Portail HAL UNIV-RENNES
Not a member yet
180610 research outputs found
Sort by
PARP1 auto-modification promotes faithful Okazaki fragment processing and limits replication fork speed
No full textInternational audiencePoly(ADP-ribose) polymerase (PARP) inhibitors have proven their efficacy for treating tumors defective in homologous recombination via synthetic lethality. In response to DNA breaks, PARP1 is the primary ADP-ribosylation writer, modifying itself (auto-modification) and other proteins to facilitate repair. However, enzymatic inhibition blocks both processes, making it difficult to dissect their distinct functional roles. Using proteomics and site-directed mutagenesis, we identified a PARP1 mutant deficient in auto-modification, yet it retains catalytic activity. This separation-of-function mutant revealed that PARP1 auto-modification slows DNA replication fork progression but is dispensable for repair factor recruitment. Instead, auto-modification promotes the timely release of PARP1 at DNA break sites and prevents the formation of replication stress. Simultaneous inhibition of FEN1 and loss of PARP1 auto-modification gives rise to synthetic lethality, implicating auto-modification in Okazaki fragment processing. Our results demonstrate that trapping of PARP at DNA breaks impedes repair factor accessibility, constituting an important dimension of PARP-inhibitor-driven cytotoxicity
Synthetic mid-urethral slings in female spina bifida patients with stress urinary incontinence: Is it worth it?
No full textInternational audienceIntroduction: The aim of this study was to report the outcomes of synthetic mid-urethral slings (MUS) in female patients with spina bifida and stress urinary incontinence (SUI).Methods: All female patients with spina bifida who were seen at a national referral center between 2007 and 2021 and who had a history of MUS for SUI were included in a retrospective study. The primary outcome of interest was the continence status at 1year as per patients' subjective perception categorized as complete continence, improved continence, unchanged or worsened SUI.Results: Out of 339 female spina bifida patients; 11 patients had undergone a MUS insertion and were included for analysis (3.2%). The median age was 30years (range: 19-52years). There were four postoperative complications (36.4%). The three patients fully continent at three months were still fully continent at one year (27.3%) while three had improved continence (27.3%) and five had unchanged continence (45.5%). After a median follow-up of 102months, only one patient was still fully continent (9.1%) and three patients had still improved continence (27.3%). Five patients (45.5%) underwent a subsequent anti-incontinence procedure. The only adverse predictor of improved/complete continence at 1year was a sacral neurological level (OR=0.05; p=0.03).Conclusion: MUS in women with spina bifida and SUI appears to be safe but less effective than in the non-neurogenic population which may be explained by different underlying pathophysiological mechanisms. These findings question the relevance of this treatment option in these complex population, especially in the current mesh controversy era
A characterization of piARNs, their biogenesis and their targets in Spodoptera frugiperda (Lepidoptera, Noctuidae)
No full textAbstract PIWI-interacting RNAs (piRNAs) and PIWI proteins were initially described as involved in gametogenesis and preservation of genome integrity through the control of transposable elements (TE). Expressed also in the soma and able to regulate protein coding gene expression, they are involved in multiple biological pathways including host-pathogens interaction, sex determination, reproductive isolation. Spodoptera frugiperda is a major invasive insect pest species consisting of two strains with different host-plant ranges. In this paper, we characterized proteins and genomic regions involved in their biogenesis as well as TE and gene transcripts regulated by piRNAs. By phylogenetic analysis, we identified two new Piwi genes conserved in the genus Spodoptera , compared to the Lepidopteran model Bombyx mori , one more than in Drosophila . One of them, more expressed in gonads then soma could be a functional homolog of Drosophila PIWI or replace AGO3. A pool of 11 sRNA-Seq libraries was used to annotate piRNA clusters with Shortstack in the genomes of the two strains of Spodoptera frugiperda . Identification of TE targeted by piRNAs revealed that active transposons differ between the two strains of S. frugiperda despite of a similar TE content, as putative cause or consequence of reproductive isolation. GO analysis of genes targeted by piRNAs shows that some are involved in protein translation initiation. A piRNA cluster in the Masc gene suggests that sex determination is regulated by piRNAs in Spodoptera frugiperda . Our analysis supports that piRNAs have additional roles than silencing of transposable elements and contributes to functional annotation of the two strains genomes of Spodoptera frugiperda
Efficiency of Estimating Smooth Functions of Parameters in Rare-Event Contexts
No full textConsider an estimand that is a known smooth function of an unknown vector of parameters, such as means, probabilities, quantiles, etc. Some but not necessarily all of the parameters relate to rare events, which typically make them difficult to estimate with naive Monte Carlo, so variance-reduction techniques must to be applied to obtain efficient estimators of those parameters. We develop conditions ensuring that the overall estimand can be efficiently estimated, providing both sufficient and necessaryand-sufficient conditions. The paper illustrates the applicability of the theory through many examples and numerical results.</div
Quantification de l'influence des morphologies sur la qualité de découpe laser
No full textInternational audienceLaser cutting is an old and multi-physical process that was quickly adopted by the metallurgical industry. However, this fast industrialisation has had a significant impact on quality control. Several studies have been carried out to characterise and minimise different types of cutting defects. Reviews published between 2008 and 2022 highlight that research often focuses on single-criterion ‘quality’ approaches, aiming to minimise specific defects such as the Heat-Affected Zone, surface roughness, or kerf geometry. Consequently, efforts have been directed at optimising specific aspects of quality rather than adopting a complete approach. Furthermore, these reviews reveal that cutting quality can be enhanced through the careful selection of laser manufacturing parameters and part parameters. However, while parameters such as material and thickness have been investigated, the influence of part morphology on cutting quality remains underexplored. Although some studies have examined the effects of material and thickness, part morphology is often limited to simple segments with varying cutting lengths or angles. While other research has investigated the impact of angle size on cutting quality, no established method exists to systematically determine the influence of each part morphology on cutting quality. In response to this gap, the present study proposes to evaluate the criticality of cutting defects, as defined by existing standards, across various part morphologies using a method adapted from Failure Modes, Effects, and Criticality Analysis (FMECA). The objective is to develop a global approach that examines the influence of all morphologies on all types of cutting defects. An industrial application shows that cutting defects, particularly thermal ones, are strongly influenced by morphologies, while thickness affects them irregularly. Improvement priorities target critical defects shaped by both factors. Burrs and adherent slag are critical in angles and arcs, while segments, often used in studies, are less sensitive. These observations lead to the definition of design limits. This method offers a detailed analysis of the influence of design data on quality, providing practical tools for improving industrial processes.
Le délit de harcèlement moral institutionnel : une histoire d'interprétation(s): Cass. crim., 21 janv. 2025, no 22-87.145, FS–BR
No full textInternational audienc
Solar Hydrogen Production with Metal/III–V Semiconductor Junction Monolithically Integrated on Si
No full textInternational audienceGaAs is an excellent candidate for high-performance photoelectrochemical water splitting due to its appropriate band-edge and bandgap energies, as well as its excellent transport properties. The most significant limitations of GaAs for photoelectrochemical applications are its instability against corrosion, the high substrate cost, and the huge overpotentials required for triggering water electrolysis. The monolithic epitaxial integration of GaAs thin films directly on the Earth-abundant Si fundamentally limits the costs associated with the substrate fabrication. Herein, photocathodes made of 1 μm thick GaAs layers epitaxially grown on p-doped Si substrates are developed and their performances are compared to those of bare p-doped GaAs electrodes. Sulfur passivation and standard interfacing with Pt catalyst are applied and analyzed for both series of photocathodes. A massive onset potential shift of 0.63 V is demonstrated for GaAs/Si photocathodes after electroless Pt deposition and sulfur passivation, reaching an onset potential of 0.4 V versus the reversible hydrogen electrode. The stability of the Pt/GaAs/Si photocathode is finally assessed over more than 112 h. These findings are essential for further development toward the fabrication of cost-efficient and stable unassisted photoelectrochemical cells for green hydrogen production
Couplage de modèles de transport réactif et de spéciation pour étudier la nanofiltration des sels métalliques provenant d'un lixiviat acide
No full textInternational audienceThis work proposes the application of membrane processes to filter the metals contained in a leachate of hyperaccumulating plant ashes. To better understand the phenomena involved in metal separation, a transport model based on the Nernst-Planck equation was used (SEDE model). The leachate was acidic and concentrated in various salts, including nickel, magnesium, and iron sulfate. It therefore exhibited a complex speciation. The objective was to study speciation influence on the modelling of the rejection rate. The leachate was diluted 2, 4, 8, 10 and 20 times to assess the quality of the nanofiltration and the influence of sulfuric acid and of salt concentration on the rejection rate of three metals of interest: nickel, iron, and magnesium. An optimum rejection rate was obtained for the leachate diluted 8-fold, at an ionic strength of 0.37 mol kg -1 , with a rejection rate of 85 % for the three metals. Pore swelling was observed for pure leachate nanofiltration, considerably reducing the rejection of all divalent ions. Iron was most affected by changes in speciation. By considering the speciation upstream of nanofiltration, the prediction of the retention rate of some divalent cations can be improved by up to 50 %, compared to experimental data. This work also constitutes a first step towards the evaluation of the quantity of recyclable protons after an acid leaching stage in hydrometallurgy.Ce travail propose l'application de procédés membranaires pour filtrer les métaux contenus dans un lixiviat provenant de cendres végétales hyperaccumulatrices. Afin de mieux comprendre les phénomènes impliqués dans la séparation des métaux, un modèle de transport basé sur l'équation de Nernst-Planck a été utilisé (modèle SEDE). Le lixiviat était acide et concentré en divers sels, notamment en nickel, magnésium et sulfate de fer. Il présentait donc une spéciation complexe. L'objectif était d'étudier l'influence de la spéciation sur la modélisation du taux de rejet. Le lixiviat a été dilué 2, 4, 8, 10 et 20 fois afin d'évaluer la qualité de la nanofiltration et l'influence de l'acide sulfurique et de la concentration en sel sur le taux de rejet de trois métaux d'intérêt : le nickel, le fer et le magnésium. Un taux de rejet optimal a été obtenu pour le lixiviat dilué 8 fois, à une force ionique de 0,37 mol kg -1 , avec un taux de rejet de 85 % pour les trois métaux. Un gonflement des pores a été observé pour la nanofiltration du lixiviat pur, réduisant considérablement le rejet de tous les ions divalents. Le fer a été le plus affecté par les changements de spéciation. En tenant compte de la spéciation en amont de la nanofiltration, la prédiction du taux de rétention de certains cations divalents peut être améliorée jusqu'à 50 % par rapport aux données expérimentales. Ce travail constitue également une première étape vers l'évaluation de la quantité de protons recyclables après une étape de lixiviation acide en hydrométallurgie
