Path constraints in semistructured data

International audienceWe consider semistructured data as multirooted edge-labelled directed graphs, and path inclusion constraints on these graphs. A path inclusion constraint pnot precedes, equalsq is satisfied by a semistructured data if any node reached by the regular query p is also reached by the regular query q. In this paper, two problems are mainly studied: the implication problem and the problem of the existence of a finite exact model. - We give a new decision algorithm for the implication problem of a constraint pnot precedes, equalsq by a set of bounded path constraints pinot precedes, equalsui where p, q, and the pi's are regular path expressions and the ui's are words, improving in this particular case, the more general algorithms of S. Abiteboul and V. Vianu, and N. Alechina et al. In the case of a set of word equalities ui≡vi, we provide a more efficient decision algorithm for the implication of a word equality u≡v, improving the more general algorithm of P. Buneman et al. We prove that, in this case, implication for nondeterministic models is equivalent to implication for (complete) deterministic ones. - We introduce the notion of exact model: an exact model of a set of path constraints Click to view the MathML source satisfies the constraint pnot precedes, equalsq if and only if this constraint is implied by Click to view the MathML source. We prove that any set of constraints has an exact model and we give a decidable characterization of data which are exact models of bounded path inclusion constraints sets

"SARGOS" : Système d'Alerte et Réponse Graduée Off Shore

International audienceLe projet SARGOS répond à l'émergence du besoin de sûreté des infrastructures offshore civiles vulnérables aux actes de malveillance, de piraterie ou de terrorisme menées à partir de la mer. Il propose le développement d'un système assurant de manière coordonnée la chaîne globale de protection : veille et surveillance automatisées ; détection d'intrusion ; évaluation de dangerosité ; plan de réaction gradué et piloté en temps réel pour rester constamment adapté au niveau de menace représenté par l'intrusion détectée. Une des capacités clefs est l'élaboration d'une stratégie complète et mutualisée de défense, incluant la mise en sûreté des personnes, la diffusion de l'alarme, la coordination des moyens d'assistance extérieure et la mise en oeuvre de moyens de dissuasion non létaux pour apporter une réponse complète à la menace. Un démonstrateur du système SARGOS illustrant toute la chaîne de protection a été déployé sur site pour des expérimentations en vraie grandeur selon des scénarios définis avec les opérationnels. Les essais ont permis de valider tous les points clefs : détection de petites embarcations - levée d'alertes pertinentes couplant analyse de comportement des embarcations et évaluation de dangerosité - Assistance intuitive à l'opérateur pour l'activation de procédures de réaction proposées en dynamique suivant une logique prédéfinie propre aux moyens disponibles

Pneumonia and New Methicillin-resistant Staphylococcus aureus Clone

Necrotizing pneumonia caused by Staphylococcus aureus strains carrying the Panton-Valentin leukocidin gene is a newly described disease entity. We report a new fatal case of necrotizing pneumonia. An S. aureus strain with an agr1 allele and of a new sequence type 377 was recovered, representing a new, emerging, community-acquired methicillin-resistant clone

The Story of the Dopamine Transporter PET Tracer LBT-999: From Conception to Clinical Use

The membrane dopamine transporter (DAT) is involved in a number of brain disorders and its exploration by positron emission tomography (PET) imaging is highly relevant for the early and differential diagnosis, follow-up and treatment assessment of these diseases. A number of carbon-11 and fluor-18 labeled tracers are to date available for this aim, the majority of them being derived from the chemical structure of cocaine. The development of such a tracer, from its conception to its use, is a long process, the expected result being to obtain the best radiopharmaceutical adapted for clinical protocols. In this context, the cocaine derivative (E)-N-(4-fluorobut-2-enyl)2β-carbomethoxy-3β-(4′-tolyl)nortropane, or LBT-999, has passed all the required stages of the development that makes it now a highly relevant imaging tool, particularly in the context of Parkinson's disease. This review describes the different steps of the development of LBT-999 which initially came from its non-fluorinated derivative (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3-(4-methylphenyl) nortropane, or PE2I, because of its high promising properties. [18F]LBT-999 has been extensively characterized in rodent and non-human primate models, in which it demonstrated its capability to explore in vivo the DAT localized at the dopaminergic nerve endings as well as at the mesencephalic cell bodies, in physiological conditions. In lesion-induced rat models of Parkinson's disease, [18F]LBT-999 was able to precisely quantify in vivo the dopaminergic neuron loss, and to assess the beneficial effects of therapeutic approaches such as pharmacological treatment and cell transplantation. Finally recent clinical data demonstrated the efficiency of [18F]LBT-999 in the diagnosis of Parkinson's disease

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

RÔLE DE L'OCCUPATION DU SOL VIS À VIS DE LA MODÉLISATION DES FLUX ENERGÉTIQUES ET HYDRIQUES EN MILIEU URBAIN ET PÉRIURBAIN

National audienceLe projet Rosenhy vise à étudier l’impact de l’occupation du sol sur la modélisation météorologique et hydrologique en termes de flux énergétiques et hydriques, en milieu urbain et périurbain. Trois sites appartenant aux observatoires français OTHU et ONEVU sont au centre de ce projet. Le quartier urbain hétérogène du Pin sec (Nantes), imperméabilisé à environ 45%, a fait l’objet d’une campagne expérimentale durant le mois de juin 2012, visant à estimer les flux de chaleur sensible et latente avec une haute résolution spatiale et temporelle par rapport aux mesures réalisées en continu sur ce site depuis 5 ans. Deux bassins versant périurbains (La Chézine à Nantes et l’Yzeron à Lyon), avec un taux d’imperméabilisation moins important (environ 10%) mais grandissant depuis plusieurs décennies, sont aussi étudiés. Ces deux derniers sites bénéficient d’un suivi hydrométéorologique depuis 10 ans pour la Chézine et 15 ans pour l’Yzeron. Sur ces trois sites, différentes sources de données d’occupation du sol à différentes résolutions sont disponibles :différentes bases de données géographiques communément utilisées par la communauté scientifique et les collectivités et des données télédétectées (multispectrales et hyperspectrales). L’utilisation de ces données en entrée de différents modèles météorologiques et hydrologiques implique un travail d’analyse et de classification pour adapter les informations aux besoins des modèles. Dans ce projet, les différents modèles adaptés au milieu urbain ou périrubain sont évalués et améliorés. Ainsi, les modèles hydrologiques périrubains sont en développement pour prendre en compte les différentes pratiques de gestion des eaux pluviales existantes (noues, toitures végétalisées, ...). L’utilisation conjointe des données simulées par les différents modèles aidera à déterminer le rôle de la part des surfaces naturelles et artificielles sur les bilans énergétique et hydrique en milieu plus ou moins urbanisé. Le milieu périurbain étant en évolution, le projet s’intéressera aussi à des scénarios d’urbanisation prospectifs en regardant d’une part l’impact de la densification sur les scénarios construits pour l’Yzeron lors du projet AVuPUR (ANR-VMCS, 2008-2011) et d’autre part, en réfléchissant conjointement avec Nantes Métropole, aux possibles voies d’évolution sur le bassin de la Chézine

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity

Patients with established type 2 diabetes display both β-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF7L2, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions