La dernière décennie a connu un intérêt croissant pour les problèmes posés par les variables instrumentales faibles dans la littérature économétrique, c’est-à-dire les situations où les variables instrumentales sont faiblement corrélées avec la variable à instrumenter. En effet, il est bien connu que lorsque les instruments sont faibles, les distributions des statistiques de Student, de Wald, du ratio de vraisemblance et du multiplicateur de Lagrange ne sont plus standard et dépendent souvent de paramètres de nuisance. Plusieurs études empiriques portant notamment sur les modèles de rendements à l’éducation [Angrist et Krueger (1991, 1995), Angrist et al. (1999), Bound et al. (1995), Dufour et Taamouti (2007)] et d’évaluation des actifs financiers (C-CAPM) [Hansen et Singleton (1982,1983), Stock et Wright (2000)], où les variables instrumentales sont faiblement corrélées avec la variable à instrumenter, ont montré que l’utilisation de ces statistiques conduit souvent à des résultats peu fiables. Un remède à ce problème est l’utilisation de tests robustes à l’identification [Anderson et Rubin (1949), Moreira (2002), Kleibergen (2003), Dufour et Taamouti (2007)]. Cependant, il n’existe aucune littérature économétrique sur la qualité des procédures robustes à l’identification lorsque les instruments disponibles sont endogènes ou à la fois endogènes et faibles. Cela soulève la question de savoir ce qui arrive aux procédures d’inférence robustes à l’identification lorsque certaines variables instrumentales supposées exogènes ne le sont pas effectivement. Plus précisément, qu’arrive-t-il si une variable instrumentale invalide est ajoutée à un ensemble d’instruments valides? Ces procédures se comportent-elles différemment? Et si l’endogénéité des variables instrumentales pose des difficultés majeures à l’inférence statistique, peut-on proposer des procédures de tests qui sélectionnent les instruments lorsqu’ils sont à la fois forts et valides? Est-il possible de proposer les proédures de sélection d’instruments qui demeurent valides même en présence d’identification faible? Cette thèse se focalise sur les modèles structurels (modèles à équations simultanées) et apporte des réponses à ces questions à travers quatre essais. Le premier essai est publié dans Journal of Statistical Planning and Inference 138 (2008) 2649 – 2661. Dans cet essai, nous analysons les effets de l’endogénéité des instruments sur deux statistiques de test robustes à l’identification: la statistique d’Anderson et Rubin (AR, 1949) et la statistique de Kleibergen (K, 2003), avec ou sans instruments faibles. D’abord, lorsque le paramètre qui contrôle l’endogénéité des instruments est fixe (ne dépend pas de la taille de l’échantillon), nous montrons que toutes ces procédures sont en général convergentes contre la présence d’instruments invalides (c’est-à-dire détectent la présence d’instruments invalides) indépendamment de leur qualité (forts ou faibles). Nous décrivons aussi des cas où cette convergence peut ne pas tenir, mais la distribution asymptotique est modifiée d’une manière qui pourrait conduire à des distorsions de niveau même pour de grands échantillons. Ceci inclut, en particulier, les cas où l’estimateur des double moindres carrés demeure convergent, mais les tests sont asymptotiquement invalides. Ensuite, lorsque les instruments sont localement exogènes (c’est-à-dire le paramètre d’endogénéité converge vers zéro lorsque la taille de l’échantillon augmente), nous montrons que ces tests convergent vers des distributions chi-carré non centrées, que les instruments soient forts ou faibles. Nous caractérisons aussi les situations où le paramètre de non centralité est nul et la distribution asymptotique des statistiques demeure la même que dans le cas des instruments valides (malgré la présence des instruments invalides). Le deuxième essai étudie l’impact des instruments faibles sur les tests de spécification du type Durbin-Wu-Hausman (DWH) ainsi que le test de Revankar et Hartley (1973). Nous proposons une analyse en petit et grand échantillon de la distribution de ces tests sous l’hypothèse nulle (niveau) et l’alternative (puissance), incluant les cas où l’identification est déficiente ou faible (instruments faibles). Notre analyse en petit échantillon founit plusieurs perspectives ainsi que des extensions des précédentes procédures. En effet, la caractérisation de la distribution de ces statistiques en petit échantillon permet la construction des tests de Monte Carlo exacts pour l’exogénéité même avec les erreurs non Gaussiens. Nous montrons que ces tests sont typiquement robustes aux intruments faibles (le niveau est contrôlé). De plus, nous fournissons une caractérisation de la puissance des tests, qui exhibe clairement les facteurs qui déterminent la puissance. Nous montrons que les tests n’ont pas de puissance lorsque tous les instruments sont faibles [similaire à Guggenberger(2008)]. Cependant, la puissance existe tant qu’au moins un seul instruments est fort. La conclusion de Guggenberger (2008) concerne le cas où tous les instruments sont faibles (un cas d’intérêt mineur en pratique). Notre théorie asymptotique sous les hypothèses affaiblies confirme la théorie en échantillon fini. Par ailleurs, nous présentons une analyse de Monte Carlo indiquant que: (1) l’estimateur des moindres carrés ordinaires est plus efficace que celui des doubles moindres carrés lorsque les instruments sont faibles et l’endogenéité modérée [conclusion similaire à celle de Kiviet and Niemczyk (2007)]; (2) les estimateurs pré-test basés sur les tests d’exogenété ont une excellente performance par rapport aux doubles moindres carrés. Ceci suggère que la méthode des variables instrumentales ne devrait être appliquée que si l’on a la certitude d’avoir des instruments forts. Donc, les conclusions de Guggenberger (2008) sont mitigées et pourraient être trompeuses. Nous illustrons nos résultats théoriques à travers des expériences de simulation et deux applications empiriques: la relation entre le taux d’ouverture et la croissance économique et le problème bien connu du rendement à l’éducation. Le troisième essai étend le test d’exogénéité du type Wald proposé par Dufour (1987) aux cas où les erreurs de la régression ont une distribution non-normale. Nous proposons une nouvelle version du précédent test qui est valide même en présence d’erreurs non-Gaussiens. Contrairement aux procédures de test d’exogénéité usuelles (tests de Durbin-Wu-Hausman et de Rvankar- Hartley), le test de Wald permet de résoudre un problème courant dans les travaux empiriques qui consiste à tester l’exogénéité partielle d’un sous ensemble de variables. Nous proposons deux nouveaux estimateurs pré-test basés sur le test de Wald qui performent mieux (en terme d’erreur quadratique moyenne) que l’estimateur IV usuel lorsque les variables instrumentales sont faibles et l’endogénéité modérée. Nous montrons également que ce test peut servir de procédure de sélection de variables instrumentales. Nous illustrons les résultats théoriques par deux applications empiriques: le modèle bien connu d’équation du salaire [Angist et Krueger (1991, 1999)] et les rendements d’échelle [Nerlove (1963)]. Nos résultats suggèrent que l’éducation de la mère expliquerait le décrochage de son fils, que l’output est une variable endogène dans l’estimation du coût de la firme et que le prix du fuel en est un instrument valide pour l’output. Le quatrième essai résout deux problèmes très importants dans la littérature économétrique. D’abord, bien que le test de Wald initial ou étendu permette de construire les régions de confiance et de tester les restrictions linéaires sur les covariances, il suppose que les paramètres du modèle sont identifiés. Lorsque l’identification est faible (instruments faiblement corrélés avec la variable à instrumenter), ce test n’est en général plus valide. Cet essai développe une procédure d’inférence robuste à l’identification (instruments faibles) qui permet de construire des régions de confiance pour la matrices de covariances entre les erreurs de la régression et les variables explicatives (possiblement endogènes). Nous fournissons les expressions analytiques des régions de confiance et caractérisons les conditions nécessaires et suffisantes sous lesquelles ils sont bornés. La procédure proposée demeure valide même pour de petits échantillons et elle est aussi asymptotiquement robuste à l’hétéroscédasticité et l’autocorrélation des erreurs. Ensuite, les résultats sont utilisés pour développer les tests d’exogénéité partielle robustes à l’identification. Les simulations Monte Carlo indiquent que ces tests contrôlent le niveau et ont de la puissance même si les instruments sont faibles. Ceci nous permet de proposer une procédure valide de sélection de variables instrumentales même s’il y a un problème d’identification. La procédure de sélection des instruments est basée sur deux nouveaux estimateurs pré-test qui combinent l’estimateur IV usuel et les estimateurs IV partiels. Nos simulations montrent que: (1) tout comme l’estimateur des moindres carrés ordinaires, les estimateurs IV partiels sont plus efficaces que l’estimateur IV usuel lorsque les instruments sont faibles et l’endogénéité modérée; (2) les estimateurs pré-test ont globalement une excellente performance comparés à l’estimateur IV usuel. Nous illustrons nos résultats théoriques par deux applications empiriques: la relation entre le taux d’ouverture et la croissance économique et le modèle de rendements à l’éducation. Dans la première application, les études antérieures ont conclu que les instruments n’étaient pas trop faibles [Dufour et Taamouti (2007)] alors qu’ils le sont fortement dans la seconde [Bound (1995), Doko et Dufour (2009)]. Conformément à nos résultats théoriques, nous trouvons les régions de confiance non bornées pour la covariance dans le cas où les instruments sont assez faibles. / The last decade shows growing interest for the so-called weak instruments problems in the econometric literature, i.e. situations where instruments are poorly correlated with endogenous explanatory variables. More generally, these can be viewed as situations where model parameters are not identified or nearly so (see Dufour and Hsiao, 2008). It is well known that when instruments are weak, the limiting distributions of standard test statistics - like Student, Wald, likelihood ratio and Lagrange multiplier criteria in structural models - have non-standard distributions and often depend heavily on nuisance parameters. Several empirical studies including the estimation of returns to education [Angrist and Krueger (1991, 1995), Angrist et al. (1999), Bound et al. (1995), Dufour and Taamouti (2007)] and asset pricing model (C-CAPM) [Hansen and Singleton (1982, 1983), Stock and Wright (2000)], have showed that the above procedures are unreliable in presence of weak identification. As a result, identification-robust tests [Anderson and Rubin (1949), Moreira (2003), Kleibergen (2002), Dufour and Taamouti (2007)] are often used to make reliable inference. However, little is known about the quality of these procedures when the instruments are invalid or both weak and invalid. This raises the following question: what happens to inference procedures when some instruments are endogenous or both weak and endogenous? In particular, what happens if an invalid instrument is added to a set of valid instruments? How robust are these inference procedures to instrument endogeneity? Do alternative inference procedures behave differently? If instrument endogeneity makes statistical inference unreliable, can we propose the procedures for selecting "good instruments" (i.e. strong and valid instruments)? Can we propose instrument selection procedure which will be valid even in presence of weak identification? This thesis focuses on structural models and answers these questions through four chapiters. The first chapter is published in Journal of Statistical Planning and Inference 138 (2008) 2649 – 2661. In this chapter, we analyze the effects of instrument endogeneity on two identificationrobust procedures: Anderson and Rubin (1949, AR) and Kleibergen (2002, K) test statistics, with or without weak instruments. First, when the level of instrument endogeneity is fixed (does not depend on the sample size), we show that all these procedures are in general consistent against the presence of invalid instruments (hence asymptotically invalid for the hypothesis of interest), whether the instruments are "strong" or "weak". We also describe situations where this consistency may not hold, but the asymptotic distribution is modified in a way that would lead to size distortions in large samples. These include, in particular, cases where 2SLS estimator remains consistent, but the tests are asymptotically invalid. Second, when the instruments are locally exogenous (the level of instrument endogeneity approaches zero as the sample size increases), we find asymptotic noncentral chi-square distributions with or without weak instruments, and describe situations where the non-centrality parameter is zero and the asymptotic distribution remains the same as in the case of valid instruments (despite the presence of invalid instruments). The second chapter analyzes the effects of weak identification on Durbin-Wu-Hausman (DWH) specification tests an Revankar-Harttley exogeneity test. We propose a finite-and large-sample analysis of the distribution of DWH tests under the null hypothesis (level) and the alternative hypothesis (power), including when identification is deficient or weak (weak instruments). Our finite-sample analysis provides several new insights and extensions of earlier procedures. The characterization of the finite-sample distribution of the test-statistics allows the construction of exact identificationrobust exogeneity tests even with non-Gaussian errors (Monte Carlos tests) and shows that such tests are typically robust to weak instruments (level is controlled). Furthermore, we provide a characterization of the power of the tests, which clearly exhibits factors which determine power. We show that DWH-tests have no power when all instruments are weak [similar to Guggenberger(2008)]. However, power does exist as soon as we have one strong instruments. The conclusions of Guggenberger (2008) focus on the case where all instruments are weak (a case of little practical interest). Our asymptotic distributional theory under weaker assumptions confirms the finite-sample theory. Moreover, we present simulation evidence indicating: (1) over a wide range cases, including weak IV and moderate endogeneity, OLS performs better than 2SLS [finding similar to Kiviet and Niemczyk (2007)]; (2) pretest-estimators based on exogeneity tests have an excellent overall performance compared with usual IV estimator. We illustrate our theoretical results through simulation experiment and two empirical applications: the relation between trade and economic growth and the widely studied problem of returns to education. In the third chapter, we extend the generalized Wald partial exogeneity test [Dufour (1987)] to non-gaussian errors. Testing whether a subset of explanatory variables is exogenous is an important challenge in econometrics. This problem occurs in many applied works. For example, in the well know wage model, one should like to assess if mother’s education is exogenous without imposing additional assumptions on ability and schooling. In the growth model, the exogeneity of the constructed instrument on the basis of geographical characteristics for the trade share is often questioned and needs to be tested without constraining trade share and the other variables. Standard exogeneity tests of the type proposed by Durbin-Wu-Hausman and Revankar-Hartley cannot solve such problems. A potential cure for dealing with partial exogeneity is the use of the generalized linear Wald (GW) method (Dufour, 1987). The GW-procedure however assumes the normality of model errors and it is not clear how robust is this test to non-gaussian errors. We develop in this chapter, a modified version of earlier procedure which is valid even when model errors are not normally distributed. We present simulation evidence indicating that when identification is strong, the standard GW-test is size distorted in presence of non-gaussian errors. Furthermore, our analysis of the performance of different pretest-estimators based on GW-tests allow us to propose two new pretest-estimators of the structural parameter. The Monte Carlo simulations indicate that these pretest-estimators have a better performance over a wide range cases compared with 2SLS. Therefore, this can be viewed as a procedure for selecting variable where a GW-test is used in the first stage to decide which variables should be instruments and which ones are valid instruments. We illustrate our theoretical results through two empirical applications: the well known wage equation and the returns to scale in electricity supply. The results show that the GW-tests cannot reject the exogeneity of mother’s education, i.e. mother’s education may constitute a valid IV for schooling. However, the output in cost equation is endogenous and the price of fuel is a valid IV for estimating the returns to scale. The fourth chapter develops identification-robust inference for the covariances between errors and regressors of an IV regression. The results are then applied to develop partial exogeneity tests and partial IV pretest-estimators which are more efficient than usual IV estimator. When more than one stochastic explanatory variables are involved in the model, it is often necessary to determine which ones are independent of the disturbances. This problem arises in many empirical applications. For example, in the New Keynesian Phillips Curve, one should like to assess whether the interest rate is exogenous without imposing additional assumptions on inflation rate and the other variables. Standard Wu-Durbin-Hausman (DWH) tests which are commonly used in applied work are inappropriate to deal with such a problem. The generalized Wald (GW) procedure (Dufour, 1987) which typically allows the construction of confidence sets as well as testing linear restrictions on covariances assumes that the available instruments are strong. When the instruments are weak, the GW-test is in general size distorted. As a result, its application in models where instruments are possibly weak–returns to education, trade and economic growth, life cycle labor supply, New Keynesian Phillips Curve, pregnancy and the demand for cigarettes–may be misleading. To answer this problem, we develop a finite-and large-sample valid procedure for building confidence sets for covariances allowing for the presence of weak instruments. We provide analytic forms of the confidence sets and characterize necessary and sufficient conditions under which they are bounded. Moreover, we propose two new pretest-estimators of structural parameters based on our above procedure. Both estimators combine 2SLS and partial IV-estimators. The Monte Carlo experiment shows that: (1) partial IV-estimators outperform 2SLS when the instruments are weak; (2) pretestestimators have an excellent overall performance–bias and MSE– compared with 2SLS. Therefore, this can be viewed as a variable selection method where the projection-based techniques is used to decide which variables should be instrumented and which ones are valid instruments. We illustrate our results through two empirical applications: the relation between trade and economic growth and the widely studied problem of returns to education. The results show unbounded confidence sets, suggesting that the IV are relatively poor in these models, as questioned in the literature [Bound (1995)].

The thesis examines the legend of Saint Procopius. At the beginning there is the description of the life of Saint Procopius and introduces genre legends. The introductory chapters will contain chapter of Sázava's monastýry founded by Saint Procopius and the last chapter of the theoretical part will be devoted to visual processing Prokop´s legend in Liber depictus. This is followed by a comparison and analysis of Prokop legends from the Middle Age to the present. The starting point is the five basic texts, which are Vita minor, Legenda Aurea by the Italian Dominican Jacobus de Voragine, which is written around 1260, traditional Czech verse processing of Prokop legends from the reign of Charles IV., Prokop legend by Jaroslav Vrchlický from 19th century and the final text is compared About Saint Prokop with legend published by M. Drahovzal, which is a part of folk culture. This comparison is supplemented with a chapter called Saint in the Baroque period. Each processing precedes the introductory part, which is either introduced the time in which the legend was created, or contains a brief description of the author, who wrote the legend.

No description available.

The biological half-life of several pro-inflammatory mediators involved in the pathogenesis of rheumatoid arthritis (RA) is controlled by molecules exhibiting dipeptidyl peptidase-IV (DPP-IV)-like enzymatic activity (Dipeptidyl peptidase-IV activity and/or structure homologues- DASH). The aim of this thesis was to identify the molecular source of the DPP-IV-like enzymatic activity in the peripheral blood and synovial fluid in patients with rheumatoid arthritis as compared to control patients with osteoarthritis (OA), and to evaluate the association of DPP-IV with the disease activity. We found that the main source of the DPP-IV-like enzyme activity in the plasma and in the synovial fluid in patients with RA is the canonical DPP-IV. DPP-IV-like enzymatic activity and canonical DPP-IV were also detected on the cell surface of blood and synovial fluid mononuclear cells. Significantly lower DPP-IV-like enzymatic activity and DPP-IV expression in the synovial fluid mononuclear cells was found in RA as opposed to OA patients. In the synovial fluid of RA patients there was also a negative correlation between the concentration of the pro-inflammatory DPP-IV substrate SDF (stromal cell-derived factor-1 and the proportion of the DPP-IV+ T cells. The blood plasma DPP-IV-like enzymatic activity and...

Nesta dissertação, tratamos do estudo das bifurcações de um modelo bi-dimensional de presa-predador, que estende e aperfeiçoa o sistema de Lotka-Volterra. Tal modelo apresenta cinco parâmetros e uma função resposta não monotônica do tipo Holling IV: $$ \\left\\{\\begin \\dot=x(1-\\lambda x-\\frac{\\alpha x^2+\\beta x +1})\\\\ \\dot=y(-\\delta-\\mu y+\\frac{\\alpha x^2+\\beta x +1}) \\end ight. $$ Estudamos as bifurcações do tipo sela-nó, Hopf, transcrítica, Bogdanov-Takens e Bogdanov-Takens degenerada. O método dos centros organizadores é usado para estudar o comportamento qualitativo do diagrama de bifurcação. / In this work are studied the bifurcations of a bi-dimensional predator-prey model, which extends and improves the Volterra-Lotka system. This model has five parameters and a non-monotonic response function of Holling IV type: $$ \\left\\{\\begin \\dot=x(1-\\lambda x-\\frac{\\alpha x^2+\\beta x +1})\\\\ \\dot=y(-\\delta-\\mu y+\\frac{\\alpha x^2+\\beta x +1}) \\end ight. $$ They studied the sadle-node, Hopf, transcritic, Bogdanov-Takens and degenerate Bogdanov-Takens bifurcations. The method of organising centers is used to study the qualitative behavior of the bifurcation diagram.

Atresia de vias biliares (AVB) é uma hepatopatia colestática específica da criança, de etiologia desconhecida, com evolução para fibrose hepática precoce. AVB é a principal causa de cirrose na infância e principal indicação de transplante hepático pediátrico (Tx). Compreender os fatores envolvidos na progressão da fibrose é fundamental para estabelecer tratamentos efetivos nas hepatopatias crônicas. Identificar padrões histopatológicos associados ao prognóstico da AVB permitiria melhor planejamento dos centros de transplante e adequado aconselhamento familiar. OBJETIVO: Estabelecer padrões de marcadores histopatológicos e de imunofluorescência para colágenos em biópsias hepáticas iniciais e finais de pacientes com AVB submetidos a tratamento cirúrgico. Correlacionar esses marcadores com o prognóstico da doença, definido com base no tempo de evolução até realização do Tx. MÉTODO: Avaliação histológica de alterações biliares e fibrose hepática e histomorfometria da fibrose marcada por picrossírius e da deposição dos colágenos tipos I, III, IV e V marcados por imunofluorescência indireta (IF), em biópsias hepáticas iniciais e finais de 36 pacientes com AVB submetidos à hepatoportoenterostomia de Kasai (KPE) e ao Tx nos últimos 20 anos em nossa instituição. RESULTADOS: A mediana das idades de realização da KPE foi de 12,5 semanas (6-20) e do Tx foi de 27 meses (6-120). Reação ductular e malformação de placa ductal foram mais intensas nas biópsias iniciais (p < 0,05), enquanto fibrose hepática e ductopenia apresentaram padrão progressivo (p < 0,001), sem correlações com a idade de realização da KPE nem com o tempo de evolução até Tx. A morfometria da fibrose hepática marcada pelo picrossírius nas biópsias iniciais apresentou correlação positiva com a idade da KPE (p = 0,01), mas não com a idade do Tx (p = 0,24). A deposição perissinusoidal dos colágenos dos tipos III e V foi mais intensa nas biópsias iniciais (p < 0,01), enquanto os colágenos dos tipos I e IV apresentaram padrão de deposição progressiva (p < 0,01). Pacientes com maior deposição perissinusoidal de colágeno tipo I nas biópsias iniciais apresentaram curva de tempo de evolução até Tx sugerindo pior prognóstico (p = 0,04). CONCLUSÃO: Marcadores histopatológicos de alterações biliares, fibrose hepática e deposição de colágenos apresentaram características evolutivas distintas nas fases inicial e final da AVB, sem correlação com o tempo de evolução até Tx. A morfometria da deposição perissinusoidal de colágeno tipo I em biopsias iniciais marcadas por IF pode ser correlacionada ao tempo de evolução até Tx em pacientes com AVB operada / Biliary atresia (BA) is a specific cholestatic liver disease of unknown etiology that affects children and progresses to early hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Understanding the factors involved in the progress of fibrosis is essential to establish effective treatment to chronic liver disease. Histopathological markers in liver biopsies could be useful to predict progression to end stage disease and to make it possible to improve planning in transplantation centers and parental orientation. OBJECTIVE: To establish histopathological or immunohistochemical markers in initial or final liver biopsies of BA patients and correlate those markers with prognosis, as defined by progression time lapse until LTx. METHOD: Histological analysis of multiple parameters of biliary alterations and morphometrical assessment of liver fibrosis were performed, besides indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA submitted to Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years in a single center. RESULTS: The median of the ages at KPE was 12.5 weeks (6-20) and at LTx was 27 months (6-120). Ductular reaction and ductal plate malformation were more severe in the initial biopsies (p < 0.05), while ductopenia and liver fibrosis were more severe in final biopsies (p < 0.001), though without correlation with age at KPE nor with progression time lapse until LTx. Morphometrical assessment of liver fibrosis marked by picrosirius red in initial biopsies demonstrated positive correlation with age at KPE (p = 0.01) but not with age at LTx (p = 0.24). The perisinusoidal deposition of type III and V collagens was more extended in the initial biopsies (p < 0.01), while type I and IV collagens deposition indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curve until LTx (p = 0.04). CONCLUSION: Biliary alterations, liver fibrosis and collagens deposition demonstrated distinctive progression findings in the initial or final phases of the BA, without prognostic correlation. Morphometrical assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsies can be correlated with progression time until LTx in patients with post-surgical BA

The present thesis deals with different aspects of the chemistry of oxovanadium(IV) complexes, their interaction with double stranded DNA, photo-induced DNA cleavage, photo-enhanced cytotoxicity in visible light and red light and localisation and cellular uptake to understand the mechanism of cell death. Chapter I presents a general introduction on potential of transition metal complexes as photochemotherapeutic agents. A brief introduction about Photodynamic Therapy (PDT) as a new alternative to chemotherapy for treating cancer has been made. Various modes of interaction of small molecules with duplex DNA are described. Recent reports on metal-based photocytotoxicity, photo-induced DNA cleavage activity and cellular localization are presented in detail. 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 ONO-donor 2-(2-hydroxybenzylideneamino)phenol (salamp) and phenanthroline bases to explore the photo-induced DNA cleavage activity in UV-A light of 365 nm and photocytotoxicity in visible light. Chapter III deals with the photo-induced DNA cleavage and photocytotoxicity of ternary oxovanadium(IV) complexes containing ONN-donor N-2-pyridylmethylidine-2-hydroxyphenylamine (Hpyamp) Schiff bases and phenanthroline bases. The objective of this work is to investigate the photo-induced DNA cleavage activity in near-IR light. Photocytotoxicity and cell cycle arrest have been studied in HeLa cancer cells. Chapter IV deals serendipitous discovery of planar triazinuim cationic species by vanadyl-assisted novel ring cyclization reaction. The compounds are synthesised, characterized and their DNA binding and anaerobic photoinduced DNA cleavage activity are presented. The importance of the thiazole moiety in the triazinuim species in cellular uptake has been investigated. Photocytotoxicity, localization and cell death mechanism have been studied in HeLa and MCF-7 cells. Chapter V describes the synthesis, characterization, DNA binding, photo-induced DNA cleavage activity and photocytotoxicity of oxovanadium(IV) complexes containing 2-(1H-benzimidazol-2-yl)-N-(pyridin-2-ylmethylene)ethaneamine (Hpy-aebmz) and curcumin as photosensitizer. The effect of conjugating naphthalimide on Hpy-aebmz on photoinduced DNA cleavage and photocytotoxicity has been studied. Cellular uptake, localization and mechanism of cell death induced by complexes have been investigated. Chapter VI presents ternary oxovanadium(IV) complexes having, 2-((1H-benzimidazol-2-yl)methylimino-methyl)phenol (Hsal-ambmz) and phenanthroline bases. The complexes were synthesized, characterized and their DNA binding property studied. Photo-induced DNA cleavage activity and photocytotoxicity in red light has been discussed. Anthracene has been conjugated to a tridentate ligand to investigate cellular uptake, localization and cell death mechanism. Mitochondria targeting property of the complexes having dipeptide has been studied and compared with clinically used drug Photofrin®. 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 unintentional omission that might have happened due to oversight or mistake is regretted.

Le domaine de la bioénergétique concerne l’étude des échanges et des transformations de l’énergie au sein des organismes vivants. Cette thèse propose une étude électrochimique et spectroscopique de protéines issues de la chaine respiratoire, les oxydases terminales, afin de comprendre l’influence de différentes propriétés de ces enzymes (potentiels des cofacteurs, dépendance pH…) sur leur mécanisme réactionnel. La première partie de ce travail décrit le développement d’une méthode d’immobilisation permettant de conserver l’intégrité et l’activité de ces enzymes. Cette technique a d’abord été utilisée pour étudier l’inhibition de la cytochrome aa3 oxydase de P. denitrificans et a permis de mettre en avant l’importance du transfert de protons sur la réaction de réduction de l’oxygène. Une deuxième étude propose de comparer deux isoformes de la cytochrome cbb3 oxydase dont aucune différence n’a été observée à ce jour. La spectroscopie IRTF couplée à l’électrochimie montre l’implication de résidus acides différents au cours de la réaction d’oxydoréduction suggérant des différences mécanistiques. La dernière partie propose une étude comparative d’oxydases terminales de différents types et met en perspective l’influence des potentiels relatifs des hèmes sur la réaction de réduction de l’oxygène. / The field of bioenergetics concerns the study of exchange and transformation of energy in living organisms. This manuscript proposes an electrochemical and spectroscopic study of the fourth complex of the respiratory chain, the terminal oxidases. The aim of this study was to understand the influence of some properties of these enzymes (potential of the cofactors, pH dependency…) on the catalytic mechanism. The first part describes an immobilization procedure which retains the protein activity and structure. This procedure has been applied for the study the inhibition of the proton pathways of cytochrome aa3 oxidase from P. denitrificans and shows the importance of proton transfer on the oxygen reduction. In a second study, two isoforms of cytochrome cbb3 oxidase were compared. No differences were observed between them until now. Our electrochemically induced FTIR spectroscopy study suggests the implication of different acidic residues during the redox reaction implying differences in the mechanism of these enzymes. The last part deals with the comparison of terminal oxidases of different types and shows the influence of the relative order of the midpoint potentials of the hemes on the oxygen reduction.

This thesis focuses on the politics of Antipope Victor IV and his successors Paschal III, Calixtus III and Innocent III, who were the opponents of Alexander III since the schismatic elections of 1159. The aim is to analyse the political thinking and actions of the antipopes, with an emphasis on the political relations of Victor IV. The thesis is divided into six thematic sections. The first deals with the pre-election developments and the election of 1159 itself. The second considers their position in relation to Alexander III, while the third turns to the papal-imperial policy and examines the relationship between the antipopes and Emperor Frederick Barbarossa. The fourth section discusses the status and relations of the antipopes outside the Holy Roman Empire. The penultimate chapter examines the attitude of the imperial clergy to the pontificates of the antipopes as well as the obedience of the imperial monasteries, according to papal documents. The final chapter constructs biographies of the antipopes, focusing on the period before their pontificates.

Title: The Last Princess of Luxembourg. The Life Elizabeth of Görlitz in the Period between Years 1390 - 1425. Abstract: The thesis aims to describe the life of the last princess of the House of Luxembourg, Elisabeth of Görlitz. Based on an analysis of narrative and diplomatic material spanning between 1390 - 1425 it describes her life from birth until the moment she ultimately became a widow. Elisabeth of Görlitz (1390 - 1451) was the granddaughter of the emperor Charles the IV. and the Swedish king Albrecht I. During a significant period she used to be the only heir of the House of Luxembourg and therefore since her childhood she was an important woman from the political point of view. She married Anthony Duke of Brabant after several unsuccessful engagements. This marriage led Elizabeth to the Western Europe, where she spent the rest of her life. Thanks to this marriage, Luxembourg became the property of the newly married couple. After few years Anthony died in one of the most famous battles of Hundred Years' War - The battle of Agincourt. Soon after that, Elizabeth got married for the second time. Her second husband was John III the Pitiless, the former Prince-Bishop of Liège, which was during this time most known for his efforts of acquiring Holland and Zeeland. However, John died a few years after the...