226280 research outputs found
Sort by
Altered striosome-matrix distribution and activity of striatal cholinergic interneurons in a model of autism-linked repetitive behaviors
No full textInternational audienceRepetitive behaviors are cardinal features of many brain disorders, including autism spectrum disorder (ASD). We previously associated dysfunction of striatal cholinergic interneurons (SCINs) with repetitive behaviors in a mouse model based on conditional deletion of the ASD-related gene Tshz3 in cholinergic neurons (Chat-cKO). Here, we provide evidence linking SCIN abnormalities to the unique organization of the striatum into striosome and matrix compartments, whose imbalances are implicated in several pathological conditions. Chat-cKO mice exhibit an altered relationship between the embryonic birthdate of SCINs and their adult striosome-matrix distribution, leading to an increased proportion of striosomal SCINs. In addition, the ratio of striosomal SCINs with slow-irregular vs. sustained-regular firing is increased, which translates into decreased activity, further stressing the striosome-matrix imbalance. These findings provide novel insights into the pathogenesis of ASD-related stereotyped behaviors by pointing to abnormal developmental compartmentalization and activity of SCINs as a substrate
A <i>h</i>‐Adaptivity Strategy for Hybridizable Discontinuous Galerkin (HDG) Simulations of Fluid Transport Models in Tokamak Plasma
No full textInternational audienceThe highly anisotropic, multi‐scale nature of fusion plasma simulations in tokamaks, combined with the complexity in the geometries of plasma‐facing components and magnetic equilibrium, challenges numerical schemes. They therefore require the development of advanced numerical techniques to enhance computational efficiency and enable codes to simulate realistic plasma configurations relevant to tokamak operation. This paper proposes an adaptive mesh refinement strategy (h‐Adaptivity) in the SolEdge‐HDG code for the resolution of 2D fluid‐drift Braginskii equations using the Hybrid Discontinuous Galerkin (HDG) method. The strategy is based on an oscillation indicator implemented to detect under‐resolved regions and dynamically refine the mesh, associated with an a posteriori accuracy indicator built on the local difference between the solution at order and the post‐processed one at order considered as reference. The method thus enables both refinement, where necessary, as well as coarsening in regions where the solution is smooth. Numerical results obtained with this method in realistic tokamak geometry and plasma conditions show significant reductions in computational resources and an improvement in code robustness while maintaining high accuracy, particularly in regions with steep gradients or near the sharp angles of the tokamak walls. This work highlights the potential of such ‐adaptivity technique to optimize transport simulations in realistic tokamak configurations, offering a fully automated, goal‐oriented mesh refinement strategy. In addition to optimizing the numerical cost of simulation, this strategy offers all users a fully automated means of designing a mesh in any tokamak geometry
Internal short circuits in lithium-ion batteries; origins, detection, and experimental reproduction: A review
No full textInternational audienceInternal short circuits constitute a significant risk to the safety and performance of lithium-ion batteries (LiBs). Internal short circuits are among the most problematic failure mechanisms in LiBs because of their ability to cause thermal runaway and catastrophic failure and inherent difficulty of detection. This review provides a comprehensive overview of the types of internal short circuits, their origins, and the experimental methods used to reproduce them. Firstly, the definition and classification of internal short circuits, as well as their associated consequences from minor performance loss to thermal runaway, are described. Secondly, the root causes of internal short circuits are investigated, including a thorough examination of each manufacturing stage where defects can appear, focusing on preventive measures. Finally, the review details experimental approaches to reproduce internal short circuits mentioning their respective advantages and drawbacks with a focus on mechanical internal short circuit reproduction devices, such as nail/needle penetration techniques. These techniques are the easiest to implement but have an important number of variable parameters that can influence the test outcome
Validation of the French Translation of the Movement Disorder Society Non‐Motor Symptoms Scale ( MDS ‐ NMS ) in Parkinson's Disease
No full textInternational audienc
DPD Ultra‐Rapid Metabolizer Status and Efficacy of 5‐Fluorouracil Treatment: A Real‐World Study
No full textInternational audienceBackground : Anticancer drug 5FU is extensively metabolized by dihydropyrimidine dehydrogenase (DPD), an enzyme with high interindividual variability. Poor metabolizer (PM, i.e., DPD deficient) patients are at risk of life‐threatening toxicities. Whether ultra‐rapid metabolizer (UM) status could conversely compromise 5FU efficacy remains to be investigated. Methods : In this real‐world study, 352 adult patients treated with a 5FU‐containing regimen were screened. Patients were classified as normal (extensive metabolizer, EM), PM, or UM on DPD function based upon baseline plasma uracil monitoring. The impact of DPD status on efficacy and safety endpoints was investigated. Results : Patients were categorized on DPD as UM (11.9%), EM (75.9%), and PM (12.2%). The response rate was 54.5%, with median PFS and OS of 13.9 and 19 months, respectively. PM patients were treated with an average 13% lower 5FU starting dose. There was no statistical difference in efficacy between UM and other patients. Severe toxicities were observed in less than 5% of patients, an incidence significantly lower than commonly reported with 5FU‐containing regimen and was comparable between UM, EM, and PM patients. Our observations suggest that UM status is not associated with the lack of efficacy of 5FU. In addition, upfront DPD testing with adaptive dosing helps to reduce the incidence of severe toxicities, as PM patients on reduced doses did not have more severe toxicities than other patients treated with standard doses, while exhibiting similar efficacy in terms of response rate and survival. Conclusion : When upfront DPD screening with adaptive dosing is performed, no difference is observed between UM, EM, and PM patients in terms of efficacy and safety. Trial Registration #PADSA3GKW
Neurophysiology of gaze direction as poly-equilibrium
No full textInternational audienceThe static orientation of the eyes during visual fixation is determined by the simultaneous operation of multiple equilibria. This phenomenon is collectively referred to as poly-equilibrium, which involves multiple systems that work together to cancel each other out and establish gaze direction. While other systems, such as audio-and cervico-ocular systems, may also contribute to gaze direction, this review focuses primarily on the commands issued by the vestibulo-and visuo-oculomotor systems that determine gaze direction, as they play a key role in the poly-equilibrium process. From the visual and vestibular activities accompanying the appearance of an object in the central visual field to the recruitment of premotor neurons responsible for the generation of slow and saccadic eye movements, a delicate balance is maintained. As long as the recruited channels convey commands that counterbalance each other, no movement is initiated. This alternative viewpoint leads to reconsidering the nature of saccadic and pursuit eye movements. Rather than viewing them as the dynamic reduction in brain signals encoding kinematic parameters such as position or velocity, they can be seen as the physical expression of intracerebral processes restoring balanced activities between sensorimotor channels whose recruitment leads to mutually opposed movements
De Novo design of α-helical heme binding proteins capable of versatile cofactor ligation
No full textInternational audienceDe novo design of artificial metalloproteins offers a powerful approach to dissect and mimic the diverse and exquisite coordination environments found in natural heme proteins. These designed heme proteins seek to replicate the broad array of metabolic, regulatory, and structural functions that hemes perform in biological systems. In this chapter, we present an amenable methodology for the preparation and characterization of de novo-designed heme-binding coiled coils featuring either His- and/or Cys-based axial ligation, which mimic the redox active sites of peroxidases, chloroperoxidases, and cytochrome P450 monooxygenases. The ability to reversibly control heme coordination and spin state through pH variations within a single scaffold provides novel insights into the principles governing catalysis in heme-containing and heme-binding proteins and paves the groundwork for engineering versatile catalysts with tailored reactivity
A thermo-mechanical cohesive zone model for damage and healing in brittle solids
No full textInternational audienceBrittle material, such as ceramics, are characterized by a complex crack behavior which undergo crack propagation, impact of discontinuities on thermal transfer and eventually healing phenomena that restore the material rigidity. In the context of healing by material diffusion welding, an original damage-healing thermo-mechanical cohesive zone model is proposed. The introduction of an internal variable to model the physical-chemical process that can induce healing phenomena, called healing reserve, is employed to partially restore cracks. Crack initiation and propagation are modelled through a damage variable. The evolution laws for both internal variables have been carefully selected to guarantee compliance with the principles of thermodynamics. Academic applications are performed to illustrate the model behavior under structural simulation. The aforementioned application enables the demonstration of the impact of certain pivotal parameters such as mixed-modes control and the viscosity parameters. Subsequently, a simulation of a nuclear fuel pellet undergoing a single irradiation cycle was conducted to reproduce the healing process observed in post-irradiation examinations. The studies highlight the ability of the model to address complex and diverse phenomena
« L’action collective étudiante face aux enjeux démocratiques en Serbie. Propos introductifs »
No full textInternational audienc
Guide des Jeunes Chercheur·euses en APS : du doctorat à l'insertion professionnelle
No full textA travers ce Guide des jeunes chercheur·euses en APS, le Réseau Jeunes Chercheur·euses de l'ACAPS souhaite centraliser des informations utiles sur le doctorat, de l’inscription à la soutenance, et sur l’insertion professionnelle académique et hors académique, afin de faciliter l’accès à l’information aux jeunes chercheur·euses en STAPS