A Comparison of TSV Etch Metrology Techniques

International audienceWe use three metrology techniques, vertical scanning interferometry (VSI), confocal chromatic microscopy (CCM), and time domain optical coherence tomography (TD-OCT), for depth measurement of through-silicon vias (TSVs) of various cross sections and depths. The merits of these techniques are discussed and compared. Introduction While sales of semiconductor equipment broke a new record this year, many metrology needs should be addressed to support the development and production of electronic chips based on "More than Moore" scaling. Among these scaling approaches, 3D integration based on TSVs offers superior integration density and reduces interconnect length/latency. Measurements are needed to evaluate the depth uniformity of etched TSVs. Indeed, upon metal filling, geometrical variations of TSVs can affect Cu nails coplanarity and can warp the wafer, resulting in a low stacking yield. Measuring the depth of TSVs is an increasingly challenging task as the diameter of many TSVs has now shrunk to only a few microns

Nonsmooth Convex Optimization for Structured Illumination Microscopy Image Reconstruction

International audienceIn this paper, we propose a new approach for structured illumination microscopy image reconstruction. We first introduce the principles of this imaging modality and review its properties in various conditions. We then propose the minimization of nonsmooth convex functionals for the recovery of the unknown image and investigate several data–fitting and regularization terms in order to tackle reconstruction of noisy data. More specifically, we consider an original approach based on sparse local patch dictionaries for the regularization of the estimate. We demonstrate the good performance of the proposed approach on a test benchmark and perform some test experiments on images acquired on two different microscopes

Le Parc Naturel Régional du Queyras vu par ses résidents permanents et secondaires

Cette note de synthèse présente les résultats de l'enquête par questionnaire réalisée auprès des résidents du périmètre du PNRQ (433 résidents permanents et 172 résidents secondaires). L'objectif est de proposer un éclairage sur leurs ressentis et leurs attentes concernant le PNRQ et son territoire

Infant rats can learn time intervals before the maturation of the striatum: evidence from odor fear conditioning

International audienceInterval timing refers to the ability to perceive, estimate and discriminate durations in the range of seconds to minutes. Very little is currently known about the ontogeny of interval timing throughout development. On the other hand, even though the neural circuit sustaining interval timing is a matter of debate, the striatum has been suggested to be an important component of the system and its maturation occurs around the third post-natal (PN) week in rats. The global aim of the present study was to investigate interval timing abilities at an age for which striatum is not yet mature. We used odor fear conditioning, as it can be applied to very young animals. In odor fear conditioning, an odor is presented to the animal and a mild footshock is delivered after a fixed interval. Adult rats have been shown to learn the temporal relationships between the odor and the shock after a few associations. The first aim of the present study was to assess the activity of the striatum during odor fear conditioning using 2-Deoxyglucose autoradiography during development in rats. The data showed that although fear learning was displayed at all tested ages, activation of the striatum was observed in adults but not in juvenile animals. Next, we assessed the presence of evidence of interval timing in ages before and after the inclusion of the striatum into the fear conditioning circuit. We used an experimental setup allowing the simultaneous recording of freezing and respiration that have been demonstrated to be sensitive to interval timing in adult rats. This enabled the detection of duration-related temporal patterns for freezing and/or respiration curves in infants as young as 12 days PN during odor fear conditioning. This suggests that infants are able to encode time durations as well as and as quickly as adults while their striatum is not yet functional. Alternative networks possibly sustaining interval timing in infant rats are discussed

De l'hémolyse intravasculaire à bas bruit est associée à la neuropathie dans le diabète de type 2

International audienceType 2 diabetes (T2D) induces hyperglycemia, alters hemoglobin (Hb), red blood cell (RBC) deformability and impairs hemorheology. The question remains whether RBC breakdown and intravascular hemolysis (IVH) occur in T2D patients. We characterized RBC-degradation products and vesiculation in a case-control study of 109 T2D patients and 65 control subjects. We quantified heme-related absorbance by spectrophotometry and circulating extracellular vesicles (EV) by flow cytometry and electron microscopy. Heme-related absorbance was increased in T2D vs. control plasma (+57%) and further elevated in obese T2D plasma (+27%). However, large CD235a+ EV were not increased in T2D plasma. EV from T2D plasma, or shed by isolated T2D RBC, were notably smaller in diameter (-27%) and carried heme-related absorbance. In T2D plasma, higher heme-related absorbance (+30%) was associated to peripheral sensory neuropathy, and no other vascular complication. In vitro, T2D RBC-derived EV triggered endothelial stress and thrombin activation in a phosphatidylserine- and heme-dependent fashion. We concluded that T2D was associated with low-grade IVH. Plasma absorbance may constitute a novel biomarker of peripheral neuropathy in T2D, while flow cytometry focusing on large EV may be maladapted to characterize RBC EV in T2D. Moreover, therapeutics limiting IVH or neutralizing RBC breakdown products might bolster vasculoprotection in T2D

Benchmarking eleven biodiversity indicators based on environmental DNA surveys: more diverse functional traits and evolutionary lineages inside marine reserves

To mitigate the ongoing threats to coastal ecosystems, and the biodiversity erosion they are causing, Marine Protected Areas (MPAs) have emerged as powerful and widespread conservation tools. Strictly no-take MPAs, also called marine reserves, undeniably promote fish biomass and density, but it remains unclear how biodiversity responds to protection. Identifying which facets of biodiversity respond to protection is critical for the management of MPAs and the development of relevant conservation strategies towards the achievement of biodiversity targets. We collected 99 environmental DNA (eDNA) samples inside and outside nine marine reserves in the Mediterranean Sea to assess the effect of protection on 11 biodiversity indicators based on fish traits, phylogeny and vulnerability to fishing. We controlled for the effect of environmental heterogeneity (habitat, bathymetry, productivity, temperature, and accessibility) using a Principal Component Analysis, and for spatial autocorrelation due to potential unmeasured factors. We found a positive and significant effect of protection on only 3 out of 11 indicators: functional and phylogenic diversity but also the ratio between demerso-pelagic and benthic species richness. Rather, total fish richness responded significantly and negatively to protection. We did not detect any significant effect of protection on threatened and elasmobranch species richness, probably due to their large home range compared to the size of Mediterranean marine reserves. Synthesis and applications: Our findings highlight the importance of looking beyond the mere number of species to fully depict and understand the effect of marine reserves on biodiversity and evaluate the effectiveness of conservation measures. Rather, we propose a dashboard of three eDNA-based indicators that can provide an early signal of ecosystem deterioration or recovery. eDNA metabarcoding offers a powerful tool to supply site-specific and standardized taxonomic-, phylogenetic- and trait-based biodiversity assessments, in complement to other classical technics, such as visual censuses or video surveys, able to estimate species abundance but also individual life-stage and size

Using Ecology, Physiology, and Genomics to Understand Host Specificity inXanthomonas: French Network on Xanthomonads (FNX)

How pathogens coevolve with and adapt to their hosts are critical to understanding how host jumps and/or acquisition of novel traits can lead to new disease emergences. The Xanthomonas genus includes Gram-negativeplant-pathogenic bacteria that collectively infect a broad range of crops and wild plant species. However, individual Xanthomonas strains usually cause disease on only a few plant species and are highly adapted to their hosts,making them pertinent models to study host specificity. This review summarizes our current understanding of the molecular basis of host specificity in the Xanthomonas genus, with a particular focus on the ecology, physiology,and pathogenicity of the bacterium. Despite our limited understanding of the basis of host specificity, type III effectors, microbe-associated molecular patterns, lipopolysaccharides, transcriptional regulators, and chemotacticsensors emerge as key determinants for shaping host specificity

Development of extracellular vesicle-based medicinal products: A position paper of the group “Extracellular Vesicle translatiOn to clinicaL perspectiVEs – EVOLVE France”

International audienceExtracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective. Recent papers, provide important guidance on regulatory aspects of pharmaceutical development, defining EVs for therapeutic applications and critical considerations for the development of potency tests. In addition, the ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics as well as the Exosomes Committee from the ISCT are expected to contribute in an active way to the development of EV-based medicinal products by providing update on the scientific progress in EVs field, information to patients and expert resource network for regulatory bodies. The contribution of our work group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France", created in 2020, can be positioned in complement to all these important initiatives. Based on complementary scientific, technical, and medical expertise, we provide EV-specific recommendations for manufacturing, quality control, analytics, non-clinical development, and clinical trials, according to current European legislation. We especially focus on early phase clinical trials concerning immediate needs in the field. The main contents of the investigational medicinal product dossier, marketing authorization applications, and critical guideline information are outlined for the transition from research to clinical development and ultimate market authorization

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study

Background: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis.Methods: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not).Results: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors.Conclusion: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival