Martin-L\"of \`a la Coq

We present an extensive mechanization of the meta-theory of Martin-L\"of Type Theory (MLTT) in the Coq proof assistant. Our development builds on pre-existing work in Agda to show not only the decidability of conversion, but also the decidability of type checking, using an approach guided by bidirectional type checking. From our proof of decidability, we obtain a certified and executable type checker for a full-fledged version of MLTT with support for $\Pi$, $\Sigma$, $\mathbb{N}$, and identity types, and one universe. Furthermore, our development does not rely on impredicativity, induction-recursion or any axiom beyond MLTT with a schema for indexed inductive types and a handful of predicative universes, narrowing the gap between the object theory and the meta-theory to a mere difference in universes. Finally, we explain our formalization choices, geared towards a modular development relying on Coq's features, e.g. meta-programming facilities provided by tactics and universe polymorphism

Bovine neosporosis: from life cycle to prophylaxis

Neospora caninum is an apicomplexan parasite, identified about twenty years ago. Although it can cause neurological symptoms in newborn cattle, its main economic and health repercussion in breeding is due to abortions. The life cycle of N. caninum is not yet fully understood. Its currently identified final hosts are dogs and coyotes, but foxes are also strongly suspected. To be effective, treatment and prophylaxis must be based on sound knowledge of the life cycle and pathophysiology of this protozoosis. There is no treatment currently available. Many vaccine studies are being performed using various strategies, but only disease control methods are possible for the moment, alongside the crucial advisory role of veterinary practitioners.Le parasite N. caninum est un protozoaires identifié il y a une vingtaine d'années.Bien que l'infection par Neospora caninum puisse se manifester par des symptômes neurologiques en pathologie bovine néonatale, sa principale répercussion économique et sanitaire en élevage est due aux avortements. Son cycle parasitaire est encore imparfaitement connu. Ses hôtes définitifs actuellement identifiés avec certitude sont le chien, le coyote et le dingo, mais le renard est aussi fortement suspecté. Une bonne connaissance du cycle évolutif du parasite et de la physiopathologie de la néosporose est indispensable pour définir des méthodes de lutte efficaces. À ce jour, il n'existe pas de traitement. De nombreux essais vaccinaux sont réalisés avec différentes stratégies. Seules des méthodes de lutte sanitaire sont envisageables avec un rôle essentiel de conseil pour le vétérinaire sanitaire

SeamlessM4T-Massively Multilingual & Multimodal Machine Translation

What does it take to create the Babel Fish, a tool that can help individuals translate speech between any two languages? While recent breakthroughs in text-based models have pushed machine translation coverage beyond 200 languages, unified speech-to-speech translation models have yet to achieve similar strides. More specifically, conventional speech-to-speech translation systems rely on cascaded systems that perform translation progressively, putting high-performing unified systems out of reach. To address these gaps, we introduce SeamlessM4T, a single model that supports speech-to-speech translation, speech-to-text translation, text-to-speech translation, text-to-text translation, and automatic speech recognition for up to 100 languages. To build this, we used 1 million hours of open speech audio data to learn self-supervised speech representations with w2v-BERT 2.0. Subsequently, we created a multimodal corpus of automatically aligned speech translations. Filtered and combined with human-labeled and pseudo-labeled data, we developed the first multilingual system capable of translating from and into English for both speech and text. On FLEURS, SeamlessM4T sets a new standard for translations into multiple target languages, achieving an improvement of 20% BLEU over the previous SOTA in direct speech-to-text translation. Compared to strong cascaded models, SeamlessM4T improves the quality of into-English translation by 1.3 BLEU points in speech-to-text and by 2.6 ASR-BLEU points in speech-to-speech. Tested for robustness, our system performs better against background noises and speaker variations in speech-to-text tasks compared to the current SOTA model. Critically, we evaluated SeamlessM4T on gender bias and added toxicity to assess translation safety. Finally, all contributions in this work are open-sourced and accessible at https://github.com/facebookresearch/seamless_communicatio

Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection

Implication du domaine intracellulaire du syndécane-4 dans l’angiogenèse et le recrutement monocytaire induits par la chimiokine RANTES/CCL5

Atherosclerosis is a pathology characterized by the formation of an atheroma plaque in the blood vessel wall. Monocyte infiltration participates to the early phase of atheroma plaque development. Plaque rupture is induced by its neovascularization. The chemokine Regulate upon Activation, Normal T-cell, Expressed and Secreted (RANTES/CCL5) is involved in monocyte recruitment. Moreover, RANTES/CCL5 induces angiogenesis through its binding to endothelial glycosaminoglycans (GAG) chains. Syndecans (SDC) are transmembrane proteoglycans with GAG chains expressed at the membrane of endothelial cells. The aim of this study is to analyze the involvement of SDC-4 intracellular domain in RANTES/CCL5-induced angiogenesis and monocyte recruitment. SDC-4 intracellular mutants were developed to analyze the role of PKC-α, PIP2 binding or PDZ domain proteins in RANTES/CCL5-induced angiogenesis and monocyte recruitment. Our data show that RANTES/CCL5 induces angiogenesis and monocyte recruitment through intracellular signaling, including the activation of PKC-α, mediated by SDC-4 intracellular domain. The development of new therapeutic strategy targeting SDC-4 activation may counteract RANTES/CCL5 physiopathological effects.L’athérosclérose est caractérisée par la formation d’une plaque d’athérome au niveau de la paroi d’un vaisseau sanguin. L’infiltration monocytaire participe à la phase précoce du développement de la plaque d’athérome. Le risque de rupture de la plaque est accru suite à sa néo-vascularisation. La chimiokine Regulated upon Activation, Normal T-cell, Expressed and Secreted (RANTES/CCL5) est impliquée dans le recrutement monocytaire. De plus, elle exerce un effet pro-angiogénique de manière dépendante de sa fixation aux glycosaminoglycanes (GAG) endothéliaux. Les syndécanes (SDC) sont des protéoglycanes transmembranaires à chaînes GAG exprimés par les cellules endothéliales. Le but de cette étude est de déterminer l’implication du domaine intracellulaire du SDC-4 dans l’angiogenèse et le recrutement monocytaire induits par la chimiokine RANTES/CCL5. Des mutants intracellulaires du SDC-4 ont été développés pour étudier le rôle de la PKC-α, de la liaison du PIP2 ou de protéines à domaine PDZ dans l’angiogenèse et le recrutement monocytaire induits par RANTES/CCL5. Nos résultats montrent que la chimiokine RANTES/CCL5 stimule l’angiogenèse et le recrutement monocytaire par le biais d’une signalisation intracellulaire induite par le domaine intracellulaire du SDC-4, activant notamment la PKC-α. Le développement de thérapies ciblant l’activation du SDC-4 pourrait permettre de réguler les effets physiopathologiques exercés par RANTES/CCL5

Involvement of syndecan-4 intracellular domain in RANTES/CCL5-induced angiogenesis and monocyte recruitment

L’athérosclérose est caractérisée par la formation d’une plaque d’athérome au niveau de la paroi d’un vaisseau sanguin. L’infiltration monocytaire participe à la phase précoce du développement de la plaque d’athérome. Le risque de rupture de la plaque est accru suite à sa néo-vascularisation. La chimiokine Regulated upon Activation, Normal T-cell, Expressed and Secreted (RANTES/CCL5) est impliquée dans le recrutement monocytaire. De plus, elle exerce un effet pro-angiogénique de manière dépendante de sa fixation aux glycosaminoglycanes (GAG) endothéliaux. Les syndécanes (SDC) sont des protéoglycanes transmembranaires à chaînes GAG exprimés par les cellules endothéliales. Le but de cette étude est de déterminer l’implication du domaine intracellulaire du SDC-4 dans l’angiogenèse et le recrutement monocytaire induits par la chimiokine RANTES/CCL5. Des mutants intracellulaires du SDC-4 ont été développés pour étudier le rôle de la PKC-α, de la liaison du PIP2 ou de protéines à domaine PDZ dans l’angiogenèse et le recrutement monocytaire induits par RANTES/CCL5. Nos résultats montrent que la chimiokine RANTES/CCL5 stimule l’angiogenèse et le recrutement monocytaire par le biais d’une signalisation intracellulaire induite par le domaine intracellulaire du SDC-4, activant notamment la PKC-α. Le développement de thérapies ciblant l’activation du SDC-4 pourrait permettre de réguler les effets physiopathologiques exercés par RANTES/CCL5.Atherosclerosis is a pathology characterized by the formation of an atheroma plaque in the blood vessel wall. Monocyte infiltration participates to the early phase of atheroma plaque development. Plaque rupture is induced by its neovascularization. The chemokine Regulate upon Activation, Normal T-cell, Expressed and Secreted (RANTES/CCL5) is involved in monocyte recruitment. Moreover, RANTES/CCL5 induces angiogenesis through its binding to endothelial glycosaminoglycans (GAG) chains. Syndecans (SDC) are transmembrane proteoglycans with GAG chains expressed at the membrane of endothelial cells. The aim of this study is to analyze the involvement of SDC-4 intracellular domain in RANTES/CCL5-induced angiogenesis and monocyte recruitment. SDC-4 intracellular mutants were developed to analyze the role of PKC-α, PIP2 binding or PDZ domain proteins in RANTES/CCL5-induced angiogenesis and monocyte recruitment. Our data show that RANTES/CCL5 induces angiogenesis and monocyte recruitment through intracellular signaling, including the activation of PKC-α, mediated by SDC-4 intracellular domain. The development of new therapeutic strategy targeting SDC-4 activation may counteract RANTES/CCL5 physiopathological effects

How to make sense of laboratory analyses in respiratory cases?

International audienc

How to make sense of laboratory analyses in respiratory cases?

International audienc

Data & Results

Here are the raw datas and the analysis we conducted, along with the results and conclutions

Ethics Approval

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