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National audience; Usually, the description of nuclear equipment by the FMEA (Failure Mode and Effects Analysis) method can be of considerable length (up to 5,000 lines); on the other hand, the number of rules used for the verification of this equipment is small. In addition, upstream, there is the question of trust in the tools that generate these descriptions for complex equipment, that is to say, made up of several thousand objects (requirements, functions, interfaces, behaviors).

International audience; We report the case of an HIV-1-infected patient, treated with anti-CD20 monoclonal antibody for a B-cell lymphoma previously treated by autologous stem cell transplant. He suffered from chronic COVID19 and we monitored by plasma SARS-CoV-2 RNA by highly sensitive droplet-based digital PCR technology (ddPCR). Under tocilizumab therapy and despite a first clinical improvement biologically associated with decreasing inflammatory markers, a slight increase of SARS-CoV-2 RNAaemia quantified by ddPCR was highlighted, confirming the absence of viral efficacy of this treatment and predicting the subsequent observed deterioration. As expected, his complete recovery, finally achieved after COVID-19 convalescent plasmatherapy, strictly paralleled plasma SARS-CoV-2 RNA clearance. With these results, we confirmed the interest of SARS-CoV-2 RNAaemia monitoring by ddPCR in COVID-19 patients, particularly during treatment, and firstly showed that this new and specific biomarker could be helpful to select eligible patient for anti-IL6 receptors therapy considering the variable levels of efficacy recently observed with such therapy.

International audience; In multiple domains, large amounts of data are daily generated and combined to be analyzed. The interpretation of these analyses requires to track back the provenance of combined data with respect to initial, raw data. The correctness of the provenance is crucial in many critical domains, such as medicine to prescribe treatments. In this article, we propose the first provenance-aware extended relational algebra formalized in a proof assistant (Coq), for a non trivial subset of database queries: queries containing aggregates, null values, and correlated sub-queries. The formalization is validated by an adequacy proof with respect to standard evaluation of queries. This development is a first step towards a posteriori certification of provenance for data manipulation, with strong guaranties.

International audience

International audience

Introduction: Intellectual disability (ID) is frequently associated as a comorbidity in autism spectrum disorders (ASD). This study investigated a) how similar the heterogeneity in the cognitive and socio-emotional developmental profiles was for children with ASD and ID, b) the difference between the subjects' profiles and those of typically developing children (TD) matched for developmental levels, c) the skills existing with the lowest and highest developmental levels, and d) the relationship between developmental profiles in ASD and the severity of autism, ID, and the overall developmental level. Participants: The sample was comprised of 119 children (101 boys and 18 girls) who ranged in chronological age (CA) from 21 months to 14 years (M = 5 years 2 months; SD = 2 years 6 months) with developmental levels lower than 24 months. They came from three countries (France = 40, Brazil = 40, and Algeria = 39). The control group was comprised of 40 TD children from these same countries who ranged in CA from 4 to 24 months (M = 1 year 3 months; SD = 5 months). The ASD diagnosis was carried out according to International Statistical Classification of Diseases and Related Health Problems-10th Edition (ICD-10), Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR), Diagnostic and Statistical Manual of Mental Disorders-5th ed (DSM-5) criteria and the Childhood Autism Rating Scale (CARS). Measures: Children were tested using the Social Cognitive Evaluation Battery (SCEB; Adrien, 2007) by trained psychologists from public and private institutions specialized in the diagnosis of autism and interventions in this field. The SCEB explores 16 functional abilities, in both cognitive and socio-emotional areas, and allows the calculation of domain and area developmental levels and heterogeneity indices for the global, cognitive, and socio-emotional areas. Results: Children with ASD developmental profiles show very high heterogeneity as opposed to TD children. Regardless of the country of origin, there are similarities between the heterogeneous cognitive and socio-emotional developmental profiles of the children with ASD, whose profiles are characterized by lower developmental levels of language and vocal imitation skills, and a relationship between these developmental heterogeneities and the degree of severity of autistic symptomatology, intellectual disability, and overall development level. The implications of this study are presented for clinical assessment and intervention purposes in ASD and ID.

International audience

International audience; Nous proposons une sémantique formelle, exécutable, mécanisée en Coq pour un fragment réaliste du langage SQL, le standard en terme de bases de données relationnelles. Ce fragment prend en compte des requêtes de la forme select [distinct] from where group by having en présence de valeurs nulles, fonctions, agrégats, quantificateurs ainsi que de requêtes imbriquées potentiellement corrélées. Nous relions ce fragment à l'algèbre relationnelle, équivalent pour SQL du λ-calcul pour les langages fonctionnels. Nous obte-nons ainsi le premier résultat d'équivalence de ce fragment et de l'algèbre, formellement prouvé. Enfin, grâce au mécanisme d'extraction, nous fournissons un analyseur sémantique du langage SQL certifié en Coq, élément central pour l'obtention d'un compilateur SQL vérifié.

International audience; In this article, we provide a Coq mechanised, executable, formal semantics for a realistic fragment of SQL consisting of select [distinct] from where group by having queries with NULL values, functions, aggregates, quantifiers and nested potentially correlated sub-queries. Relying on the Coq extraction mechanism to Ocaml, we further produce a Coq certified semantic analyser for a SQL compiler. We then relate this fragment to a Coq formalised (extended) relational algebra that enjoys a bag semantics hence recovering all well-known algebraic equivalences upon which are based most of compilation optimisations. By doing so, we provide the first formally mechanised proof of the equivalence of SQL and extended relational algebra.

International audience; In this article, we use the Coq proof assistant to specify and verify the low level layer of SQL's execution engines. To reach our goals, we first design a high-level Coq specification for data-centric operators intended to capture their essence. We, then, provide two Coq implementations of our specification. The first one, the physical algebra, consists in the low level operators found in systems such as Postgresql or Oracle. The second, SQL algebra, is an extended relational algebra that provides a semantics for SQL. Last, we formally relate physical algebra and SQL algebra. By proving that the physical algebra implements SQL algebra, we give high level assurances that physical algebraic and SQL algebra expressions enjoy the same semantics. All this yields the first, to our best knowledge, formalisation and verification of the low level layer of an RDBMS as well as SQL's compilation's physical optimisation: fundamental steps towards mechanising SQL's compilation chain.

SQL is the standard language for manipulating data stored in relational database systems. In theory, SQL is based on the relational data model. However, there is an important mismatch between the theoretical foundations and the corresponding standard specification, as SQL history spread over decades. Briefly, the disparities concern the treatment of relations: finite sets in theory, finite bags in practice, the treatment of attributes and the chosen corresponding algebra used to compile queries. We propose SQLCert, a Coq mechanisation of three, among four, central steps of SQL's compilation chain: the syntactic analysis, the semantics analysis and the logical optimisation steps. To this purpose, we propose SQLCoq a Gallina grammar and associated Coq-mechanised semantics accounting for the native fragment of SQL described in the ISO/IEC 2006 Final Committee draft. As SQL compilers' logical optimisation is based on algebraic rewritings, we also define ExtAlg a Coq-mechanised extended bag-set-algebra, deeply relate SQLCoq to it and prove, using Coq, most of the commonly used in practice (SQL's queries) rewritings, yielding strong guarantees for the optimiser. Doing so, we thus formally reconcile SQL and its theoretical algebraic counterpart and provide the first, to our knowledge, executable mechanisation proposal of a (realistic fragment of) SQL compiler.

International audience; We propose a SSReflect library for logic programming in the Datalog setting. As part of this work, we give a first mechanization of standard Datalog and of its extension with stratified negation. The library contains a formalization of the model theoretical and fix-point semantics of the languages, implemented through bottom-up and, respectively, through stratified evaluation procedures. We provide corresponding soundness, termination, completeness and model minimality proofs. To this end, we rely on the Coq proof assistant and SSReflect. In this context, we also construct a preliminary framework for dealing with stratified programs. We consider this to be a necessary first step towards the certification of security-aware data-centric applications.

International audience

Le developpement cognitif et socio-emotionnel est particulierement altere chez les enfants avec trouble du spectre de l’autisme (TSA) qui ont un tres faible niveau de developpement (entre 4 mois et 24 mois). La question est de savoir si cette alteration developpementale est identique selon l’âge de l’enfant et son degre de retard ou de deficience intellectuelle. L’etude porte sur 69 enfants issus de 7 pays (9 filles et 60 garcons) repartis en deux groupes d’âge reel, avec soit un retard leger, soit une deficience intellectuelle severe (Groupe 1 : N = 39 ; 1 an 7 mois-3 ans et QD moyen 60 = ; et Groupe 2 : N = 30 ; 8 ans-14 ans et QD moyen = 15). Le developpement est evalue a l’aide de la Batterie d’evaluation cognitive et socio-emotionnelle (BECS). Si on ne note aucune difference significative entre les niveaux de developpement global, cognitif et socio-emotionnel des deux groupes, les plus jeunes enfants avec TSA presentent une plus grande heterogeneite socio-emotionnelle. Par ailleurs, il existe des differences pour les domaines « relation affective » et « interaction sociale » (les niveaux sont plus eleves chez les enfants les plus jeunes) et « image de soi » et « imitation gestuelle » (les niveaux sont plus eleves chez les enfants les plus âges). Les implications pour les pratiques d’evaluation et d’intervention en fonction de l’âge et du degre de retard de l’enfant sont abordees.

Resume L’identification des symptomes du trouble du spectre autistique (TSA) par le diagnostic clinique permet de determiner les capacites de communication et de socialisation a stimuler ou aider a la regulation du comportement par une prise en charge de l’enfant avec TSA. L’exigence croissante d’une mise en evidence de ces symptomes de facon precoce rend necessaire une bonne comprehension des modeles theoriques sous-jacents. Parmi ces derniers, les modeles traitant de l’attention conjointe, l’une des premieres capacites communicatives du jeune enfant, sont particulierement importants pour l’evaluation precoce. Cet article a pour but d’etablir un lien entre ces modeles et les outils cliniques utilises pour le diagnostic et l’evaluation du developpement, en se focalisant sur les capacites d’attention conjointe. Une revue de la litterature des modeles existants et des experimentations dans le cadre de l’autisme permet de definir les principaux mecanismes comportementaux de l’attention conjointe chez le tres jeune enfant. Un tableau de correspondance a ete elabore pour identifier leur presence dans les outils cliniques. Les elements qui se retrouvent simultanement dans les quatre outils etudies sont concentres sur la comprehension des intentions. Bien que ce resultat reflete le consensus de la recherche sur ce sujet, deux elements constitutifs de l’attention conjointe, lies a l’exploration visuelle et au desengagement attentionnel ne sont pas repris dans les outils cliniques. Il s’agit de mecanismes explores par des modeles theoriques recents et utilisant des methodes innovantes comme le detecteur de mouvement oculaire ( eye-tracking ). Ces nouvelles technologies sont aujourd’hui couramment utilisees dans le domaine de la recherche et suggerent une evolution des modeles theoriques de l’attention conjointe, mais leur application clinique n’est pas encore mise en place, ce qui pourrait expliquer l’absence de ces elements dans les outils actuels. Il serait interessant de les integrer dans les outils d’evaluation clinique et favoriser leur integration dans le depistage precoce de l’autisme.

Ce document présente les recherches que j'ai effectuées ces dernières années dans le domaine des preuves automatqiues et/ou assistées par ordinateurs, ainsi que les liens entre ces deux approches.

Ce document présente les recherches que j'ai effectuées ces dernières années dans le domaine des preuves automatqiues et/ou assistées par ordinateurs, ainsi que les liens entre ces deux approches.

AC-completion efficiently handles equality modulo associative and commutative function symbols. When the input is ground, the procedure terminates and provides a decision algorithm for the word problem. In this paper, we present a modular extension of ground AC-completion for deciding formulas in the combination of the theory of equality with user-defined AC symbols, uninterpreted symbols and an arbitrary signature disjoint Shostak theory X. Our algorithm, called AC(X), is obtained by augmenting in a modular way ground AC-completion with the canonizer and solver present for the theory X. This integration rests on canonized rewriting, a new relation reminiscent to normalized rewriting, which integrates canonizers in rewriting steps. AC(X) is proved sound, complete and terminating, and is implemented to extend the core of the Alt-Ergo theorem prover., Comment: 30 pages, full version of the paper TACAS'11 paper "Canonized Rewriting and Ground AC-Completion Modulo Shostak Theories" accepted for publication by LMCS (Logical Methods in Computer Science)

International audience; Over the last 20 years, melatonin, a pineal hormone synthesized from serotonin, has been implicated in various studies on the autism spectrum disorder (ASD) and altered melatonin levels were detected in subgroups of subjects with ASD. Its effect on sleep disturbances got the attention of clinicians and several investigations were carried out to determine the usefulness and safety of melatonin administration in this disorder. Hypotheses were also raised regarding the possibility that the dysfunctional synthesis and secretion of melatonin detected in subgroups of subjects with ASD may increase the risk as well the severity of ASD. The purpose of this paper is to review our pharmacokinetic knowledge on melatonin and present results from recent studies on sleep disorders in autism, their treatment with melatonin and the impact of melatonin prescription in children with ASD evaluated in a Diagnostic Center for Autism Spectrum Disorder in Paris, France.

International audience; AC-completion efficiently handles equality modulo associative and commutative function symbols. When the input is ground, the procedure terminates and provides a decision algorithm for the word problem. In this paper, we present a modular extension of ground ACcompletion for deciding formulas in the combination of the theory of equality with user-defined AC symbols, uninterpreted symbols and an arbitrary signature disjoint Shostak theory X. Our algorithm, called AC(X), is obtained by augmenting in a modular way ground AC-completion with the canonizer and solver present for the theory X. This integration rests on canonized rewriting, a new relation reminiscent to normalized rewriting, which integrates canonizers in rewriting steps. AC(X) is proved sound, complete and terminating, and is implemented to extend the core of the Alt-Ergo theorem prover.

International audience; Software engineering, automated reasoning, rule-based programming or specifications often use rewriting systems for which termination, among other properties, may have to be ensured. This paper presents the approach developed in Project A3PAT to discover and moreover certify, with full automation, termination proofs for term rewriting systems. It consists of two developments: the Coccinelle library formalises numerous rewriting techniques and termination criteria for the Coq proof assistant; the CiME3 rewriting tool translates termination proofs (discovered by itself or other tools) into traces that are certified by Coq assisted by Coccinelle. The abstraction level of our formalisation allowed us to weaken premises of some theorems known in the literature, thus yielding new termination criteria, such as an extension of the powerful subterm criterion (for which we propose the first full Coq formalisation). Techniques employed in CiME3 also improve on previous works on formalisation and analysis of dependency graphs.

National audience; We present some experiments with CiME/Coccinelle about standard first-order unification of deep-embedded terms in the Coq proofassistant. We have modelled parts of the usual inference rules forunification, namely Decompose, Merge and Coalesce as Coq functions and we proved their soundness and completeness. Regarding the Generalized Occur-Check, we use the CiME rewriting toolbox as an oracle either to provide a total ordering compatible with Occur-Check, or to exhibit a cycle. Then, using these informations, it is possible to prove in Coq that there is no most general unifier (mgu), or to compute it and prove that it actually enjoys the mgu properties. All together, it means that it is possible to compute an mgu for deep-embedded terms in Coq. This is a first step towards formal proofs of confluence for TRS.

National audience; Nowadays, formal methods rely on tools of different kinds: proof assistants with which the user interacts to discover a proof step by step; and fully automated tools which make use of (intricate) decision procedures. But while some proof assistants can check the soundness of a proof, they lack automation. Regarding automated tools, one still has to be satisfied with their answers Yes/No/Do not know, the validity of which can be subject to question, in particular because of the increasing size and complexity of these tools. In the context of rewriting techniques, we aim at bridging the gap between proof assistants that yield formal guarantees of reliability and highly automated tools one has to trust. We present an approach making use of both shallow and deep embeddings. We illustrate this approach with a prototype based on the CiME rewriting toolbox, which can discover involved termination proofs that can be certified by the coq proof assistant, using the Coccinelle library for rewriting.

For a long time, term orderings defined by polynomial interpretations were scarcely used in computer-aided termination proof of TRSs. But recently, the introduction of the dependency pairs approach achieved considerable progress w.r.t. automated termination proof, in particular by requiring from the underlying ordering much weaker properties than the classical approach. As a consequence, the noticeable power of a combination dependency pairs/polynomial orderings yielded a regain of interest for these interpretations. We describe criteria on polynomial interpretations for them to define weakly monotonic orderings. From these criteria, we obtain new techniques both for mechanically checking termination using a given polynomial interpretation and for finding such interpretations with full automation. With regard to automated search, we propose an original method for solving Diophantine constraints. We implemented these techniques into the CiME rewrite tool, and we provide some experimental results that show how useful polynomial orderings actually are in practice.

Our general goal is to provide better automation in interactive proof assistants such as Coq. We present an interpreter of proof traces in first-order multi-sorted logic with equality. Thanks to the reflection ability of Coq, this interpreter is both implemented and formally proved sound — with respect to a reflective interpretation of formulae as Coq properties — inside Coq's type theory. Our generic framework allows to interpret proofs traces computed by any automated theorem prover, as long as they are precise enough: we illustrate that on traces produced by the CiME tool when solving unifiability problems by ordered completion. We discuss some benchmark results obtained on the TPTP library.

In this report, we present an algorithm for solving {\em directly} linear Diophantine systems of both equations and inequations. Here directly means without adding slack variables for encoding inequalities as equalities. This algorithm is an extension of the algorithm due to Contejean and Devie \cite{contejean94ic} for solving linear Diophantine systems of equa­tions, which is itself a generalization of the algorithm of Fortenbacher \cite{clausen89} for solving a single linear Diophantine equation. All the nice properties of the algorithm of Contejean and Devie are still satisfied by the new algorithm: it is complete, {\em i.e.} provides a (finite) description of the set of solutions, it can be implemented with a {\em bounded} stack, and it admits an incremental version. All of these characteristics enable its easy integration in the CLP paradigm.

The purpose of this paper is to show how the introduction of new primitive constraints (e.g., among, diffn, cycle) over finite domains in the constraint logic programming system CHIP result in finding very rapidly good solutions for a large class of difficult sequencing, scheduling, geometrical placement and vehicle routing problems. The among constraint allows us to specify sequencing constraints in a very concise way. For the first time, the diffn constraint allows us to express and to solve directly multi-dimensional placement problems, where one has to consider nonoverlapping constraints between n-dimensional objects (e.g., rectangles, parallelepipeds). The cycle constraint makes it possible to specify a wide range of graph partitioning problems that could not yet be expressed by using current constraint logic programming languages. One of the main advantages of all these new primitives is to take into account more globally a set of elementary constraints. Finally, we point out that all the previous primitive constraints enhance the power of the CHIP system significantly, allowing us to solve real life problems that were not within reach of constraint technology before.

With the introduction of Java 5.0 the type system has been extended by parameterized types, type variables, type terms, and wildcards. As a result very complex types can arise. The term Vector is for example a correct type in Java 5.0. In this paper we present a type unification algorithm for Java 5.0 type terms. The algorithm unifies type terms, which are in subtype relationship. For this we define Java 5.0 type terms and its subtyping relation, formally. As Java 5.0 allows wildcards as instances of generic types, the subtyping ordering contains infinite chains. We show that the type unification is still finitary. We give a type unification algorithm, which calculates the finite set of general unifiers.

In this paper we extend the work of Campeanu, Salomaa and Yu on extended regular expressions featured in the Unix utility egrep and the popular scripting language Perl. We settle the open issue of closure under intersection and provide an improved pumping lemma that will show that a larger class of languages is not recognizable by extended regular expressions.

We present resolution-based decision procedures for the positive theory of certain finitely-generated varieties of algebras. The method is based on the existence of natural dualities for such classes of algebras.

Distributed Algorithm is among domains where informal reasoning is not an option, especially when Byzantine errors may occur. It is also characterized by a large variety of models whose subtle modulations imply radically different properties.We are interested in "robotic network": clouds of autonomous entities performing a cooperative task. The applications that these swarms of agents offer are extremely promising: exploration and search for survivors in devasted areas, patrols and drone flights in formation, etc. These few potentially critical exemples underline the high dynamicity of the model; they also indicate how failures of robots or errors in the distributed protocols that equip them can have distastrous consequences.To ensure the safety of the protocols and the security of tasks, we aim to optain, with the help of the Coq proof assistant, foraml mechanical validations of properties of certain distributed protocols. A prototype of Coq's formal model for robot network, Pactole, has recently shown the feasibility of an proof assistant verification in this framework. It captures quite naturally many variants of these networks, especially with regard to topology or the properties of demons. This model is of course in the higher order, and is based on coinductive types. It makes it possible to demonstrate in Coq both positive roperties: the embedded program makes it possible to carry out the task regardless of the initial configuration, as negative properties: there is no embedded program to complete the task.In the emerging framework of robot networks, the models are distinguished by the characteristics and capabilities of the robots, the topology of the space in which they evolve, the degree of synchronism (modelled by the properties of the activation demon), the error that can occure, etc. The prototype Pactole expresses only some of these variants. Thought in a theoretical framework (point robots, instantaneous movement, etc.), hypotheses remain out of reach, in particular realistic hypothesis such as totally asynchronous executions, or risk of collision. The absence of collision is fundamental in all applications relates to formation flights (drones) and critical safety condition as soon as one is interested in air transport. Formal validation of this property is therefore of great importance.The work consits of extending the formal model to take into account asynchronous evolutions of large robots. This modelling should allow easy formulation of protocols and the task they are supposed to perform. Particular attention will be given to ensuring the absence of collisions during potentially complex movements., L’algorithmique distribuée fait partie des domaines où le raisonnement informel n’est pas une option, en particulier lorsque des erreurs dites byzantines peuvent survenir. Elle est également caractérisée par une grande diversité de modèles dont les modulations subtiles impliquent des propriétés radicalement différentes. Nous nous intéressons aux « réseaux de robots » : nuages d’entités autonomes devant accomplir une tâche en coopération. Les applications que laissent envisager ces essaims d’agents sont extrêmement prometteuses : exploration et recherche de survivants dans des zones dévastées, patrouilles et vols de drones en formation, etc. Ces quelques exemples potentiellement critiques soulignent la grande dynamicité du modèle; ils indiquent également à quel point des défaillances des robots ou des erreurs dans les protocoles distribués qui les équipent peuvent avoir de désastreuses conséquences.Pour garantir la sûreté des protocoles et la sécurité des tâches, nous visons à l’obtention, à l’aide de l’assistant à la preuve Coq, de validations mécaniques formelles de propriétés de certains protocoles distribués.Un prototype de modèle formel Coq pour les réseaux de robots, Pactole, a récemment montré la faisabilité d’une approche de vérification par assistant à la preuve dans ce cadre. Il capture assez naturellement de nombreuses variantes de ces réseaux, notamment en ce qui concerne la topologie ou les propriétés des démons. Ce modèle est bien sûr à l’ordre supérieur et s’appuie sur des types coinductifs. Il permet de démontrer en Coq à la fois des propriétés positives : le programme embarqué permet de réaliser la tâche quelle que soit la configuration de départ, comme des propriétés négatives : il n’existe aucun programme embarqué permettant de réaliser la tâche.Dans le cadre émergent des réseaux de robots, les modèles sont distingués par les caractéristiques et capacités des robots, la topologie de l’espace dans lequel ils évoluent, le degré de synchronisme (modélisé par les propriétés du démon d’activation), les erreurs pouvant survenir, etc. Le prototype Pactolen’exprime que certaines de ces variantes. Pensé dans un cadre théorique (robots ponctuels, déplacements instantanés, etc.), des hypothèses restent hors de sa portée, en particulier des hypothèses réalistes comme des exécutions totalement asynchrones ou des risques de collision. L’absence de collision est fondamentale dans toutes les applications liées aux évolutions en formation (drones) et unecondition de sécurité critique dès qu’on s’intéresse au transport aérien. Une validation formelle de cette propriété revêt donc une grande importance.Le travail consiste à étendre le modèle formel afin de prendre en compte des évolutions asynchrones de robots volumineux. Cette modélisation doit permettre une formulation aisée de protocoles et des tâches qu’ils sont censés réaliser. On s’intéressera en particulier à garantir l’absence de collision au cours de déplacements potentiellement complexes.

Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. 706 , p. 712 , p. 718 ; see also p. 626

This thesis presents a formalization of fundamental database theories and algorithms. This furthers the maturing state of the art in formal specification development in the database field, with contributions stemming from two foundational approches to database models: relational and logic based.As such, a first contribution is a Coq library for the relational model. This contains a mechanization of integrity constraints and of their inference procedures. We model two of the most common dependencies, namely functional and multivalued, together with their corresponding axiomatizations. We prove soundness of their inference algorithms and, for the case of functional ones, also completeness. These types of dependencies are instances of equality and, respectively, tuple generating dependencies, which fall under the yet wider class of general dependencies. We model these and their inference procedure,i.e, the chase, for which we establish soundness.A second contribution consists of a Coq/Ssreflect library for logic programming in the Datalog setting. As part of this work, we give (one of the) first mechanizations of the standard Datalog language and of its extension with negation. The library includes a formalization of their model theoretical semantics and of their fixpoint semantics, implemented through bottom-up and, respectively, through stratified evaluation procedures. This is complete with the corresponding soundness, termination and completeness proofs. In this context, we also construct a preliminary framework for dealing with stratified programs. This work paves the way towards the certification of data-centric applications., Cette thèse présente une formalisation en Coq des langages et des algorithmes fondamentaux portant sur les bases de données. Ainsi, ce fourni des spécifications formelles issues des deux approches différentes pour la définition des modèles de données: une basée sur l’algèbre et l'autre basée sur la logique.A ce titre, une première contribution de cette thèse est le développement d'une bibliothèque Coq pour le modèle relationnel. Cette bibliothèque contient les modélisations de l’algèbre relationnelle et des requêtes conjonctives. Il contient aussi une mécanisation des contraintes d'intégrité et de leurs procédures d'inférence. Nous modélisons deux types de contraintes: les dépendances, qui sont parmi les plus courantes: les dépendances fonctionnelles et les dépendances multivaluées, ainsi que leurs axiomatisations correspondantes. Nous prouvons formellement la correction de leurs algorithmes d'inférence et, pour le cas de dépendances fonctionnelles, aussi la complétude.Ces types de dépendances sont des instances de contraintes plus générales : les dépendances génératrices d'égalité (equality generating dependencies, EGD) et, respectivement, les dépendances génératrices de tuples (tuple generating dependencies, TGD), qui appartiennent a une classe encore plus large des dépendances générales (general dependencies). Nous modélisons ces dernières et leur procédure d'inférence, i.e, "the chase", pour lequel nous établissons la correction. Enfin, on prouve formellement les théorèmes principaux des bases de données, c'est-à-dire, les équivalences algébriques, la théorème de l' homomorphisme et la minimisation des requêtes conjonctives.Une deuxième contribution consiste dans le développement d'une bibliothèque Coq/ssreflect pour la programmation logique, restreinte au cas du Datalog. Dans le cadre de ce travail, nous donnons la première mécanisations d'un moteur Datalog standard et de son extension avec la négation. La bibliothèque comprend une formalisation de leur sémantique en theorie des modelés ainsi que de leur sémantique par point fixe, implémentée par une procédure d'évaluation stratifiée. La bibliothèque est complétée par les preuves de correction, de terminaison et de complétude correspondantes. Cette plateforme ouvre la voie a la certification d' applications centrées données.

In this thesis, we propose new automation capabilities for the Coq proof assistant. We obtain this mechanization via an integration into Coq of decision procedures for propositional logic, equality reasoning and linear arithmetic which make up the core of the Alt-Ergo SMT solver. This integration is achieved through the reflection technique, which consists in implementing and formally proving these algorithms in Coq in order to execute them directly in the proof assistant. Because the algorithms formalized in Coq are exactly those in use in Alt-Ergo's kernel, this work significantly increases our trust in the solver. In particular, it embeds an original algorithm for combining equality modulo theory reasoning, called CC(X) and inspired by the Shostak combination algorithm, and whose justification is quite complex. Our Coq implementation is available in the form of tactics which allow one to automatically solve formulae combining propositional logic, equality and arithmetic. In order to make these tactics as efficient as may be, we have taken special care with performance in our implementation, in particular through the use of classical efficient data structures, which we provide as a separate library.; Dans cette thèse, nous proposons une amélioration de l'automatisation des preuves dans l'assistant de preuve Coq. Cette automatisation est obtenue en intégrant à Coq les procédures de décision pour la logique propositionnelle, l'égalité et l'arithmétique linéaire constituant le noyau du solveur SMT Alt-Ergo. Cette intégration est réalisée en utilisant la technique de preuve par réflexion, qui consiste à développer en Coq ces algorithmes et à prouver formellement leur correction de manière à les exécuter directement dans l'assistant de preuve. Comme les algorithmes formalisés en Coq sont exactement ceux utilisés dans le noyau d'Alt-Ergo, notre travail permet également d'augmenter considérablement la confiance que l'on peut avoir dans ce dernier. En particulier, il utilise un algorithme original de combinaison de l'égalité modulo une théorie, inspiré de la combinaison de Shostak et appelé CC(X), et dont la justification est relativement complexe.Notre développement Coq est utilisable sous la forme de tactiques qui permettent de valider automatiquement des formules combinant logique propositionnelle, égalité et arithmétique. Afin que ces tactiques soient le plus efficaces possibles, nous avons attaché une grande importance aux performances de notre implantation Coq, et en particulier à l'utilisation de structures de données efficaces courantes, dont nous proposons ici une bibliothèque.

In this thesis, we propose new automation capabilities for the Coq proof assistant. We obtain this mechanization via an integration into Coq of decision procedures for propositional logic, equality reasoning and linear arithmetic which make up the core of the Alt-Ergo SMT solver. This integration is achieved through the reflection technique, which consists in implementing and formally proving these algorithms in Coq in order to execute them directly in the proof assistant. Because the algorithms formalized in Coq are exactly those in use in Alt-Ergo's kernel, this work significantly increases our trust in the solver. In particular, it embeds an original algorithm for combining equality modulo theory reasoning, called CC(X) and inspired by the Shostak combination algorithm, and whose justification is quite complex. Our Coq implementation is available in the form of tactics which allow one to automatically solve formulae combining propositional logic, equality and arithmetic. In order to make these tactics as efficient as may be, we have taken special care with performance in our implementation, in particular through the use of classical efficient data structures, which we provide as a separate library.; Dans cette thèse, nous proposons une amélioration de l'automatisation des preuves dans l'assistant de preuve Coq. Cette automatisation est obtenue en intégrant à Coq les procédures de décision pour la logique propositionnelle, l'égalité et l'arithmétique linéaire constituant le noyau du solveur SMT Alt-Ergo. Cette intégration est réalisée en utilisant la technique de preuve par réflexion, qui consiste à développer en Coq ces algorithmes et à prouver formellement leur correction de manière à les exécuter directement dans l'assistant de preuve. Comme les algorithmes formalisés en Coq sont exactement ceux utilisés dans le noyau d'Alt-Ergo, notre travail permet également d'augmenter considérablement la confiance que l'on peut avoir dans ce dernier. En particulier, il utilise un algorithme original de combinaison de l'égalité modulo une théorie, inspiré de la combinaison de Shostak et appelé CC(X), et dont la justification est relativement complexe.Notre développement Coq est utilisable sous la forme de tactiques qui permettent de valider automatiquement des formules combinant logique propositionnelle, égalité et arithmétique. Afin que ces tactiques soient le plus efficaces possibles, nous avons attaché une grande importance aux performances de notre implantation Coq, et en particulier à l'utilisation de structures de données efficaces courantes, dont nous proposons ici une bibliothèque.