Etude de la sûreté de fonctionnement d'un aménagement hydraulique de génie civil: application à des ouvrages de protection contre les inondations de la ville de Nîmes

National audienceCemagref and ISL consulting engineers produced for Nîmes city (FRANCE) a reliability study concerning a hydraulic works system, composed of several dams, singular civil works, canals and collectors networks, and intended to ensure protection against floods. This study constitutes one of the first quantitative reliability studies of a hydraulic works system realized in France. This article presents the step and the methodologies used in a reliability quantitative analysis. The methodological developments are illustrated all along the text through this remarkable application.Le Cemagref et le bureau d'ingénieurs conseils ISL ont réalisé, pour le compte de la ville de Nîmes, une étude de sûreté de fonctionnement portant sur un aménagement hydraulique, constitué de plusieurs barrages, ouvrages singuliers et réseaux à ciel ouvert et enterrés, et destiné à assurer une protection contre les inondations. Cette étude constitue l'une des premières études quantitatives de sûreté de fonctionnement d'un aménagement hydraulique de génie civil réalisée en France. Le présent article présente la démarche et les méthodologies mises en ½uvre dans le cadre d'une analyse quantitative de sûreté de fonctionnement. Les développements méthodologiques sont illustrés tout le long du texte à travers cette application remarquable

An integrative bioinformatics approach to decipher adipocyte-induced transdifferentiation of osteoblast

International audienceIn human, bone loss is associated with increased marrow adipose tissue and recent data suggest that medullary adipocytes could play a role in osteoporosis by acting on neighboring bone-forming osteoblasts. Supporting this hypothesis, we previously showed, in a coculture model based on human bone marrow stromal cells, that factors secreted by adipocytes induced the conversion of osteoblasts towards an adipocyte-like phenotype. In this work, we employed an original integrative bioinformatics approach connecting proteomic and transcriptomic data from adipocytes and osteoblasts, respectively, to investigate the mechanisms underlying their crosstalk. Our analysis identified a total of 271 predicted physical interactions between adipocyte-secreted proteins and osteoblast membrane protein coding genes and proposed three pathways for their potential contribution to osteoblast transdifferentiation, the PI3K-AKT, the JAK2-STAT3 and the SMAD pathways. Our findings demonstrated the effectiveness of our integrative omics strategy to decipher cell-cell communication events

Retour d'expérience sur les désordres des digues de l'Agly maritime. Analyse des phénomènes de "sand-boils"

International audienceThe numerous floods experienced by the levees of the downstream Agly River (13.2 km of river leveed on both banks) caused more or less significant damage to their structure, including two breaches and flooding of the "protected" plain. Different mechanisms of deterioration have been implicated, and some areas of the levees have exhibited recurring damages. This paper, after the structures and protected assets, presents a description of each of these events in terms of (i) hydrology and hydraulics, (ii) description of the observed damages, (iii) investigations carried out and (iv) ) reinforcement or repair works that has been undertaken. It also presents the lessons that could be drawn from these observations in terms of management and reinforcement of structures, and in terms of mechanisms of degradation and failure as well as the remaining uncertainties in this regard. Sand-boil phenomena appear regularly in two well-identified sectors; the foundation is composed of a cohesive and weakly permeable surface layer (sandy loams and silty sands, 1 to 5 m thick) on a permeable layer (fine sands with gravelly sands up to at least 10 m under the natural terrain). The mechanisms at work in the foundation can combine liquefaction and different forms of internal erosion (certainly suffusion and regressive erosion, potentially contact erosion and concentrated leak erosion). The trigger mechanism(s) in the superficial cohesive layer are less or even poorly identified, despite the conventionally used equilibrium laws. Finally, the sequences of mechanisms leading from the eroded or decompressed zones in foundation to sinkholes on the surface are also poorly identified. The need for future research on these issues appears, in order to, among other things, better adapt the design repair works.Les nombreuses crues notables subies par les digues de l'aval du fleuve Agly (13,2 km de cours d'eau endigué sur ses deux rives) ont causé des dégâts plus ou moins importants à leur structure, allant à deux reprises jusqu'à des brèches et à l'inondation de la plaine "protégée". Différents mécanismes de détérioration ont été mis en cause, et certains secteurs de digue ont manifesté des désordres récurrents. Cet article, après les ouvrages et les enjeux protégés, présente une description de chacun de ces événements en termes (i) d'hydrologie et d'hydraulique, (ii) de description des désordres observés, (iii) des investigations effectuées et (iv) des travaux de confortement ou de réparation qui ont été entrepris. Il présente également les leçons qui ont pu être tirées de ces observations en termes de gestion et de confortement des ouvrages, et en termes de mécanismes de dégradation et de rupture à l'oeuvre et des incertitudes qui subsistent à cet égard. Des phénomènes de sand-boils, apparaissent régulièrement sur deux secteurs bien identifiés ; la fondation y est composée d'une couche superficielle cohésive et faiblement perméable (limons sableux et sables limoneux, de 1 à 5 m d'épaisseur) sur une couche perméable (sables fins à sables graveleux jusqu'à au moins 10 m sous le terrain naturel). Les mécanismes à l'oeuvre en fondation peuvent combiner de la liquéfaction et différents mécanismes d'érosion interne (suffusion et érosion régressive certainement, érosion de contact et érosion de conduit potentiellement). Le ou les mécanismes déclencheurs dans la couche cohésive superficielle sont, eux, moins bien voire mal identifiés (le soulèvement hydraulique ou le "claquage" entre autres), malgré les lois d'équilibre classiquement utilisées. Enfin, les enchaînements de mécanismes conduisant depuis les zones érodées ou décomprimées en fondation jusqu'aux aux fontis en surface sont également mal identifiés. Il apparaît la nécessité de recherches futures sur ces questions, afin, entre autres de mieux asseoir la conception et le dimensionnement des confortements

Retour d'expérience sur les désordres des digues de l'Agly maritime. Analyse des phénomènes de "sand-boils"

International audienceThe numerous floods experienced by the levees of the downstream Agly River (13.2 km of river leveed on both banks) caused more or less significant damage to their structure, including two breaches and flooding of the "protected" plain. Different mechanisms of deterioration have been implicated, and some areas of the levees have exhibited recurring damages. This paper, after the structures and protected assets, presents a description of each of these events in terms of (i) hydrology and hydraulics, (ii) description of the observed damages, (iii) investigations carried out and (iv) ) reinforcement or repair works that has been undertaken. It also presents the lessons that could be drawn from these observations in terms of management and reinforcement of structures, and in terms of mechanisms of degradation and failure as well as the remaining uncertainties in this regard. Sand-boil phenomena appear regularly in two well-identified sectors; the foundation is composed of a cohesive and weakly permeable surface layer (sandy loams and silty sands, 1 to 5 m thick) on a permeable layer (fine sands with gravelly sands up to at least 10 m under the natural terrain). The mechanisms at work in the foundation can combine liquefaction and different forms of internal erosion (certainly suffusion and regressive erosion, potentially contact erosion and concentrated leak erosion). The trigger mechanism(s) in the superficial cohesive layer are less or even poorly identified, despite the conventionally used equilibrium laws. Finally, the sequences of mechanisms leading from the eroded or decompressed zones in foundation to sinkholes on the surface are also poorly identified. The need for future research on these issues appears, in order to, among other things, better adapt the design repair works.Les nombreuses crues notables subies par les digues de l'aval du fleuve Agly (13,2 km de cours d'eau endigué sur ses deux rives) ont causé des dégâts plus ou moins importants à leur structure, allant à deux reprises jusqu'à des brèches et à l'inondation de la plaine "protégée". Différents mécanismes de détérioration ont été mis en cause, et certains secteurs de digue ont manifesté des désordres récurrents. Cet article, après les ouvrages et les enjeux protégés, présente une description de chacun de ces événements en termes (i) d'hydrologie et d'hydraulique, (ii) de description des désordres observés, (iii) des investigations effectuées et (iv) des travaux de confortement ou de réparation qui ont été entrepris. Il présente également les leçons qui ont pu être tirées de ces observations en termes de gestion et de confortement des ouvrages, et en termes de mécanismes de dégradation et de rupture à l'oeuvre et des incertitudes qui subsistent à cet égard. Des phénomènes de sand-boils, apparaissent régulièrement sur deux secteurs bien identifiés ; la fondation y est composée d'une couche superficielle cohésive et faiblement perméable (limons sableux et sables limoneux, de 1 à 5 m d'épaisseur) sur une couche perméable (sables fins à sables graveleux jusqu'à au moins 10 m sous le terrain naturel). Les mécanismes à l'oeuvre en fondation peuvent combiner de la liquéfaction et différents mécanismes d'érosion interne (suffusion et érosion régressive certainement, érosion de contact et érosion de conduit potentiellement). Le ou les mécanismes déclencheurs dans la couche cohésive superficielle sont, eux, moins bien voire mal identifiés (le soulèvement hydraulique ou le "claquage" entre autres), malgré les lois d'équilibre classiquement utilisées. Enfin, les enchaînements de mécanismes conduisant depuis les zones érodées ou décomprimées en fondation jusqu'aux aux fontis en surface sont également mal identifiés. Il apparaît la nécessité de recherches futures sur ces questions, afin, entre autres de mieux asseoir la conception et le dimensionnement des confortements

CNV-LDC: an optimised method for copy number variation discovery in low depth of coverage data

Recent advances in sequencing technologies led to an increasing number of highly accurate ways of identifying and studying copy number variations (CNVs). Many methods and software packages have been developed for the detection of CNVs, generally these methods are based on four approaches: Assembly Based, Split Read, Read-Paired mapping and Read Depth. In this paper, we introduce an alternative method for detecting CNVs from short sequencing reads, CNV-LDC (Copy Number Variation-Low Depth of Coverage), that complements the existing method named CNV-TV (Copy Number Variation-Total Variation). To evaluate the performance of our method we compared it with some of the commonly used methods that are freely available and use different approaches to identify CNVs: Pindel, CNVnator and DELLY2. We used for this comparative study simulated data to gain control over deletions and duplications, then we used real data from the 1000 genome project to further test the quality of detected CNVs

A Specific Diplotype H1j/H2 of the MAPT Gene Could Be Responsible for Parkinson’s Disease with Dementia

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease. Five to ten percent of patients have monogenic form of the disease, while most of sporadic PD cases are caused by the combination of genetic and environmental factors. Microtubule-associated protein tau (MAPT) has been appointed as one of the most important risk factors for several neurodegenerative diseases including PD. MAPT is characterized by an inversion in chromosome 17 resulting in two distinct haplotypes H1 and H2. Studies described a significant association of MAPT H1j subhaplotype with PD risk, while H2 haplotype was associated with Parkinsonism, particularly to its bradykinetic component. We report here an isolated case displaying an akinetic-rigid form of PD, with age of onset of 41 years and a good response to levodopa, who developed dementia gradually during the seven years of disease progression. The patient does not carry the LRRK2 G2019S mutation, copy number variations, nor pathogenic and rare variants in known genes associated with PD. MAPT subhaplotype genotyping revealed that the patient has the H1j/H2 diplotype, his mother H1j/H1j, his two healthy brothers H1j/H1v and his deceased father was by deduction H1v/H2. The H1j/H2 diplotype was shown in a total of 3 PD patients among 80, who also did not have known PD-causing mutation and in 1 out of 92 healthy individual controls. The three patients with this diplotype all have a similar clinical phenotype. Our results suggest that haplotypes H1j and H2 are strong risk factor alleles, and their combination could be responsible for early onset of PD with dementia

Evidence for prehistoric origins of the G2019S mutation in the North African Berber population.

The most common cause of the monogenic form of Parkinson's disease known so far is the G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) gene. Its frequency varies greatly among ethnic groups and geographic regions ranging from less than 0.1% in Asia to 40% in North Africa. This mutation has three distinct haplotypes; haplotype 1 being the oldest and most common. Recent studies have dated haplotype 1 of the G2019S mutation to about 4000 years ago, but it remains controversial whether the mutation has a Near-Eastern or Moroccan-Berber ancestral origin. To decipher this evolutionary history, we genotyped 10 microsatellite markers spanning a region of 11.27 Mb in a total of 57 unrelated Moroccan PD patients carrying the G2019S mutation for which the Berber or Arab origin was established over 3 generations based on spoken language. We estimated the age of the most recent common ancestor for the 36 Arab-speaking and the 15 Berber-speaking G2019S carriers using the likelihood-based method with a mutation rate of 10-4. Data analysis suggests that the shortest haplotype originated in a patient of Berber ethnicity. The common founder was estimated to have lived 159 generations ago (95% CI 116-224) for Arab patients, and 200 generations ago (95% CI 123-348) for Berber patients. Then, 29 native North African males carrying the mutation were assessed for specific uniparental markers by sequencing the Y-chromosome (E-M81, E-M78, and M-267) and mitochondrial DNA (mtDNA) hypervariable regions (HV1 and HV2) to examine paternal and maternal contributions, respectively. Results showed that the autochthonous genetic component reached 76% for mtDNA (Eurasian and north African haplogroups) and 59% for the Y-chromosome (E-M81 and E-M78), suggesting that the G2019S mutation may have arisen in an autochthonous DNA pool. Therefore, we conclude that LRRK2 G2019S mutation most likely originated in a Berber founder who lived at least 5000 years ago (95% CI 3075-8700)

mtDNA and Y-chomosomeuniparental markers analysis for the 29 G2019S male carriers.

<p>mtDNA and Y-chomosomeuniparental markers analysis for the 29 G2019S male carriers.</p

Shared haplotype inferred from five G2019S homozygous patients.

<p>Shared haplotype inferred from five G2019S homozygous patients.</p

Map of the Mediterranean Basin illustrating the distribution of the G2019S mutation frequencies and the main conquests and invasions that the Maghreb has experienced since antiquity.

<p>Map of the Mediterranean Basin illustrating the distribution of the G2019S mutation frequencies and the main conquests and invasions that the Maghreb has experienced since antiquity.</p