108 research outputs found

    Length orthospectrum of convex bodies on flat tori

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    In analogy with the study of Pollicott-Ruelle resonances on negatively curved manifolds, we define anisotropic Sobolev spaces that are well-adapted to the analysis of the geodesic vector field on the flat torus. Among several applications of this functional point of view, we study properties of geodesics that are orthogonal to two convex subsets of the torus (i.e. projection of the boundaries of strictly convex bodies of the Euclidean space). Associated to the set of lengths of such orthogeodesics, we define a geometric Epstein function and prove its meromorphic continuation. We compute its residues in terms of intrinsic volumes of the convex sets. We also prove Poisson-type summation formulas relating the set of lengths of orthogeodesics and the spectrum of magnetic Laplacians

    SNP discovery and genetic mapping using genotyping by sequencing of whole genome genomic DNA from a pea RIL population

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    International audienceBackground - Progress in genetics and breeding in pea still suffers from the limited availability of molecular resources. SNP markers that can be identified through affordable sequencing processes, without the need for prior genome reduction or a reference genome to assemble sequencing data would allow the discovery and genetic mapping of thousands of molecular markers. Such an approach could significantly speed up genetic studies and marker assisted breeding for non-model species. Results - A total of 419,024 SNPs were discovered using HiSeq whole genome sequencing of four pea lines, followed by direct identification of SNP markers without assembly using the discoSnp tool. Subsequent filtering led to the identification of 131,850 highly designable SNPs, polymorphic between at least two of the four pea lines. A subset of 64,754 SNPs was called and genotyped by short read sequencing on a subpopulation of 48 RILs from the cross 'Baccara' x 'PI180693'. This data was used to construct a WGGBS-derived pea genetic map comprising 64,263 markers. This map is collinear with previous pea consensus maps and therefore with the Medicago truncatula genome. Sequencing of four additional pea lines showed that 33 % to 64 % of the mapped SNPs, depending on the pairs of lines considered, are polymorphic and can therefore be useful in other crosses. The subsequent genotyping of a subset of 1000 SNPs, chosen for their mapping positions using a KASP™ assay, showed that almost all generated SNPs are highly designable and that most (95 %) deliver highly qualitative genotyping results. Using rather low sequencing coverages in SNP discovery and in SNP inferring did not hinder the identification of hundreds of thousands of high quality SNPs. Conclusions - The development and optimization of appropriate tools in SNP discovery and genetic mapping have allowed us to make available a massive new genomic resource in pea. It will be useful for both fine mapping within chosen QTL confidence intervals and marker assisted breeding for important traits in pea improvement

    RAPTEE: Leveraging trusted execution environments for Byzantine-tolerant peer sampling services

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    International audiencePeer sampling is a first-class abstraction used in distributed systems for overlay management and information dissemination. The goal of peer sampling is to continuously build and refresh a partial and local view of the full membership of a dynamic, large-scale distributed system. Malicious nodes under the control of an adversary may aim at being over-represented in the views of correct nodes, increasing their impact on the properoperation of protocols built over peer sampling. State-of-the-art Byzantine resilient peer sampling protocols reduce this bias as long as Byzantines are not overly present. This paper studies the benefits brought to the resilience of peer sampling services when considering that a small portion of trusted nodes can run code whose authenticity and integrity can be assessed within a trusted execution environment, and specifically Intel’s software guard extensions technology (SGX). We present RAPTEE, a protocol that builds and leverages trusted gossip-based communications to hamper an adversary’s ability to increase its system-wide representation in the views of all nodes. We apply RAPTEE to BRAHMS, the most resilient peer sampling protocol to date. Experiments with 10,000 nodes show that with only 1% of SGX-capable devices, RAPTEE can reduce the proportion of identifiers of Byzantine nodes in the view of honest ones by up to 17%, when the system contains 10% of Byzantine nodes. In addition, the security guarantees of RAPTEE hold even in the presence of a powerful attacker attempting to identify trusted nodes and injecting view-poisoned trusted nodes

    DISC-NG : Robust Service Discovery in the Ethereum Global Network

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    The Ethereum Global Network (EGN) hosts a complete ecosystem of decentralized services, including blockchains such as Ethereum mainnet but also exchange markets, content delivery networks, and many more. Service discovery is a fundamental mechanism in the EGN, allowing new nodes to look up and connect to other nodes already participating in one of these services. The current service discovery of the EGN, DISCv5, is not scalable and efficient enough to support the current and future needs of the ecosystem. We present DISC-NG, a novel service discovery protocol for the EGN that is scalable, efficient, and secure. DISC-NG leverages the EGN-wide DHT to allow service participation advertisements to meet service discovery requests. DISC- NG compensates the unbalance in service popularity and minimizes the potential for abuse by malicious nodes. We implement DISC-NG in devp2p, the network stack used by the majority of clients connecting to the EGN, as well as in a large-scale simulator. DISC-NG can discover services in the EGN faster than DISCv5 while being more robust to malicious nodes. DISC-NG is now in a staging phase and scheduled for deployment as an improvement to DISCv5

    Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

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    Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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    SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

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    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.Peer reviewe

    Experimental Evaluation of Ubiquitous Mobile Systems

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    Extended abstract: 2 pagesIn the ubiquitous computing area, evaluation of solutions remains an open problem. In most cases, proposed algorithms are evaluated and validated using wireless network simulators such as NS-2 [NS2], Glomosim [GLO] or JiST/SWANS [BHvR05]. Since simulators use a model of physical components, such as network cards and location systems, this raises concerns as to the representativity of the assumptions that underlie the simulation [CSS02]. Little work concerning the evaluation of algorithms in a realistic environment is available. Of course, this is due to practical reasons: how can one realistically set up a platform allowing the execution of algorithms dealing with mobility and ubiquity? In this work, we focus on the development of a realistic platform, at the laboratory scale, to evaluate and validate fault-tolerance algorithms (e.g., group membership protocols, replication protocols) targeting systems comprising a large number of mobile devices equipped with various sensors and actuators. Our goal is to have an experimentation platform allowing for reproducible experiments (including movements) that will complement validation through simulation. Our platform must account for issues related to changes of scale so as to emulate as many various systems as possible

    Nonlinear Baroclinic Dynamics of Surface Cyclones Crossing a Zonal Jet

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    International audienceMechanisms leading a synoptic surface cyclone to cross an upper-level zonal jet and its subsequent deepening are investigated using a two-layer model on a β plane. The baroclinic interaction of a low-level circular cyclonic perturbation with an upper-level one is first studied in vertical and horizontal cyclonic or anticyclonic uniform shears. A first nonlinear effect acting on the shape and energetics of the perturbations is analyzed. If the background shear is anticyclonic, the perturbations are stretched horizontally; they lose energy barotropically but gain it baroclinically by a well-maintained westward tilt with height. Conversely, if the shear is cyclonic, perturbations remain quite isotropic, but they do not keep a favorable vertical tilt with time and the baroclinic interaction is thus only transient. The latitudinal motion of the perturbations also results from a nonlinear effect. It is found to depend strongly on the background potential vorticity (PV) gradient. This effect is a baroclinic equivalent of the so-called nonlinear barotropic "β drift" and combines the nonlinear advection and vertical stretching terms.These results are confirmed when the anomalies are initially located south of a confined westerly jet. The poleward shift of the lower cyclonic anomaly occurs faster when the vertically averaged PV gradient is strongly positive, which happens when the jet has a large barotropic component. The lower anomaly crosses the jet from the warm to the cold side and deepens afterward. After a detailed description of this regeneration process with the help of an energy budget, it is shown that linear dynamics are not able to reproduce such behavior

    Joint Bayesian cortical sulci recognition and spatial normalization.

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    International audienceIn this paper, we study the recognition of about 60 sulcal structures over a new T1 MRI database of 62 subjects. It continues our previous work [7] and more specifically extends the localization model of sulci (SPAM). This model is sensitive to the chosen common space during the group study. Thus, we focus the current work on refining this space using registration techniques. Nevertheless, we also benefit from the sulcuswise localization variability knowledge to constrain the normalization. So, we propose a consistent Bayesian framework to jointly identify and register sulci, with two complementary normalization techniques and their detailed integration in the model: a global rigid transformation followed by a piecewise rigid-one, sulcus after sulcus. Thereby, we have improved the sulci labeling quality to a global recognition rate of 86%, and moreover obtained a basic but robust registration technique
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