Les centrosomes sont les centres organisateurs des microtubules et jouent un rôle crucial dans l’organisation du fuseau bipolaire pendant la mitose. Plus récemment, le rôle des centrosomes dans la régulation de l’entrée en mitose a été mis en évidence. Les centrosomes semblent également contribuer à l’activation du point de contrôle en G2/M en réponse aux lésions de l’ADN en servant de point de rencontre pour les régulateurs du cycle cellulaire et les gènes de réponse aux dommages à l’ADN. L’amplification du nombre de centrosomes est une caractéristique des cellules tumorales mais de façon intéressante, elle constitue aussi une réponse des cellules aux dommages à l’ADN. Les mécanismes qui régulent l’homéostasie et la dynamique des centrosomes sont encore mal compris. Pour mieux comprendre le rôle des centrosomes dans la régulation du point de contrôle en G2/M en réponse aux dommages à l’ADN, le recrutement et/ou l’activation au niveau des centrosomes des kinases impliquées dans les voies de signalisation de ce point de contrôle ont été étudiés par immunofluorescence indirecte sur cellules HeLaS3 ou par Western blot sur des fractions enrichies en centrosomes. Nos résultats montrent que les kinases ATM, ATR, CHK1 et CHK2 sont actives dans les centrosomes de cellules en phase G2. En réponse à l’activation du point de contrôle en G2/M, les formes actives de ces kinases diminuent au niveau des centrosomes. Pour identifier de nouveaux acteurs centrosomaux potentiellement impliqués dans la régulation de ce point de contrôle, une analyse comparative des protéomes de centrosomes purifiés a également été réalisée par spectrométrie de masse. Pour étudier plus particulièrement la fonction de CHK2 au niveau des centrosomes, nous avons développer des outils moléculaires qui serviront à déterminer le rôle de la sous population de CHK2 localisée aux centrosomes 1) dans la régulation de l’entrée en mitose au cours d’un cycle normal 2) dans l’activation et la stabilité du point de contrôle en G2/M en réponse aux lésions l’ADN et 3) dans l’homéostasie et la dynamiques des centrosomes en réponse aux dommages à l’ADN. Cette étude permettra de mieux comprendre la fonction des centrosomes dans la réponse cellulaire au stress génotoxiques anti-cancereux et de révéler de nouvelles fonctions potentielles pour la kinase CHK2. / Centrosomes function primarily as microtubule-organizing centres that play a crucial rôle in the equal segregation of chromosomes by organizing the bipolar spindle during mitosis. Recent studies have revealed the involvement of centrosomes in regulating G2/M transition during normal cell cycle progression. Moreover, increasing evidence suggests that centrosomes also play roles in the DNA damage response and cell cycle checkpoint signalling by serving as “meeting points” where DNA-damage-responsive genes and cell cycle regulators communicate. Numerical centrosome aberrations, or centrosome amplification, is a common feature of most human cancers that promotes aneuploidy and is involved in tumorigenesis as well as tumor progression. Interestingly, centrosome amplification and fragmentation have also been shown to constitute a cellular response to impaired DNA integrity that triggers cell death by mitotic failure. Although their roles are critical in tumorigenesis and the DNA damage response, the mechanisms that regulate centrosome homeostasis and dynamics remain poorly understood. To gain a better understanding of the role of the centrosomes in checkpoint regulation at G2/M transition in response to DNA damage; the recruitment and/or centrosomal activation of the kinases implicated in this checkpoint pathways were studied by indirect immunofluorescence on HeLaS3 cells or western blot on purified centrosomal fractions. Our results showed that the kinases CHK1, CHK2, ATM and ATR are activated at the centrosomes in cell synchronised in G2. However, after activation of the G2/M checkpoint, these activated kinases moved from centrosomes. Finally, to identify new centrosomal actors potentially involved in the regulation of this checkpoint, a comparative analysis of the proteome of purified centrosomes was also realized by mass spectrometry. To study more specifically the function of CHK2 at the centrosomes, we developped molecular tools wich will serve to determine the role of the sub-population of CHK2 localized at the centrosomes in 1) in regulating entry into mitosis during unperturbed cell cycle progression, 2) in checkpoint regulation at G2/M transition in response to DNA damage induced by ionizing radiations and genotoxic drugs and 3) in centrosomal homeostasis and dynamics by regulating centrosomal amplification, fragmentation and clustering during normal cell cycle progression and in response to genotoxic drugs. This study will further elucidate the importance of centrosomes in regulating the cell response to genotoxic stress induced by anti-cancer treatments and reveal potential new functions for the kinase CHK2 in unperturbed cell cycle progression and in response to DNA damage.

As every breach of a contract not only conditions destabilization of business relations, but also causes a social conflict, and an aggrieved party must be compensated for damage incurred in connection with non-performance or defective performance of obligations under the contract. A breach of a private interest as a result of non-performance or defective performance of a contract gives grounds for contractual civil liability to arise. As the compensatory function is the main function of civil liability, only proper implementation of it can guarantee protection of the breached interests of the parties and restore the stability of business relations. Thus, in order to restore the balance of legal relations, it is necessary to have a good knowledge of the legal regulation of damages in contractual relations. This research work gives a comprehensive analysis of legal regulation of damages in contractual relations in the Republic of Lithuania, as well as peculiarities and problems of regulation of this institution. Contractual liability is researched as one of the forms of civil liability, different from tortious liability; it is also discussed which of these two forms of civil liability should be applied in different stages of pre-contractual relations. The essence of damages as one of the forms of contractual liability is disclosed by studying the types of damage that are compensated for in case of breach of a contract, differences between damages and penalties, conditions for... [to full text]

Universiẗat, Diss., 2006--Mannheim.

Thesis (doctoral)--Universität, Hamburg, 2006. / Includes bibliographical references (p. [215]-225) and index.

Zugleich: Diss. Mainz, 2008. / Literaturverz.

Thesis (LL. M.)--George Washington University, 1992. / Typescript. Includes bibliographical references.

Thesis (doctoral)--Universiẗat Bonn, 2006. / Includes bibliographical references (p. 257-269).

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Le carbure de silicium (SiC) est un matériau qui est considéré comme un semi-conducteur à large bande interdite ou une céramique suivant ses applications en microélectronique ou comme matériau nucléaire. Dans ces deux domaines d'application les défauts générés par l'implantation/irradiation d'ions (dopage, matériau de structure) doivent être contrôlés. Ce travail est une étude des défauts générés par l'implantation de gaz rares suivant les conditions d'implantation (fluence et température). La déformation élastique a plus particulièrement été étudiée dans le cas d'implantation de xénon à des températures pour lesquelles la recombinaison dynamique empêche la transition amorphe. Un modèle phénoménologique basé sur le recouvrement des cascades a été proposé pour comprendre l'évolution de la déformation maximale avec la dose. Des observations complémentaires en particulier par microscopie électronique à transition nous ont permis de préciser la nature des défauts créés et d'étudier leur évolution sous recuit. La formation de cavités a été observée pour des conditions sévères d'implantation/recuit ; ces cavités sont de nature différente (vide ou pleine) suivant la répartition du xénon. Cette étude est également reliée aux propriétés de gonflement sous irradiation, gonflement qui doit être anticipé dans les domaines d'application du SiC. / Silicon carbide is a material that can be considered as a wide band gap semiconductor or as a ceramic according to its applications in microelectronics and in nuclear energy system (fission and fusion). In both fields of application defects or damage induced by ion implantation/ irradiation (doping, material structure) should be controlled. This work is a study of defects induced by noble gas implantation according to the implantation conditions (fluence and temperature). The elastic strain buildup, particularly in the case of xenon implantation, has been studied at elevated temperatures for which the dynamic recombination prevents the amorphization transition. A phenomenological model based on cascade recovery has been proposed to understand the strain evolution with increasing dose and for different noble gases. In addition, with the help of transmission electron microscopy the evolution of defects under subsequent annealing was studied. The formation of nanocavities was observed under severe implantation/annealing conditions. These cavities are of different nature (full of gas or empty) according to the xenon and damage distribution. This study is also linked to swelling properties under irradiation that should be projected in the SiC application fields.

This diploma thesis deals with international shipping. Transportation in international trade holds, despite unstable developments during the last few years, is of vital importance. The main factor that affects most of the weaknesses associated with the current issue of transportation, the effect of the impact of the global economic crisis. The thesis also focuses on detail to frequent damage of cargo and proposes measures for their elimination.