Les thrombopathies congénitales sont des pathologies au phénotype hémorragique hétérogène dues à des anomalies fonctionnelles des plaquettes sanguines parfois associées à des anomalies morphologiques et/ou à une thrombopénie. Les outils diagnostic disponibles permettent de corréler une anomalie fonctionnelle plaquettaire à un déficit protéique voire à une mutation d’un gène spécifique. Cependant, en 2015, au moins 50% des thrombopathies restent non étiquetées. Dans ce contexte, le laboratoire d’hémostase de l’EFS Alsace et l’unité INSERM UMR S949 travaillent de concert à l’identification et à la caractérisation de ces pathologies. Ainsi, nous avons mis en évidence trois nouvelles mutations du récepteur P2Y12 dans trois familles différentes. La mutation p.His187Gln a été entièrement caractérisée sur des plaquettes fraiches du patient et dans un modèle cellulaire adapté. La reproduction des deux autres mutations (p.Tyr259Cys et p.Phe95Ser) est en cours. Nous avons par ailleurs identifié une famille dont trois membres sont atteints d’une maladie du pool vide non syndromique et nous suspectons grâce au séquençage d’exome effectué que le transporteur de nucléotides VNUT est impliqué dans la pathologie. / Inherited platelets disorders (IPD) are pathologies associated with heterogeneous bleedingphenotypes. They are due to functional platelets deficiency that may come with morphological abnormalities and/or thrombocytopenia. Available diagnosis tools are used to link a functional deficiency to a protein defect and in some instances to a specific genetic mutation. However, in 2015 at least 50% of IPD are still not identified. In this context, the haemostasis laboratory of the EFS Alsace together with INSERM UMR S949 team are working to diagnose and characterize these pathologies. Thus, we found three new P2Y12 receptor variants in three different families. The mutation p.His187Gln has been fully characterized on blood fresh platelets coming from one patient and in an appropriate cellular model. The reproduction of the two other mutations (p.Tyr259Cys and p.Phe95Ser) is currently ongoing. We also studied a family in which three members are carrying a delta storage pool disease. The full exome sequencing analysis leads us to suspect the involvement of the nucleotides transporter VNUT in this pathology.

The diploma thesis is focused on the description of the properties of humid air, its evaporation and its chemical composition. Calculation of the amount of evaporated water from the water surface or condensate evaporation during the drying process using domestic appliances, for rooms with permanent humidity and wet operation. In the theoretical part I will deal specifically with the methods of calculation of the evaporation and the properties of the inner microclimate depending on the external conditions with its influence on the building structures and the persons who will be present in such a microclimate. A solution of the air-conditioning unit is taken from the bachelor's thesis and three other variants of air-conditioning units are designed, which are compared in the framework of the optimal and economical solution for operation in the pool environment. The experimental part is focused on specific examples of calculation and measurement. The measurement deals with year-round moisture measurements in damp rooms in family buildings, specifically in bathrooms. Another part of the experimental measurement will be the determination of the amount of evaporated water from a domestic appliance designed to dry the laundry in a condensing manner. And the main, fundamental measurement is the amount of evaporated water on a particular model of the pool hall.

The subject of the diploma thesis is to introduce the problems of communal spas, namely the treatment of water for swimming pools. Following is a proposal of reconstruction of the treatment plant for a real, operated area of the summer swimming pool. The thesis is divided into theoretical and practical part. At the beginning of the theoretical part I make research of the history of balneology, the effects of bathing and swimming on the human body, possible resources for spa purposes and hygiene requirements for these waters. I also describe commonly used methods of treatment of swimming pool water. In the practical part I first describe the summer swimming pool in the town of Břeclav. There is a description of the swimming pool, its history and equipment. In the next chapter I present the currently operated technological line. Based on a personal visit, the next chapter evaluates the technical condition of the plant. Based on this evaluation, a new technological line for treatment of swimming pool water of the Břeclav summer swimming pool is proposed.

La stabilité du génome est compromise par les déséquilibres du pool de dNTPs qui affectent la vitesse de progression des fourches de réplication. Par exemple, la déficience en cytidine désaminase (CDA) conduit à un excès de dCTP qui induit un ralentissement des fourches de réplication. Les résultats obtenus au cours de ma thèse ont permis de mettre en évidence un nouveau mécanisme par lequel un déséquilibre du pool de nucléotides compromet la complétion de la réplication et la ségrégation correcte des chromosomes. En utilisant des techniques de peignage moléculaire, de microscopie électronique et d’imagerie cellulaire permettant de quantifier le niveau basal de PAR, nous avons montré que la réplication incomplète de l’ADN lorsque la CDA est absente est due à l’inhibition partielle de PARP-1, et n’est pas liée au ralentissement de la vitesse de progression des fourches de réplication. En effet, l’accumulation intracellulaire de dCTP inhibe l’activité de PARP-1 ce qui réduit l’activation de Chk1 et l’efficacité des points de contrôle situés en aval, favorisant ainsi l’accumulation de séquences d’ADN non répliquées en mitose. Celles-ci conduisent alors à la formation de ponts anaphasiques ultrafins (UFBs) entre les chromatides sœurs au niveau de sites difficiles à répliquer tels que les centromères et les sites fragiles. Ces résultats ont des implications directes dans le syndrome de Bloom (BS), une maladie génétique rare combinant prédisposition aux cancers et instabilité génétique. Ce syndrome est la conséquence de la mutation du gène BLM, codant pour une hélicase RecQ du même nom. La déficience en BLM conduit à une chute de l’expression de la CDA résultant en une augmentation des UFBs entièrement due à l’inhibition de PARP-1 par la dCTP, indépendamment de BLM. Ces travaux décrivent ainsi une conséquence pathologique encore inconnue du déséquilibre du pool de nucléotides et révèlent un rôle inattendu de PARP-1 dans la surveillance des séquences d’ADN non répliquées prévenant leur accumulation en mitose et les défauts de ségrégation des chromosomes associés. / Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA) deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that in CDA-deficient cells DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. Indeed, the intracellular accumulation of dCTP inhibits PARP-1 activity compromising the activation of Chk1 and the downstream checkpoints efficiency, allowing the subsequent accumulation of unreplicated DNA in mitosis. This unreplicated DNA leads to the formation of ultrafine anaphase bridges (UFBs) between sister-chromatids at “difficult-to-replicate” sites such as centromeres and fragile sites. These results have direct implications for Bloom syndrome (BS), a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3’-5’ DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of UFBs due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our results describe previously unknown pathological consequences of the distortion of dNTP pools and reveal an unexpected role for PARP-1 in preventing unreplicated DNA accumulation in mitosis and in preventing chromosome segregation defects.

This project was performed to evaluate if waste heat from hotel kitchens is enough to heat outdoor swimming pools in southern Europe or if it can be used as a compliment to another heat source. Another aim was to analyze the simulations and calculations of the pools and the heat recovery system. Then estimate how much annual costs would be reduced when using the exhaust air in the heat recovery system, in comparison with the original heating system. If the project showed positive results the purpose was to select a waste heat recovery system that can integrate with Ozonetech’s ozone generator, keep a high temperature in the pool and reduce emissions of greenhouse gas by using waste heat. Ozonetech would also conduct a pilot study in Stockholm and eventually develop their own product. A simulation model of three different outdoor pool sizes were conducted. The models were constructed and meshed in COMSOL Multiphysics. Average weather conditions for Malaga, Spain, were implemented in the model. The models were simulated by integrating each physical phenomenon in COMSOL, by using the Multiphysics interface. This created convection, emitted radiation and evaporation as thermal heat losses from the pool models. The pools were simulated to determine heating demand, heating period and required inlet temperature to make up for thermal heat losses. A mathematical model of the thermal heat losses and gains were conducted to easily receive a result for the heat demand each month of the year. A mathematical model of the possible heat recovery from hotel kitchens were performed to determine heat recovery for various kitchen sizes. By knowing the heat demand and possible heat recovery from different kitchens, a heat exchanger was selected. The heat exchanger was selected based on literature review, requirements and discussions with manufacturers. A life cycle cost analysis and calculated payback time compared original heating systems with new heat recovery system. A sensitivity analysis using Gauss error propagation concluded the project. The simulations showed that all investigated outdoor pools require additional heat during the night, due to extensive heating periods. Since the kitchen is only active during the day, the pool requires an additional heat source during the night. This conclude that the new heat exchanger only can replace the original heating system during the day. The mathematical model of the heat transfer from the kitchen determined that the maximum heat capacity approximately is 350 kW ± 10.5 kW. The waste heat can only be used to heat small and medium sized pools, since the heat loss is too great for a large pool. Selected air to water heat exchanger that meets the requirements is an air cooler with finned tubes from Alfa Laval. The fins and the coil should be treated to form an e-coat. After calculating the life cycle cost it was determined not profitable to replace a heat pump for a small pool, since the life cycle cost was greater for the new heating system. However, it is profitable to replace an electric heater with the new heat exchanger together with three of the smallest ozone generators during the day, for a small pool. Costs will be reduced by 44 600 – 202 000 kr ± 5%. Payback time will be 2.4 – 3.2 years ± 9%. It is also profitable to replace a water to water heat exchanger heated with either electricity or oil, during the day, with the new heat exchanger combined with either of the ozone generators for a small pool. Costs will be reduced by 310 000 – 698 000 kr ± 5%. Payback time will be 1.8 – 2.5 years ± 9%. It is profitable to replace all original heating systems during the day with the new heat exchanger combined with either of the ozone generators for medium sized pools. Costs will be reduced by 689 000 – 12 600 000 kr ± 5%. Payback time will be 2.2 – 22 months ± 7%.

This paper concerns the planning for sustainable development of a global common pool resource within an autocratic region. The study is focused on the coral reef of the Red Sea, shared between the basin countries; Djibouti, Egypt, Saudi Arabia, Sudan, Yemen, Somalia, Israel, Jordan and Eritrea, where most nations are autocracies and developing countries. The viewpoint of this research is the only multinational project within the region focused on the conservation and sustainability of the coral reefs in the Red Sea, the “Regional Action Plan for the Conservation of Coral Reefs in the Red Sea and Gulf of Aden (RAP CCRRSGA)”. The aim of the research in this paper is to study the planning of this project in relation to sustainable development, through an interpretation of Ostrom’s framework using seven out of eight design principles. This research is executed through a method of ideal-type analysis, in order to assess how ideal-types of these design principles correlate with the planning of this project through similarities between the project and the design principles. This research has resulted in and demonstrated the importance of clarified compliance and cooperation, to reach effective and successful planning of sustainable development pertaining to a shared common pool resource within an autocratic region.

La société en participation ne s’analyse pas comme une société classique. Elle ne se dissout pas, elle est résolue ou résiliée, comme tout contrat de partenariat. Sa force, sa réalité, demeure dans le contrat librement choisi par les participants, tant dans son élaboration que dans l’organisation même de la société, situation intermédiaire entre un contrat classique et les sociétés institution. C’est l’application du principe d’autonomie de la volonté. Dans ce cas de figure, l’affectio societatis se rapproche le plus de la notion de jus fraternitatis, du moins lors de l’élaboration des statuts, ce que certains auteurs nomment l’affectio contractus. Finalement, en raison de son caractère éminemment contractuel, à la place de société en participation, ne faudrait-il pas plutôt l’appeler contrat de société en participation ? Il s’agit dès lors de lui reconnaître son caractère de contrat à part entière, un contrat nommé du Code civil. La jurisprudence semble aller dans ce sens. / The joint-venture company cannot be analysed like a typical firm. It cannot be dissolved; it is solved or cancelled, as is any partnership agreement. Its strength, its reality, remains in the contract freely chosen by the participants, both in its elaboration and in the very organization of the firm, which consists in an intermediate situation between a classic contract and an “institution firm”. It is the application of the principle of will autonomy. In such a case, the “affectio societatis” is as close as it gets to the notion of “jus fraternitatis”, at least during the elaboration of the statutes which some authors name the “affectio contractus”. Eventually, because of this eminently contractual character, instead of joint-venture firm, should we not call it a firm participation partnership? What’s at stake here is the acknowledgment of its full contract character, as a contract named by the Civil code. The jurisprudence seems to go in that direction.

Master's thesis deals with description of a new trading system known as BitCoin. Bitcoin is a unique type of virtual cash in the current world without the influence of large corporations. The system is protected through the use of cryptographic methods that are discussed in detail.  The work explains the principles of integrity of transactions exchange transactions and the acquisition of new money through so-called miners. Individual miners services are mediated through software clients including a description of mining. The paper focuses on protocols for communication. It analyzes the different types of software purses for platforms Windows, Linux and Android. Examining reengineering of purses for Android. This document in no small part discusses the implementation own wallets for the Windows Phone platform 8th.

Les vésicules synaptiques (VSs) sont essentielles pour la neurotransmission. Les recherches actuelles se focalisent sur la caractérisation de leur contenu en neurotransmetteurs, leur cinétique de libération, leur distribution et leur mobilité. Les VS ne sont pas présentes exclusievement en paquet dans les boutons présynaptiques mais sont echangées de façon dynamique avec le reste de l’axone dans un super-contingent (super-pool). Notre laboratoire a précédement montré que le transporteur vésiculaire de glutamate de type 1 (VGLUT1) jouerait un rôle dans la régulation du super-pool. Mon projet de thèse se focalise sur la mobilité des VS dans les axones. En premier lieu, j’ai généré une souris gain de fonction VGLUT1mEos2 afin d'étudier la mobilité des VSs et de mieux caractériser le super-pool. Ensuite j’ai engagé une étude des relation entre la structure de VGLUT1 et ses fonctions afin d’identifier les signatures moléculaires responsable de la régulation de la taille du super-pool. J’ai identifié le second motif poly-proline à l’extremité C-terminale de VGLUT1 comme étant nécessaire et suffisante pour induire une diminution de la taille du super-pool des VSs. Pour conclure mes travaux de thèse ont contribué à la compréhension du rôle de VGLUT1 dans la régulation de la mobilité des VSs et à fournir les outils nécessaires pour de futures investigations concernant la physiologie du super-pool. / Synaptic vesicles (SVs) are essential for neurotransmission, and more efforts are needed for better understanding their neurotransmitter content, release kinetics, distribution and mobility. SVs are not only clustered in presynaptic boutons, but also dynamically shared among multiple en passant presynaptic boutons, a phenomenon named SV super‐pool. Previous work from our laboratory suggested that the Vesicular GLUtamate Transporter 1 (VGLUT1) may play a role in regulating SV super-­pool size beyond loading glutamate into SV. My Ph.D project is focused on SVs mobility in axons. Firstly, I generated a VGLUT1mEos2 knock-in (KI) mouse line, which provides extended possibilities to study the SV trafficking and characterize SV super‐pool. Secondly, I engaged in a thorough VGLUT1 structure‐function analysis. I identified that VGLUT1 tends to cluster SVs in the presynaptic boutons and reduce SVs exchange with the super‐pool via the second poly‐proline motif of its C­‐terminus. Overall, my Ph.D work contributes to the knowledge of the role of VGLUT1 in regulating SVs mobility and provides new tools for the further investigations on SV super-­pool physiology.

Cette thèse consiste en trois recherches sur le financement bancaire des entreprises. Le premier essai met l’accent sur l’influence des relations bancaires et des connexions politiques sur l’accès des entreprises au crédit. Il utilise un ensemble de données collectées manuellement sur les moyennes entreprises vietnamiennes pour montrer que les relations bancaires (durée de la relation avec la banque principale et le nombre de banques) et les connexions politiques ont des effets complémentaires sur la maximisation de la disponibilité du crédit pour les entreprises. Cette recherche a des implications politiques pour les économies émergentes caractérisées par la corruption gouvernementale locale ; elle suggère que les décideurs politiques devraient préférer les systèmes bancaires transactionnels aux systèmes bancaires relationnels, et elle expose le côté obscur des relations bancaires. Le deuxième essai examine les effets des connexions politiques et de la corruption locale sur les structures du pool bancaire des entreprises. En utilisant le même ensemble de données que dans notre premier essai, nous constatons que les entreprises politiquement connectées ont tendance à établir leurs relations bancaires principales avec les banques connectées. Nous constatons également que les entreprises connectées réduisent le nombre de banques et la diversité des types de propriétés des banques dans leurs pools bancaires lorsqu’elles établissent des relations avec les banques connectées ; ces entreprises maintiennent ces structures de pool bancaire lorsque la corruption est répandue dans leur province d’origine. Les résultats montrent que la corruption locale est associée positivement au nombre de banques et à la diversification des types de propriétés des banques. Le dernier essai explore la structure du pool bancaire des entreprises dans les économies émergentes caractérisées par la corruption. Dans le modèle théorique proposé, les gestionnaires d’entreprise maximisent une fonction d’utilité attendue qui dépend à la fois de la valeur de l’entreprise et de la consommation personnelle. En fonction du poids qu’ils attribuent à chaque composante, les gestionnaires choisissent parmi trois structures du pool bancaire pour combiner un certain nombre de banques et le choix d’une banque principale plus ou moins corrompue. Le test de ce modèle repose sur un riche ensemble de données provenant d’entreprises vietnamiennes que dans notre premier essai. Les résultats confirment que les entreprises et les banques sont de même niveau d’intégrité. En outre, les entreprises ont tendance à augmenter le nombre de banques dans le pool bancaire lorsqu’elles ne peuvent pas établir une relation avec une banque principale souhaitable. / This thesis consists of three research on the firms’ bank financing. The first essay focuses the influences of bank–firm relationships and political connections on firms’ access to credit. It uses a manually collected data set of Vietnamese medium-sized enterprises to show that bank–firm relationships (length of relationship with main bank and number of banks) and political connections have complementary effects on maximizing firms’ availability of credit. This research has policy implications for emerging economies characterized by local government corruption; it suggests that policymakers should prefer transactional banking systems to relationship banking systems, and it exposes the dark side of bank–firm relationships. The second essay investigates the effects of political connections and local corruption on the structures of firms’ bank pools. Using the same data set with our first essay, it finds that politically connected firms tend to establish their main bank relationships with connected banks. It also finds that connected firms reduce their numbers of banks and their diversity of bank ownership types in their bank pools when they achieve main bank relationships with connected banks; such firms maintain these bank pool structures when corruption is prevalent in their home provinces. Results demonstrate that local corruption is associated positively with number of banks and diversification of bank ownership types. The last essay explores the structure of firms’ bank pools in emerging economies characterized by corruption. In the proposed theoretical model, firm managers maximize an expected utility function that depends on both firm value and personal consumption. According to the weight they assign to each component, managers choose among three bank pool structures to combine some number of banks and the choice of a main bank that is more or less corrupt. The test of this model relies on the same rich data set with our first essay. The results confirm that firms and banks match, in terms of their levels of integrity. Moreover, firms tend to increase the number of banks in the bank pool when they cannot achieve a relationship with a desirable main bank.