SPHERE IRDIS and IFS astrometric strategy and calibration

We present the current results of the astrometric characterization of the VLT planet finder SPHERE over 2 years of on-sky operations. We first describe the criteria for the selection of the astrometric fields used for calibrating the science data: binaries, multiple systems, and stellar clusters. The analysis includes measurements of the pixel scale and the position angle with respect to the North for both near-infrared subsystems, the camera IRDIS and the integral field spectrometer IFS, as well as the distortion for the IRDIS camera. The IRDIS distortion is shown to be dominated by an anamorphism of 0.60+/-0.02% between the horizontal and vertical directions of the detector, i.e. 6 mas at 1". The anamorphism is produced by the cylindrical mirrors in the common path structure hence common to all three SPHERE science subsystems (IRDIS, IFS, and ZIMPOL), except for the relative orientation of their field of view. The current estimates of the pixel scale and North angle for IRDIS are 12.255+/-0.009 milliarcseconds/pixel for H2 coronagraphic images and -1.75+/-0.08 deg. Analyses of the IFS data indicate a pixel scale of 7.46+/-0.02 milliarcseconds/pixel and a North angle of -102.18+/-0.13 deg. We finally discuss plans for providing astrometric calibration to the SPHERE users outside the instrument consortium.Comment: 12 pages, 6 figures, 3 table

Identification of Pathway-Biased and Deleterious Melatonin Receptor Mutants in Autism Spectrum Disorders and in the General Population

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Δ502–505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients

The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI): instrument and pre-launch testing

This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI), to be launched onboard of ESA's Herschel Space Observatory, by 2008. It includes the first results from the instrument level tests. The instrument is designed to be electronically tuneable over a wide and continuous frequency range in the Far Infrared, with velocity resolutions better than 0.1 km/s with a high sensitivity. This will enable detailed investigations of a wide variety of astronomical sources, ranging from solar system objects, star formation regions to nuclei of galaxies. The instrument comprises 5 frequency bands covering 480-1150 GHz with SIS mixers and a sixth dual frequency band, for the 1410-1910 GHz range, with Hot Electron Bolometer Mixers (HEB). The Local Oscillator (LO) subsystem consists of a dedicated Ka-band synthesizer followed by 7 times 2 chains of frequency multipliers, 2 chains for each frequency band. A pair of Auto-Correlators and a pair of Acousto-Optic spectrometers process the two IF signals from the dual-polarization front-ends to provide instantaneous frequency coverage of 4 GHz, with a set of resolutions (140 kHz to 1 MHz), better than < 0.1 km/s. After a successful qualification program, the flight instrument was delivered and entered the testing phase at satellite level. We will also report on the pre-flight test and calibration results together with the expected in-flight performance

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Folliculite pseudolymphomateuse (à propos d'un cas)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Transfert de techniques et de technologies dans le cadre de la convention DF Mexico - LCPC France

Le LCPC dispose d'une grande expérience dans le domaine des techniques routières, l'accompagnement de l'innovation et l'adaptation des technologies à l'étranger. Une convention cadre de partenariat entre le LCPC et le DF de Mexico va faciliter le transfert de technologie sur la mise au point d'enrobés pour l'entretien des grandes avenues de Mexico. Préalablement, à ces études de formulation en laboratoire, une étude d'entretien selon les méthodes françaises d'auscultation de la structure et de l'analyse des propriétés résiduelles des matériaux sera conduite en collaboration avec le bureau d'étude Mexicain en charge de ces essais, sur une ou deux grandes artères de la ville. L'interprétation des résultats se fera à partir de la méthodologie d'entretien, ayant récemment fait l'objet d'un nouveau guide technique. Deux ou trois scénarios d'entretien seront proposés, à partir de vérification de dimensionnement, utilisant une méthode rationnelle de calcul des structures de chaussées. Ce même logiciel ALIZE sera utilisé pour dimensionner des ouvrages plus spécifiques, conçus pour l'infrastructure métro-bus de Mexico. Là encore, l'expérience de nombreuses réalisations, dans les grandes villes françaises de ces nouveaux moyens de transport, en site propre, sera mise à profit. La formulation des enrobés en laboratoire répond à des objectifs de respect de performances pour des usages et applications donnés, et non à des recettes s'appuyant sur des compositions types. Elle autorise le développement des innovations, tout en intégrant la notion de qualité et de durabilité des matériaux dans la structure. Compte tenu de l'importance du trafic lourd et des conditions de température élevées, il sera recherché des matériaux présentant de très bonnes propriétés mécaniques, tant en terme de module que de fatigue, mais également de très bonnes résistances à l'orniérage et au désenrobage par l'eau. La mise au point d'enrobé à module élevé (EME), en couche d'assise, en épaisseur réduite (8 à 10 cm), mais assurant un bon renforcement structurel, sera recherchée. De même, l'emploi d'enrobés minces en couche de roulement, de 3 à 4 cm d'épaisseur, composés de bitume modifié par des polymères, devra permettre d'améliorer l'adhérence et donc la sécurité des usagers, avec une longévité accrue, tout en réduisant les coûts. La méthode française de formulation constitue un excellent outil pour la mise au point de ces produits. L'article présentera, de façon synthétique, les outils et méthodes utilisés, les principaux résultats attendus de ces études tant de formulation des matériaux, de dimensionnement, que d'entretien des chaussées. Il mettra en évidence l'intérêt de ces méthodes, sur la qualité des ouvrages et sur le développement des innovations ou l'adaptation supportées dans les pays étrangers