantee the supervision of AI tools from design, development, deployment, and daily use will thus ensure the long-term safety of patients.La recherche sur l’intelligence artificielle (IA) appliquée à la médecine d’urgence et son utilisation au quotidien dans les structures d’urgences (SU) ont augmenté significativement ces dernières années. L’IA doit être considérée comme un outil d’aide à la prise en charge diagnostique et thérapeutique des patients et d’amélioration de l’organisation des SU, notamment par la prise en compte de contraintes « métiers », contextuelles, relatives aux patients et plus généralement structurelles. L’IA comporte des avantages (reproductibilité, rapidité) mais aussi des risques (erreur, perte d’esprit critique). À l’image du Règlement général sur la protection des données et notamment de santé, la Commission européenne a publié un projet de règlement nommé « AI Act » pour la conception, le développement et l’utilisation des algorithmes d’IA. Elle souhaite imposer, entre autres, une garantie humaine, autrement dit une supervision humaine pour assurer la sécurité des patients, des soignants et des institutions. La mise en place d’un collège de garantie humaine pluriprofessionnel visant à garantir la supervision des outils d’IA de la conception au développement, au déploiement et à l’utilisation quotidienne permettra ainsi d’assurer durablement la sécurité des patients

    Autonomic nervous system involvement in the giant axonal neuropathy (GAN) KO mouse: implications for human disease

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    PURPOSE: Giant axonal neuropathy (GAN) is an inherited severe sensorimotor neuropathy. The aim of this research was to investigate the neuropathologic features and clinical autonomic nervous system (ANS) phenotype in two GAN knockout (KO) mouse models. Little is known about ANS involvement in GAN in humans, but autonomic signs and symptoms are commonly reported in early childhood. METHODS: Routine histology and immunohistochemistry was performed on GAN KO mouse specimens taken at various ages. Enteric dysfunction was assessed by quantifying the frequency, weight, and water content of defecation in GAN KO mice. RESULTS: Histological examination of the enteric, parasympathetic and sympathetic ANS of GAN KO mice revealed pronounced and widespread neuronal perikaryal intermediate filament inclusions. These neuronal inclusions served as an easily identifiable, early marker of GAN in young GAN KO mice. Functional studies identified an age-dependent alteration in fecal weight and defecation frequency in GAN KO mice. CONCLUSIONS: For the first time in the GAN KO mouse model, we described the early, pronounced and widespread neuropathologic features involving the ANS. In addition, we provided evidence for a clinical autonomic phenotype in GAN KO mice, reflected in abnormal gastrointestinal function. These findings in GAN KO mice suggest that consideration should be given to ANS involvement in human GAN, especially when considering treatments and patient care
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