Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

La gestion des déchets radioactifs et la nécessité d'une loi nucléaire en France

The law of 30 december 1991 on research into the management of radioactive waste could represent the first step towards the comprehensive nuclear législation needed in France. Nowadays, the short- and medium-term management of radioactive waste no longer présents insurmountable technical problems and can be regulated by a specially-adapted legal framework. However, this is not the case for the long-term management of long-life or highly active waste. The technical aspects of such management have not yet been mastered and the long-term uncertainty is further complicated by social and ethical factors. The role of law is this long-term management is open to many questions (should it address the concept of irreversibility ? how should the polluter-pays principle and the precautionary principle by implemented ?) which can only be answered, however imperfectly, by recourse to legislation.La loi du 30 décembre 1991 relative aux recherches sur la gestion des déchets radioactifs pourrait constituer l'amorce de la législation nucléaire d'ensemble dont la France a besoin. Si la gestion à court et moyen terme des déchets radioactifs ne pose plus actuellement de difficultés techniques insurmontables et peut faire l'objet d'un encadrement juridique adapté, il n'en va pas de même de la gestion à long terme des déchets à vie longue et/ou haute activité. Les aspects techniques de cette gestion sont encore mal maîtrisés et les incertitudes du long terme se doublent ici d'aspects sociaux-éthiques. L'approche juridique de cette gestion à long terme soulève de nombreuses questions (faut-il organiser l'irréversibilité ? quelle application du principe du pollueur/payeur, du principe de précaution ?) dont la solution, même imparfaite, implique nécessairement le recours à la loi.Colson Jean-Philippe, Schapira Jean-Paul. La gestion des déchets radioactifs et la nécessité d'une loi nucléaire en France. In: Revue Juridique de l'Environnement, n°3, 1996. pp. 247-260

Physique associée au contrôle et à la sûreté des systèmes hybrides

Dans le cadre du retraitement des déchets radioactifs, les ADS sont à considérer en tant qu'incinérateurs massifs d'actinides mineurs. Dans une première partie, l'analyse critique des différentes filières nucléaires montre qu'un spectre rapide, un caloporteur hélium et un combustible nitrure chargé à 100 % d'actinides mineurs, répondraient idéalement aux exigences de transmutation massive des ADS. La démonstration du contrôle et de la sûreté de ces systèmes représente l'objectif majeur de cette étude. Tout d'abord, la compréhension du comportement dynamique et spatial du flux dans les ADS est indispensable. Nous avons donc défini un indicateur permettant la quantification des découplages spatiaux. Il met en évidence les insuffisances de la cinétique point pour l'étude de transitoires très localisés, et les différences de propagation des perturbations dans les ADS et les cœurs critiques. Puis, plus concrètement, les conséquences de situations accidentelles (transitoire de source, défocalisation de faisceau, insertion de réactivité, perte de débit et dépressurisation) sont évaluées dans ces cœurs massivement chargés en actinides mineurs. On montre alors que la coupure automatique de faisceau répond à l'ensemble des transitoires étudiés, en préservant des marges de sûreté importantes. L'arrêt d'urgence de l'accélérateur est alors initié par une évolution anormale des paramètres de contrôle du cœur. Ceux-ci, à l'exception de la réactivité, peuvent être mesurés en sous critique comme en critique. En ce qui concerne la réactivité, nous proposons une méthode permettant sa détermination absolue dans les ADS : lors du démarrage du réacteur, la réactivité doit être étalonnée en couplant deux méthodes relatives de mesure de la réactivité (Source Pulsée et Multiplication de Source Approchée) pour plusieurs niveaux de sous criticité successifs. Par la suite, le suivi en ligne de la réactivité à partir de l'étalon initial est réalisé de façon analogue aux cœurs critiques.Regarding nuclear waste management, ADS can be considered as large minor actinides burners. In a first part, a critical analysis of different reactor types shows that fast spectrum, helium coolant and nitride fuel, containing 100% minor actinides, agree perfectly with the high transmutation requirements of ADS. The control and safety demonstration of this system represents the main purpose of this study. Understanding spatial and dynamic behavior of ADS flux is absolutely necessary. For this purpose, we have defined an indicator to quantify spatial decoupling. It shows, on the one hand, point kinetic deficiency to study local transients, and on the other hand, perturbations propagation differences between ADS and critical cores. Then, in a more concrete approach, accidental sequences (source transient, beam defocalisation, reactivity insertions, loss of flow, depressurization) are evaluated for this core, strongly loaded with minor actinides. It is shown that the automatic beam shutdown leads to preserve large safety margins for all studied transients. The accelerator emergency stop is induced by an unexpected evolution of the core control parameters. These parameters, except reactivity, can be directly measured in subcritical systems like in critical ones. Concerning reactivity, we suggest a new method for its absolute determination in ADS : at the time of reactor startup, the reactivity must be calibrated by coupling two methods of relative reactivity measurements (pulsed source and Approached Source Multiplication) for successive subcritical levels. After that, the on-line follow-up of reactivity is obtained from this calibration like in a critical core.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Les enjeux d'une loi nucleaire en France

Available at INIST (FR), Document Supply Service, under shelf-number : RP 185 (3512) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts

We have studied complex I (NADH-ubiquinone reductase) defects of the mitochondrial respiratory chain in 2 infants who died in the neonatal period from 2 different neurological forms of severe neonatal lactic acidosis. Specific and marked decrease in complex I activity was documented in muscle, liver, and cultured skin fibroblasts. Biochemical characterization and study of the genetic origin of this defect were performed using cultured fibroblasts. Immunodetection of 6 nuclear DNA–encoded (20, 23, 24, 30, 49, and 51 kDa) and 1 mitochondrial DNA–encoded (ND1) complex I subunits in fibroblast mitochondria revealed 2 distinct patterns. In 1 patient, complex I contained reduced amounts of the 24- and 51-kDa subunits and normal amounts of all the other investigated subunits. In the second patient, amounts of all the investigated subunits were severely decreased. The data suggest partial or extensive impairment of complex I assembly in both patients. Cell fusion experiments between 143B206 ρ° cells, fully depleted of mitochondrial DNA, and fibroblasts from both patients led to phenotypic complementation of the complex I defects in mitochondria of the resulting cybrid cells. These results indicate that the complex I defects in the 2 reported cases are due to nuclear gene mutations

Spallation study with proton beams around 1 GeV: Neutron production

Experiments performed at Lab. Nat. SATURNE on neutron produced by spallation from proton beams in the range 0.8 - 1.6 GeV are presented. Experimental data compared with codes show a significant improvement of the recent intra-nuclear cascade (J. Cugnon). This is also true in the same way for the neutron production from thick targets. However the model underestimates the energetic neutrons produced in the backward direction and other quantities as residual nuclei cross sections are not accurately predicted.SCOPUS: ar.jinfo:eu-repo/semantics/publishe