10 research outputs found
Capteur inertiel compact à atomes froids piégés sur puce
No full textThe work presented in this manuscript focuses on the development of an inertial sensor based on cold atoms trapped on an atom chip for inertial navigation. Based on the principles of atom interferometry, these devices exploit the quantum properties of cold atoms to accurately measure accelerations and rotations. The experimental complexity and bulk of these laboratory experiments pose major obstacles for some embedded applications. In the late 1990s, the possibility of trapping and manipulating atoms on atom chips was demonstrated, enabling a significant reduction in the size of cold atom sensors as well as their power consumption. This thesis is part of an effort to miniaturize and optimize quantum sensors, aiming to demonstrate the feasibility of a compact architecture.Our inertial sensor is based on a Ramsey sequence with a spatial splitting of internal states, making the interferometer sensitive to accelerations. In particular, we demonstrate a noise level of 3 mg at one shot on the acceleration measurement, and an in-depth study of the accelerometer's noise budget is also being conducted.In addition to reducing the size of the sensor itself with an atom chip, work is being done on miniaturizing the optical system required to prepare the laser beams for the experiment. In collaboration with Exail, we have designed a miniature optical bench with a volume of 4.4 L for cooling atoms in a 3D magneto-optical trap and promises to further reduce the size of cold atom sensors for embedded applications.Le travail présenté dans ce manuscrit porte sur le développement d'un capteur inertiel basé sur des atomes froids piégés sur une puce atomique pour la navigation inertielle. Basés sur les principes de l'interférométrie atomique, ces dispositifs exploitent les propriétés quantiques des atomes froids pour mesurer avec précision les accélérations et les rotations. La complexité expérimentale et l'encombrement de ces expériences de laboratoire constituent des obstacles majeurs pour certaines applications embarquées. A la fin des années 1990, il a été démontré la possibilité de piéger et manipuler des atomes sur des puces atomiques, rendant possible une réduction significative de la taille des capteurs à atomes froids ainsi que de leur consommation énergétique. Ces travaux de thèse s'inscrivent dans un effort de miniaturisation et d'optimisation des capteurs quantiques, visant à démontrer la faisabilité d'une architecture compacte.Notre capteur inertiel est basé sur une séquence de Ramsey avec une séparation spatiale des états internes, rendant l'interféromètre sensible aux accélérations.Nous démontrons en particulier un bruit sur la mesure d'accélération de 3 mg par coup et une étude approfondie du budget de bruit de l'accéléromètre est également réalisée.En plus de la réduction de la taille du capteur lui-même avec une puce atomique, un travail est effectué sur la miniaturisation du système optique nécessaire à la préparation des faisceaux laser de l'expérience. En collaboration avec Exail, nous avons conçu un banc optique miniature d'un volume de 4,4 L permettant de refroidir les atomes dans un piège magnéto-optique 3D et promet de réduire davantage la taille des capteurs à atomes froids pour des applications embarquées
Capteur inertiel compact à atomes froids piégés sur puce
No full textThe work presented in this manuscript focuses on the development of an inertial sensor based on cold atoms trapped on an atom chip for inertial navigation. Based on the principles of atom interferometry, these devices exploit the quantum properties of cold atoms to accurately measure accelerations and rotations. The experimental complexity and bulk of these laboratory experiments pose major obstacles for some embedded applications. In the late 1990s, the possibility of trapping and manipulating atoms on atom chips was demonstrated, enabling a significant reduction in the size of cold atom sensors as well as their power consumption. This thesis is part of an effort to miniaturize and optimize quantum sensors, aiming to demonstrate the feasibility of a compact architecture.Our inertial sensor is based on a Ramsey sequence with a spatial splitting of internal states, making the interferometer sensitive to accelerations. In particular, we demonstrate a noise level of 3 mg at one shot on the acceleration measurement, and an in-depth study of the accelerometer's noise budget is also being conducted.In addition to reducing the size of the sensor itself with an atom chip, work is being done on miniaturizing the optical system required to prepare the laser beams for the experiment. In collaboration with Exail, we have designed a miniature optical bench with a volume of 4.4 L for cooling atoms in a 3D magneto-optical trap and promises to further reduce the size of cold atom sensors for embedded applications.Le travail présenté dans ce manuscrit porte sur le développement d'un capteur inertiel basé sur des atomes froids piégés sur une puce atomique pour la navigation inertielle. Basés sur les principes de l'interférométrie atomique, ces dispositifs exploitent les propriétés quantiques des atomes froids pour mesurer avec précision les accélérations et les rotations. La complexité expérimentale et l'encombrement de ces expériences de laboratoire constituent des obstacles majeurs pour certaines applications embarquées. A la fin des années 1990, il a été démontré la possibilité de piéger et manipuler des atomes sur des puces atomiques, rendant possible une réduction significative de la taille des capteurs à atomes froids ainsi que de leur consommation énergétique. Ces travaux de thèse s'inscrivent dans un effort de miniaturisation et d'optimisation des capteurs quantiques, visant à démontrer la faisabilité d'une architecture compacte.Notre capteur inertiel est basé sur une séquence de Ramsey avec une séparation spatiale des états internes, rendant l'interféromètre sensible aux accélérations.Nous démontrons en particulier un bruit sur la mesure d'accélération de 3 mg par coup et une étude approfondie du budget de bruit de l'accéléromètre est également réalisée.En plus de la réduction de la taille du capteur lui-même avec une puce atomique, un travail est effectué sur la miniaturisation du système optique nécessaire à la préparation des faisceaux laser de l'expérience. En collaboration avec Exail, nous avons conçu un banc optique miniature d'un volume de 4,4 L permettant de refroidir les atomes dans un piège magnéto-optique 3D et promet de réduire davantage la taille des capteurs à atomes froids pour des applications embarquées
Une genèse pour l’Espagne
No full textLa Estoria de España, rédigée sous l’égide du roi Alphonse X le Sage, roi de Castille et León (1252-1284), retrace l'histoire de la péninsule Ibérique et plus spécifiquement de la Castille, des origines jusqu'au XIIIe siècle. Si beaucoup de chercheurs de renom ont étudié la Estoria, tous ces travaux, par ailleurs indispensables, ne proposent qu’une vision partielle de la première partie de la chronique. Aucune étude d’ensemble n’a en effet été consacrée au récit des origines. Or, il faut, afin de mesurer la richesse et la complexité de l’histoire péninsulaire, prendre en compte ce large intervalle de temps entre les débuts de l’humanité et l’année 711. Les dominations grecque, carthaginoise et wisigothique, l’effondrement du Royaume de Tolède et les prémisses du Royaume des Asturies constituent bien un récit des origines. L’auteur de l’ouvrage part donc du postulat que les 565 premiers chapitres de la Estoria ne peuvent être considérés comme un simple préliminaire sans aucune signification politique. Plusieurs questionnements sont ainsi à l’origine de ce travail : de quelle façon les nouveaux enjeux du XIIIe siècle (dilatation des frontières du royaume, fecho del Imperio, nouvelles conceptions politiques, contestations de la noblesse et du clergé, accaparement de l’écriture par le roi…) influencent-ils la conception du passé de l’Espagne ? Comment le Roi Sage fonde-t-il la grandeur de la péninsule Ibérique, comment en légitime-t-il les fondements et comment définit-il l’exercice du pouvoir royal ? L’analyse des différents épisodes, des nombreux portraits, des relations entre les personnages, ainsi que des procédés d’écriture permet de mettre au jour l’originalité textuelle et idéologique de cette partie de la chronique et les liens entre la Estoria et l’idéal alphonsin défendu dans les autres œuvres du Roi Sage. Démêlant les structures et les topiques bibliques, antiques et médiévaux exploités par le Roi Sage, l’auteur dévoile les différents réseaux de transmission symbolique, politique, sapientielle et spirituelle qui sont à l’œuvre dans le récit et met ainsi en évidence la façon dont le souverain, en célébrant un territoire et un passé communs, garants de l’identité hispanique, développe un mythe de création nationale ; ce qui permet à Soizic Escurignan de conclure que le récit des origines se veut programmatique, et plus que cela, performatif.La Estoria de España, escrita bajo la égida del rey Alfonso X el Sabio, rey de Castilla y León (1252-1284), traza la historia de la Península Ibérica y sobre todo de Castilla, desde sus orígenes hasta el siglo XIII. Si muchos investigadores de renombre han estudiado la Estoria, todos estos trabajos, esenciales, ofrecen solo una visión parcial de la primera parte de la crónica. De hecho, no se ha dedicado ningún estudio de conjunto al relato de los orígenes. Sin embargo, para medir la riqueza y complejidad de la historia peninsular, es necesario tener en cuenta este gran intervalo de tiempo entre los inicios de la humanidad y el año 711. Los dominios griego, cartaginés, romano, bárbaro y visigodo, el derrumbe del reino de Toledo y los inicios del reino de Asturias constituyen ciertamente un relato de los orígenes. Por tanto, la autora del libro parte del postulado de que los primeros 565 capítulos de la Estoria no pueden considerarse un simple preliminar sin ningún significado político. Varias preguntas están en el origen de este trabajo: ¿cómo los nuevos desafíos del siglo XIII (ampliación de las fronteras del reino, fecho del Imperio, nuevas concepciones políticas, oposición de la nobleza y del clero, monopolización de la escritura por el rey...) influyen en la concepción del pasado de España? ¿Cómo funda el Rey Sabio la grandeza de la Península Ibérica, cómo legitima sus fundamentos y cómo define el ejercicio del poder real? El análisis de los diferentes episodios, de los numerosos retratos, de las relaciones entre los personajes, así como de los procesos de escritura, nos permite sacar a la luz la originalidad textual e ideológica de esta parte de la crónica y los vínculos entre la Estoria y el ideal alfonsino defendido en las demás obras del Rey Sabio. Desentrañando las estructuras y temas bíblicos, antiguos y medievales utilizados por el Rey Sabio, la autora revela las diferentes redes de transmisión simbólica, política, sapiencial y espiritual que operan en el relato y así pone de realce la forma en que el soberano, al celebrar un territorio y un pasado comunes, garantes de la identidad hispánica, desarrolla un mito de creación nacional; lo que permite a Soizic Escurignan concluir que el relato de los orígenes está destinado a ser programático y, más que eso, performativo.La Estoria de España, written under the aegis of Alfonso X the Wise, King of Castile and León (1252-1284), traces the history of the Iberian Peninsula and more specifically of Castile, from its origins to the 13th century. While many renowned researchers have studied the Estoria, all of this work, which is also essential, only offers a partial view of the first part of the chronicle. No comprehensive study has in fact been devoted to the story of the origins. However, in order to measure the richness and complexity of peninsular history, it is necessary to take into account this large time interval between the beginnings of humanity and the year 711. The domination of the Greeks, the Carthaginians, the Romans, the Barbarians and the Visigoths, the collapse of the Kingdom of Toledo and the beginnings of the Kingdom of Asturias do indeed constitute a story of the origins. The author of the book therefore starts from the premise that the first 565 chapters of the Estoria cannot be considered as a mere preliminary without any political significance. Several questions are thus at the origin of this work: how do the new challenges of the 13th century (expansion of the borders of the kingdom, fecho del Imperio, new political conceptions, opposition of the nobility and the clergy, monopolization of writing by the king…) influence the conception of Spain's past? How does the Wise King found the greatness of the Iberian Peninsula, how does he legitimize its foundations and how does he define the exercise of royal power? The analysis of the different episodes, of the numerous portraits, of the relationships between the characters, as well as of the writing processes makes it possible to bring to light the textual and ideological originality of this part of the chronicle and the links between the Estoria and the Alphonsine ideal defended in the other works of the Wise King. Unraveling the biblical, ancient and medieval structures and topics used by the Wise King, the author reveals the different networks of symbolic, political, sapiential and spiritual transmission that are at work in the story and thus highlights the way in which the sovereign, by celebrating a common territory and past, guarantors of Hispanic identity, develops a myth of national creation; which allows Soizic Escurignan to conclude that the story of the origins is meant to be programmatic, and more than that, performative
The design of a formula 28 catamaran
No full textHaving done a project of designing a motorboat in the 2nd year, the author’s interest of designing a sailing boat for his 3rd year project was reinforced. The choice was then between a multihull and a monohull. The advantage of the students of Southampton Institute is that they can use some modern tools like the towing tank, or the wind tunnel. The choice of dissertation was then turned to experimentations and testing.
Looking to the past dissertation, most of the designs have been done on monohull. Hence, a large quantity of information is available. The interest of doing some testing on multihulls was an evidence for the author.
In order to compare the results to existing boats, a choice has been done to use a class of boat that is regulated by rules. Consequently, the dissertation is about designing a formula 28 catamaran. This class is regulated by very precise rules. It is a racing boat that has to be habitable.
After a quick calculation, it has been proved that the boat is too light, compared to the length and the beam, to fit in the towing tank. The formula 28 catamaran weights 750 kg for 8.53m long and 5.4m width around.
Today, the formula 28 boats are not used for cruising, despite the boats have a minimum of accommodations. The design was then orientated to use the catamaran for cruising as much as racing
Does facial amimia impact the recognition of facial emotions? An EMG study in Parkinson's disease
No full textInternational audienceAccording to embodied simulation theory, understanding other people's emotions is fostered by facial mimicry. However, studies assessing the effect of facial mimicry on the recognition of emotion are still controversial. In Parkinson's disease (PD), one of the most distinctive clinical features is facial amimia, a reduction in facial expressiveness, but patients also show emotional disturbances. The present study used the pathological model of PD to examine the role of facial mimicry on emotion recognition by investigating EMG responses in PD patients during a facial emotion recognition task (anger, joy, neutral). Our results evidenced a significant decrease in facial mimicry for joy in PD, essentially linked to the absence of reaction of the zygomaticus major and the orbicularis oculi muscles in response to happy avatars, whereas facial mimicry for expressions of anger was relatively preserved. We also confirmed that PD patients were less accurate in recognizing positive and neutral facial expressions and highlighted a beneficial effect of facial mimicry on the recognition of emotion. We thus provide additional arguments for embodied simulation theory suggesting that facial mimicry is a potential lever for therapeutic actions in PD even if it seems not to be necessarily required in recognizing emotion as such. © 2016 Argaud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Mechanism of action of sprG1-encoded type I toxins in Staphylococcus aureus: from membrane alterations to mesosome-like structures formation and bacterial lysis
No full textInternational audiencesprG1/ SprF1 is a type I toxin-antitoxin system located on Staphylococcus aureus prophage. It has previously been shown that the two toxins, SprG1 31 and SprG1 44 , encoded by the sprG1 gene, are two membrane-associated peptides structured in a single α-helix. Overexpression of these two peptides leads to growth inhibition and even S. aureus death. In this study, we investigated the involvement of each peptide in this toxicity, the sequence requirements necessary for SprG1 31 toxicity, and the mechanism of action of these two peptides. Our findings show that both peptides, when expressed individually, are able to stop growth, with higher toxicity observed for SprG1 31 . The combination of a hydrophobic domain and a charged domain located only at the C-terminus is necessary for this toxicity, likely to retain the orientation of the transmembrane domain. A net cationic charge for SprG1 31 is not essential to induce a growth defect in S. aureus . Furthermore, we established a chronology of toxic events following overexpression to gain insights into the mode of action of SprG1 44 and SprG1 31 . We demonstrated that mesosome-like structures are already formed when membrane is depolarized, about 20 min after peptides induction. This membrane depolarization occurs concomitantly with a depletion of intracellular ATP, leading to S. aureus growth arrest. Moreover, we hypothesized that SprG1 44 and SprG1 31 do not form large pores in the S. aureus membrane, as ATP is not excreted into the extracellular medium, and membrane permeabilization is delayed relative to membrane depolarization. The next challenge is to identify the conditions under which SprG1 44 and SprG1 31 are naturally expressed, and to uncover their potential roles during staphylococcal growth, colonization, and infection
A community perspective on the concept of marine holobionts: current status, challenges, and future directions
No full textABSTTRACT
Host-microbe interactions play crucial roles in marine ecosystems, but we still have very little understanding of the mechanisms that govern these relationships, the evolutionary processes that shape them, and their ecological consequences. The holobiont concept is a renewed paradigm in biology that can help to describe and understand these complex systems. It posits that a host and its associated microbiota, living together in a stable relationship, form the holobiont, and have to be studied together as a coherent biological and functional unit to understand its biology, ecology, and evolution. Here we discuss critical concepts and opportunities in marine holobiont research and identify key challenges in the field. We highlight the potential economic, sociological, and environmental impacts of the holobiont concept in marine biological, evolutionary, and environmental sciences with comparisons to terrestrial sciences where appropriate. Given the connectivity and the unexplored biodiversity specific to marine ecosystems, a deeper understanding of such complex systems requires further technological and conceptual advances, e.g. the development of controlled experimental model systems for holobionts from all major lineages and the modeling of (info)chemical-mediated interactions between organisms. The most significant challenge is to bridge cross-disciplinary research on tractable model systems in order to address key ecological and evolutionary questions. This will be crucial to decipher the roles of marine holobionts in biogeochemical cycles, but also developing concrete applications of the holobiont concept e.g. to increase yield or disease resistance in aquacultures or to protect and restore marine ecosystems through management projects.ACKNOWLEDGEMENTS
This paper is based on the results of a foresight workshop funded by the EuroMarine network, Sorbonne University, and the UMRs 8227 and 7144 of the Roscoff Biological Station. We are grateful to Catherine Boyen for useful advice and helpful discussions. We thank Sylvie Kwayeb-Fagon for workshop facilitation; Maryvonne Saout and Léna Corre for administrative support; and Marc Trousselier, Sébastien Villéger, Arthur Escalas, Yvan Bettarel, Thierry Bouvier for help writing a part of the manuscript. EMM was partially funded by an Australian Research Council Discovery Project (DP180104041), and JP was partially funded by the Galician Innovation Agency (IN607A 2017/4). The work of SD ad CL was partially funded by the ANR project IDEALG (ANR-10-BTBR-04). CG, CL, and SD received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska- Curie grant agreement number 624575 (ALFF). The work of FN was partially funded by the ANR project IMPEKAB (ANR-15-CE02-001). UC was partially funded by the Research Council of Lithuania project INBALANCE (09.3.3-LMT-K-712-01-0069). JD was supported by the LabEx GRAL (ANR-10-LABX-49-01) and Pȏle CBS from the University of Grenoble Alpes. PC received support from the European Union's Horizon 2020 research and innovation program through the SponGES project (grant agreement No. 679849). EKAZ was funded by a Marie Curie Individual Fellowship (Horizon 2020, IRONCOMM). AHE was supported by Portuguese national funds from FCT - Foundation for Science and Technology through project UID/Multi/04326/2019. This document reflects only the authors' view and the Executive Agency for Small and Medium-sized Enterprises (EASME) is not responsible for any use that may be made of the information it contains.
AUTHOR CONTRIBUTIONS
Simon M Dittami prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Enrique Arboleda authored or reviewed drafts of the paper, approved the final draft.
Jean-Christophe Auguet authored or reviewed drafts of the paper, approved the final draft.
Arite Bigalke authored or reviewed drafts of the paper, approved the final draft.
Enora Briand authored or reviewed drafts of the paper, approved the final draft.
Paco Cardenas authored or reviewed drafts of the paper, approved the final draft.
Ulisse Cardini authored or reviewed drafts of the paper, approved the final draft.
Johan Decelle authored or reviewed drafts of the paper, approved the final draft.
Aschwin H Engelen authored or reviewed drafts of the paper, approved the final draft.
Damien Eveillard authored or reviewed drafts of the paper, approved the final draft.
Claire M.M. Gachon authored or reviewed drafts of the paper, approved the final draft.
Sarah M Griffiths authored or reviewed drafts of the paper, approved the final draft.
Tilmann Harder authored or reviewed drafts of the paper, approved the final draft.
Ehsan Kayal authored or reviewed drafts of the paper, approved the final draft.
Elena Kazamia authored or reviewed drafts of the paper, approved the final draft.
François H Lallier authored or reviewed drafts of the paper, approved the final draft.
Mónica Medina authored or reviewed drafts of the paper, approved the final draft.
Ezequiel Marzinelli authored or reviewed drafts of the paper, approved the final draft.
Teresa Morganti authored or reviewed drafts of the paper, approved the final draft.
Laura Núñez Pons authored or reviewed drafts of the paper, approved the final draft.
Soizic Prado authored or reviewed drafts of the paper, approved the final draft.
José Pintado authored or reviewed drafts of the paper, approved the final draft.
Mahasweta Saha authored or reviewed drafts of the paper, approved the final draft.
Marc-André Selosse authored or reviewed drafts of the paper, approved the final draft.
Derek Skillings authored or reviewed drafts of the paper, approved the final draft.
Willem Stock prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Shinichi Sunagawa authored or reviewed drafts of the paper, approved the final draft.
Eve Toulza authored or reviewed drafts of the paper, approved the final draft.
Alexey Vorobev authored or reviewed drafts of the paper, approved the final draft.
Catherine Leblanc prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Fabrice Not prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
FUNDING
EMM was partially funded by an Australian Research Council Discovery Project (DP180104041), and JP was partially funded by the Galician Innovation Agency (IN607A 2017/4). The work of SD ad CL was partially funded by the ANR project IDEALG (ANR-10-BTBR-04). CG, CL, and SD received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement number 624575 (ALFF). The work of FN was partially funded by the ANR project IMPEKAB (ANR-15-CE02-001). UC was partially funded by the Research Council of Lithuania project INBALANCE (09.3.3-LMT-K-712-01-0069). JD was supported by the LabEx GRAL (ANR-10-LABX-49-01) and Pȏle CBS from the University of Grenoble Alpes. PC received support from the European Union's Horizon 2020 research and innovation program through the SponGES project (grant agreement No. 679849). EKAZ was funded by a Marie Curie Individual Fellowship (Horizon 2020, IRONCOMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Putting collective intelligence to the enforcement of the Digital Services Act: Report on possible collaborations between the European Commission and civil society organisations
No full textWhile underlying the many ways to build strong cooperation settings between regulators and CSOs, this report focuses on making concrete recommendations for the design of an efficient and influential expert group with the European Commission. The creation of an expert group finds its roots in article 64 and recital 137 of the DSA which require the Commission to develop Union expertise and capabilities. Once established, the experts of this group will be able to bring evidence-based information directly to the Commission and specific expertise on the protection of fundamental rights and the safety of users online. By instituting an expert group, the Commission will not only benefit from valuable expert knowledge but will also demonstrate its willingness to put in place an efficient enforcement system based on collective intelligence. Aside from the establishment of an expert group, other cumulative mechanisms will also help the DSA’s enforcement to thrive. Civil society organisations should, for instance, consider organising regular crowdsourcing events to deep-dive and analyse the data published by entities covered by the transparency obligations. As it has done in the past, the Commission can sponsor these events and be a direct beneficiary of their results. Another way for civil society organisations to bring information to the Regulator is by legal action, including by making complaints to the regulators
Putting collective intelligence to the enforcement of the Digital Services Act: Report on possible collaborations between the European Commission and civil society organisations
No full textWhile underlying the many ways to build strong cooperation settings between regulators and CSOs, this report focuses on making concrete recommendations for the design of an efficient and influential expert group with the European Commission. The creation of an expert group finds its roots in article 64 and recital 137 of the DSA which require the Commission to develop Union expertise and capabilities. Once established, the experts of this group will be able to bring evidence-based information directly to the Commission and specific expertise on the protection of fundamental rights and the safety of users online. By instituting an expert group, the Commission will not only benefit from valuable expert knowledge but will also demonstrate its willingness to put in place an efficient enforcement system based on collective intelligence. Aside from the establishment of an expert group, other cumulative mechanisms will also help the DSA’s enforcement to thrive. Civil society organisations should, for instance, consider organising regular crowdsourcing events to deep-dive and analyse the data published by entities covered by the transparency obligations. As it has done in the past, the Commission can sponsor these events and be a direct beneficiary of their results. Another way for civil society organisations to bring information to the Regulator is by legal action, including by making complaints to the regulators
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
No full textInterindividual clinical vari-ability is vast in humans infected withsevere acute respiratory syndrome corona-virus 2 (SARS-CoV-2), ranging from silent in-fection to rapid death. Three risk factors forlife-threatening coronavirus disease 2019(COVID-19) pneumonia have been identified—being male, being elderly, or having othermedical conditions—but these risk factorscannot explain why critical disease remainsrelatively rare in any given epidemiologicalgroup. Given the rising toll of the COVID-19pandemic in terms of morbidity and mortality,understanding the causes and mechanisms oflife-threatening COVID-19 is crucial.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. 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 (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013,” by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence” (reference no. ANR-15-IDEX-04-LUE) (45); and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology; by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to F.R.-L.); and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by 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 Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw; NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program (“poste d’accueil Inserm”). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091; the Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; and the American Academy of Allergy, Asthma, and Immunology
