Developing a multi-scale math-based model for powder metallurgy (PM) component design and performance prediction requires experimental calibration and validation. Monotonic tension, compression and torsion tests were performed at various porosity and temperatures to obtain the set of plasticity and damage constants required for model calibration. Uniaxial fatigue experiments were performed to determine the constants required for capturing the low cycle and high cycle fatigue characteristics of a PM steel. Tension tests on two different Bridgman notched specimens were undertaken to study the damage-triaxiality dependence for model validation. Validation of the model is further being performed by monotonic component testing using PM bearing caps. Fracture surface analysis was performed using Scanning Electron Microscopy (SEM) to quantify the void nucleation and void sizes of the different specimens. The developed model will be used for optimizing component performance and design for PM parts.

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2010-2011 / En liant la portion constante des IgGs, les récepteurs Fcy (FcyRs) participent à l'ingestion des pathogènes opsonisés et des complexes immuns. La régulation fine de cette fonction est requise pour éviter le développement de pathologies autoimmunitaires. Le neutrophile humain est un phagocyte particulier puisqu'il exprime constitutivement deux isoformes activateurs (FcyRIIa et FcyRIIIb), sans toutefois posséder l'isoforme inhibiteur (FcyRIIb). Cette particularité est à l'origine des deux projets présentés dans cette thèse. D'une part, nos travaux ont étudié la coordination des signaux entre les deux isoformes lors de la stimulation du neutrophile humain avec du zymosan opsonisé par des IgGs et avec des complexes d'IgGs aggrégées (HA-IgG). D'abord, une forte interdépendance entre les deux isoformes nécessaire aux fonctions de phagocytose et de production d'anion superoxyde ainsi que pour la génération du profil de phosphorylation sur résidus tyrosine a été observée. Cependant, un influx de calcium extracellulaire essentiel à la phagocytose a été attribué à l'engagement spécifique du FcyRIIIb. Ce rôle exclusif du FcyRIIIb s'avère dépendant de l'intégrité des domaines membranaires résistants aux détergents (DRMs) dans lesquels les deux isoformes sont co-recrutés à la suite de leur engagement. D'autre part, un nouveau mode de régulation de l'activation des FcyRs a été décrit, indépendant de l'inhibition par le FcyRIIb. Par l'entremise de l'ubiquitine-ligase c-Cbl, le FcyRIIa est poly-ubiquitinylé puis dégradé par le protéasome. Ce processus de régulation est contrôlé positivement par la protéine adaptatrice CIN85 de manière dépendante des PKCs classiques. Cette voie s'avère également dépendante de l'intégrité des DRMs, plateforme de colocalisation entre le FcyRIIa, c-Cbl et CTN85. En conclusion, ces travaux ont permis de comprendre la signification biologique de l'expression combinée du FcyRIIa et du FcyRIIIb et l'interdépendance entre ces deux isoformes, tant du point de vue de la signalisation intracellulaire que des fonctions qui en découlent. De plus, un nouveau mode de régulation est proposé pour pallier à l'absence de l'isoforme FcyRIIb sur le neutrophile humain et ainsi éviter l'activation exacerbée des fonctions du neutrophile humain dépendantes de l'engagement des FcyRs.

Expression of sTGFbetaRII-Fc-Jun from recombinant vaccinia virus TGFß has a biphasic role in tumorigenesis. In early phases it acts as tumor sup-pressor. However, in late phases when cells have escaped selectively from the antimito-genic response of TGFß, it may act as a promoter of tumor progression and invasion. One way of control tumor formation and progression is blocking of TGFß signalling pathways in late phases of tumorigenesis. We have constructed recombinant vaccinia virus P13 expressing soluble TGFbeta type II receptor fused with the Fc fragment of IgG1 and with Jun fragment (sTbetaRII-Fc-Jun). This sTbetaRII-Fc-Jun is supposed to increase the effect of antitumor vaccinia virus vaccine expressing SigE7LAMP, which is investigated for the treatment of the HPV-16 associated cervical cancer. Binding of sTbetaRII-Fc-Jun to protein G were tested by SDS-PAGE and by im-munoblotting. We found that Jun fragment and sTbetaRII fragment do not block Fc bind-ing site for protein G. sTbetaRII-Fc-Jun was characterised using SDS-PAGE and immunoblot analysis. We observed that the amount of sTbetaRII-Fc-Jun was higher in cell supernatans of in-fected cells in comparison to cell lysates. In cell lysates we observed higher amount of sTbetaRII than sTbetaRII-Fc-Jun. The expression of sTbetaRII-Fc-Jun was stronger under...

Objectives: The main objective of this thesis is to analyse football club FC Bayern Munich. This thesis analyse organizational structure, finances, infrastructure of the club, its market position and marketing. The other objective is to create prognosis of future finance development of the club. Methods: Document analysis, interviews and SWOT analysis are the main methods used in this thesis. Results: FC Bayern Munich is very well organized club. It belongs amongst the best teams in the world by the sport results. It is one of a little, that has profit every year and has no depts. As the prognosis say, Bayern will be one of the best teams in the world in the future and will set course in football development. Key words: Football, analysis, FC Bayern Munich, prognosis

Sepse é a primeira causa de morte em Unidades de Terapia Intensiva. A gravidade dessa doença é considerada conseqüência de um desequilíbrio da resposta inflamatória e, apesar dos avanços em diagnóstico e tratamento, os índices de mortalidade se mantêm inalterados. O papel dos receptores Fc de immunoglobulinas nesta situação é pouco esclarecido. Tais receptores deflagram respostas imunes opostas, que dependem do receptor envolvido e podem ser tanto ativatórias, quanto inibitórias. As respostas ativatórias são atribuídas a um motivo chamado ITAM, enquanto as inibitórias são relacionadas ao motivo ITIM. Camundongos apresentam dois receptores de IgG ativatórios (FcγRI e FcγRIII), que portam motivos ITAM, associados a uma sub-unidade conhecida como cadeia gamma, assim como um receptor de IgG que apresenta um motivo ITIM na sua porção intra-citoplasmática (FcγRII). Este trabalho teve como objetivo o estudo do papel destes receptores em bacteremias e sepse. Para isso, utilizamos um modelo de peritonite induzida por ligadura e punção cecal. Este projeto descreve pela primeira vez, um papel importante do FcRγII na indução de apoptose em linfócitos B, durante infecção bacteriana severa. Nossos resultados colocaram em evidência, ainda, o fato de que animais deficientes em cadeia gamma apresentam mortalidade diminuída, quando submetidos a esse modelo de peritonite, e que essa diminuição é associada a menores valores de TNFα no soro e nos fluidos peritoneais, menor recrutamento peritoneal de células inflamatórias, assim como a um surpreendente aumento na fagocitose de E. coli. Hemocultura e cultura do lavado peritoneal desses animais revelaram uma flora multimicrobiana, enquanto camundongos selvagens apresentaram uma forte predominância de E. coli e um número total bastante superior de bactérias. Esse papel inibitório da cadeia gamma pode estar relacionado a mecanismos de auto-tolerância. Lisado total de células peritoneais de camundongos deficientes em cadeia gamma apresentam fosforilação aumentada de diversas proteínas, quando comparados a lisados obtidos, a partir de camundongos selvagens. Estudos semelhantes realizados com camundongos transgênicos para o receptor de IgA (FcαRI), entretanto, não demonstraram um papel crucial desse receptor nesta doença. Este trabalho abre, portanto, novas perspectivas para o tratamento de doenças infecciosas, através de intervenção sobre a cadeia gamma e coloca em rediscussão os conceitos atuais de ITAM e ITIM. / Sepsis is the first cause of death in Critical Care Units and despite the development in its diagnosis and treatment, mortality remains unaffected. The role of immunoglobulin Fc receptors in sepsis is not clearly understood. These receptors initiate opposing responses, depending on their aggregation by the ligand and can induce activating or inhibitory responses. The activating responses are attributed to a motif known as ITAM, and the inhibitory responses to another one called ITIM. Mice express two activating IgG receptors (FcγRI et FcγRIII) which have ITAM motifs in the intracytoplasmic domain of an associated subunit, called the FcRγ chain, as well as an inhibitory IgG receptor which possesses an ITIM motif in its intracytoplasmic domain. The objective of this work is to study the importance of these receptors in bacteremia and in sepsis. To this aim, we have used a peritonitis model, induced by cecal ligation and puncture (CLP). This project describes for the first time, an important role of FcγRII in B lymphocytes apoptosis. Moreover, our results show that FcRγ chain knockout mice have a decreased mortality in this model, which is associated to diminished TNFα serum and peritoneal fluids levels, to a reduced recruitment of peritoneal inflammatory cells and to a surprising increase in E. coli phagocytosis. Blood and peritoneal fluid cultures have shown a polymicrobial flora 24 hours post-CLP for FcRγ-chain deficient mice, whereas wild-type mice present a strong predominance of E. coli in the same cultures and an increased bacteria total count. Lysates from FcRγ-chain deficient peritoneal cells revealed augmented phosphorylation of many proteins, as compared to wild-type cells. This FcRγ chain inhibitory role could be related to self-tolerance mechanisms. This work opens new perspectives for the treatment of bacterial diseases, proposing FcRγ chain targeting and the reexamination of the actual concepts of ITAM and ITIM.

Reproduction de : Thèse de doctorat : Immunologie : Lille 2 : 2008. / Résumé en français et en anglais. Titre provenant de l'écran-titre. Bibliogr. f. 60-79.

Les récepteurs Fc jouent un rôle important en permettant aux cellules de l’immunité d’interagir avec lesanticorps, notamment thérapeutiques. Dans cette thèse, nous montrons que des mécanismes de recombinaisonhomologue, de knock-in par insertion rétrovirale et de duplication segmentale ont permis l’acquisition chez lesPrimates (FCGR2A) puis chez les Hominidés (FCGR2C et FCGR3B) de gènes codant des récepteurs Fc ayantde nouvelles propriétés, tout en rendant instable ce cluster (variation de nombre de copies), et très complexeson analyse chez l’Homme. Grâce à une approche originale de pyroséquencage, nous sommes parvenus àétudier simultanément le polymorphisme allélique ORF/STOP du FCGR2C, ainsi que son nombre de copies.Nous avons ainsi révélé de nouveaux déséquilibres de liaison, s’ajoutant au déséquilibre FCGR3A-FCGR2Adont nous avons montré l’importance d’une prise en compte adaptée dans les études d’association avec laréponse aux anticorps thérapeutiques. Ces résultats devraient contribuer à améliorer le développement préclinique(pertinence des modèles animaux) et clinique (variabilité des effets) des anticorps thérapeutiques. / Fc receptors play an important allowing connexion between immune cells and antibody notably therapeutic. Inthis thesis, we have shown that homologous recombination events, knock-in by retroviral insertion andsegmental duplication led to the acquisition in primates (FCGR2A) then in Hominids (FCGR2C and FCGR3B)of genes coding for Fc receptors with new properties, led to genomic instability of the cluster (copy numbervariation) and to complex analysis in human. Through a original pyrosequencing approach, we have studiedsimultaneously ORF/STOP polymorphism and copy number variation of FCGR2C. We have also revealed newlinkage disequilibrium, additionnaly to FCGR3A-FCGR2A disequilibrium which we have shown theimportance of a suitable methdology in association studies with responses to therapeutic antibodies. Theseresults contribute to improve pre-clinical (of animal models) and clinical (variability effects) development oftherapeutic antibodies.

Sepse é a primeira causa de morte em Unidades de Terapia Intensiva. A gravidade dessa doença é considerada conseqüência de um desequilíbrio da resposta inflamatória e, apesar dos avanços em diagnóstico e tratamento, os índices de mortalidade se mantêm inalterados. O papel dos receptores Fc de immunoglobulinas nesta situação é pouco esclarecido. Tais receptores deflagram respostas imunes opostas, que dependem do receptor envolvido e podem ser tanto ativatórias, quanto inibitórias. As respostas ativatórias são atribuídas a um motivo chamado ITAM, enquanto as inibitórias são relacionadas ao motivo ITIM. Camundongos apresentam dois receptores de IgG ativatórios (FcγRI e FcγRIII), que portam motivos ITAM, associados a uma sub-unidade conhecida como cadeia gamma, assim como um receptor de IgG que apresenta um motivo ITIM na sua porção intra-citoplasmática (FcγRII). Este trabalho teve como objetivo o estudo do papel destes receptores em bacteremias e sepse. Para isso, utilizamos um modelo de peritonite induzida por ligadura e punção cecal. Este projeto descreve pela primeira vez, um papel importante do FcRγII na indução de apoptose em linfócitos B, durante infecção bacteriana severa. Nossos resultados colocaram em evidência, ainda, o fato de que animais deficientes em cadeia gamma apresentam mortalidade diminuída, quando submetidos a esse modelo de peritonite, e que essa diminuição é associada a menores valores de TNFα no soro e nos fluidos peritoneais, menor recrutamento peritoneal de células inflamatórias, assim como a um surpreendente aumento na fagocitose de E. coli. Hemocultura e cultura do lavado peritoneal desses animais revelaram uma flora multimicrobiana, enquanto camundongos selvagens apresentaram uma forte predominância de E. coli e um número total bastante superior de bactérias. Esse papel inibitório da cadeia gamma pode estar relacionado a mecanismos de auto-tolerância. Lisado total de células peritoneais de camundongos deficientes em cadeia gamma apresentam fosforilação aumentada de diversas proteínas, quando comparados a lisados obtidos, a partir de camundongos selvagens. Estudos semelhantes realizados com camundongos transgênicos para o receptor de IgA (FcαRI), entretanto, não demonstraram um papel crucial desse receptor nesta doença. Este trabalho abre, portanto, novas perspectivas para o tratamento de doenças infecciosas, através de intervenção sobre a cadeia gamma e coloca em rediscussão os conceitos atuais de ITAM e ITIM. / Sepsis is the first cause of death in Critical Care Units and despite the development in its diagnosis and treatment, mortality remains unaffected. The role of immunoglobulin Fc receptors in sepsis is not clearly understood. These receptors initiate opposing responses, depending on their aggregation by the ligand and can induce activating or inhibitory responses. The activating responses are attributed to a motif known as ITAM, and the inhibitory responses to another one called ITIM. Mice express two activating IgG receptors (FcγRI et FcγRIII) which have ITAM motifs in the intracytoplasmic domain of an associated subunit, called the FcRγ chain, as well as an inhibitory IgG receptor which possesses an ITIM motif in its intracytoplasmic domain. The objective of this work is to study the importance of these receptors in bacteremia and in sepsis. To this aim, we have used a peritonitis model, induced by cecal ligation and puncture (CLP). This project describes for the first time, an important role of FcγRII in B lymphocytes apoptosis. Moreover, our results show that FcRγ chain knockout mice have a decreased mortality in this model, which is associated to diminished TNFα serum and peritoneal fluids levels, to a reduced recruitment of peritoneal inflammatory cells and to a surprising increase in E. coli phagocytosis. Blood and peritoneal fluid cultures have shown a polymicrobial flora 24 hours post-CLP for FcRγ-chain deficient mice, whereas wild-type mice present a strong predominance of E. coli in the same cultures and an increased bacteria total count. Lysates from FcRγ-chain deficient peritoneal cells revealed augmented phosphorylation of many proteins, as compared to wild-type cells. This FcRγ chain inhibitory role could be related to self-tolerance mechanisms. This work opens new perspectives for the treatment of bacterial diseases, proposing FcRγ chain targeting and the reexamination of the actual concepts of ITAM and ITIM.

Title: FC Hradec Kralove football match benefits for spectators Objectives: The object of this work is analysis and descriptions of benefits, resulting from the visit FC Hradec Kralove football games to spectators in the season 2015/2016 and 2016/2017. Finding satisfaction with individual benefits and propose measures that could lead to increase satisfaction and traffic of a home football games FC Hradec Kralove. Methods: observation, electronic survey, written interview, personal interview Results: Proposals and recommendations to increase spectator satisfaction and traffic. Keywords: spectator satisfaction, football, FC Hradec Kralove, marketing research

The thesis deals with the valuation of the European football clubs. The main aim of the thesis is to determine the value of the English football club Arsenal FC for the purpose of entering a potential investor to the company. The value of the club refers to the May 31 2012. Valuation is based on data from publicly available sources, mainly information from the annual reports of the club are used. First, the basic valuation terms and methods are explained. Then specifics of football environment and approaches for valuation of sport clubs are discussed. Subsequently, financial and strategic analysis of the company is applied in the process of valuation. The yield method of discounted free cash flow to the firm (FCFF) is applied for the company valuation. Asset methods (book value of property and property valuation on the principle of market prices) and market method (market capitalization) are used as additional methods.