Th. licence--Droit--Paris, 1878-08-05.

Th. licence--Droit--Paris, 1864-03-17.

Th. licence--Droit--Paris, 1869-08-12.

L’analyse protéomique par spectrométrie de masse s’est imposée comme une méthode incontournable pour la caractérisation des protéines. Grâce aux progrès de l’instrumentation et de la bioinformatique, l’interprétation automatisée des spectres MS/MS permet aujourd’hui d’identifier des milliers de protéines dans un type cellulaire. Cependant, cette méthodologie s’applique encore difficilement aux organismes dont les génomes n’ont pas été séquencés, et donc pour lesquels il n’existe pas de banques de séquences peptidiques de référence. Notre travail a porté sur le développement et l’application d’une méthodologie d’interprétation des données MS/MS pour les organismes à génomes non séquencés. Cette méthodologie est basée sur le séquençage de novo suivi de recherche MS-BLAST. Ainsi nous avons pu : Identifier les différents partenaires de complexes protéiques tels que les protéines des complexes TgGAP50, TgAlba, TgSORTLR impliqués dans la motilité, la virulence ou le trafic intracellulaire des protéines du parasite Toxoplasma gondii, Identifier et caractériser des variants d’hémoglobine humaine, Identifier les protéines différentiellement exprimées lors des interactions vigne et champignons à génomes non séquencés dans la maladie de l’esca, Caractériser finement la N-glycosylation de l’invertase vacuolaire du raisin. Nous avons pu réaliser nos études sur des échantillons d’origines très différentes : homme, plantes, champignons, parasites et nous avons apporté des éléments de réponses moléculaires aux questions biologiques. / The proteomic analysis by mass spectrometry is now an essential method for the characterization of proteins. Thanks to advances in instrumentation and bioinformatics, automated interpretation of MS/MS spectra can now identify thousands of proteins in a cell type. However, this methodology remains poorly applied to the organisms that genomes are not sequenced and therefore where there is no database of reference for peptides sequences. Our work has focused on the development and application of a methodology for the interpretation of MS/MS data for the organisms that genomes are not sequenced. This methodology is based on the de novo sequencing followed by MS-BLAST search. Thus we have: Identify different partners of protein complexes such as proteins TgGAP50, TgAlba and TgSORTLR complex, involved in motility, virulence or intracellular protein trafficking of Toxoplasma gondii, Identify and characterize human hemoglobin variants, Identify the proteins differentially expressed during interaction of vines and fungi that genomes are not sequenced in esca disease, Finely characterize the N-glycosylation of the grape vacuolar invertase. We have achieved our studies on samples of very different origins: human, plants, fungi, parasites, and we provided evidence of molecular responses to biological questions.

Le comportement en fluage et à la relaxation d’aciers au chrome est étudié par indentation instrumentée, ce qui permet de solliciter le matériau dans des conditions de chargement proches de celles des essais classiques. L’objectif principal n’est pas ici de se substituer à eux mais de proposer un classement des matériaux selon leur sensibilité en fluage / relaxation par indentation.Pour cela, nous déterminons, d’abord à température ambiante, les conditions optimales d’indentation en termes de temps de maintien, de charge de maintien, de vitesse de chargement et de forme de l’indenteur. La méthodologie proposée est appliquée ensuite à plus hautes températures jusqu’à 400 °C (limitation de l’instrument). A température ambiante, le coefficient de sensibilité à la contrainte obtenu correspond à la valeur extrapolée à température ambiante des données obtenues par fluage classique à hautes températures. Malheureusement, cette corrélation n’est pas vérifiée par indentation à chaud probablement à cause de la dérive thermique subie par l’instrument. Le comportement en relaxation par indentation a également été étudié à température ambiante. Nous proposons deux méthodes analytiques permettant de déterminer le coefficient d’homothétie défini dans la théorie de Hart. L’inverse de ce coefficient, déduit de la relaxation par indentation, est comparable au coefficient de sensibilité à la contrainte déterminé par fluage, ce qui permet de comparer les deux modes de sollicitation. Malgré les difficultés expérimentales rencontrées, nous proposons un classement des matériaux selon leur sensibilité au fluage. / The creep and relaxation behaviors of based-chromium steels are studied by instrumented indentation, which allows the application of loading conditions close to those of conventional tests to the material. The main objective here is not to substitute the classical tests by the indentation one, but to give a classification of materials according to their sensitivity in creep/relaxation by indentation.For that, we first determine at room temperature the optimum conditions of indentation in terms of holding time, indentation loading, the unloading and loading rates and indenter shape. The proposed methodology is afterwards applied at higher temperatures below 400 °C due to instrument limitation. At room temperature, we obtained the stress sensitivity exponent that corresponds to the extrapolated value at ambient temperature of data obtained by classical creep tests performed at high temperatures. Unfortunately, this correlation is not obtained by indentation at higher temperatures probably due to thermal drift of the instrument. We have also studied at room temperature the behavior in relaxation by indentation. We propose two analytical methods for determining the coefficient of scale defined in Hart's theory. The interest of this coefficient inferred from the relaxation by indentation is that its inverse is comparable to the stress sensitivity exponent determined by indentation creep, which allows to compare these two modes of solicitation. Despite the experimental difficulties encountered, we propose a classification of the tested materials according to their creep sensitivity.

Disputats, Linköpings universitet, 2008. / Findes også på internet (PDF-format): http://www.diva-portal.org/diva/getDocument?urn_nbn_se_liu_diva-10489-1__fulltext.pdf. På cd-rom: Supplerende materiale i PDF-format. Med litteraturhenvisninger.

<p> </p><div> <div> <div> <p> </p><div> <div> <div> <p> </p><div> <div> <div> <p>The current state of the art in biopotential recordings rely on radiative electromagnetic (EM) fields. In such transmissions, only a small fraction of this energy is received since the EM fields are widely radiated resulting in lossy inefficient systems. Using the body as a communication medium (similar to a ’wire’) allows for the containment of the energy within the body, yielding order(s) of magnitude lower energy than radiative EM communication. The first part of this work introduces Animal Body Communication for untethered rodent biopotential recording and for the first time this work develops the theory and models for animal body communication circuitry and channel loss. In vivo experimental analysis proves that ABC successfully transmits acquired electrocardiogram (EKG) signals through the body with correlation greater than 99% when compared to traditional wireless communication modalities, with a 50x reduction in power consumption. The second part of this work focusses on the analysis and design of an Electro-Quasistatic Human Body Communication (EQS-HBC) system for simultaneous sensing and transmission of biopotential signals. In this work, detailed analysis on the system level interaction between the sensing and transmitting circuitry is studied and a design to enable simultaneous sensing and transmission is proposed. Experimental analysis was performed to understand the interaction between the Right Leg-Drive circuitry and the HBC transmission along with the effect of the ADC quantization on signal quality. Finally, experimental trials proves that EKG signals can be transmitted through the body with greater than 96% correlation when compared to Bluetooth systems at extremely low powers. </p> </div> </div> </div> </div> </div> </div> </div> </div> </div>

T follicular helper cells (T-FH) are a specialized subset of CD4 T cells that reside in B cell follicles and promote B cell maturation into plasma cells and long-lived memory B cells. During chronic infection prior to the development of AIDS, HIV-1 (HIV) replication is largely concentrated in T-FH. Paradoxically, T-FH numbers are increased in early and midstages of disease, thereby promoting HIV replication and disease progression. Despite increased T-FH numbers, numerous defects in humoral immunity are detected in HIV-infected individuals, including dysregulation of B cell maturation, impaired somatic hypermutation, and low quality of antibody production despite hypergammaglobulinemia. Clinically, these defects are manifested by increased vulnerability to bacterial infections and impaired vaccine responses, neither of which is fully reversed by antiretroviral therapy (ART). Deficits in T-FH function, including reduced HIV-specific IL-21 production and low levels of co-stimulatory receptor expression, have been linked to these immune impairments. Impairments in T-FH likely contribute as well to the ability of HIV to persist and evade humoral immunity, particularly the inability to develop broadly neutralizing antibodies. In addition to direct infection of T-FH, other mechanisms that have been linked to T-FH deficits in HIV infection include upregulation of PD-L1 on germinal center B cells and augmented follicular regulatory T cell responses. Challenges to development of strategies to enhance T-FH function in HIV infection include lack of an established phenotype for memory T-FH as well as limited understanding of the relationship between peripheral T-FH and lymphoid tissue T-FH. Interventions to augment T-FH function in HIV-infected individuals could enhance immune reconstitution during ART and potentially augment cure strategies.

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p < 0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.

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