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1. Evolutionary insights into the emergence of virulent Leptospira spirochetes.

Author

Alexandre Giraud-Gatineau, Cecilia Nieves, Luke B Harrison, Nadia Benaroudj, Frédéric J Veyrier, and Mathieu Picardeau

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Pathogenic Leptospira are spirochete bacteria which cause leptospirosis, a re-emerging zoonotic disease of global importance. Here, we use a recently described lineage of environmental-adapted leptospires, which are evolutionarily the closest relatives of the highly virulent Leptospira species, to explore the key phenotypic traits and genetic determinants of Leptospira virulence. Through a comprehensive approach integrating phylogenomic comparisons with in vitro and in vivo phenotyping studies, we show that the evolution towards pathogenicity is associated with both a decrease of the ability to survive in the environment and the acquisition of strategies that enable successful host colonization. This includes the evasion of the mammalian complement system and the adaptations to avoid activation of the innate immune cells by the highly-virulent Leptospira species (also called P1+ species), unlike other species belonging to the phylogenetically related P1- and P2 groups, as well as saprophytes. Moreover, our analysis reveals specific genetic determinants that have undergone positive selection during the course of evolution in Leptospira, contributing directly to virulence and host adaptation as demonstrated by gain-of-function and knock-down studies. Taken together, our findings define a new vision on Leptospira pathogenicity, identifying virulence attributes associated with clinically relevant species, and provide insights into the evolution and emergence of these life-threatening pathogens.

Published
2024
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2. A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection.

Author

Alexandra Maure, Emeline Lawarée, Francesco Fiorentino, Alexandre Pawlik, Saideep Gona, Alexandre Giraud-Gatineau, Matthew J G Eldridge, Anne Danckaert, David Hardy, Wafa Frigui, Camille Keck, Claude Gutierrez, Olivier Neyrolles, Nathalie Aulner, Antonello Mai, Mélanie Hamon, Luis B Barreiro, Priscille Brodin, Roland Brosch, Dante Rotili, and Ludovic Tailleux

Subjects
Biology (General), QH301-705.5
Abstract

Antituberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multiresistant strains of Mycobacterium tuberculosis (MTB) are constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high-content imaging, we identified novel 1,2,4-oxadiazole-based compounds, which allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds, MTB became even more sensitive to antituberculosis drugs, in vitro and in vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.

Published
2024
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3. Lipid A structural diversity among members of the genus Leptospira

Author

Helena Pětrošová, Abanoub Mikhael, Sophie Culos, Alexandre Giraud-Gatineau, Alloysius M. Gomez, Matthew E. Sherman, Robert K. Ernst, Caroline E. Cameron, Mathieu Picardeau, and David R. Goodlett

Subjects
lipid A, Leptospira, mass spectrometry, structure-activity relationship, molecular typing, lipopolysaccharide (LPS), Microbiology, QR1-502
Abstract

Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.

Published
2023
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4. Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication

Author

Ignacio Santecchia, Delphine Bonhomme, Stylianos Papadopoulos, Pedro Escoll, Alexandre Giraud-Gatineau, Maryse Moya-Nilges, Frédérique Vernel-Pauillac, Ivo Gomperts Boneca, and Catherine Werts

Subjects
Leptospira interrogans, Leptospira biflexa, macrophages, intracellularity, TLRs, high content confocal microscopy, Microbiology, QR1-502
Abstract

Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million people per year worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore considered as sensitive to leptospirosis. In contrast, mice and rats remain asymptomatic upon infection, although they get chronically colonized in their kidneys. Upon infection, leptospires are stealth pathogens that partially escape the recognition by the host innate immune system. Although leptospires are mainly extracellular bacteria, it was suggested that they could also replicate within macrophages. However, contradictory data in the current literature led us to reevaluate these findings. Using a gentamicin–protection assay coupled to high-content (HC) microscopy, we observed that leptospires were internalized in vivo upon peritoneal infection of C57BL/6J mice. Additionally, three different serotypes of pathogenic L. interrogans and the saprophytic L. biflexa actively infected both human (PMA differentiated) THP1 and mouse RAW264.7 macrophage cell lines. Next, we assessed the intracellular fate of leptospires using bioluminescent strains, and we observed a drastic reduction in the leptospiral intracellular load between 3 h and 6 h post-infection, suggesting that leptospires do not replicate within these cells. Surprisingly, the classical macrophage microbicidal mechanisms (phagocytosis, autophagy, TLR–mediated ROS, and RNS production) were not responsible for the observed decrease. Finally, we demonstrated that the reduction in the intracellular load was associated with an increase of the bacteria in the supernatant, suggesting that leptospires exit both human and murine macrophages. Overall, our study reevaluated the intracellular fate of leptospires and favors an active entrance followed by a rapid exit, suggesting that leptospires do not have an intracellular lifestyle in macrophages.

Published
2022
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5. The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Author

Alexandre Giraud-Gatineau, Juan Manuel Coya, Alexandra Maure, Anne Biton, Michael Thomson, Elliott M Bernard, Jade Marrec, Maximiliano G Gutierrez, Gérald Larrouy-Maumus, Roland Brosch, Brigitte Gicquel, and Ludovic Tailleux

Subjects
host-pathogen interaction, innate immunity, macrophages, tuberculosis, antibiotics, Medicine, Science, Biology (General), QH301-705.5
Abstract

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed cells into potent bactericidal phagocytes. We found that 579 and 1,495 genes were respectively differentially expressed in naive- and M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of lysosome-associated genes. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB, involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.

Published
2020
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6. Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection

Author

Juan Manuel Coya, Laura De Matteis, Alexandre Giraud-Gatineau, Anne Biton, Inés Serrano-Sevilla, Anne Danckaert, Marie-Agnès Dillies, Brigitte Gicquel, Jesus M. De la Fuente, and Ludovic Tailleux

Subjects
Chitosan nanocarriers, Surface grafting, Macrophages, Mycobacterium tuberculosis, Host response, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract Background Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown. Results Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism. Conclusions The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs.

Published
2019
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8. Author response: The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Author

Juan Manuel Coya, Alexandra Maure, Roland Brosch, Maximiliano G. Gutierrez, Jade Marrec, Ludovic Tailleux, Gerald Larrouy-Maumus, Michael Thomson, Alexandre Giraud-Gatineau, Anne Biton, Brigitte Gicquel, and Elliott M. Bernard

Subjects
chemistry.chemical_compound, Innate immune system, chemistry, medicine.drug_class, Host (biology), Antibiotics, medicine, Macrophage, Bedaquiline, Biology, Microbiology
Published
2020
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9. The antibiotic bedaquiline activates host macrophage innate immune resistance to bacterial infection

Author

Anne Biton, Gerald Larrouy-Maumus, Elliott M. Bernard, Maximiliano G. Gutierrez, Alexandre Giraud-Gatineau, Ludovic Tailleux, Michael Thomson, Alexandra Maure, Juan Manuel Coya, Roland Brosch, and Brigitte Gicquel

Subjects
Innate immune system, medicine.drug_class, Antibiotics, Autophagy, Biology, Microbiology, chemistry.chemical_compound, medicine.anatomical_structure, Immune system, chemistry, Lysosome, Gene expression, medicine, TFEB, Bedaquiline
Abstract

Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host’s immune system. Here we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages. Genome-wide gene expression analysis revealed that BDQ reprogramed macrophages into potent bactericidal phagocytes. We found that 1,495 genes were differentially expressed in M. tuberculosis-infected macrophages incubated with the drug, with an over-representation of genes involved in metabolism, lysosome biogenesis and activation. BDQ treatment triggered a variety of antimicrobial defense mechanisms, including nitric oxide production, phagosome-lysosome fusion, and autophagy. These effects were associated with activation of transcription factor EB (TFEB), involved in the transcription of lysosomal genes, resulting in enhanced intracellular killing of different bacterial species that were naturally insensitive to BDQ. Thus, BDQ could be used as a host-directed therapy against a wide range of bacterial infections.

Published
2019
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10. Tri-mannose grafting of chitosan nanocarriers remodels the macrophage response to bacterial infection

Author

Laura De Matteis, Anne Biton, Jesús M. de la Fuente, Brigitte Gicquel, Inés Serrano-Sevilla, Alexandre Giraud-Gatineau, Anne Danckaert, Ludovic Tailleux, Marie-Agnès Dillies, Juan Manuel Coya, Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Instituto de Nanociencia de Aragón [Saragoza, España] (INA), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad. The text represents the authors’ views and does not necessarily represent the position of the Commission who are not liable for the publication of this information. The funders had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript., European Project: 604237,EC:FP7:NMP,FP7-NMP-2013-LARGE-7,NAREB(2014), European Commission, Institut Pasteur, Diputación General de Aragón, Ministerio de Economía y Competitividad (España), Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pharmaceutical Science, Medicine (miscellaneous), Mannose, 02 engineering and technology, Drug resistance, 01 natural sciences, Applied Microbiology and Biotechnology, chemistry.chemical_compound, Drug Delivery Systems, Macrophage, Cells, Cultured, Drug Carriers, Chemistry, Bacterial Infections, 021001 nanoscience & nanotechnology, 3. Good health, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:R855-855.5, Drug delivery, Host-Pathogen Interactions, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Metabolic Networks and Pathways, lcsh:Medical technology, lcsh:Biotechnology, Biomedical Engineering, Bioengineering, 010402 general chemistry, Immune system, Phagocytosis, lcsh:TP248.13-248.65, Host response, Humans, Surface grafting, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Chitosan, Innate immune system, Research, Macrophages, Mycobacterium tuberculosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, 0104 chemical sciences, MRNA Sequencing, Chitosan nanocarriers, Nanoparticles, Nanocarriers, Transcriptome
Abstract

[Background]: Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria. However, how nanocarriers influence the response of innate immune cells to bacterial infection is mostly unknown., [Results]: Here, we used Mycobacterium tuberculosis as a model of bacterial infection to examine the impact of mannose functionalization of chitosan nanocarriers (CS-NCs) on the human macrophage response. Both ungrafted and grafted CS-NCs were similarly internalized by macrophages, via an actin cytoskeleton-dependent process. Although tri-mannose ligands did not modify the capacity of CS-NCs to escape lysosomal degradation, they profoundly remodeled the response of M. tuberculosis-infected macrophages. mRNA sequencing showed nearly 900 genes to be differentially expressed due to tri-mannose grafting. Unexpectedly, the set of modulated genes was enriched for pathways involved in cell metabolism, particularly oxidative phosphorylation and sugar metabolism., [Conclusions]: The ability to modulate cell metabolism by grafting ligands at the surface of nanoparticles may thus be a promising strategy to reprogram immune cells and improve the efficacy of encapsulated drugs., This research project was co-financed by the Institut Pasteur and the European Commission as part of the European Seventh Framework Program Nanotherapeutics against Resistant Emerging Bacterial Pathogens (NAREB Project 604237), public funding from the Fondo Social de la DGA (grupos DGA), Ministerio de Economía y Competitividad del Gobierno de España for the public founding of the Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad.

Published
2019
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12. Decoherence and thermalization of a pure quantum state in quantum field theory

Author

Julien Serreau, Alexandre Giraud, AstroParticule et Cosmologie (APC (UMR_7164)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7), APC - THEORIE, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut für theoretische Physik, Universität Hamburg (UHH)-Universität Hamburg (UHH), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Institut für theoretische Physik, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut für theoretische Physik

Subjects
High Energy Physics - Theory, Quantum decoherence, [PHYS.NUCL]Physics [physics]/Nuclear Theory [nucl-th], Nuclear Theory, Quantum dynamics, FOS: Physical sciences, General Physics and Astronomy, 01 natural sciences, Nuclear Theory (nucl-th), Open quantum system, Quantization (physics), High Energy Physics - Phenomenology (hep-ph), Quantum error correction, Quantum mechanics, 0103 physical sciences, Quantum operation, 010306 general physics, Physics, [PHYS.HTHE]Physics [physics]/High Energy Physics - Theory [hep-th], 010308 nuclear & particles physics, Condensed Matter - Other Condensed Matter, High Energy Physics - Phenomenology, High Energy Physics - Theory (hep-th), [PHYS.HPHE]Physics [physics]/High Energy Physics - Phenomenology [hep-ph], [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other], Quantum electrodynamics, Quantum process, Quantum dissipation, Other Condensed Matter (cond-mat.other)
Abstract

We study the real-time evolution of a self-interacting O(N) scalar field initially prepared in a pure quantum state. We present a complete solution of the nonequilibrium quantum dynamics from a 1/N-expansion of the two-particle-irreducible effective action at next-to-leading order, which includes scattering and memory effects. Restricting one's attention (or ability to measure) to a subset of the infinite hierarchy of correlation functions, the system is described by an effective (reduced) density matrix which, unlike the full density matrix, has a nontrivial time evolution. In particular, starting from a pure quantum state, we observe the loss of putity/coherence and, on longer time scales, thermalization of the reduced density matrix. We point out that the physics of decoherence is well described by classical statistical field theory., 4 pages, 3 figures. To appear in Phys. Rev. Lett

Published
2009
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13. Elaboration of a non intrusive diagnosis tool for the detection of water management defaults and CO poisoning in PEMFC stacks

Author

Steiner, N., Sébastien Wasterlain, Daniel Hissel, Denis Candusso, Harel, F., Vincent Raimbault, Pierre-Alexandre Bliman, Michel Sorine, Alexandre Giraud, Auzanneau, F., Rosini, S., Xavier François, Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire des Technologies Nouvelles (INRETS/LTN), Institut National de Recherche sur les Transports et leur Sécurité (INRETS), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), SIgnals and SYstems in PHysiology & Engineering (SISYPHE), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire d'Electrochimie et de Physico-chimie des Matériaux et des Interfaces (LEPMI ), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Laboratoire commun de recherche (FC LAB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), and Institut de Chimie du CNRS (INC)-Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SPI.NRJ]Engineering Sciences [physics]/Electric power, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2009

15. Nonlinear dynamics of fermions during preheating

Author

Alexandre Giraud, Julien Serreau, AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Inflation (cosmology), Physics, Nuclear and High Energy Physics, Field (physics), Scalar (mathematics), Yukawa potential, Astrophysics::Cosmology and Extragalactic Astrophysics, Fermion, Inflaton, symbols.namesake, Dirac fermion, Quantum electrodynamics, symbols, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Boson
Abstract

International audience; We study the role of dynamical fermions during preheating after inflation. We compute the nonequilibrium dynamics of Dirac fermions coupled to a scalar (inflaton) field at next-to-next-to-leading order in a coupling expansion of the 2PI effective action. Besides the well-known parametric production of bosons and fermions and their back-reaction on the background inflaton field, this includes direct interactions between produced particles, which have been neglected in previous studies. We present preliminary numerical results in 3+1 dimensions which indicates that, for intermediate Yukawa couplings, the latter can dramatically affect the usual picture of preheating.

Published
2009
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17. [Colonic and sigmoid diverticulosis]

Author

Alexandre, Giraud and Denis, Sautereau

Subjects
Diagnosis, Differential, Sigmoid Diseases, Diverticulosis, Colonic, Humans, Hemorrhage, Diverticulitis
Published
2006

18. S1279 Treatment of Neoplastic Stenosis of the Biliary Tract With Self Expandable Metal Stents: A Retrospective Study of 211 Consecutive Procedures Comparaison of Percutaneous Versus Endoscopic Drainage

Author

Alexandre Giraud, Denis Sautereau, Sébastien Seillan, Paul Carrier, Anne Le Sidaner, Romain Legros, François Cessot, Virginie Valgueblasse, and Leila Kanafi

Subjects
medicine.medical_specialty, Percutaneous, Hepatology, business.industry, Gastroenterology, Retrospective cohort study, medicine.disease, Surgery, Self Expandable Metal Stents, Endoscopic drainage, Stenosis, Biliary tract, medicine, Radiology, business
Published
2010
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20. P.267 Evaluation du traitement par coagulation au plasma argon (CPA) des rectites radiques chroniques hémorragiques (RRC) au CHU de LIMOGES

Author

François Cessot, Alexandre Giraud, Virginie Valgueblasse, A. Cypierre, A. Le Sidaner, D. Sautereau, A. Bouygues, S. Seillan, and Romain Legros

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Medicine, General Medicine, business
Abstract

Objectif Notre etude a pour objectif d’evaluer notre prise en charge des RRC par CPA [1, 2] et de proposer une nouvelle echelle d’evaluation des lesions endoscopiques et sa correlation therapeutique afin d’optimiser la procedure. Patients et Methodes 34 patients ont ete inclus de facon retrospective entre 2002 et 2008 dans notre service d’endoscopie digestive. La CPA etait realisee en per endoscopique avec ou sans anesthesie apres preparation par voie haute de type PEG, puis un suivi clinique et endoscopique systematique etait mis en place. Resultats Le score clinique de Chutkan initial de 3,09 etait de 0,57 apres CPA, le taux d’hemoglobine a augmente de 1,7 g/dL et aucun patient n’a eu besoin de transfusion apres notre prise en charge. Le score endoscopique est ameliore de 2,3 points (p Discussion Nos resultats, conformes a la litterature, confirment l’efficacite de la CPA sur les lesions de RRC. Elle permet de traiter tous les stades de lesions de RRC par spotting ou par balayage, en vision directe ou retro bequillage. Nous n’avons pas retrouve de facteur predictif d’efficacite ou d’echec de la CPA, lie aux antecedents cardiovasculaires, a la prise d’un traitement anti-hemostatique, ni a la prise en charge princeps du cancer (radiotherapie, chirurgie, chimiotherapie ou hormonotherapie). Le risque de complications est augmente si D > 0,8 L/mn ou P > 50 W, sans modification d’efficacite. Conclusion L’utilisation prospective, a chaque seance, de cette nouvelle echelle des lesions endoscopiques de RRC pourrait permettre de juger, selon des criteres objectifs, du stade initial et de l’amelioration des lesions. L’application de la CPA se ferait en fonction du stade endoscopique trouve, minimisant ainsi la survenue de complications (ulcere, microrectie) en optimisant le traitement.

Published
2009
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21. Influence du spectre de l’induction magnétique sur les pertes fer dans les stators de machines électriques

Author

Alexandre Giraud, Alix Bernot, Jean-Francois LLIBRE, Yvan Lefèvre, LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, IRT Saint Exupéry - Institut de Recherche Technologique, Groupe de Recherches en Electrodynamique (LAPLACE-GREM3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), IRT Saint Exupéry, Toulouse (France), Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), IRT Saint Exupéry - Institut de Recherche Technologique (FRANCE), Laboratoire Plasma et Conversion d'Energie - LAPLACE (Toulouse, France), and Institut National Polytechnique de Toulouse - INPT (FRANCE)

Subjects
Hystéresis Matériaux magnétique, Machines électriques, [SPI]Engineering Sciences [physics], Pertes fer, Harmoniques, Matériaux, Spectre complexe, [SPI.MAT]Engineering Sciences [physics]/Materials
Abstract

International audience; Cet article propose d'étudier expérimentalement la pertinence d'une analyse harmonique pour le calcul des pertes fer dans les matériaux magnétiques des machines électriques afin d'améliorer la représentativité de leurs modèles. Un banc d'essai avec un hystérésigraphe pouvant générer diverses formes d'ondes et mesurer les pertes fer induites sur des échantillons magnétiques sera utilisé. Des formes d'ondes sinusoïdales de différentes fréquences et amplitudes ont été étudiées seules, puis combinées entres elles. Ensuite l'influence de la phase des harmoniques a été observée. Il a ainsi été possible d'analyser l'impact de formes d'ondes complexes sur les pertes fer et collecter de nouvelles données afin d'établir ultérieurement des modèles de pertes fer sous spectre d'induction complexe.

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