Diagnostic d'un laser digital de 61 fibres cophasées par interférométrie PISTIL

International audienceCoherent beam combining (CBC) opens the way to a new paradigm in laser architecture [1] . The quest to high peak and average power indeed faces several fundamental limitations (transverse amplified spontaneous emission in wide amplifiers, thermal management issues) which can be addressed when relying on numerous smaller scale reliable lasers coherently combined. Achieving CBC for a large number of amplifiers will not only rely on the use of an efficient phase-locking scheme but also on fiber management inside the laser head (such as accurate angular and lateral positioning, at µm or mrad levels), optics, and amplifiers management as well as laboratory environment control. An accurate diagnosis of the laser array is mandatory in order to get significant feedback on its design, and potentially improve or stabilize its behavior, either in phase-locked loop or in free run.La combinaison cohérente de faisceaux (CBC) ouvre la voie à un nouveau paradigme dans l'architecture laser [1] . La recherche d'une puissance de crête et d'une puissance moyenne élevées se heurte en effet à plusieurs limitations fondamentales (émission spontanée amplifiée transversale dans les amplificateurs larges, problèmes de gestion thermique) qui peuvent être résolues en s'appuyant sur de nombreux lasers fiables à plus petite échelle combinés de manière cohérente. La réalisation de la CBC pour un grand nombre d'amplificateurs ne dépendra pas seulement de l'utilisation d'un système de verrouillage de phase efficace, mais aussi de la gestion des fibres à l'intérieur de la tête laser (comme le positionnement angulaire et latéral précis, à des niveaux de µm ou de mrad), de la gestion des optiques et des amplificateurs, ainsi que du contrôle de l'environnement du laboratoire. Un diagnostic précis du réseau laser est obligatoire pour obtenir un retour d'information significatif sur sa conception, et potentiellement améliorer ou stabiliser son comportement, que ce soit en boucle à verrouillage de phase ou en fonctionnement libre

Phase noise measurements and diagnoses of a large array of fiber lasers by PISTIL

International audienceOne of the most promising solutions to access high power laser chains is to achieve a coherent combination of a large number of elementary lasers. To interfere constructively, these laser sources should be identical and operate under the same conditions. However, despite these efforts, differential delays appear in the course of time, which must be compensated for. While designing the required correction system, knowing the behavior of a laser as a function of the environmental conditions is not crucial, whereas having access to the differences in the behaviors of identical lasers is, leading to difficulties in modeling. The purpose of this paper is to illustrate how a large set of lasers can be simultaneously analyzed to estimate their variations and optimize a correction system. The X-Coherent Amplified Network laser relies on 61 fiber amplifiers, which are as identical as possible. This state of the art femtosecond digital laser therefore appears as an ideal candidate to study a large number of fiber lasers working under controlled conditions

Orbital Angular Momentum beams generation from 61 channels Coherent Beam Combining femtosecond Digital Laser

International audienceWe report on the use of a 61 beamlets Coherent Beam Combination femtosecond fiber amplifiers as a digital laser source to generate high power Orbital Angular Momentum beams. Such approach opens the path for higher order non-symmetrical user-defined far field distributions

Myxoma Virus Leukemia-Associated Protein Is Responsible for Major Histocompatibility Complex Class I and Fas-CD95 Down-Regulation and Defines Scrapins, a New Group of Surface Cellular Receptor Abductor Proteins

Down-modulation of major histocompatibility class I (MHC-I) molecules is a viral strategy for survival in the host. Myxoma virus, a member of the Poxviridae family responsible for rabbit myxomatosis, can down-modulate the expression of MHC-I molecules, but the viral factor(s) has not been described. We cloned and characterized a gene coding for an endoplasmic reticulum (ER)-resident protein containing an atypical zinc finger and two transmembrane domains, which we called myxoma virus leukemia-associated protein (MV-LAP). MV-LAP down-regulated surface MHC-I and Fas-CD95 molecules upon transfection; the mechanism probably involves an exacerbation of endocytosis and was lost when the ER retention signal was removed. In addition, the lytic activity of MHC-I-restricted antigen-specific cytolytic T lymphocytes (CTL) against myxoma virus-infected antigen-presenting target cells was significantly reduced, revealing a strong correlation between MHC-I down-regulation by MV-LAP and CTL killing in vitro. In vivo experiments with a knockout virus showed that MV-LAP is a virulence factor, potentially involved in the immunosuppression characteristic of myxomatosis. Data bank analysis revealed that MV-LAP has homologs in herpesviruses and other poxviruses. We propose the name “scrapins” to define a new group of ER-resident surface cellular receptor abductor proteins. The down-regulation of cell surface molecules by scrapins probably helps protect infected cells during viral infections

Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature

Purpose: Pathogenic variants in genes involved in the epigenetic machinery are an emerging cause of neurodevelopment disorders (NDDs). Lysine-demethylase 2B (KDM2B) encodes an epigenetic regulator and mouse models suggest an important role during development. We set out to determine whether KDM2B variants are associated with NDD. Methods: Through international collaborations, we collected data on individuals with heterozygous KDM2B variants. We applied methylation arrays on peripheral blood DNA samples to determine a KDM2B associated epigenetic signature. Results: We recruited a total of 27 individuals with heterozygous variants in KDM2B. We present evidence, including a shared epigenetic signature, to support a pathogenic classification of 15 KDM2B variants and identify the CxxC domain as a mutational hotspot. Both loss-of-function and CxxC-domain missense variants present with a specific subepisignature. Moreover, the KDM2B episignature was identified in the context of a dual molecular diagnosis in multiple individuals. Our efforts resulted in a cohort of 21 individuals with heterozygous (likely) pathogenic variants. Individuals in this cohort present with developmental delay and/or intellectual disability; autism; attention deficit disorder/attention deficit hyperactivity disorder; congenital organ anomalies mainly of the heart, eyes, and urogenital system; and subtle facial dysmorphism. Conclusion: Pathogenic heterozygous variants in KDM2B are associated with NDD and a specific epigenetic signature detectable in peripheral blood

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

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Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (6 month embargo), submitted versio