Increased angiogenesis is an important characteristic of remodeling in asthmatic airways which stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. The focus of this thesis is to investigate the effect of Semaphorin 3E (Sema3E) on angiogenesis events within the airways of murine model of allergic asthma. The role of Sema3E in asthma angiogenesis was tested in wild type and Sema3e-/- mice exposed to House Dust Mite (HDM) and monitored for changes in blood vessels number in the lungs. In addition, the potential of Sema3E, in reversing features of allergen inflammation, was tested in mouse model. In both cases immunohistochemistry and immunofluorescence staining of lung tissues used to assess the changes in the level of angiogenesis. Moreover, the expression of pro- and anti-angiogenic factors in total lung homogenate was assessed by ELISA and Real-Time PCR. The results showed that WT and Sema3e-/- mice both developed the HDM induced allergic asthma phenotype, but, the lung sections of HDM exposed Sema3e-/- mice had enhanced number of blood vessels compared to WT mice. The enhanced angiogenesis in Sema3-/- mice was coupled with increased level of angiogenesis driving factors VEGF and it receptor VEGFR-2. However, in WT mice the level of soluble VEGFR-1 secretion increased significantly which inhibited VEGF / VEGFR-2 binding. Besides, Sema3E treatment reduced the level of angiogenesis and inhibited HDM-induced secretion of VEGF and the expression of its receptor VEGFR-2 while increased the level of soluble VEGFR-1. Analyzing the ratio of VEGF / soluble VEGFR-1 revealed that in the presence of Sema3E in both models, soluble VEGFR-1 is the dominant factor which has an inhibitory role on angiogenic effect of VEGF. Taken together, this study provided the first evidence that Sema3E can modulate angiogenesis in allergic asthmatic airways. / February 2016

No description available.

Les Sémaphorines constituent une grande famille de protéines sécrétées et membranaires, qui ont été initialement impliquées dans le guidage axonal au cours du développement du système nerveux, mais qui jouent aussi un rôle important dans la cancérogenèse. Ainsi, les Sémaphorines agissent via leurs récepteurs, qui font partie de la famille des Neuropilines et des Plexines, pour réguler des fonctions multiples qui contribuent au développement des cancers et à la progression métastatique, telles que l'adhésion cellulaire, la motilité, la survie, l'angiogenèse et la réponse immunitaire. Mon travail de thèse a visé à mieux comprendre le rôle de la signalisation induite par la Sémaphorine-3E (Sema3E) et son récepteur Plexine-D1 dans le cancer du sein. Il a été proposé récemment, que la signalisation autocrine induite par le couple Sema3E/Pleixne-D1 dans les cellules tumorales, favorise l’apparition de métastases via l’augmentation de leurs capacités de migration et d’intravasation/extravasation.Dans ce travail de recherche, nous avons trouvé qu’une nouvelle signalisation autocrine induite par Sema3E/Plexine-D1 régit à la fois la tumorigenèse et la formation de métastases. Ainsi, la sécrétion de Sema3E par les cellules tumorales favorise leur survie grâce à l’inhibition d’une voie de mort induite par le récepteur à dépendance Plexine-D1. Bloquer l’interaction entre Sema3E et son récepteur Plexine-D1, via l’utilisation d’un ligand TRAP dans des modèles murins de cancer du sein, permet de tuer spécifiquement les cellules tumorales et exerce une action anti-tumorale et anti-métastatique. Des données préliminaires sur la voie de mort induite par le récepteur Plexine-D1, suggèrent un rôle important du clivage de son domaine intracellulaire par les Caspases et/ou une translocation nucléaire. Ensemble, ces résultats indiquent que l’expression de Sema3E dans les cancers du sein chez la femme, permet un avantage sélectif pour la survie des cellules tumorales. Bloquer l’interaction entre Sema3E/Plexine-D1 apparaît donc comme une stratégie thérapeutique prometteuse pour traiter ces cancers. De plus, ces données permettent une nouvelle approche dans l’étude des fonctions du couple Sema3E/Plexine-D1 dans d’autres contextes physiologiques et pathologiques. / The Semaphorins constitute a large family of secreted and membrane-bound proteins, which have initially been implicated in axon guidance during development of the nervous system, but also have an important role in cancer. Semaphorins signal through Neuropilin and Plexin receptors to regulate multiple functions contributing to cancer development and progression, including cell adhesion and motility, cell survival, angiogenesis and immune response. My work is aimed at better understanding the role of the secreted glycoprotein Semaphorin 3E (Sema3E) and its binding receptor PlexinD1 in breast cancer. It has been recently proposed that Sema3E/PlexinD1 autocrine signaling in tumor cells promotes metastasis by enhancing cancer cell migration and intravasation/extravasion steps. Here we found another mechanism by which Sema3E/PlexinD1 autocrine signaling regulates both tumorigenesis and metastasis. We show that release of Sema3E by tumor cells promoted their survival through inhibition of an endogenous cell death pathway triggered by the unbound PlexinD1 “dependence receptor”. Interrupting Sema3E/PlexinD1 binding using a ligand-TRAP for PlexinD1 receptor specifically increased tumor cell death and exerted anti-tumoral and anti-metastatic activities in animal models of breast cancers. Preliminary investigations of the underlying cell death pathway suggested a crucial role of PlexinD1 intracellular domain via its cleavage by caspases or its possible translocation to the nucleus. Together, the results indicate that up-regulation of Sema3E in human breast cancers provides a selective advantage for tumor cell survival and that antagonizing Sema3E binding to PlexinD1 may represent a promising therapeutic strategy. Moreover, these data may provide new insight into the functions of Sema3E/PlexinD1 in other physiological and pathological contexts.

Diploma thesis presents information about electronic toll system in the Czech Republic with the gist being aimed on economy and effectiveness of the system in use. The theme is discussed in separate parts, where the first part consists of explanation of basic terms about road infrastructure, toll system and its functionality in the Czech Republic. Next part is revealing information about public sector and its economy, efficiency and effectiveness that are essential for measuring public sector, and its administrative costs. In the analytical part is evaluated economy of electronic toll with the usage of findings from administrative costs of electronic toll and with its earning. Electronic toll is analyzed as well from the view where are put into comparison domestic and foreign and their weight on the toll and as well from the view of the amount of truck carriers that were using Czech road system before and after electronic toll was introduced. Part of the analysis compares the administrative costs of electronic toll with administrative costs of other taxes in the Czech Republic and it compares systems of electronic tolling in chosen neighboring countries.

No description available.

No description available.

A l'heure actuelle, l'industrie représente environ le tiers de la consommation énergétique et des émissions de CO2. Des opportunités substantielles existent pour faire face aux enjeux environnementaux et économiques, passant par l'efficacité énergétique en général et l'utilisation de l'énergie, en particulier dans les parcs industriels. Les Systèmes à Energie Distribuée (SED) correspondent en ce sens à une solution courante et prometteuse. Nous avons donc entrepris une démarche d'approche globale de site, incluant l'agrégation de l'ensemble des variables énergétiques, économiques, environnementales et managériales influentes dans une installation de ce type. Une mise en application sur une installation pilote et sa validation ont permis d'identifier les verrous scientifiques et techniques et de mesurer pertinence et efficacité des éléments et modes opératoires des systèmes en mode stationnaire. Cette étude offre une méthode d'utilisation coopérative des indicateurs des domaines impactés et ouvre également des perspectives sur des développements en mode dynamique à des fins d'aide à la conduite optimale. / Nowadays, industry accounts for about one third of energy consumption and CO2 emissions. Substantial opportunities exist to address environmental and economic challenges, including energy efficiency in general and the use of energy, especially in industrial parks. Distributed Energy Systems (DES) correspond in this sense to a common and promising solution. We have therefore undertaken a global site approach, including the aggregation of all influential energy, economic, environmental and managerial variables in an installation of this type. Implementation on a pilot plant and its validation have made it possible to identify the scientific and technical locks and to measure the relevance and efficiency of the elements and stationary operating modes of the systems. This study offers a method of cooperative use of the indicators of impacted domains and also opens perspectives on developments in dynamic mode for the purposes of optimum driving assistance.

The thesis discusses very actual issues concerning the management of the 3E principle in decisions related to the public funds expenditure decisions, especially in context of EU funding, and expands on the problems and deficiencies in the actual system of publicly funded procurement and related control. In the theoretical part, the thesis provides an insight into the basic terms and the relevant theoretical, legislative and methodological framework. The practical part then analyzes and assesses the conclusions of a review of 33 publicly funded projects financed both from EU funds and/or the national budget, in a cumulated value of 11.3 billion CZK. Further on, the thesis detects fraudulent schemes occurring repeatedly in the mentioned population of reviewed projects which are then categorized by the author. In the thesis's conclusion the author defines public funding fraud detection methods and delimits several proposals and recommendations on how to amend the identified deficiencies, both on the system and organizational levels.

La présente thèse porte sur les enjeux de la progression dans la formation doctorale en sciences de l’humain et du social (SHS). Dans la plupart des pays occidentaux, les administrations universitaires se disent préoccupées par les délais d’achèvement et les faibles taux de diplomation au doctorat. S’il est admis que les aptitudes intellectuelles ne suffisent pas pour progresser dans les études doctorales, les recherches menées jusqu’ici montrent que les modalités de la formation, ainsi que le milieu et le contexte d’études dans lesquels celle-ci s’inscrit ont des répercussions sur l’expérience doctorale. Peu d’études portent toutefois sur la façon dont l’interaction de facteurs individuels et structurels peut affecter la progression dans ce processus de formation. En nous appuyant sur la théorie de la structuration de Giddens (2005), nous postulons dès lors que certaines valeurs, traditions et pratiques propres au monde académique – perpétuées, volontairement ou non, par les acteurs universitaires – peuvent nuire à la progression des doctorant-e-s. Afin d’examiner la question, une étude de cas instrumentale à visée compréhensive (Stake, 1994) a été réalisée. Six facultés des SHS d’une université canadienne ont été ciblées pour constituer le cas à l’étude. Outre l’analyse d’un ensemble de documents institutionnels relatif à la formation doctorale dans le contexte étudié, 36 doctorant-e-s issus de 19 disciplines ainsi que quatorze professeur-e-s et cinq administrateurs universitaires (directions de programmes/doyens/vices-doyens) ont été rencontrés dans le cadre d’entretiens semi-directifs. Nos résultats ont dans un premier temps permis de tracer un portrait descriptif détaillé du cas à l’étude. Les particularités de l’organisation formelle et tacite de la formation doctorale en SHS dans le contexte étudié ainsi que les défis qu’elle sous-tend ont été circonscrits, de même que les stratégies à privilégier – du point de vue des participant-e-s – pour progresser dans la formation. Dans un deuxième temps, il a été possible de montrer, d’une part, que c’est bien à la jonction de facteurs individuels et structurels que se situe la problématique de la progression dans la formation doctorale en SHS et des faibles taux de diplomation qui la caractérisent. D’autre part, la portée systémique d’une telle problématique a été mise au jour : à travers leurs choix, leurs attitudes et leurs pratiques, les acteurs universitaires contribuent à la reproduction de façon de faire et de penser « attendues » ou « admises » dans leur milieu, dont certaines ont le potentiel de nuire à la progression dans la formation doctorale. / This thesis addresses the challenges of progressing through PhD training in the human and social sciences. In most Western countries, universities express concern about completion times and graduation rates at the doctorate level. While, admittedly, intellectual abilities alone are not sufficient to successfully progress through a PhD program, the current knowledge indicates that modes of training and the contexts and conditions in which the training takes place also have a major impact on the process. However, few studies examine how individual and structural factors interact and impact PhD students’ paths. Based on Giddens’ theory of structuration (2005), we postulate that some traditions, practices and mentalities specific to the academic world — perpetuated, deliberately or not, by the scholarly community — likely impede students’ progress and maintain low graduation rates over time. To address this issue, we opted for a comprehensive, instrumental case study approach (Stake, 1994). Six human and social sciences faculties at a Canadian university were selected to define the case. In addition to analyzing institutional documents pertaining to PhD training in this specific context, we carried out semi-structured interviews with 36 PhD students from 19 different programs, 14 thesis supervisors and five academic administrators (program directors, deans and vice deans). Our results first provided a descriptive overview of the case under study. The specificity and the underlying challenges of the formal and tacit organization of the selected PhD training context were outlined, as well as the strategies that participants considered the most effective to progress. Second, the results verified that the challenges of PhD training in the human and social sciences are situated at the junction of individual and structural factors. Moreover, these issues may be understood at a systemic level: through their choices, attitudes and practices, PhD students, thesis supervisors and academic administrators contribute to perpetuated “expected” or “taken for granted” ways of acting and thinking, some of which potentially hinder PhD students’ progress.

Volumes one and two of Annees de Pelerinage contain travel impressions. The pieces in volume three serve as a means of expressing a religious pilgrimage. The religiousmeaning is implied by the titles and by letters Liszt wrote concerning specific pieces. For the pieces to have programmatic significance, the music must support the verbal clues. This dissertation maintains that selected pieces in Annees de Pelerinage III are programmatic and that Liszt provided musical clues that have not been discovered or, if noticed, have not been analyzed in detail. Also, the dissertation explores similarities between selected pieces of Annees de Pelerinage III and other programmatic or texted works by Liszt sharing the same subject. The findings reinforce the premise that Liszt deliberately intended to express certain extra-musical ideas within the music itself. The paper briefly analyzes the musical reasons for labeling Annees de Pelerinaae III a cycle. Different sources call these pieces cyclic, citing the shared common religious theme as the reason. This dissertation discusses musical reasons that reinforce the idea of a cycle. Chapter II discusses Liszt's views on program music. Chapter III identifies common themes in Liszt's programmatic works and discusses the symbolic significance of thematic transformation. Chapter IV suggests an approach to analyzing program music. Chapter V discusses Liszt's musical narrative and his use of common rhetorical devices. Chapter VI analyzes extra-musical associations in selected pieces from the Annees de Pelerinaae—Troisieme Annee. Five pieces have been selected for analysis—Anaelus1. Aux Cypres de la Villa d'Este I and II, Marche funebre. and Sursum corda.