Cette thèse a pour objet l'obligation de sécurité en matière la responsabilité contractuelle à la lumière du droit français et du droit libyen. La recherche tend à répondre aux questions suivantes : Qu'entend-on par sécurité des produits médicaux ? Sur quel fondement juridique peut-on justifier cette obligation ? Quelles sont les difficultés d'application de cette obligation pour traiter les problèmes de produits de santé ? C'est quoi le produits de santé ? Et Le droit de la responsabilité civile libyen est-il parfaitement adapté à la protection de la victime des produits de santé comme dans le droit de la responsabilité français ? Ce questionnement a conduit l'auteur à développer une analyse approfondie de l'obligation de sécurité en manière de la responsabilité contractuelle et le droit de la santé français et libyen. Dans la première partie de la thèse, on constate que la notion d'obligation de sécurité, y compris en matière de la responsabilité contractuelle, a connu une évolution majeure par rapport à l'époque précédant. En fait, l'apparition de la notion d'obligation de sécurité est ancienne puisqu'elle a été créée en France le 21 novembre 1911 à l'occasion du contrat de transport. Elle peut être définie comme « l'obligation de veiller à la sécurité d'une personne ou d'un bien, qui peut être une obligation de résultat ou de moyen ». Certains codes du monde proche-oriental ont adopté la résolution que la Cour de cassation française a prise en 1911 dans le domaine du transport de personnes, comme l'Egypte et le Liban. En 1956, la Cour d'Appel à Alexandrie a conformé l'obligation de sécurité dans le domaine du transport de personnes / This thesis focuses on the safety obligation regarding contractual liability in the light of French law and Libyan law. Research tends to answer the following questions: What is safety of medical products? On what legal basis can we justify that obligation? What are the difficulties in applying this requirement to address issues of health products? What is the health products? The law and civil liability Libya is it perfectly suited to the protection of the victim of health products as in the French liability law? This questioning has led the author to develop a thorough analysis of the safety obligation by way of contractual liability and health law French and Libyan. In the first part of the thesis, we see that the notion of bond security, including with respect to contractual liability, has experienced a major change from the time before. In fact, the emergence of the concept of safety obligation is old since it was founded in France 21 November 1911 at the contract of carriage. It can be defined as "the obligation to ensure the safety of any person or property which may be an obligation of result or means." Some codes of Near Eastern world have adopted the resolution that the French Supreme Court has taken in 1911 in the transportation of persons, such as Egypt and Lebanon. In 1956, the Appeal Court in Alexandria has complied with the requirement of safety in the transportation of persons. Similarly, in Lebanon in the Code of Obligations and Contracts provides in Article 688 that the contract of carriage of persons is the responsibility of the carrier's obligation to lead the traveler, unharmed, to the destination

Made available in DSpace on 2016-04-26T20:29:50Z (GMT). No. of bitstreams: 1 Everton Luiz Zanella.pdf: 738576 bytes, checksum: cb65e315a47b20be7656d15b7afbfe6a (MD5) Previous issue date: 2009-09-30 / The purpose of the present essay is to produce a critical analysis of the criminal system for transgressions against tax laws, reputed as lenient and deficient, and to demonstrate the need of a readjustment, in order to adapt it to the current constitutional order, indications the appropriate changes. Beginning with a review on the origins, evolution and features of the Democratic Rule of Law, adopted on the Federal Constitution of 1988 and rooted on values of democracy and human dignity, this essay will demonstrate the obsolescence of the Criminal Law and the inconsistency between it and the Federal Constitution, considering its inefficiency on fighting felonies against the rights of the society, as tax crimes. After such prior conjecture, I propose a restructuration of the criminal system by electing the most relevant legal goods, whose materiality derives from the Constitution, and the bestowed criminalization powers, i.e. the mandatory punishment of those human actions that harms collective goods of social importance, in the light of fundamental rights declared by the Federal Constitution. Within this scope, while selecting what should or shouldn t be penalized and how such penalization should be performed, it s presented a study about the proportionality principle and its twofold availability: the prevention against excesses, as a way to guarantee individual freedoms (negative actions of the State), and prevention against defective protection, in order to assure the proper State guardianship on restraining and punishing harmful actions against important legal goods (whose protection comes from criminalization powers). After that, comes a specific assessment of crimes against the economy (genre) and, in more details, of tax crimes (specie), which harm legal goods of utmost importance for society and hinder the achievement of the social justice aimed by the Democratic Rule of Law, which is characterized by the implementing of individual, social and collective rights. Finally, I prove that the current protection system against tax crimes is far from being efficient, mostly because of unjustifiable legal benefits granted to offenders, which are expanded by jurisprudence. This can be exemplified, for instance, by the extinction of punishableness for tax evaders, although unrepentant, after the enforced payment; as well as by the indulgence of the State, when refuses to file criminal charges against the tax evader, provided that a settlement is signed, or even by allowing the administrative discussion of the debt. These facts lead to the conclusion that the punishment system for such felonies contradicts the guidelines of the Constitution and need to be reconsidered, in order to allow an effective establishment of the Democratic Rule of the Law / O presente trabalho tem por objetivo realizar uma análise crítica do sistema punitivo nos crimes contra a ordem tributária, extremamente brando e deficiente, e demonstrar a necessidade de adequá-lo à ordem constitucional hoje vigente, indicando as mudanças cabíveis. Partindo de um estudo sobre a origem, a evolução e as características do Estado Democrático de Direito, adotado na Constituição Federal de 1988, radicado nos valores da democracia e da dignidade da pessoa humana, demonstra-se que o Direito Penal pátrio é ultrapassado e incompatível com a Constituição, por não combater de forma eficiente condutas criminosas de grande gravidade que afrontam direitos de toda a sociedade, como os crimes contra a ordem tributária. Dado este pressuposto, é feita uma proposta de relegitimação do sistema punitivo, através da abordagem da eleição dos bens jurídicos penalmente relevantes, os quais possuem carga valorativa constitucional, e dos mandados de criminalização, ou seja, da obrigatória penalização daquelas ações humanas que atentem contra os bens de maior relevância social, à luz dos direitos fundamentais previstos na Constituição Federal. Nesta seara, na busca da seleção sobre o que deve ou não ser penalizado e de que forma e intensidade deve ser concretizada esta penalização, é feito um estudo sobre o princípio da proporcionalidade e sua dupla face: proibição do excesso, como forma de garantir as liberdades individuais (atuação negativa do Estado), e proibição da proteção deficiente, com o objetivo de garantir a adequada prestação de tutela estatal para repressão e punição dos comportamentos lesivos aos bens jurídicos de maior importância (cuja proteção advém dos mandados de criminalização). Em continuidade, é feita uma análise específica sobre os delitos econômicos (gênero) e mais detidamente sobre os crimes contra a ordem tributária (espécie), que atingem bens jurídicos de extrema importância para toda a coletividade e impedem o alcance da almejada justiça social mirada pelo Estado Democrático de Direito, caracterizada pela efetivação dos direitos individuais, sociais, difusos e coletivos. Constata-se, afinal, que o sistema atual de proteção contra delitos tributários é bastante deficiente para combatê-los, em decorrência, sobretudo, de injustificáveis benesses previstas em lei e ampliadas pela jurisprudência, como a causa de extinção da punibilidade para os sonegadores, ainda que habituais, pelo simples pagamento, ainda que não espontâneo, do tributo sonegado, e o óbice à responsabilização penal do agente em decorrência do parcelamento do débito ou até mesmo da mera discussão do lançamento tributário na esfera administrativa, chegando-se à conclusão de que o mecanismo punitivo no tocante aos delitos estudados contraria o escopo constitucional e necessita ser alterado para permitir a real implementação do Estado Democrático de Direito

O presente trabalho visa apresentar um panorama geral a respeito da terceira espécie de inadimplemento no Direito brasileiro, considerando os esforços da doutrina e da jurisprudência em nosso sistema jurídico no trato deste tema, bem como considerando aspectos relevantes colhidos na experiência estrangeira. Na tentativa de contribuir para debate, será apresentada uma proposição para a identificação dessa terceira espécie de inadimplemento no Direito brasileiro. / The present work aims to present an overview regarding the third kind of default in Brazilian law, considering the efforts of the doctrine and of the jurisprudence in our legal system in dealing with this issue, as well as considering relevant aspects gathered from the experience of foreign law. In an attempt to contribute to debate, a proposition will be presented for the identification of this third kind of default in Brazilian law.

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O presente trabalho visa apresentar um panorama geral a respeito da terceira espécie de inadimplemento no Direito brasileiro, considerando os esforços da doutrina e da jurisprudência em nosso sistema jurídico no trato deste tema, bem como considerando aspectos relevantes colhidos na experiência estrangeira. Na tentativa de contribuir para debate, será apresentada uma proposição para a identificação dessa terceira espécie de inadimplemento no Direito brasileiro. / The present work aims to present an overview regarding the third kind of default in Brazilian law, considering the efforts of the doctrine and of the jurisprudence in our legal system in dealing with this issue, as well as considering relevant aspects gathered from the experience of foreign law. In an attempt to contribute to debate, a proposition will be presented for the identification of this third kind of default in Brazilian law.

Malgré les améliorations significatives apportées par la thérapie antirétrovirale à la durée et à la qualité de vie des personnes vivant avec le VIH, elle ne permet pas de complètement éliminer le virus de l’organisme. La persistance du virus est due à l’existence de réservoirs viraux, des cellules infectées de manière latente par le VIH. Ces réservoirs nécessitent un traitement antirétroviral à vie, car le virus réapparait en cas d’interruption du traitement, signifiant que l’immunité des cellules T spécifiques du VIH n’est pas restaurée. Bien que cela soit théoriquement possible, seule une fraction de personne vivant avec le VIH, appelée Contrôleurs Élites, parvient à contrôler le virus en absence de traitement. Pour la majorité des individus, l’infection par le VIH entraîne une évasion virologique ainsi qu’un épuisement et une altération des réponses cellulaires spécifiques au VIH. À ce jour, les stratégies thérapeutiques visant à éliminer les réservoirs viraux ont échoué, en partie en raison de la présence de provirus principalement défectifs dans ces réservoirs. Dans cette thèse, nous avons identifié et caractérisé les provirus défectifs latents du VIH pouvant être transcrits et/ou traduits, ainsi que la relation entre ces réservoirs et les réponses immunitaires spécifique du virus. Dans un premier temps, nous avons montré que bien que défectifs et potentiellement incapable de donner lieu à la réplication virale, ces provirus peuvent être transcrits et traduits soit par réactivation à l’aide d’agents de réversion de la latence, soit de manière spontanée. Ces réservoirs donnent lieu à plusieurs populations de réservoirs, en fonction de la présence ou de l’absence certains gènes viraux. Nous avons déterminé que ces différentes populations sont régies par le profil génomique des cellules infectées. Les provirus identifiés étaient très rarement intacts, mais l’intégrité du génome était associée à la processivité de la transcription et de la traduction. Dans un second objectif, nous avons caractérisé les réponses T CD4+ et CD8+ spécifiques du VIH avant et après le début du traitement antirétroviral. Nous avons observé que les réponses T CD4+ spécifiques étaient comparables pendant l’infection chronique et après le traitement. En revanche, les réponses T CD8+ diminuaient considérablement après l’initiation de la thérapie antirétrovirale. Nous avons également constaté que la taille du réservoir traductionnellement actif pendant le traitement antirétroviral était négativement associée aux réponses T CD8+ spécifiques avant le début de la thérapie, tandis que le réservoir incapable de traduire les protéines du VIH subsistait. Ces observations mettent en évidence le rôle des cellules T CD8+ dans le contrôle de l’infection par le VIH, comme nous l’avons observé chez les Contrôleurs Élites. Nos travaux contribuent à une meilleure compréhension des réservoirs viraux du VIH, qui pourraient potentiellement être impliqués dans l’inflammation chronique et la dysfonction immunitaire associé à la pathogénèse du VIH. / Despite the significant improvement brought by antiretroviral therapy in the duration and quality of life for people living with HIV, it does not completely eliminate the virus from the body. The persistence of the virus is due to the existence of viral reservoirs, which are cells latently infected with HIV. These reservoirs require lifelong antiretroviral treatment because of the viral rebound reoccurring in case of treatment interruption. This suggests that HIV-specific T cell immunity is not restored. Although theoretically possible, only a fraction of people living with HIV, known as Elite Controllers, are able to control the virus in the absence of treatment. For the majority of individuals, HIV infection leads to virologic escape, as well as exhaustion and altered cellular responses to HIV. To date, therapeutic strategies aimed at eliminating viral reservoirs have failed, partly due to the presence of predominantly defective proviruses in these reservoirs. In this thesis, we have identified and characterized latent defective proviruses of HIV that can be transcribed and/or translated. We also have characterized the relationship between these reservoirs and the specific immune responses to the virus. Firstly, we have shown that although defective and potentially replication-incompetent, these proviruses can be transcribed and translated either through reactivation using latency reversal agents or spontaneously. These reservoirs give rise to several populations of reservoirs, depending on the presence or absence of certain viral genes. We have determined that these different populations are governed by the genomic profile of infected cells. The identified proviruses were rarely intact, and genome integrity was associated with the processivity of transcription and translation. Then, we characterized the specific CD4+ and CD8+ T cell responses to HIV before and after the initiation of antiretroviral treatment. We observed that specific CD4+ T cell responses were comparable during chronic infection and after treatment. However, CD8+ T cell responses decreased significantly after the initiation of antiretroviral therapy. We also found that the size of the translationally active reservoir during antiretroviral treatment was negatively associated with the specific CD8+ T cell responses prior to treatment initiation, while the translation-incompetent cells persisted. These observations highlight the role of CD8+ T cells in the control of HIV infection, as observed in Elite Controllers. Our work contributes to a better understanding of HIV viral reservoirs, which could potentially be involved in chronic inflammation and immune dysfunction associated with HIV pathogenesis.

1 ABSTRACT CHVÁTALOVÁ, Daniela: Contract of Sale in Private Law. [Dissertation thesis]. Charles University. Faculty of Law; Department of Civil Law. Tutor: prof. JUDr. Jan Dvořák, CSc., Head of Department of Civil Law, Vice-Dean for the Doctoral Study Programme and Rigorosum Procedure. Level of professional qualification: Ph.D., Praha: PF UK, 2015. Key words: Civil Code No. 40/1964 Sb. Commercial Code No. 53/1991 Sb. Civil Code No. 89/2012 Sb. Principles of civil law. Purchase. Dual regulation. Precontracting negotiations. Offer and acceptance of the offer. Contract of sale. Purchase of personal property. Purchase of real property. Subject of the contract. Superficies solo cedit. Construction is a part of the land. Hardship clause. Purchase price and manner for determining the purchase price. Commercial terms and conditions. Decrease in a purchase price. Unreasonable decrease in the purchase price Laesio enormis. Price clause. Delivery of goods. Seller's delay in delivery of goods. Transfer of title. Rights in case of defective performance. Quality, quantity, type, and package. Rebus sic stantibus clause. Contractual penalty. Cancellation of a contract of sale. Sale of a plant. Advance payment and retainer. Supranational projects. Draft Common Frame of Reference (DCFR). Principles of European Contract Law...

L'activació sostinguda de Hog1 porta a una inhibició del creixement cel·lular. En aquest treball, hem observat que el fenotip de letalitat causat per l'activació sostinguda de Hog1 és parcialment inhibida per la mutació del complexe SCFCDC4. La inhibició de la mort causada per l'activació sostinguda de Hog1 depèn de la via d'extensió de la vida. Quan Hog1 s'activa de manera sostinguda, la mutació al complexe SCFCDC4 fa que augmenti l'expressió gènica depenent de Msn2 i Msn4 que condueix a una sobreexpressió del gen PNC1 i a una hiperactivació de la deacetilassa Sir2. La hiperactivació de Sir2 és capaç d'inhibir la mort causada per l'activació sostinguda de Hog1. També hem observat que la mort cel·lular causada per l'activació sostinguda de Hog1 és deguda a una inducció d'apoptosi. L'apoptosi induïda per Hog1 és inhibida per la mutació al complexe SCFCDC4. Per tant, la via d'extensió de la vida és capaç de prevenir l'apoptosi a través d'un mecanisme desconegut. / Sustained Hog1 activation leads to an inhibition of cell growth. In this work, we have observed that the lethal phenotype caused by sustained Hog1 activation is prevented by SCFCDC4 mutants. The prevention of Hog1-induced cell death by SCFCDC4 mutation depends on the lifespan extension pathway. Upon sustained Hog1 activation, SCFCDC4 mutation increases Msn2 and Msn4 dependent gene expression that leads to a PNC1 overexpression and a Sir2 deacetylase hyperactivation. Then, hyperactivation of Sir2 is able to prevent cell death caused by sustained Hog1 activation. We have also observed that cell death upon sustained Hog1 activation is due to an induction of apoptosis. The apoptosis induced by Hog1 is decreased by SCFCDC4 mutation. Therefore, lifespan extension pathway is able to prevent apoptosis by an unknown mechanism.