This thesis describes a molecular-based study undertaken to analyse the expression of the RAMOSUS1 (RMS1) and RAMOSUS5 (RMS5) genes in pea (Pisum sativum). Both genes encode carotenoid cleavage dioxygenase (CCD) enzymes that are together proposed to control the synthesis of an inhibitor of bud outgrowth termed SMS (Shoot Multiplication Signal). SMS was recently identified as strigolactone. Expression analyses of RMS1 presented here have built upon earlier experiments which demonstrate it to be a highly regulated transcript. RMS1 mRNA levels are known to be rapidly decreased following removal of the shoot apex but are subsequently restored to that of intact plants by auxin (indole-3-acetic acid or IAA). This regulatory mechanism is retained in all five ramosus mutants tested to date. Together with physiological data, this indicates RMS1, and therefore SMS, are required in IAA-mediated suppression of bud outgrowth. Another significant aspect of RMS1 regulation identified in previous studies involves a graft-transmissible, long-distance feedback signal that moves from shoot to root. This feedback regulation is dependent on the RMS2 gene and enhances RMS1 expression levels. Prior to the cloning of RMS5 and its discovery as a second CCD enzyme in the RMS network, reciprocal grafting studies with the rms mutants indicated RMS5 may act in the same pathway as RMS1 to produce SMS. Multiple studies presented here demonstrate that these two CCD genes are expressed in similar tissues and are regulated by the same signals, specifically IAA and the RMS2-dependent feedback signal. Like RMS1, the RMS5 gene also retains its IAA response in the rms mutants. However, RMS5 is generally less responsive to changes in IAA and RMS2-dependent feedback, as it exhibits smaller fluctuations than RMS1 in its expression levels. Together these findings support a general view that RMS1 is more likely to control a rate-limiting step in SMS synthesis. A previous study indicated that RMS1 expression may be up-regulated by IAA through a posttranscriptional mechanism. This thesis sought to more closely examine the RMS1 and RMS5 IAA response by separately observing the effect of IAA on subsequent transcription. New transcripts, termed heterogenous nuclear RNAs (hnRNAs), were relatively quantified in parallel with existing mRNAs in the steady-state cytoplasmic pool. The experiments conducted here provide further evidence that IAA may act post-transcriptionally to stabilise RMS1 mRNA because the changes in hnRNA are not proportional to the changes in mRNA following IAA-modifying treatments. IAA may still function to induce transcription of RMS1, but this does not appear to be a significant mechanism by which IAA regulates RMS1 expression. In contrast, the IAA induction of RMS5 occurs predominantly via new transcription and RMS5 either lacks or is not as strongly subjected to the IAA-mediated mRNA stabilisation mechanism proposed for RMS1. Initial studies described in this thesis also suggest that IAA could act to regulate the expression of the Arabidopsis orthologues MORE AXILLARY BRANCHING (MAX) genes via a post-transcriptional mechanism. Analyses of MAX hnRNA and mRNA levels in Arabidopsis to date indicate it is the RMS5 orthologue MAX3 which exhibits an IAA response most like RMS1. Additional studies into the regulation of RMS1 and RMS5 presented in this thesis provide further insights into the molecular mechanisms controlling their expression levels. In vitro experiments with the translation inhibitor cycloheximide demonstrate that RMS5 expression levels are increased when protein synthesis is reduced, as previously shown for RMS1. Relative quantification of RMS1 and RMS5 hnRNA levels further demonstrate that the induction by cycloheximide is due primarily to an increase in new transcription, indicating that RMS1 and RMS5 are negatively regulated by a rapidly turned-over transcriptional repressor. Tissue specific effects on RMS1 expression were also observed which are consistent with a protein degradation function of the RMS4 F-box in the shoot. This thesis provides further evidence to suggest that SMS acts in concert with IAA to inhibit the sustained outgrowth of axillary buds. RMS1 and RMS5 expression levels are not regulated by a hypothetical fast decapitation signal which is proposed to cause the initial bud outgrowth occurring prior to decapitation-induced IAA depletion. RMS1, RMS5 and SMS are therefore unlikely to control the initial exit of buds from dormancy to an intermediate transition state. Studies here also suggest that enhanced shoot auxin transport and cytokinin biosynthesis are associated with axillary bud outgrowth because the rms mutants contain elevated shoot expression levels of a gene encoding the auxin efflux carrier PIN1 and two genes controlling cytokinin biosynthesis. Several approaches described in this study were used to characterise the RMS1 and RMS5 proteins. Anti-peptide antibodies were generated against both proteins and the results obtained show that although the antibodies are likely to recognise the full-length proteins, further work is required to effectively detect RMS1 and RMS5 in plant tissues via western blotting. Preliminary in situ immunolocalisation results indicate the RMS1 and RMS5 proteins are localised to the vasculature, consistent with gene expression analyses.

The human immunodeficiency virus is presently one of the most significant global health issues to date, with a disease burden that encumbers developing and developed nations alike. Although current antiretroviral therapy can help patients maintain undetectable levels of the virus throughout their bodies, once the treatment is ceased, the virus will rebound and disease progression continues. Thus, modalities to; 1- stop HIV transmission and spread, or 2- eradicate the virus once it is acquired are both urgently needed. In this project, we seek to evaluate and understand the impact of a candidate vaccine therapy that targets the HIV protease cleavage sites (PCS) on viral fitness. Vaccination with this modality in a monkey model induces mutations at virus regions that are intolerant to change, presumably affecting the "fitness" of viral strains recovered from vaccines. Preliminary results of the study show that in the vaccine group (n=11), a disruption to one or more of the HIV protease cleavage sites results in improved maintenance of CD4+ T cells compared to unvaccinated controls (n=5). Furthermore, a correlation between the percentage of PCS mutations and reductions in viral load were seen. Our data indicate that the most common sites of mutation occur at two cleavage regions PCS2 and PCS12. We used site directed mutagenesis to introduce multiple PCS mutations into infectious clones of SIV. Our ongoing studies are evaluating the viral fitness of the SIV mutants in a cell lines and PBMC using competitive viral fitness assays. The data from these studies will help inform in the areas of vaccine and therapy development for HIV-1.

La prédiction du clivage des aciers ferritiques a été largement étudiée à l’aide de l’approchelocale de la rupture, et des modèles macroscopiques identifiés phénoménologiquement comme celui de Beremin. Cette prédiction reste cependant difficile dans le domaine de transition ductilefragile. Cela a conduit à des études micromécaniques par les approches polycristallines afin de décrire l’évolution de la contrainte de clivage en fonction de la température pour les aciers bainitiques. Dans cette étude, on utilise une approche polycristalline, puis on développe un modèle macroscopique de prédiction du clivage d’un acier de microstructure plus simple, un acier sphéroïdisé. De nombreux résultats de la littérature indiquent que leur rupture est due à la microfissuration des carbures. Le comportement mécanique et la rupture d'un acier sphéroïdisé C35R sont obtenus par des essais de traction simple et de ténacité dans une gamme de température entre -196 et 20°C. Les analyses microstructurales sont effectuées pour déterminer la distribution de taille des grains et des carbures. Des modélisations simplifiées de la microstructure de l’acier sont proposées. L’aspect polycristallin du matériau est pris en compte. Une étude paramétrique concernant la distribution des contraintes dans les carbures est réalisée. On montre que les paramètres du modèle polycristallin n’influencent pas cette distribution à la condition de représenter le même comportement global en traction. La prédiction de la rupture par clivage est basée sur une approche probabiliste, considérant la dispersion des contraintes dans les carbures due à l'hétérogénéité des champs mécaniques issue de la modélisation polycristalline. La probabilité élémentaire de rupture des carbures est ainsi obtenue. Différents modèles de rupture macroscopiques sont alors développés, basés sur des critères en germination et propagation des microfissures. Ils sont appliqués à une éprouvette SENT afin de prédire la ténacité dans le bas de la transition ductile-fragile. La comparaison avec les résultats expérimentaux montre que l’on doit prendre en compte l’évolution de la densité volumique des microfissures avec le chargement, l’extension des microfissures de taille variable ou leur émoussement. L’importance des différents critères dépend de la température. / The cleavage fracture prediction of the ferritic steels has been widely studied using the localapproach to fracture and macroscopic phenomenological models like Beremin. This prediction remains difficult in the ductile-brittle transition domain. Therefore, micromechanical studies have been carried out using polycrystalline approaches to describe the evolution of the cleavage stress in function of temperature for the bainitic steels. In this study, a macroscopic model using a polycrystalline approach is developed to predict the cleavage of one steel with a simple microstructure: a spheroidized steel. Many results in the literature indicate that its fracture is due to carbide microcracking. The mechanical and fracture behavior of a spheroidized steel C35R are obtained by tensile and toughness tests in a temperature range between -196°C and 20°C. The microstructural analyses are performed to determine the grain and carbide size distribution. Simplified microstructure models of the steel are proposed. The polycrystalline aspect of the material is taken into account. A parametric study on the carbide stress distribution is carried out. It is shown that the parameters of the polycrystalline model do not influence the carbide stress distribution if the same global tensile behavior is represented. The cleavage fracture prediction is based on the probabilistic approach, considering the stress scatter in the carbides due to the mechanical fields’ heterogeneity related to the polycrystalline modelling. Thus, the elementary fracture probability function is obtained. Different macroscopic fracture models are then developed based on the criteria based on nucleation and propagation of microcracks. The models are applied to a SENT specimen to predict the toughness in the bottom of the ductile-brittle transition domain. The comparison with experimental results shows that the evolution of the microcracks volume density with the loading, the extension of the microcracks with various sizes or their blunting, must be taken into account. The importance of the different criterions depends on the temperature.

EDF souhaite conforter la justification de l’intégrité des cuves de réacteurs nucléaires à eau pressurisée, basées sur l’amorçage de fissure, par le concept d’arrêt de fissure. L'objectif de la thèse est de consolider les travaux de prévision de l’arrêt des fissures fragiles dans l’acier de cuve. Des essais d'arrêt de fissure isothermes réalisés entre -150°C et -50°C sur des éprouvettes CT et sur des anneaux en compression ont été analysés. Les analyses fractographiques montrent que la propagation et l’arrêt de fissure se produisent en clivage même si de la déchirure ductile précède la propagation instable de fissure. Un critère local d’arrêt de fissure fragile est appliqué lors de calculs par éléments finis en élastoviscoplasticité et en dynamique : la rupture se produit si la contrainte principale maximale est égale à une contrainte critique. Ce critère permet de bien prédire les vitesses de propagation ainsi que les longueurs de fissure à l’arrêt. La contrainte critique augmente avec la température en relation avec les signes de dissipation observés sur les surfaces de rupture. Une dépendance du critère à la géométrie est observée. Elle peut être liée aux hypothèses de calculs réalisés en bidimensionnel. L’étude de la dynamique de la structure montre que le phénomène d’arrêt de fissure est fortement lié à la dynamique globale de la structure : l’arrêt et la fermeture de la fissure interviennent simultanément. / EDF wants to complete the assessment of reactor pressure vessels usually based on crack initiation concept by crack arrest concept. The work aims at improving the knowledge of cleavage crack arrest in reactor pressure vessel steel. For that purpose, isothermal crack arrest experiments were performed for temperatures ranging from –150°C up to –50°C on compact tensile specimens and on pre-cracked rings submitted to compressive loading. Fractographic observations revealed that the whole crack propagation and arrest occurs by cleavage even if ductile tearing occurs before initiation of the unstable crack propagation. A local cleavage crack arrest criterion is applied in finite element computations carried out in elastoviscoplasticity and in full dynamics: the crack propagates since the largest principal stress reaches a critical stress. The application of this criterion on the experiments leads to a good prediction of the crack speed and of the crack length and shows that the critical stress increases with the temperature in relation with dissipation features observed on the fracture surfaces. Dependence to the geometry is observed; it can be due to the assumption used for the 2D computations. The study of the structural dynamic shows that the crack arrest phenomenon is very linked to the global dynamics of the structure: crack arrest and crack closure occur approximately at the same time.

L’objectif de cette thèse est de comprendre les micro-mécanismes physiques de propagation et d’arrêt de fissure de clivage dans l’acier de cuve 16MND5 et de proposer un modèle de prédiction robuste et physiquement fondé, en s’appuyant sur une campagne d’essais de rupture fragile sur éprouvettes de laboratoire finement instrumentées, associée à la modélisation numérique de ces essais. Dans un premier temps, des expériences ont été menées sur des éprouvettes CT25 de différentes épaisseurs à cinq températures (-150°C, -125°C, -100°C, -75°C, -50°C). Des trajets de fissures rectilignes et branchées (deux fissures se développant de manière quasi-symétrique) ont été observés. Pour estimer la vitesse de propagation, une caméra ultra-rapide a été utilisée, associée à la mise au point d’un protocole expérimental permettant d’observer la face de l’éprouvette dans l’enceinte thermique, sans givrage. Des observations à 500 000 images.s-1 ont permis de caractériser finement la vitesse instantanée de la fissure sur le ligament complet de la CT (~25 mm). En parallèle, pour pouvoir analyser les essais et l’impact de la viscosité sur la réponse mécanique autour de la fissure, le comportement élasto-viscoplastique du matériau a été étudié jusqu’à une vitesse de déformation de 104 s-1 pour les températures étudiées. La méthode des éléments finis étendus (X-FEM) a été utilisée dans le code de calcul CAST3M pour modéliser la propagation de fissure. Les simulations numériques associent l’approche locale de la rupture en dynamique non linéaire et un critère de propagation en contrainte critique de type RKR à une distance caractéristique. Les travaux réalisés ont permis de confirmer la forme du critère proposé par Prabel à -125°C, et d’identifier les dépendances de ce critère à la température et à la vitesse de déformation. A partir d’analyses numériques en 2D et 3D, un critère multi-température fonction croissante de la vitesse de déformation est proposé. Des modélisations prédictives ont permis de valider le critère sur deux géométries d’éprouvettes (CT et anneau) en mode I à différentes températures. Des observations MEB et des analyses 3D au microscope optique montrent que le mécanisme de rupture est le clivage associé à des zones de cisaillement ductile entre les différents plans de fissuration. L’étude de la fraction surfacique des marches de cisaillement et des contraintes de fermeture associées tend à justifier le critère mis en place. Un modèle analytique est proposé permettant de justifier le critère déduit des modélisations numériques. Ce modèle considère que les ligaments retiennent la lèvre de la fissure et induisent donc des contraintes de fermeture au niveau de la pointe de fissure qu’il faut compenser pour atteindre la contrainte de clivage effective en pointe de fissure. Cette résistance des ligaments est directement reliée à la loi de comportement du matériau et justifie la dépendance du critère de rupture identifié à la vitesse de déformation. Enfin, les branchements de fissure ont été analysés via le dépouillement des vidéos obtenues avec la caméra rapide qui mettent en évidence un amorçage initial rectiligne, puis un amorçage de fissures multiples de part et d’autre du plan de fissure qui conduisent à l’arrêt de la fissure initiale, l’une de ces fissures ‘secondaires’ conduisant ensuite à la rupture de l’éprouvette. Les rôles essentiels de l’épaisseur et du chargement dans ce mécanisme de branchement sont soulignés. L’augmentation de l’épaisseur réduit la fréquence d’apparition de ce mécanisme et finit même par l’annuler. Logiquement l’intensité du chargement doit être suffisamment importante pour créer cette zone plastique étendue : les essais qui présentent une propagation rectiligne sont les essais pour lesquels les chargements à l’amorçage sont les plus faibles. / The purpose of this PhD thesis is to understand physical mechanisms of cleavage crack propagation and arrest in the 16MND5 PWR vessel steel and to propose a robust predicting model based on a brittle fracture experimental campaign of finely instrumented laboratory specimens associated with numerical computations. First, experiments were carried out on thin CT25 specimens at five temperatures (-150°C, -125°C, - 100°C, -75°C, -50°C). Two kinds of crack path, straight or branching path, have been observed. To characterize crack propagation and to measure crack speed, a high-speed framing camera system was used, combined with the development of an experimental protocol which allowed to observe CT surface without icing inside the thermal chamber and on the specimen. The framing camera (520 000 fps) has allowed to have a very accurate estimation of crack speed on the complete ligament of CT (~ 25 mm). Besides, to analyse experiments and to study the impact of viscosity on the mechanical response around the crack tip, the elastic-viscoplastic behavior of the ferritic steel has been studied up to a strain rate of 104 s-1 for the tested temperatures.The eXtended Finite Element Method (X-FEM) was used in CAST3M FE software to model crack propagation. Numerical computations combine a local non linear dynamic approach with a RKR type fracture stress criterion to a characteristic distance. The work carried out has confirmed the form of the criterion proposed by Prabel at -125°C, and has identified the dependencies of the criterion on temperature and strain rate. From numerical analyzes in 2D and 3D, a multi-temperature fracture stress criterion, increasing function of the strain rate, was proposed. Predictive modeling were used to confirm the identified criterion on two specimen geometries (CT and compressive ring) in mode I at different temperatures. SEM observations and 3D analyzes made with optical microscope showed that the fracture mechanism was the cleavage associated with ductile shear zones between the different planes of cracking. The study of the surface fraction of ductile shear zones and associated closing stress tends to justify the established criterion. An analytical model is proposed to justify the criterion deduced from numerical modeling. This model assumes that the ligaments hold the crack lips and therefore induce closing stress at the crack tip which has to be compensated to achieve the effective cleavage stress at the crack tip. This resistance of ligaments is directly related to the mechanical behavior of the material and justifies the dependence of fracture stress criterion with strain rate. Lastly, the crack branching was analyzed thanks to movies obtained with the high-speed camera. The cleavage crack propagates in a straight way over few millimeters. Then, new cracks appear on both sides of the initial crack lips which leads to the arrest of the initial crack. One of the new cracks leads to the failure of the CT specimen. The essential role of the thickness and loading on this branching mechanism is emphasized. The increased thickness reduces the frequency of occurrence of this mechanism and eventually even cancel. Low thicknesses lead to more extensive plasticity at the crack tip and generates the germs for the triggering of secondary cracks that appear. Logically, the intensity of loading must be large enough to create this extended plastic zone : the experiments with a straight path are the tests for which the initial loadings are the lowest.

L’objectif de la thèse est la prédiction de la propagation et de l’arrêt de fissure de clivage dans un acier de cuve de type 16MND5 par un critère local en contrainte critique, calculé en pointe de fissure. Les travaux précédents ont montré que le mécanisme de rupture était du clivage,associé à des zones de cisaillement ductile entre les différents plans de fissuration. Ceci explique la dépendance de la contrainte critique de rupture à la vitesse de déformation en pointe de fissure du fait du comportement visqueux des aciers ferritiques aux vitesses de propagation considérées. Cette thèse consiste à optimiser la méthode numérique mise en oeuvre pour simuler la propagation dynamique de fissure, identifier et valider un critère local de propagation et d’arrêt sur des chargements thermomécaniques complexes, rendre compte des trajets de fissuration variés, et approfondir les connaissances sur les micro-mécanismes physiques de la rupture pour renforcer le contenu physique du critère utilisé.L’identification du critère de propagation et d’arrêt a été faite par la simulation numérique des essais de rupture fragile réalisés sur des éprouvettes CT25 à quatre températures (-150°C, -125°C, -100°C et -75°C). La méthode des éléments finis étendus (X-FEM) a été utilisée dans le code de calcul CAST3M pour ces modélisations. Les résultats des analyses en 2D et 3D ont montré que la contrainte critique de rupture augmentait avec la vitesse de déformation plastique et ils ont donc permis d’établir un critère de propagation et d’arrêt basé sur cette contrainte.Une formulation analytique du critère a été développée pour justifier le critère identifié. La contrainte critique du critère a été considérée comme la somme de la contrainte critique de clivage et de la contrainte générée par la déformation des ligaments (ponts de matières résistants sollicités en cisaillement) en arrière du front de la fissure. Afin de quantifier ce phénomène, des mesures de caractérisations des ligaments ont été effectuées sur les faciès de rupture et sur les coupes transversales des éprouvettes. Le profil de contrainte sur les lèvres de la fissure, généré par les ligaments tendant à résister à l’ouverture de la fissure, a été calculé à l’aide de modélisations éléments finis de multifissures représentatives de la géométrie réelle de la fissure observée sur une coupe transversale. Ceci a permis d’obtenir la contribution de l’effort des ligaments à la contrainte critique en pointe de fissure, et de développer ensuite une formulation analytique pour la contrainte critique. La courbe de la formulation analytique présente un très bon accord avec le critère empirique identifié.Afin de tester la pertinence de ce critère, la prédiction de la propagation et de l’arrêt de fissure a d’abord été menée sur des essais isothermes, à la fois sur des éprouvettes CT25 (la fissure étant sollicitée en mode I) et ensuite sur des anneaux fissurés sollicités en mode mixte. Les résultats numériques des prédictions ont présenté une bonne cohérence avec les expériences.Ceci montre la pertinence du critère sous chargement isotherme. Pour étudier la propagation et l’arrêt de fissure sous choc thermique, un essai a ensuite été réalisé sur un anneau fissuré. Le chargement pour l’essai est plus complexe avec un couplage des chargements mécaniques et thermiques. La prédiction par le critère a été effectuée en 2D et en 3D. Les résultats prédits sont de bonne qualité en termes de cinétique de propagation et de longueur de fissure à l’arrêt. Ceci complète la validation du critère sous chargement thermomécanique.En parallèle, des expériences ont été menées sur des éprouvettes CT25 rallongées (de même hauteur qu’une CT25 mais de largeur double), présentant une bifurcation de la trajectoire de la fissure. [...] / The purpose of this PhD study is to predict the propagation and arrest of cleavage cracks in a French PWR vessel steel (16MND5). This is accomplished through use of a local criterion based on the critical stress calculated ahead of crack tip. Previous work has shown that fracture mechanism was cleavage associated with the ductile shear zone between the different planes of cracking. Thus, the critical stress at crack tip depends on stain rate. This thesis consists ofnumerical optimization, identification and validation of a local criterion based on experimentswhich have complex thermomechanical loads. The criterion accounts for various crack paths,deepening the knowledge about micro mechanisms during crack propagation in order to justify the established criterion.Criterion identification was carried out by using numerical simulations of tension tests performed on CT (Compact Tension) specimens at four different temperatures (-150°C, -125°C,-100°C and -75°C). The eXtended Finite Element Method (X-FEM) was used in CAST3M FEsoftware to model dynamic crack propagation and arrest. The analysis results in 2D and 3Dshowed that the critical stress at crack tip increased with the inelastic strain rate. Therefore, acriterion based on the critical stress was established. An analytical model was developed to justify the identified criterion. The critical stress givenby the local criterion was considered as the sum of the critical cleavage stress and the stress generated by the deformation of ligaments behind the crack tip. In order to quantify this phenomenon, measurements of ligaments’ characteristics have been performed on facture surfaces and on cross-sections of the specimens. The stress profile of the crack lips generated by ligaments was calculated by modeling of multi-cracks on specimen’s cross-section. The contribution of stress generated by ligaments to the critical stress at crack tip was obtained with this method, and then the analytical model of the critical stress was developed. The results of this analytical model is in good agreement with the empirical criterion identified.In order to test the validity of the identified criterion, the prediction of the crack propagation and arrest by the criterion was first performed for isothermal tests. It was performed both onCT25 specimens (crack was solicited in mode I) and on ring specimens in mixed mode loadingwhich were carried out at three different temperatures. The numerical results of prediction were in good agreement with experiments. They showed the validity of the criterion for experiments under isothermal loading for two different specimen geometries. In order to test the validity of criterion for the situation of thermal shock, experiments were carried out on ring specimens. At first, one ring specimen was cooled down to -150°C, and then hot water (≈90°C) was injected through the inner side of the ring specimen. At the same time of thermal shock, this specimen was submitted to a mechanical compressive loading (-750kN). The prediction of crack propagation and arrest by the criterion for this situation was calculated in both 2D and 3D. The predicted results were in good agreement with experiments for both crack speed and crack length. This confirmed that the criterion is relevant to predict the crack propagation and arrest for thermal shock.In parallel, some experiments were performed on extended CT25 specimens (same height but double the width of the CT25 specimen). The crack path on this kind of specimen was curved.A statistical effect by a random selection in the propagation direction was introduced to takeinto account the instability during the crack propagation. The numerical results correctlyreproduce the curvature and the dispersion of the crack paths.

The present thesis deals with different aspects of the chemistry of oxovanadium(IV) complexes, their interaction with DNA and protein and photo-induced DNA and protein cleavage activity and photocytotoxicity. Chapter I presents a general introduction on various modes of interactions of organic compounds and transition metal complexes capable of targeting DNA leading to DNA strand scission, emphasizing particularly the photo-induced DNA cleavage activities for their potential application in PDT. The mechanistic pathways associated with the DNA cleavage are discussed. A comparison has been made on the advantages of photoactive metal complexes over organic conjugates. Objective of the present investigation is also dealt in this Chapter. Chapter II of the thesis deals with the synthesis, characterization, DNA binding and photo-induced DNA cleavage activity of ternary oxovanadium(IV) complexes of N-salicylidene-S-methyldithiocarbazate (salmdtc) and phenanthroline bases to explore the photo-induced DNA cleavage activity in UV-A light of 365 nm. Chapter III presents the synthesis, characterization, DNA binding and photo-induced DNA cleavage activity of ternary oxovanadium(IV) complexes containing N-salicylidene-L-methionate (salmet) and N-salicylidene-L-tryptophanate (saltrp) Schiff bases and phenanthroline bases. The objective of this work is to investigate the photo-induced DNA cleavage activity in near-IR light and to see the effect of pendant thiomethyl and indole moieties in the DNA cleavage reactions. Chapter IV deals with the synthesis, characterization, DNA binding, red-light induced DNA cleavage activity and photocytotoxicity of ternary oxovanadium(IV) complexes having N-salicylidene-L-arginine (sal-argH) and N-salicylidene-L-lysine (sal-lysH) Schiff bases and phenanthroline bases. The important results include the visible light-induced DNA cleavage activity and photocytotoxicity of the complexes in human cervical HeLa cancer cells. Chapter V describes the synthesis, characterization, DNA binding and photo-induced DNA and protein cleavage activity and photocytotoxicity of oxovanadium(IV) complexes containing bis(2-benzimidazolylmethyl)amine and phenanthroline bases. The significant results include DNA cleavage activity in near-IR light and photocytotoxicity of the dppz complex in non-small cell lung carcinoma/human lung adenocarcinoma A549 cells in visible light. Further, we have studied the protein cleavage activity of the complexes in UV-A light of 365 nm by using bovine serum albumin (BSA) and lysozyme. Finally, Chapter VI presents the binary oxovanadium(IV) complexes of phenanthroline bases. We have studied their synthesis, characterization, DNA binding and photo-induced DNA and protein cleavage activity and photocytotoxicity. Photocytotoxicity of dppz complex has been studied in human cervical HeLa cancer cells in visible light. Photo-induced protein cleavage activity of the complexes has been studied in UV-A light of 365 nm by using BSA and lysozyme. The references have been compiled at the end of each chapter and indicated as superscript numbers in the text. The complexes presented in this thesis are represented by bold-faced numbers. Crystallographic data of the complexes, characterized structurally by single crystal X-ray crystallography, are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any omission that might have happened due to oversight or mistake is regretted.

The attempts to understand discontent and populist surges in the West, especially in recent years, led to an abundance of research, comments, and speculations. Some thinkers asserted that such events are the symptoms of a cleavage restructuration in liberal democratic societies that would be centered around the question of merit. Research generally links higher education and general success in life to satisfaction and relative support of the established order. On the contrary, lesser educated and successful individuals tend to question this state of affairs. A cleavage revolving around success and education would consequently replace previous divisions, such as the usual right-left opposition, but also come on top of other schisms, mainly spatial ones. This thesis offers to verify the existence of such a cleavage with a case study of the Yellow Vests movement, in France. Analyzing the discourse of the representants of the meritocracy, Emmanuel Macron and his government, it finds trends that support the existence of such an underlying conflict.

The diploma thesis Sport as Local Cleavages: Case Study of Vysočina Region analyses whether sport and sport related topics (sport financing and other support, organization of sports events, operation and building of sport facilities, association activities, etc.) are able to divide a society, or whether it can be one of the cleavages at the local level in the Vysočina Region and what intensity this cleavage could have in the examined municipalities. The theoretical part contains the concept of conflict lines of S. Rokkan and S. M. Lipset. The research put emphasis on the local level of politics, the Czech environment and the cleavage connected with a sport. Authors such as S.Balík, V. Bubeníček, J. Čmejrek, J. Čopík, V. Hloušek and M. Kubálek are dealing with these issues. The analytical part of the thesis is a case study that examines the presence of cleavage, its intensity and the approach of actors through both semi-structured interviews with representatives of selected municipalities, records of municipalities and as well through media news monitoring. Based on research it is obvious that sport could evoke and develop conflicts and, in some cases, can indeed significantly divide a society and establish a new local policy player.

Oviparous amniotes produce a large yolky egg that gives rise to a free-living hatchling. Structural characteristics and functional attributes of the egg are best known for birds, which have a large mass of fluid yolk surrounded by an extraembryonic yolk sac. Yolk nutrients are delivered to the embryo via the vascular yolk sac. This developmental pattern and nutrient transport mechanism is thought to be representative of all other lineages of amniotes. Recent discovery of a snake with cellularized yolk organized around a meshwork of blood vessels reveals an additional pattern for yolk mobilization, which may also occur in other squamate reptiles (lizards and snakes). This complex yolk sac raises interesting questions about developmental mechanisms and suggests a possible model for the transition between the egg of anamniotes and that of amniotes.