Le cancer du col de l'utérus est le troisième cancer le plus fréquent chez la femme, dont l'agent étiologique majeur est l'infection par les papillomavirus humain (notamment HPV-16 et 18), qui sont de petits virus infectant les épithéliums muqueux et cutanés, et pouvant induire la formation de tumeurs. L'inducteur majeur du processus oncogène est le processus d'intégration des régions codantes pour les oncoprotéines E6 et E7, au sein de la cellule hôte suite à l'infection. Elles interférent avec le cycle cellulaire et induisent notamment l'immortalisation, voire la transformation des cellules. Les fonctions les plus connue de ces deux oncoprotéines sont la dégradation des suppresseurs de tumeur p53 et pRb, respectivement. Mon travail de thèse à consisté en la mise au point des vecteurs adénoviraux exprimant des miARN dirigés contre l'oncoprotéine E6. Exprimés in vitro ils induisent l'induction de la mort cellulaire par apoptose des cellules tumorales traitées, via l'activation de la voie de caspases, et in vivo permettent le ralentissement de la croissance de tumeurs xénogreffées à des souris Nude. De plus, la stratégie thérapeutique adénovirale a montré ses extensions possibles sur d'autres types de cancers HPV-positifs, mais également via l'expression de différentes moléculaires thérapeutiques, visant à empêcher l'interaction des oncoprotéines telles qu'E6 avec leurs partenaires cellulaires et ainsi les empêcher d'exercer les activités biologiques impliquées dans le développement de cancers. Pour finir, les adénovirus peuvent également être vu comme des outils d'extinction fonctionnels d'E6 et permettant d'étudier les répercutions sur d'autres processus cellulaires.

Résumé Le premier article de la thèse se veut une revue systématique des données empiriques mettant en lumière les antécédents à la base de l’émergence du leadership narcissique dans les organisations, ses composantes psychologiques ainsi que ses incidences tant pour les organisations que pour leurs membres. Conséquemment, cette étude brosse initialement une recension détaillée des principaux facteurs idiosyncrasiques, culturels, environnementaux et structurels participant à la manifestation du leadership narcissique dans les organisations. Par la suite, elle en sonde la teneur en isolant l’existence de cinq composantes psychologiques, soit le charisme, l’influence intéressée, la motivation fallacieuse, l’inhibition intellectuelle et la considération simulée. Enfin, elle souligne les conséquences négatives de son actualisation dont les principales sont : la production de prises de décisions volatiles et risquées; la création d’un climat organisationnel toxique; la destruction de la confiance des subordonnés; la détérioration de l’efficacité organisationnelle; l’émergence d’une gestion dysfonctionnelle; et la manifestation de comportements non-éthiques. Le deuxième article s’avère une analyse comparative de deux types de leadership se révélant, de prime abord, trompeusement analogues. Ces deux types sont le leadership transformationnel et le leadership narcissique. Quoique se situant aux antipodes en matière de satisfaction de besoins (influence idéalisée versus influence intéressée), de promotion de visions (motivation inspirationnelle versus motivation fallacieuse), de réceptivité à la rétroaction d’autrui (stimulation intellectuelle versus inhibition intellectuelle) et de traitement des relations interpersonnelles (considération individualisée versus considération simulée), les leaderships transformationnel et narcissique partagent entre eux un élément commun : le charisme du leader. C’est précisément cette dernière caractéristique, conférant à son détenteur un puissant halo magnétisant, qui se révèle le creuset de la spéciosité du leadership narcissique opérant essentiellement lors des tout premiers contacts avec le leader. En fait, le charisme du leader narcissique sert en quelque sorte de fard, composé de charme et de fascination, masquant une décevante réalité psychologique et dont les propriétés captieuses s’étiolent rapidement. Le troisième article de la thèse est une étude conceptuelle examinant la structuration idiosyncrasique des criminels en col blanc ayant commis des fraudes financières se chiffrant à plusieurs dizaines de millions de dollars. Exploitant le croisement des deux dimensions fondamentales de l’agression, soit sa fonction (proactive ou réactive) et sa forme (directe ou indirecte), cette étude propose une taxonomie archétypique de différents types de psychopathie susceptible de mieux cerner la psychologie du criminel en col blanc d’envergure. L’agression est dite proactive lorsqu’elle est motivée par des impératifs de prédation indépendants de l’état émotionnel de l’individu. L’action de l’individu prédateur est intentionnelle et instrumentale. Elle vise l’atteinte d’objectifs préétablis avant l’actualisation de l’agression. Par contre, elle est considérée réactive lorsque la préservation de l’intégrité physique ou psychologique de l’individu est l’objet d’une menace émergeant de son environnement externe immédiat. Dans ce cas, la réaction agressive de l’individu est émotionnellement conditionnée. Par ailleurs, nonobstant la nature de sa fonction, l’agression peut s’exprimer directement ou indirectement. Elle est considérée directe lorsqu’elle a pour cible l’agressé en tant que tel. La forme physique d’agression peut être physique (sévices corporels) ou verbale (menaces et insultes). Par contre, lorsqu’elle emprunte des modes d’expression plus subtils, tels les rumeurs, l’humour malicieux et la tromperie, l’agression est dite indirecte. Le pairage des deux dimensions fondamentales de l’agression permet la construction d’un modèle d’analyse bidimensionnelle englobant quatre types de psychopathie, à savoir les psychopathies parasitique (préservation indirecte), colérique (préservation directe), cynégétique (prédation directe) et sympathique (prédation indirecte). C’est précisément cette dernière forme de psychopathie, le type sympathique caractérisé par un étaiement idiosyncrasique narcissico-machiavélique, qui traduit le mieux la psychologie des criminels en col blanc d’envergure. Enfin, le quatrième et dernier article de la présente thèse se propose d’explorer une problématique de recherche n’ayant reçu que très peu d’attention de la part des membres de la communauté scientifique, à savoir l’examen de l’adéquation d’un modèle dimensionnel du narcissisme pathologique inspiré du modèle développé par Roche, Pincus, Lukowitsky, Ménard et Conroy (2013). Au moyen d’une étude de cas exploratoire, il a été possible d’associer la vulnérabilité narcissique au segment décompensatoire (échec des stratégies inadaptées d’agrandissement de soi) du modèle théorique inspiré de celui de Roche et al. (2013) et ce, conformément à ses prescriptions. En effet, la comparaison des résultats de l’un des deux participants de l’étude, madame H, obtenus lors des deux saisies de données espacées d’un intervalle d’une année, indique une diminution de la vulnérabilité narcissique lors de la période de re-compensation. En outre, cette diminution est accompagnée de celle de la grandiosité narcissique. En somme, la relation positive entre les deux dimensions du narcissisme pathologique se révèle, sur un plan longitudinal, constante dans les deux segments – compensatoire (recours à des stratégies inadaptées d’agrandissement de soi) et décompensatoire – du modèle théorique inspiré de celui de Roche et al. (2013). Par ailleurs, les résultats obtenus auprès des deux participants à l’étude de cas, monsieur B et de madame H, s’avèrent éclairants eu égard à la prépondérance respective de chacune des dimensions (grandiosité et vulnérabilité) narcissiques en fonction des segments compensatoire et décompensatoire du modèle théorique inspiré de celui de Roche et al. (2013). Se trouvant en mode de compensation narcissique lors des deux saisies de données, monsieur B affiche une grandiosité narcissique supérieure à sa vulnérabilité narcissique. Cette constatation respecte en tous points les prescriptions théoriques du modèle. Quant à madame H, qu’elle soit en mode de compensation ou de décompensation narcissique (postulat non démontré eu égard aux prescriptions du modèle théorique utilisé), sa vulnérabilité narcissique demeure constamment plus élevée que sa grandiosité narcissique. Théoriquement, selon les prescriptions du modèle, la prépondérance devrait être observée chez la dimension « grandiosité narcissique » en période de compensation. De toute évidence, les données obtenues auprès de madame H s’écartent de ces prescriptions. / The first article of the thesis offers a systematic review of the empirical data highlighting the precursors to the emergence of narcissistic leadership in organizations, its psychological components, as well as its impact on both organizations and their members. Accordingly, this study begins by compiling a detailed list of the main idiosyncratic, cultural, environmental and structural factors at play in the manifestation of narcissistic leadership in organizations. It then explores their nature by identifying the existence of five psychological components: charisma, self-interested influence, deceptive motivation, intellectual inhibition and simulated consideration. Finally, it underscores the negative consequences of the emergence of narcissistic leadership, including, notably: the production of volatile and risky decision making; the creation of a toxic organizational climate; the destruction of subordinates’ trust; the degradation of organizational effectiveness; the emergence of dysfunctional management; and the manifestation of unethical behaviour. The second article proposes a comparative analysis of two types of leadership that appear at first glance to be deceptively similar. These two types of leadership are transformational leadership and narcissistic leadership. Although diametrically opposed in terms of the satisfaction of needs (idealized influence versus self-interested influence), the promotion of visions (inspirational motivation versus deceptive motivation), the receptiveness to feedback (intellectual stimulation versus intellectual inhibition) and the treatment of interpersonal relations (individualized consideration versus simulated consideration), transformational and narcissistic leadership share a common element: the charisma of the leader. This charisma places a powerful, magnetic halo on the head of the leader and it is precisely this characteristic that is the crucible of the deceptive attractiveness of narcissistic leadership that is felt upon the very first contact with the leader. In fact, the narcissistic leader’s charisma serves as a sort of mask that combines charm and fascination to conceal a disappointing psychological reality and whose attractive qualities quickly fall away. The third article of the thesis is a conceptual study of the idiosyncratic patterns of white-collar criminals who have committed fraud in the tens of millions of dollars. Based on the intersection of the two basic dimensions of aggression – i.e., its function (proactive or reactive) and its form (direct or indirect), this study proposes an archetypal taxonomy of the different types of psychopathy with a view to gaining a better understanding of the psychology of large-scale white-collar criminals. Aggression is said to be proactive when it is motivated by predatory imperatives that are independent of the individual’s emotional state. The action taken by the predatory individual is intentional and instrumental. Its aim is to meet predetermined objectives prior to the actualization of the aggressive behaviour. On the other hand, it is considered reactive when the preservation of the individual’s physical or psychological integrity is threatened by the immediate, external environment. In this case, the individual’s aggressive reaction is emotionally conditioned. Moreover, notwithstanding the nature of its function, aggression can be expressed directly or indirectly. It is considered direct when it targets the victim specifically. The form of the aggression can be physical (bodily injury) or verbal (threats and insults). On the other hand, when it is expressed in more subtle forms, such as rumours, malicious jokes and deception, the aggression is said to be indirect. Pairing the two main dimensions of aggression allows for the construction of a two-dimensional model of analysis encompassing four types of psychopathy, namely: parasitic psychopathy (indirect preservation), choleric psychopathy (direct preservation), cynegetic psychopathy (direct predation) and sympathetic psychopathy (indirect predation). It is precisely this last form of psychopathy – the sympathetic form characterized by a narcissistic and Machiavellian underpinnings idiosyncratic – that best reflects the psychology of large-scale white-collar criminals. Finally, the fourth and last article of this thesis proposes to explore a research problem that has received very little attention from members of the scientific community, namely how adequate is a dimensional model of pathological narcissism based on the model developed by Roche, Pincus, Lukowitsky, Ménard and Conroy (2013). On the basis of exploratory case study, it was possible to link narcissistic vulnerability to decompensatory segment (failure of maladaptive self-enhancement strategies) of this model. This linkage conforms to the hypothesis of the model. Indeed, the results of one of two study participants, Ms. H, indicate a decrease of narcissistic vulnerability in the re-compensatory period. Furthermore, this decrease is accompanied by a decrease of narcissistic grandiosity. In others words, on a one year longitudinal plane, the positive relationship between the two dimensions (narcissistic grandiosity and vulnerability) of pathological narcissism is found to be constant in two segments – compensation (use of maladaptive self-enhancement strategies) and decompensation – of the theoretical model based on the model of Roche et al. (2013). Moreover, the results for two study participants, Mr. B and Ms. H, prove to be enlightening according to respective preponderance of each narcissistic dimension of theoretical model based on the model developed by of Roche et al. (2013). In tests in 2012 and in 2013, Mr. B displays greater narcissistic grandiosity greater than narcissistic vulnerability, and was deemed to be in compensatory mode. This observation conforms to the hypothesis of the model. As for Ms. H, her narcissistic vulnerability remains consistently much higher than her narcissistic grandiosity. Theoretically, whether she is in narcissistic compensatory or decompensatory mode (unproven assumption in view of the theoretical model used), narcissistic vulnerability should only be dominant in the period of decompensation. Obviously, the results of Ms. H do not conform to the model.

Le virus du papillome humain (HPV) est l’infection sexuellement transmise la plus fréquente au monde. Plusieurs études ont établi son implication dans l’étiologie de pratiquement tous les cancers du col de l’utérus, une maladie qui constitue un problème de santé majeur dans les pays pauvres. Le HPV est également responsable de 90% des cancers de l’anus, 40-50% des cancers du pénis, de la vulve et du vagin, et 30% des cancers de la tête et du cou. L’objectif général de cette thèse est de combler les lacunes relatives aux connaissances sur la distribution génotypique du HPV dans les lésions néoplasiques cervicales utérines et de la tête et du cou, plus particulièrement en Afrique. Les objectifs spécifiques sont les suivants: 1) analyser la distribution génotypique du HPV dans les cancers du col de l’utérus et faire une analyse comparative de cette distribution dans cinq pays africains en fonction de la prévalence du VIH; 2) évaluer la présence du HPV dans les cancers de la tête et du cou au Sénégal; 3) faire une revue de la littérature et une méta-analyse sur la distribution du HPV dans les cancers de la tête et du cou dans toutes les régions du monde. Pour le premier et le second objectifs, qui découlent d’un large projet international coordonné par l’Institut Catalan d’Oncologie pour l’Organisation Mondiale de la Santé (OMS), une étude transversale multicentrique a été menée au Mali et au Sénégal pour collecter des blocs de paraffine de patientes diagnostiquées entre 2001 et 2010 du cancer invasif du col et des cancers de la tête et du cou. Pour le troisième objectif, une revue exhaustive de la littérature a permis d’identifier tous les articles qui ont été publiés sur les cancers de la tête et du cou dans tous les pays du monde et d’effectuer une méta-analyse sur la prévalence de l’ADN du HPV selon le site du cancer et la région géographique. Notre analyse montre que les principaux types de HPV ciblés dans les vaccins prophylactiques (HPV16/18) représentent la majorité des types de HPV détectés dans le cancer invasif du col de l’utérus en Afrique subsaharienne. Par contre, le HPV45 vient au second rang dans certains pays d’Afrique, dont le Mali et le Sénégal. Nos données suggèrent également que le VIH aurait un rôle dans la contribution relative du HPV18 et HPV45 dans le développement du cancer du col de l’utérus. Au Sénégal, notre étude montre que la prévalence du HPV dans les cancers de la tête et du cou est très faible et ne semble pas jouer un rôle important dans l’oncogenèse. Finalement, la méta-analyse a mesuré la prévalence des HPV dans les cancers de la cavité orale, de l’oropharynx, du larynx et de l’hypopharynx, et confirme l’importante contribution relative du HPV16 dans ces cancers. Globalement, cette thèse permet de mieux comprendre l’impact potentiel des vaccins prophylactiques sur l’incidence des cancers associés au HPV. / Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Several studies have shown its involvement in the etiology of virtually all cancers of the cervix, which is a major health problem in poor countries. HPV is also responsible for 90% of anal cancers, 40-50% of penile, vulvar and vaginal cancers, and 30% of head and neck cancers. The overall objective of this thesis is to fill the gaps in knowledge on the genotype distribution of HPV in anogenital and head and neck neoplasia, especially in sub-Saharan Africa. The specific objectives are to: 1) analyze HPV genotype distribution in cervical cancer and compare this distribution in five African countries according to HIV prevalence; 2) evaluate the presence of HPV in cancers of the head and neck in Senegal; 3) review the literature on the distribution of HPV in cancers of the head and neck in all regions of the world and perform a meta-analysis. For the first and second objectives, which were derived from a larger international project coordinated by the Catalan Institute of Oncology for the World Health Organization (WHO), a cross-sectional multicentric study was conducted to collect paraffin-embedded blocks of invasive cervical cancer and head and neck cancer diagnosed between 2001 and 2010 in Mali and Senegal. For the third objective, a comprehensive search of the literature was conducted to identify all articles published to date on head and neck cancer. A meta-analysis was performed to estimate the prevalence of HPV DNA according to cancer site and geographical region. Our analysis shows that the main HPV types targeted in the prophylactic vaccines (HPV16/18) accounted for the majority of the HPV types found in invasive cervical cancer in sub-Saharan Africa. Our data also suggests that HIV may play a role in the contribution of HPV18 and HPV45 to the development of cervical cancer. However, HPV45 ranks second in many African countries, notably in Mali and Senegal. In Senegal, our study shows that HPV DNA prevalence in head and neck cancer is very low and is not importantly involved in the oncogenesis. Finally, the meta-analysis measured the prevalence of HPV in cancers of the oral cavity, oropharynx, larynx and hypopharynx, and confirmed the significant relative contribution of HPV16 in these cancers. Overall, this thesis contributes to a better understanding of the potential impact of HPV prophylactic vaccines on the incidence of HPV-associated cancers.

La present tesi tracta d’aprofundir en el coneixement dels orígens del pactisme valencià. És per això que analitza de forma exhaustiva les diverses negociacions politicofiscals que tingueren lloc entre la monarquia i la comunitat política del regne de València des de mitjan segle XIII fins a la dècada de 1360. Així, tot plegat, estudia la trajectòria d’unes transformacions estretament imbricades entre si: d’una banda, el progressiu desenvolupament de la pràctica parlamentària fins a esdevenir la principal forma de resolució de greuges entre els estaments i el monarca, i, d’una altra banda, l’evolució de la fiscalitat reial i local fins a donar lloc a uns sistemes fiscals generals i municipals que quedaren controlats pels dirigents estamentals. D’aquesta manera, mitjançant l’anàlisi d’aquells canvis, es determinen amb major detall les fases i les característiques del procés de configuració del pactisme al territori valencià. / The purpose of this thesis is to deepen the knowledge on the origins of Valencian pactism. In order to achieve that, it analyzes exhaustively the various political/fiscal negotiations that took place between the monarchy and the political community of the kingdom of Valencia from the mid-thirteenth century until the 1360’s. It is, therefore, a study on the history of transformations closely imbricated in each other: on the one hand, the gradual development of the parliamentary practice until it became the main way for resolving grievances between the king and the estates of the realm and, on the other hand, the evolution of the royal and local taxation to general and local fiscal systems that were controlled by the heads of the estates. Thus, by means of analyzing these changes, the different stages and characteristics of the configuration process of pactism in the kingdom of Valencia can be more precisely determined.

L’ oncoprotéine E6 - qui joue un rôle crucial dans le processus d’oncogenèse induit par les papillomavirus a longtemps résisté à toute analyse. Depuis 1995 l’équipe Oncoprotéines a concentré ses efforts sur cette problématique. Ce qui a permis la résolution par RMN de la structure du domaine C-terminal de E6 en 2006. C’est dans ce cadre que j’ai commencé ce Doctorat en 2008, avec objectif de continuer la quête de données structurales sur E6 tout en acquérant des informations sur ses modes d’interaction avec ses cibles cellulaires. Les travaux de cette thèse ont permis l’obtention de la structure cristallographique de E6 (HPV16) en complexe avec un peptide de E6AP, en utilisant une approche originale capable de produire des protéines E6 stables et solubles. Cette structure constitue la première information structurale publiée sur des protéines E6 entières, attendue depuis plus de 20 ans par la communauté scientifique. J’ai effectué également durant cette thèse une analyse du système d’interaction de la protéine E6 basée sur une large étude d’interaction entre les protéines E6 (7 types) et 93 peptides porteurs de motif LxxLL. / The oncoprotein E6 which plays a crucial role in the process of carcinogenesis induced by HPV, has withstood all tests for a long time. Since 1995 the team « oncoproteins » has focused on this issue. This allowed the resolution of structure of C-terminal domain of E6 by NMR analysis, in 2006. In this context, i started my PhD in 2008 with aim to continue the pursuit of structural data on E6 while also acquiring information about its modes of interaction with its cellular targets. The work of this thesis has enabled us to obtain the crystal structure of E6 (HPV16) in complex with a peptide of E6AP, using an original approach capable of producing stable and soluble proteins E6. This structure represents the first structural information on full-length E6, awaited for over 20 years by the scientific community. I also performed during this thesis an analysis of the interaction system of the E6 protein based on a large study of interaction between proteins E6 (7 types) and 93 peptides bearing LxxLL motif.

Made available in DSpace on 2014-12-17T14:13:48Z (GMT). No. of bitstreams: 1 AcariliaES_TESE.pdf: 9221805 bytes, checksum: 71876e327362584aeb9dcac7d3652c4d (MD5) Previous issue date: 2013-04-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit? S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB / Esta tese teve como objetivo o desenvolvimento de novos sistemas de libera??o para duas mol?culas distintas. Na primeira parte, micropart?culas ? base de xilana e Eudragit? S-100 foram produzidas para encapsular ?cido 5-aminosalic?lico visando ? libera??o c?lonespec?fica. A xilana foi extra?da de sabugos de milho e caracterizada quanto ?s suas propriedades f?sico-qu?micas, reol?gicas e toxicol?gicas. Em seguida, dois m?todos de microencapsula??o foram utilizados: reticula??o interfacial polim?rica e secagem por aspers?o. Os sistemas produzidos foram caracterizados quanto ? morfologia, tamanho m?dio e distribui??o, estabilidade t?rmica, cristalinidade, taxa de encapsula??o e libera??o do f?rmaco in vitro. Foram obtidas micropart?culas com adequadas caracter?sticas f?sicas e rendimentos satisfat?rios atrav?s dos dois m?todos, embora os sistemas aspergidos tenham apresentado maior estabilidade t?rmica e sejam considerados mais interessantes devido a sua maior estabilidade t?rmica e aus?ncia de agentes t?xicos. No entanto, ajustes precisam ser feitos para melhorar a encapsula??o e libera??o do f?rmaco. Na segunda parte, microemuls?es do tipo ?leo em ?gua (MEs O/A) com base em triglicer?deos de cadeia m?dia (MCT) foram produzidas visando ao carreamento de anfotericina B (AmB) e aumento da sua solubilidade. Foram obtidas MEs O/A sem e com AmB com got?culas em torno de 80 e 120 nm, respectivamente, e ?ndices de polidispers?o de 0,25 e 0,31, respectivamente. A taxa de incorpora??o da AmB foi alta e dependente do volume da fase dispersa. A viabilidade celular n?o foi afetada at? 25 μg/mL da AmB. Portanto, MEs O/A a partir de MCT podem ser promissores sistemas de libera??o para AmB

Made available in DSpace on 2015-02-24T19:48:44Z (GMT). No. of bitstreams: 1 SilvanaPPG_TESE_pag119_final.pdf: 4384081 bytes, checksum: f4e3889e03bd2b77ef4e8f1b271723a8 (MD5) Previous issue date: 2012-08-06 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / The Northeast relief was described by the Pediplanation Model. This action discards the theoretical basis of post-Cretaceous tectonic evolution of the landscape. Through this model the Massif Pereiro - MP, Borborema Province, was established as part of the Tablelands Area Residual Sertanejos. The present work aims to establish the post- Cretaceous morphotectonic evolution of the MP by geomorphological and geological mapping using Geographic Information System, Remote Sensing and dating of sediments by Single Aliquot Regenerative-dose (SAR). The MP is contained in the core semi-arid, annual precipitation of 600-800 mm / year. The MP is NE-SW, is limited by Shear Zone Jaguaribe (ZCJ) and Portalegre Shear Zone (ZCPa), the same attitude, and crossed by several other shear zones. These shear zones show evidence of brittle Cenozoic reactivation, mostly as normal faults and shallow crustal level. The Quaternary sedimentation around the MP focuses on fault escarpments in a general pattern cascade, where ages decrease from the summits of the steep foothills. The ages of 51 sediment samples indicate a correlation with global climate following pulses: Last Interestadial-UI, the Last Glacial Maximum - LGM and the transition Pleistocene / Holocene, while the latter focus on 18 of 51 samples dated. This study also finds evidence of a new quaternary basin, here called Merejo Basin. Through these results it is concluded that no evidence of post-Cretaceous tectonic evolution of morphological MP, as their retreat along the fault scarps, invariably following the trend of the shear zones. The erosion of cliffs in large time scale is controlled by weakness zones generated by faults on the other hand the erosion of cliffs in short time, with the formation of deposits and colluvial horizons pedogenizados, has climate control. It was also found that in the study area there is a preponderance of past and current tectonic erosion processes on the morphological evolution / O relevo do Nordeste foi descrito por meio do modelo de pediplana??o. Esta base te?rica descarta a atua??o da tect?nica p?s-cret?cea na evolu??o da paisagem. Atrav?s deste modelo o Maci?o do Pereiro MP, Prov?ncia Borborema, foi definido como parte do Dom?nio dos Planaltos Residuais Sertanejos. O presente trabalho tem por objetivo estabelecer a evolu??o morfotect?nica p?s-cret?cea do MP, atrav?s da cartografia geol?gica e geomorfol?gica com uso de Sistema de Informa??o Geogr?fica, Sensoriamento Remoto e data??o de sedimentos por Single Aliquot Regenerative-dose (SAR). O MP est? contido no n?cleo semi?rido, de precipita??o anual entre 600 a 800 mm/ano. O MP tem dire??o NE-SW, ? limitado pela Zona de Cisalhamento de Jaguaribe (ZCJ) e Zona de Cisalhamento Portalegre (ZCPa), de mesma atitude, e atravessado por v?rias outras zonas de cisalhamento. Estas zonas de cisalhamento apresentam evid?ncias de reativa??o fr?gil cenozoica, na sua maioria como falhas normais e de n?vel crustal raso. A sedimenta??o quatern?ria em torno do MP se concentra em escarpas de falhas, em um padr?o geral em cascata, onde as idades diminuem das cimeiras aos sop?s das escarpas. As idades de 51 amostras de sedimentos indicam correla??o com seguintes pulsos clim?ticos globais: ?ltimo Interestadial- UI, o ?ltimo M?ximo Glacial - UMG e a transi??o Pleistoceno/Holoceno, sendo que nesta ?ltima concentram-se 18 das 51 amostras datadas. O presente trabalho tamb?m encontra evid?ncias de uma nova bacia quatern?ria, aqui denominada de Bacia Merejo. Atrav?s destes resultados conclui-se que h? evidencia de tect?nica p?s-cret?cea na evolu??o morfol?gica do MP, pois as suas escarpas recuam paralelamente ?s falhas, seguindo invariavelmente o trend das zonas de cisalhamento. A eros?o das escarpas em grande escala de tempo ? controlada pelas zonas de fraqueza geradas pelos falhamentos, por outro lado ? eros?o das escarpas em curtos espa?os de tempos, com a forma??o dos dep?sitos coluvionares e horizontes pedogenizados, possui controle clim?tico. Concluise ainda que na ?rea de estudo haja a preponder?ncia da tect?nica pret?rita e atual sobre os processos erosivos na evolu??o morfol?gica

Made available in DSpace on 2015-03-03T15:47:46Z (GMT). No. of bitstreams: 1 LeonardoCTB_DISSERT.pdf: 2119704 bytes, checksum: 5bdd21de8bfa668bba821593cdd5289f (MD5) Previous issue date: 2011-02-07 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Multi-objective combinatorial optimization problems have peculiar characteristics that require optimization methods to adapt for this context. Since many of these problems are NP-Hard, the use of metaheuristics has grown over the last years. Particularly, many different approaches using Ant Colony Optimization (ACO) have been proposed. In this work, an ACO is proposed for the Multi-objective Shortest Path Problem, and is compared to two other optimizers found in the literature. A set of 18 instances from two distinct types of graphs are used, as well as a specific multiobjective performance assessment methodology. Initial experiments showed that the proposed algorithm is able to generate better approximation sets than the other optimizers for all instances. In the second part of this work, an experimental analysis is conducted, using several different multiobjective ACO proposals recently published and the same instances used in the first part. Results show each type of instance benefits a particular type of instance benefits a particular algorithmic approach. A new metaphor for the development of multiobjective ACOs is, then, proposed. Usually, ants share the same characteristics and only few works address multi-species approaches. This works proposes an approach where multi-species ants compete for food resources. Each specie has its own search strategy and different species do not access pheromone information of each other. As in nature, the successful ant populations are allowed to grow, whereas unsuccessful ones shrink. The approach introduced here shows to be able to inherit the behavior of strategies that are successful for different types of problems. Results of computational experiments are reported and show that the proposed approach is able to produce significantly better approximation sets than other methods / Problemas de otimiza??o combinat?ria multiobjetivo apresentam caracter?sticas peculiares que exigem que t?cnicas de otimiza??o se adaptem a esse contexto. Como muitos desses problemas s?o NP-?rduos, o uso de metaheur?sticas tem crescido nos ?ltimos anos. Particularmente, muitas abordagens que utilizam a Otimiza??o por Col?nias de Formigas t?m sido propostas. Neste trabalho, prop?e-se um algoritmo baseado em col?nias de formigas para o Problema do Caminho mais Curto Multiobjetivo, e compara-se o algoritmo proposto com dois otimizadores encontrados na literatura. Um conjunto de 18 inst?ncias oriundas de dois tipos de grafos ? utilizado, al?m de uma metodologia espec?fica para a avalia??o de otimizadores multiobjetivo. Os experimentos iniciais mostram que o algoritmo proposto consegue gerar conjuntos de aproxima??o melhores que os demais otimizadores para todas as inst?ncias. Na segunda parte do trabalho, uma an?lise experimental de diferentes abordagens publicadas para col?nias de formigas multiobjetivo ? realizada, usando as mesmas inst?ncias. Os experimentos mostram que cada tipo de inst?ncia privilegia uma abordagem algor?tmica diferente. Uma nova met?fora para o desenvolvimento deste tipo de metaheur?stica ? ent?o proposta. Geralmente, formigas possuem caracter?sticas comuns e poucos artigos abordam o uso de m?ltiplas esp?cies. Neste trabalho, uma abordagem com m?ltiplas esp?cies competindo por fontes de comida ? proposta. Cada esp?cie possui sua pr?pria estrat?gia de busca e diferentes esp?cies n?o tem acesso ? informa??o dada pelo ferom?nio das outras. Como na natureza, as popula??es de formigas bem sucedidas tem a chance de crescer, enquanto as demais se reduzem. A abordagem apresentada aqui mostra-se capaz de herdar o comportamento de estrat?gias bem-sucedidas em diferentes tipos de inst?ncias. Resultados de experimentos computacionais s?o relatados e mostram que a abordagem proposta produz conjuntos de aproxima??o significativamente melhores que os outros m?todos

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-02-03T22:09:09Z No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-02-04T20:35:03Z (GMT) No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) / Made available in DSpace on 2016-02-04T20:35:03Z (GMT). No. of bitstreams: 1 JonasIvanNobreOliveira_TESE.pdf: 11177037 bytes, checksum: 2b572f71c5a1ab5e1c3a798571af4fed (MD5) Previous issue date: 2015-02-26 / Esta tese trata de duas pesquisas no campo da modelagem molecular, com diferentes naturezas conceituais, por?m, baseadas em semelhantes princ?pios te?ricos da f?sica qu?ntica e da qu?mica computacional. No primeiro estudo, com o intuito de esclarecer os aspectos estruturais e energ?ticos da estabilidade da tripla-h?lice do col?geno humano, foram quantificadas as energias de intera??o entre os res?duos de amino?cidos que comp?em o pept?deo homotrim?rico T3-785, por interm?dio de c?lculos de Mec?nica Qu?ntica na luz da Teoria do Funcional da Densidade (DFT) e do m?todo de Fracionamento Molecular com Capuzes Conjugados (MFCC). Assim, as for?as de atra??o e repuls?o de cada um dos 90 res?duos que comp?em o sistema foram assinadas e as regi?es com alta/baixa estabilidade identificadas e comparativamente analisadas. Os dados obtidos aprofundaram as discuss?es sobre a estabilidade conformacional do col?geno. Na segunda pesquisa, propriedades de transporte eletr?nico de dois modelos biol?gicos foram exploradas. Nesse sentido, 27 miRNAs associados ao autismo e pept?deos formados pelas sequ?ncias (Thr-Ala)n e (Ala-Lys)n tiveram suas curvas de corrente-voltagem (I x V) calculadas. Os c?lculos computacionais foram parcialmente executados pelo m?todo qu?ntico DFT e, fundamentalmente, dentro de um modelo tight-binding, em conjunto com a t?cnica de matriz de transfer?ncia. No caso dos miRNAs, os resultados sugerem que um tipo de biosensor pode ser desenvolvido para distinguir diferentes tipos de autismo. J? os pept?deos analisados, demonstraram-se como bons candidatos para a constru??o de um diodo molecular. Ambos os resultados podem fundamentar e estimular pesquisas experimentais com essas biomol?culas no campo da nanoeletr?nica.

Made available in DSpace on 2014-12-17T15:07:04Z (GMT). No. of bitstreams: 1 MariaASM.pdf: 63217 bytes, checksum: 05be60dbf83ca4b7d547db7cb4c02508 (MD5) Previous issue date: 2008-04-14 / This work has as objective generality to make a multidimensional analysis in the genre journalistic assay, communicative genre that, beyond complex and multimodal, presents hybrid characteristics. Specifically, with the intention to propose defining criteria of the cited genre, this research looks for to establish differences and similarities between the assay and other genres of the same sphere, from the description and interpretation of used multimodal resources. The analysis of the formal, schematical and rhetorical resources identified in the formatting of the journalistic assay sample that the analyses are supported in the socio-semiotic and socio-rhetorical approaches. In the formal dimension, we contemplate elements that constitute design of the text, including the forms of representation from the typography, the colors, images, as well as the aspects communicative-linguistics: the modalization indices, the communicative operators and the category time; in the schematical dimension, we present the organizational structure, considering the rhetorical movements postulates for Swales (1990) and in the rhetorical dimension we observe the categories: who writes, for who it writes, on what it writes and where writes. The adopted methodologicals postulates are of qualitative nature and the procedure is documentary, data that in we are valid them written texts of this genre as analysis object. Corpus it is constituted by a composed sample for 14 extracted texts of a set of 173 propagated journalistic assays weekly for the magazine Veja, in the period between August of 2004 and January of 2008. The analysis of the data showed that the journalistic assay, object of this study, materializes through multiple symbolic representations and multiple subjects that turn since a small episode of the daily facts of great social relevance in the present time, of historical and cultural nature, nationwide or international. Used for the first time by Montaigne in 1580, to assign, in saying of the proper author, written fast on its life and historical events, which could nor be remembered later , the term `assay' was enriched with other specifications, of form to enclose the one that if they call scientific assay today, academic assay, journalistic assay and other types of specific assays. These denominations have to see with the enrollment of the members of diverse of practices communities, in virtue of the multiplicity of activities carried through in these spheres. The conclusions the one that we arrive had been the following ones: 1. the discursive genre is not a pure entity, in virtue of the multiplicity of situations where the sorts if insert in the social actions; 2. the institutions define the configuration of one definitive genre, also its proper assignment, since for backwards of all discursive genre a voice exists to discipline - institutional voice, and in the case of the assays for analyzed us, the institutional voice if it presents, really, as a defining trace; 3. the journalistic assay, for its multiple symbolic representations, multiple subjects and for passing explicit or implicit opinions of its author, resembles it other genres, being able, therefore, to be inserted in a colony of opinionatives genres / Este trabalho tem como objetivo geral fazer uma an?lise multidimensional no g?nero ensaio jornal?stico, g?nero discursivo que, al?m de complexo e multimodal, apresenta caracter?sticas h?bridas. Especificamente, com o intento de propor crit?rios definidores do referido g?nero, esta pesquisa procura estabelecer diferen?as e semelhan?as entre o ensaio e outros g?neros da mesma esfera, a partir da descri??o e interpreta??o de recursos multimodais utilizados. A an?lise dos recursos formais, esquem?ticos e ret?ricos identificados na formata??o do ensaio jornal?stico mostra que as an?lises se enquadram nas abordagens s?cio-semi?ticas e s?cio-ret?ricas. Na dimens?o formal, contemplamos elementos que constituem o design do texto, incluindo as formas de representa??o a partir da tipografia, das cores, imagens, bem como os aspectos ling??stico-discursivos: ?ndices de modaliza??o, os operadores discursivos e a categoria tempo; na dimens?o esquem?tica, apresentamos a estrutura organizacional, considerando os movimentos ret?ricos postulados por Swales (1990) e na dimens?o ret?rica observamos as categorias: quem escreve, para quem escreve, sobre o que escreve e onde escreve. Os postulados metodol?gicos adotados s?o de natureza qualitativa e o procedimento ? documental, dado que nos valemos de textos escritos desse g?nero como objeto de an?lise. O corpus ? constitu?do por uma amostra composta por 14 textos extra?dos de um conjunto de 173 ensaios jornal?sticos veiculados semanalmente pela revista Veja, no per?odo entre agosto de 2004 e janeiro de 2008. A an?lise dos dados mostrou que o ensaio jornal?stico, objeto desse estudo, materializa- se atrav?s de m?ltiplas representa??es simb?licas e m?ltiplos temas que versam desde um pequeno epis?dio do cotidiano a fatos de grande relev?ncia social na atualidade, de natureza hist?rica e cultural, de ?mbito nacional ou internacional. Empregado pela primeira vez por Montaigne em 1580, para designar, no dizer do pr?prio autor, escritos ligeiros sobre sua vida e sobre acontecimentos hist?ricos, os quais poderiam nem ser lembrados depois , o termo ensaio foi enriquecido com outras especifica??es, de forma a abranger o que se denominam hoje ensaio cient?fico, ensaio acad?mico, ensaio jornal?stico e outros tipos de ensaios espec?ficos. Essas denomina??es t?m a ver com o engajamento dos membros de comunidades de pr?ticas diversas, em virtude da multiplicidade de atividades realizadas nessas est?ncias. As conclus?es a que chegamos foram as seguintes: 1. o g?nero discursivo n?o ? uma entidade pura, em virtude da multiplicidade de situa??es em que os g?neros se inserem nas a??es sociais; 2. as institui??es definem a configura??o de um determinado g?nero, inclusive a sua pr?pria designa??o, visto que por tr?s de todo g?nero discursivo existe uma voz disciplinar a voz institucional e, no caso dos ensaios por n?s analisados, a voz institucional se apresenta, realmente, como um tra?o definidor; 3. o ensaio jornal?stico, por suas m?ltiplas representa??es simb?licas, m?ltiplos temas e por passar opini?es expl?citas ou impl?citas do seu autor, assemelha-se a outros g?neros, podendo, portanto, ser inserido em uma col?nia de g?neros opinativos