Fluid-driven slow slip and earthquake nucleation on a slip-weakening circular fault

We investigate the propagation of fluid-driven fault slip on a slip-weakening frictional interface separating two identical half-spaces of a three-dimensional elastic solid. Our focus is on axisymmetric circular shear ruptures as they capture the most essential aspects of the dynamics of unbounded ruptures in three dimensions. In our model, fluid-driven aseismic slip occurs in two modes: as an interfacial rupture that is unconditionally stable, or as the quasi-static nucleation phase of an otherwise dynamic rupture. Unconditionally stable ruptures progress through four stages. Initially, ruptures are diffusively self-similar and the interface behaves as if it were governed by a constant friction coefficient equal to the static friction value. Slip then accelerates due to frictional weakening while the cohesive zone develops. Once the latter gets properly localized, a finite amount of fracture energy emerges along the interface and the rupture dynamics is governed by an energy balance of the Griffith's type. In this stage, fault slip transition from a large-toughness to a small-toughness regime. Ultimately, self-similarity is recovered and the fault behaves again as having a constant friction coefficient, but this time equal to the dynamic friction value. When slow slip is the result of a frustrated dynamic instability, slip also initiates self-similarly at a constant peak friction coefficient. The maximum aseismic rupture size varies from a critical nucleation radius (shear modulus divided by slip-weakening rate) to infinity near the limit that separates the two modes of aseismic sliding. We provide analytical and numerical solutions for the problem solved over its full dimensionless parameter space. Due to its three-dimensional nature, the model enables quantitative comparisons with field observations as well as preliminary engineering design of hydraulic stimulation operations.Comment: 51 pages, 11 figure

La déficience intellectuelle (du diagnostic en puces ADN à l'identification de gènes candidats)

L'analyse chromosomique sur puce ADN (ACPA) tend à devenir le principal examen diagnostique dans la déficience intellectuelle (DI). Parmi les techniques d'ACPA, les puces SNP ont l'intérêt de pouvoir détecter les pertes d'hétérozygotie, et par conséquent d identifier les isodisomies uniparentales (iUPD) et les zones d'identité liées à la consanguinité. Nous avons étudié une cohorte de 1 187 patients atteints de DI, dans un cadre diagnostique, sur puces SNP. Nous avons réalisé, par cette étude, 145 diagnostics (12%) dont 2 iUPD et 6 délétions n'incluant qu'un seul gène. De plus, nous avons détecté 639 CNV rares non décrits chez des sujets contrôles et incluant des séquences codantes, ce qui nous a permis d'identifier 11 gènes candidats dans la DI : CAMTA1, SP3, CNTNAP4, NUDT12, STXBP6, DOCK8, DOCK10, SMARCA2, NYAP2, ATAD3A et ATAD3B. Nous avons tenté de valider l'implication de ces gènes par séquençage, mais n'avons trouvé de seconde mutation pour aucun d'entre eux. Toutefois, des réarrangements de CAMTA1 ont été retrouvés dans 2 autres familles avec un phénotype homogène (DI et ataxie congénitale) ce qui nous a permis d affirmer qu'il s'agit d'un gène de DI. Par ailleurs, l'homozygosity mapping, réalisé avec puces SNP, a identifié, par séquençage whole exome, une mutation non-sens homozygote du gène BUD13 dans une famille de DI syndromique. Enfin, de façon fortuite, nous avons caractérisé en ACPA une translocation familiale entraînant une disruption d'un gène d'ataxie spino-cérébelleuse, ATXN10, ce qui a permis de mieux comprendre la physiopathologie de cette maladie. Au total, notre étude démontre l'intérêt des puces SNP dans la DI, d'une part en diagnostic et d'autre part pour l'identification de nouveaux gènes responsables de DI.Chromosomal Microarray Analysis (CMA) has become the main diagnostic test in the field of intellectual disability (ID). Among CMA techniques, SNP arrays have the advantage of identifying losses of heterozygosity in addition to Copy Number Variants (CNVs). Therefore they can detect uniparental isodisomies (iUPD) and regions of identity by descent. We screened a cohort of 1,187 patients with ID, in diagnostic setting, by CMA using SNP arrays. Causal abnormalities, including 2 iUPDs and 6 deletions comprising only one gene, were detected in 145 patients (12%). Moreover we found 639 rare CNVs, absent from control individuals, which included coding sequences. Our results allowed us to identify 11 genes possibly involved in or contributing to ID: CAMTA1, SP3, CNTNAP4, NUDT12, STXBP6, DOCK8, DOCK10, SMARCA2, NYAP2, ATAD3A and ATAD3B. We then screened additional patients with similar phenotypes in order to find a second mutation, but no second mutation was identified in any of them. Besides, CAMTA1 rearrangements were also found among two other families with homogeneous phenotypes (ID and congenital ataxia), which confirms that this gene is involved in ID. Furthermore, thanks to homozygosity mapping made possible by SNP arrays combined with exome sequencing, we identified a homozygous nonsense mutation in the BUD13 gene, in a family with syndromic ID. Finally we incidentally characterized a familial translocation resulting in the disruption of ATXN10, a gene responsible for spinocerebellar ataxia. This translocation has helped to better understand the pathophysiology of the disease. Overall, our study shows the importance of SNP arrays for the molecular diagnosis of ID and as a tool to identify genes responsible for ID.PARIS5-Bibliotheque electronique (751069902) / SudocSudocFranceF

Identification of a DAGLB Mutation in a Non-Chinese Patient with Parkinson's Disease

Liu et al. recently reported that biallelic mutations in DAGLB are responsible for autosomal recessive early-onset Parkinson's disease. They identified six patients carrying DAGLB mutations, all of Chinese origin and presenting with typical Parkinson disease. No additional cases outside China have been reported so far.To assess the causality of DAGLB in our cohort, we used data mining in the exomes of 684 index cases with either autosomal recessive or sporadic early onset Parkinson disease (< 50 years). We identified a homozygous p.Pro357Leu missense variant in a single consanguineous PD case. This mutation predicted deleterious, affects a conserved amino acid localized in the catalytic domain of the protein nearby the pathological p.Asp363Gly mutation described in the previous paper. As the most frequent genes involved in AR-PD (PRKN, PINK1), the DAGLB-associated disease presents and evolves like typical PD.This work reinforces the fact that DAGLB is involved in early onset Parkinson disease, but given the fact that we identified a single patient among 684 index cases screened, we conclude that DAGLB is a very rare cause of early onset autosomal recessive Parkinson disease. However, we demonstrate that, mutations in DAGLB are not limited to the Chinese population but can also account for PD in North Africa.We feel that these new data indicate that DAGLB variants should be considered in non-Chinese cases with early-onset typical Parkinson disease

Recent advances in understanding dominant spinocerebellar ataxias from clinical and genetic points of view [version 1; referees: 3 approved]

Abstract Spinocerebellar ataxias (SCAs) are rare types of cerebellar ataxia with a dominant mode of inheritance. To date, 47 SCA subtypes have been identified, and the number of genes implicated in SCAs is continually increasing. Polyglutamine (polyQ) expansion diseases (ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, CACNA1A/SCA6, ATXN7/SCA7, TBP/SCA17, and ATN1/DRPLA) are the most common group of SCAs. No preventive or curative treatments are currently available, but various therapeutic approaches, including RNA-targeting treatments, such as antisense oligonucleotides (ASOs), are being developed. Clinical trials of ASOs in SCA patients are already planned. There is, therefore, a need to identify valid outcome measures for such studies. In this review, we describe recent advances towards identifying appropriate biomarkers, which are essential for monitoring disease progression and treatment efficacy. Neuroimaging biomarkers are the most powerful markers identified to date, making it possible to reduce sample sizes for clinical trials. Changes on brain MRI are already evident at the premanifest stage in SCA1 and SCA2 carriers and are correlated with CAG repeat size. Other potential biomarkers have also been developed, based on neurological examination, oculomotor study, cognitive assessment, and blood and cerebrospinal fluid analysis. Longitudinal studies based on multimodal approaches are required to establish the relationships between parameters and to validate the biomarkers identified

Comfortable and Safe Decelerations for a Self-Driving Transit Bus

International audienceWe propose a combination of Model Predictive Control and Lexicographic Programming to address complex scenarios with conflicting goals related to various aspects of comfort and safety of passengers in a transit bus, generating different deceleration profiles depending on the speed of the bus and distance to obstacles, validated in experiments with a standard transit bus equipped with self-driving capabilities

Assessment of in situ nest decay rate for chimpanzees (Pan troglodytes ellioti Matschie, 1914) in Mbam-Djerem National Park, Cameroon : implications for long-term monitoring

Accurate assessment of great ape populations is a prerequisite for conservation planning. Indirect survey methods using nest and dung, and a set of conversion parameters related to nest decay rates, are increasingly used. Most surveys use the standing crop nest count (SCNC) method, whereby nests are counted along transects and the estimated nest density is converted into chimpanzee density using an often non-local nest decay rate. The use of non-local decay rate is thought to introduce substantial bias to ape population estimates given that nest decay rates vary with location, season, rainfall, nest shape, and tree species used. SCNC method has previously been applied in Mbam-Djerem National Park (MDNP) in Cameroon, for chimpanzee surveys using a non-local nest decay rate. This current study aimed to measure a local nest decay rate for MDNP and implications for chimpanzee population estimates in the MDNP. The mean nest decay rate estimated using a logistic regression analysis was 127 [95% CI (100-160)] days. Moreover, the results suggested that rainfall strongly infuenced the nest decay rate over the early stage of the lifetime of the nests. The study confrms that estimates of chimpanzee density and abundance using non-local decay rates should be treated with caution. Our research emphasized the importance of using local nest decay rates and other survey methods which do not depend on decay rates to obtain more accurate estimates of chimpanzee densities in order to inform conservation strategies of these great apes in MDNP

Le risque de feux de brousse sur la Grande Terre de Nouvelle-Calédonie : l’Homme responsable, mais pas coupable

Depuis des années en Nouvelle-Calédonie, les feux anthropiques croissent en nombre, fréquence et étendue, menaçant la conservation des écosystèmes et devenant un danger pour les populations. Les estimations montrent que les feux de forêt et de brousse dévastent en moyenne chaque année de 20 000 à 50 000 ha soit près de 3 % de la superficie totale de l’archipel. Au delà de la perte de biodiversité, il en résulte le cortège des risques d’impacts indirects des incendies : assèchement des cours d’eau en saison sèche, appauvrissement des sols, accélération du processus de désertification, aggravation du ruissellement, augmentation de l’érosion des sols, phénomènes d’hypersédimentation, étouffement des récifs coralliens, etc., autant de maux qui affectent directement les populations locales et leur milieu de vie dont une grande partie se nourrit des produits d’une agriculture vivrière traditionnelle et ou d’une pêche artisanale. Cependant malgré les enjeux liés à la gestion de ce risque majeur, l’une des constatations que nous pouvons faire, au-delà du manque de moyens humains et techniques de lutte, est une connaissance fragmentaire sur la répartition et les causes des incendies en Nouvelle-Calédonie. Cette communication, présentant quelques résultats du programme ANR INC (Incendies et biodiversité des écosystèmes en Nouvelle-Calédonie), aura comme objectifs d’analyser la distribution spatiale de l’occurrence des feux détectés par les satellites MODIS. Ces informations seront croisées au travers d’un SIG à des indicateurs spatialisés de type statuts fonciers (terrains coutumiers/privé) socio-économiques (taux de chômage, niveau scolaire, origine ethnique..) afin d’identifier des facteurs corrélés aux départs d'incendies. Dans un deuxième temps, l’étude de la perception de ce risque chez les populations Kanak nous permettra de mettre en évidence les causes principales des feux de brousse non maîtrisés.In New Caledonia, for many years, anthropogenic fires have been increasing in number, frequency and extent, posing a threat to the conservation of ecosystems and a danger to human populations. Estimates show that forest fires and bushfires devastate an average of 20,000 to 50,000 ha a year, which represents about 3% of the total surface area of the archipelago. Above and beyond biodiversity loss, fires can cause a range of indirect negative impacts (dried-up watercourses in the dry season, soil depletion, accelerated desertification, increased run-off and soil erosion, hypersedimentation phenomena, smothering of coral reefs etc.), which directly affect the environment and local populations, many of whom rely on subsistence farming and/or small-scale fishing. However, despite the challenges associated with managing this major risk, it is clear that, in addition to the shortage of human and technical fire-fighting resources, the knowledge about the distribution and causes of fires in New Caledonia is fragmentary. This paper describes some of the results of the research project (Fires and ecosystem biodiversity in New Caledonia) and aims to analyse the spatial distribution of fires detected by the MODIS satellites. This information will be cross-referenced in a GIS with spatial indicators highlighting both land tenure (customary/private land) and socio-economic status (unemployment rates, educational attainment, ethnicity etc.) in order to identify factors relating to outbreaks of fire. Second, studying the perception of risk among the Kanak populations will allow us to highlight the main causes of uncontrolled bushfires