Les canaux calciques dépendants du voltage sont impliqués dans de nombreux processus cellulaires tels que la contraction musculaire, la libération des neurotransmetteurs et la régulation de l’expression génique. Ces canaux sont constitués d’une sous-unité canalaire α1, qui permet l’entrée des ions calciques dans le milieu intracellulaire, généralement associée à différentes sous-unités auxiliaires (α2δ, γ et β) qui régulent les fonctions du canal. La sous-unité auxiliaire β (Cavβ) joue un rôle capital dans l’adressage membranaire du canal et dans la régulation de ses propriétés biophysiques. Des études récentes décrivent cette sous-unité comme une protéine multifonctionnelle capable d’accomplir des fonctions indépendantes du canal. Quatre différentes isoformes de Cavβ sont codées par 4 gènes différents et caractérisées par des similarités structurales mais une distribution tissulaire différente. L’isoforme Cavβ4 est principalement exprimée dans le cerveau et le cervelet jouant ainsi un rôle important dans la régulation des courants calciques neuronaux. L’importance des fonctions neuronales de Cavβ4 a été soulignée par le fait que la mutation R482X de Cavβ4 a été associée à une forme d’épilepsie humaine.Mon travail de thèse a porté sur l’étude du rôle de Cavβ4 dans le contrôle de la division cellulaire et son implication dans la voie de signalisation Wnt. J’ai également étudié l’influence de la mutation R482X sur cette nouvelle fonction de Cavβ4.Dans ce but, des cellules CHO exprimant de manière stable Cavβ4 ou son mutant épileptique (Cavβ1-481) ont été générées et la localisation subcellulaire des deux protéines ainsi que leur implication dans la prolifération et la progression du cycle cellulaire ont été étudiées. Dans ces cellules, Cavβ4 subit une translocation nucléaire et se retrouve préférentiellement dans les nucléoles. Néanmoins, la délétion de 38 acides aminés de l’extrémité C-terminale de Cavβ4, correspondante à la mutation R482X, empêche sa translocation nucléolaire. L’expression de Cavβ4 réduit considérablement la capacité proliférative des cellules. Cette réduction semble être dépendante de la localisation nucléaire, voir nucléolaire de Cavβ4, parce que le mutant Cavβ1-481 n’induit aucune inhibition de la prolifération. D’un autre côté, l’expression de chacune de ces protéines entraine une modification du cycle cellulaire et l’altération de l’expression de certains gènes liés au cycle.Étant donné que la voie de signalisation Wnt/β-caténine est connue comme l'une des voies les plus importantes contrôlant la prolifération cellulaire, j’ai étudié l'effet de l’expression de Cavβ4 sur cette voie. J’ai ainsi pu montrer que Cavβ4, mais pas Cavβ1-481, réduit considérablement la transcription des gènes cibles de la β-caténine et ralenti la prolifération cellulaire. Cette inhibition est due à une interaction directe entre Cavβ4 et TCF4 qui empêche l’interaction de TCF4 avec la β-caténine et prévient la transcription des gènes cibles.L’ensemble de ces résultats suggèrent que Cavβ4 peut jouer un rôle dans le contrôle de la prolifération au cours du développement, en particulier dans les cellules neuronales. / The voltage gated calcium channels are involved in many cellular processes such as muscle contraction, neurotransmitter release and regulation of gene expression. These channels consist of the pore-forming subunit α1 usually associated with different regulatory subunits: α2δ, β and γ. The auxiliary subunit β (Cavβ) plays a key role in regulating membrane trafficking of the channel and its biophysical properties. Recent studies describe this subunit as a multifunctional protein that can also perform calcium channel-independent functions such as gene regulation. Four different isoforms of Cavβ are encoded by 4 different genes and are characterized by structural similarities but different tissue distribution. Cavβ4 isoform is mainly expressed in the brain and cerebellum, thus, playing an important role in the regulation of neuronal calcium currents. The importance of Cavβ4 neuronal functions has been highlighted by its R482X mutation that was associated to a form of human epilepsy.The aim of my thesis was to study the role of Cavβ4 in the control of cell division and its involvement in the Wnt signaling pathway. I also studied the influence of the R482X mutation on this new function of Cavβ4.To this end, CHO cells stably expressing Cavβ4, or its epileptic mutant (Cavβ1-481), were generated and the subcellular localization of the two proteins and their implication in the proliferation and cell cycle progression were studied. In these cells, Cavβ4 undergoes nuclear translocation and is found preferentially in the nucleoli. However, the deletion of 38 amino acids in the C-terminus domain of Cavβ4, corresponding to the R482X mutation, prevents its nucleolar translocation. In addition, the expression of Cavβ4 significantly reduces the proliferative rate of the cells. This reduction seems to be linked to Cavβ4 nuclear localization because the epileptic mutant is unable to slow down cell proliferation. On the other hand, the expression of each of these proteins is able to deregulate cell cycle progression and to alter the expression of many genes linked to the cycle.Since the Wnt/β-catenin pathway is known as one of the most important pathways controlling cell proliferation, I studied the effect of Cavβ4 expression on this signaling pathway. Indeed, Cavβ4, but not Cavβ1-481, substantially reduces the transcription of β-catenin-dependant genes and therefore slows down cell proliferation. This inhibition is due to a direct interaction between Cavβ4 and TCF4 that prevents the interaction of TCF4 with β-catenin, and thereafter negatively regulates the transcription of targeted genes.These findings suggest that Cavβ4 can play a role in the control of proliferation during development, particularly in neuronal cells.

La magnétocardiographie (MCG) et la magnétoencéphalographie (MEG) sont deux techniques d'imagerie non-invasives mesurant respectivement les champs magnétiques cardiaques et cérébraux. Les dispositifs actuels utilisent des capteurs supraconducteurs de haute performance mais nécessitant un dispositif de refroidissement cryogénique, engendrant de fortes contraintes tant techniques que financières. Les magnétomètres à pompage optique (OPM) tendent à constituer une réelle alternative. Parmi eux figurent ceux développés au CEA-LETI, basés sur l'utilisation de l'hélium 4. Cette thèse a pour objectif de développer des magnétomètres vectoriels à 4He (fonctionnant à température ambiante) dédiés aux applications MCG et MEG.Après une optimisation des paramètres-clés d'un prototype non-miniaturisé préexistant, une sensibilité inférieure à 100 fT/sqrt(Hz) a pu être obtenue suivant deux axes. Afin de respecter les besoins spécifiques de la MCG et de la MEG une étape de miniaturisation a dû être menée et une architecture gradient-métrique a été mise en place. Parallèlement, des tests précliniques menés à Clinatec nous ont permis de concevoir un nouveau conditionnement du prototype, ainsi qu'un système réduisant les perturbations magnétiques. Une analyse des principales sources de bruit a révélé que les deux principaux contributeurs au bruit sont le laser et le système de décharge HF. Nous avons ainsi envisagé plusieurs pistes d'amélioration du niveau de bruit dont une nouvelle technique de détection. Le prototype issu de ces travaux comporte une pièce élémentaire (la cellule) d'un centimètre de côté, et présente une sensibilité intrinsèque de 350 fT/sqrt(Hz).Le dispositif a ensuite été testé avec succès dans le cadre de mesures MCG sur un sujet sain, précédées de tests sur fantôme ayant permis de prouver l'opérabilité de nos capteurs dans un environnement clinique. Par ailleurs, la reproductibilité des résultats ainsi que la possibilité de réduire à 30 s le temps d'acquisition des données ont pu être démontrées. Une optimisation spécifique de la partie optique du prototype a permis d'obtenir une sensibilité de l'ordre de 210 fT/sqrt(Hz) entre 3 et 300 Hz, compatible avec l'application MEG. Après des tests menés avec succès sur fantôme, trois séries d'essais ont été réalisées sur un sujet sain. Nous avons pu ainsi détecter des potentiels évoqués auditifs, visuels ainsi qu'une modulation de l'activité cérébrale spontanée sous l'effet de l'ouverture des paupières. L'ensemble des résultats obtenus constitue les premières preuves de concept cliniques du dispositif en MCG et MEG. / Magnetocardiography (MCG) and magnetoencephalography (MEG) are non-invasive techniques consisting in measuring respectively cardiac and brain magnetic fields. Despite their performance, the sensors currently used need a cryogenic cooling system which engenders technical and financial constraints. New cryogenic-free sensors have recently emerged: the OPMs (Optically-Pumped Magnetometers). Among them, vector 4He magnetometers developed by CEA-LETI which work at room-temperature. This thesis is focused on the development of 4He magnetometers dedicated to MCG and MEG.After having optimized the key-parameters of a first non-miniaturized prototype, a sensitivity inferior to 100 fT/sqrt(Hz) has been obtained along two axes. In order to meet biomedical constraints, a miniaturization of the device has been processed. In parallel, preclinical tests were carried out which have enabled us to design a gradiometer mode, a new packaging, and a magnetically isolated system. A noise analysis revealed that laser and HF discharge were the main sources of disturbance, and lead us to consider improvements such as a new detection mode. Eventually, a sensor, with a 1cm-sided cell, and an intrinsic sensitivity of 350 fT/√Hz has been developed.Then, device has been successfully tested in the frame of the MCG application from a healthy subject, preceded by a simulation study with a phantom which enables us to demonstrate its operability within a clinical environment. Moreover, we have proved the reproducibility of the measurements and the possibility to detect the main features of the cardiac cycle within a 30 s recording time. A specific optimization of the optical part has enabled us to obtain a 210 fT/sqrt(Hz) sensitivity between 3 and 300 Hz, suitable for the MEG application. After having tested our device with a phantom, three MEG experiments were performed with a healthy subject: auditory evoked field, visual evoked field and spontaneous activities have been detected. The obtained results form the first clinical proof of concept of the device for MCG and MEG applications.

Orientador: Cleverton Roberto de Andrade / Resumo: O terpinen-4-ol (TP-4-ol) é um monoterpeno que constitui de 30-48% dos quimiotipos de óleos essenciais de plantas, como a Melaleuca alternifólia, laranjeira, pimenteira entre outras, apresentando propriedade anti-inflamatória, anticancerígena entre outras, caracterizadas como agentes quimiopreventivos e citoprotetores, respectivamente, contra as lesões com potencial de malignização e/ou malignas (LPMM) de língua e as hepato ou nefrotoxicidade. Sendo assim, o objetivo de nosso estudo foi avaliar o TP-4-ol quanto às propriedades quimiopreventivas sobre LPMM de língua e citoprotetoras ou citotóxicas sobre o fígado e rim de ratos quimicamente induzidos por óxido de 4-nitroquinolina (4-NQO). Além disso, avaliamos o TP-4-ol quanto ao seu potencial indutor de hepato e nefrotoxicidade em ratos saudáveis. Os 64 ratos foram divididos aleatoriamente para o experimento de 16 semanas, nos grupo 1 ratos saudáveis ou grupo 2 ratos oncológicos de língua (n=8) e os grupos de intervenções com [g/Kg de TP-4-ol] ratos saudáveis tratados [0,035] do grupo 3 e [0,0035] grupo 4, ratos oncológicos tratados [0,035] do grupo 5 e [0,0035] grupo 6 (n=12). Foram analisados os parâmetros biométricos (peso do corpo, língua, fígado e rim; consumo de água e ração); bioquímicos do fígado (alanina aminotransferase, aspartato aminotransferase, fosfatase alcalina) e rim (ureia e creatinina); macroscópicos da língua (tamanho e lesões fundamentais), fígado e rim (tamanho); e microscópicos da língu... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

L'étude du comportement sous incendie des bétons a particulièrement pris son essor depuis des incendies répétés de tunnels comme celui sous la Manche ou du Mont-Blanc. La problématique de résistance au feu est essentielle puisque les éclatements qui peuvent accompagner la diminution de résistance du matériau sont de nature à fragiliser fortement les structures. Depuis plusieurs décennies, le domaine de la résistance au feu des bétons ordinaires et à hautes performances a été exploré tant expérimentalement que théoriquement. Cependant il existe des matériaux plus récents, que sont les bétons fibrés à ultra performances (BFUP), pour lesquels le phénomène d'instabilité thermique est accentué et dont le comportement mécanique à chaud n'a pas été beaucoup exploré. L'étude menée ici a pour vocation de s'intéresser à un BFUP particulier, le BCV®, fourni par l'entreprise Vicat. Les résultats exposés permettent de mieux comprendre l'efficacité des fibres de polypropylène face aux autres fibres synthétiques, grâce à une approche expérimentale originale complétée par une étude à l'échelle microscopique. Cette dernière est constituée de nombreuses analyses au microscope électronique à balayage ainsi que d'études de porosimétrie au mercure. Cette première phase est suivie d'un vaste programme de caractérisations mécaniques à chaud sur le BCV® à des températures variant de 20°C à 1100°C, essais peu courants pour ce genre de matériau. Ce travail contribue à la compréhension du comportement des BFUP à haute température, et montre que l'évolution avec la température de leurs caractéristiques mécaniques principales (résistance en flexion, résistance en compression et module d'élasticité) est assez semblable à celle des bétons ordinaires. Les résultats de cette étude contribuent à une meilleures connaissance du comportement à haute température des bétons fibrés à ultra performances. / Study of concrete behaviour under fire has really increased since the occurence of several fires in tunnels such as the Chunnel or the Mont-Blanc tunnel. Fire resistance of concrete is a very important subject because the possible spalling coupled with a decrease of the strength of the material can deeply weaken the structures. For decades the fire resistance field of ordinary concrete and high performance concrete was studied experimentally and theorically. However more recent materials such as ultra-high performance fibre reinforced concrete (UHPFRC), for which spalling phenomenon is emphasized and whose high temperature mechanical behaviour has not been studied so much. The present study is aimed to study a particular UHPFRC, the BCV®, supplied by Vicat. The results enable to better understand the effenciency of polypropylene fibres compared to other synthetic fibres, thanks to an original experimental approach coupled with a study at the microscopic scale. The latter consists in various scanning electron microscope analysis and mercury intrusion porosimetry. This first part is followed by a wide number of experimental results which characterize the mechanical behaviour of BCV® for a range of temperatures from 20°C to 1100°C. Experiments in such testing conditions are not common for this material. The work achieved contributes to a better understanding of the high performance behaviour of UHPFRC. It reveals also that the evolution with temperature of main mechanical characteristics (bending strength, compression strength and Young Modulus) is really close to those of ordinary concretes. The results of this study contributes to a better knowledge of ultra-high performance fibre reinforced concrete under high temperature.

Personal informatics are important tools in health self-management as they support individuals to quantify and self-reflect on their lifestyle. Human-computer interaction researchers have devoted resources on studying how to design such tools. Various motivational strategies have been explored for their capabilities in improving user engagement. However, such strategies are developed with an assumption that the targeted consumer of information is the one directly manipulating user interfaces of the system that has information. This may not always be the case for users in developing regions. As a result, such systems may not scale well in contexts where a targeted consumer (beneficiary) may use technology through the facilitation of another person (intermediary) whom is responsible for manipulating user interfaces, because such facilitators are not recognized as part of the system, hence motivational strategies don't cater for them. In order to uncover design implications for intermediated technology use in the context of personal health informatics (PHI), the researcher started with the theoretical framing of the work followed by a contextual enquiry which led to development of mobile applications' prototypes for tracking nutrition and physical activity. Evaluation of the prototypes revealed that a familial relationship is a prerequisite for such an intervention. The most promising combination involves family members, possibly a child and a parent working together. The study used self-determination theory to understand how a collaborative gamified system can increase engagement. The result revealed that gamification as the source of a significant increase in perceived competence in intermediary users whom also tended to consider themselves as co-owners of the interaction experience. Therefore, gamification was found to be a catalyst for increasing collaboration between an intermediary and beneficiary user of technology, provided that the two users that formed a pair had a prior social relationship. In the absence of gamification, intermediary users tended to be less engaged in the intervention. The study highlights both the positive and negative aspects of gamification in promoting collaboration in intermediated use and its general implications in health settings. Design considerations required in order to improve the overall user experience of both users involved are proposed. In general, this work contributes to both theory and empirical validation of factors for, supporting proximate-enabled intermediated use of personal health informatics.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-07-31T19:16:12Z No. of bitstreams: 2 thiago_coimbra_pimenta.pdf: 3361101 bytes, checksum: 026e379b14e8e90fdfd54a1c94b5e25d (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-08-14T15:21:20Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) thiago_coimbra_pimenta.pdf: 3361101 bytes, checksum: 026e379b14e8e90fdfd54a1c94b5e25d (MD5) / Made available in DSpace on 2017-08-14T15:21:20Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) thiago_coimbra_pimenta.pdf: 3361101 bytes, checksum: 026e379b14e8e90fdfd54a1c94b5e25d (MD5) Previous issue date: 2017 / A Dengue ? uma doen?a infecciosa viral de transmiss?o vetorial pelo mosquito Aedes aegypti, cujo controle tem se mostrado de solu??o complexa. Al?m disso, o diagn?stico cl?nico ? dif?cil de ser realizado, principalmente na fase aguda da doen?a, em que os sintomas s?o muito similares aos de outras infec??es febris agudas, e por essa raz?o o desenvolvimento de m?todos de detec??o mais efetivos para o seu controle, ganha relev?ncia. M?todos moleculares est?o sendo cada vez mais utilizados para o diagn?stico precoce por serem mais r?pidos e sens?veis. Nesse sentido, o uso de biossensores ganha relev?ncia por serem dispositivos vers?teis, de f?cil constru??o e utiliza??o, sens?veis e seletivos. Combinado com o uso de pol?meros modificadores da superf?cie transdutora, o que favorece a etapa de imobiliza??o das biomol?culas, os biodispositivos assim constru?dos se mostram mais sens?veis devido ? compatibilidade das caracter?sticas do elemento biol?gico e do filme polim?rico. Desta forma, este trabalho visou desenvolver um imunossensor impedim?trico para diagn?stico de Dengue utilizando eletrodos impressos de grafite (EI) funcionalizados com filmes polim?ricos derivados do ?cido 4-aminofenilac?tico (4-AFA). O imunossensor baseou-se na intera??o espec?fica entre o ant?geno da Dengue, a prote?na NS1, e os anticorpos anti-NS1. No estudo de caracteriza??o por voltametria c?clica (VC) da plataforma funcionalizada, observou-se que o filme polim?rico formado apresentou dois picos de oxida??o em +0,17 e +0,35 V em meio de solu??o de ?cido sulf?rico 0,50 M, o que mostra sua adsor??o e eletroatividade na superf?cie do eletrodo. Medidas de espectroscopia de imped?ncia eletroqu?mica (EIE) mostraram maior resist?ncia ? transfer?ncia eletr?nica do EI modificado com o filme polim?rico quando comparado ao EI sem modifica??o, corroborando o estudo anterior. Para o estudo de melhor concentra??o de NS1 para imobiliza??o, verificou-se que 1,00 ng/mL apresentou melhor sinal anal?tico, devido ? diminui??o nas intera??es que ocorre entre os ant?genos. O tempo de imunorrea??o entre ant?geno (Ag) e anticorpo (Ac) tamb?m foi estudado, no qual observou-se que o tempo ideal para que ocorra a imunocomplexa??o foi de 20 minutos. Em seguida, foi realizado estudo de dilui??o dos soros positivos e negativos por EIE, no qual foi poss?vel observar, para o soro positivo, que quanto mais dilu?do o soro maior foi o valor de Rct encontrado. O soro negativo tamb?m apresentou sinal anal?tico, provavelmente devido ? presen?a de anticorpos n?o espec?ficos, por?m, o sinal gerado apresentou valores mais pr?ximos do sinal da NS1, mostrando a seletividade da plataforma proposta. O estudo foi repetido em eletrodo sem modifica??o a fim de verifica a import?ncia do filme polim?rico na constru??o do biossensor. Observou-se que quando a NS1 ? imobilizada ao eletrodo n?o modificado, o Rct aumento muito pouco quando comparado ao eletrodo modificado com o filme derivado do 4-AFA, o que mostra a efici?ncia e sensibilidade da plataforma proposta. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / Dengue is a viral infectious disease transmitted by the Aedes aegypti mosquito, whose control has shown a complex solution. In addition, the clinical diagnosis is difficult to perform, especially in the acute phase of the disease, in which the symptoms are very similar to other acute febrile infections, and for this reason the development of more effective detection methods for its control gains relevance. Molecular methods are being increasingly used for early diagnosis because they are faster and more sensitive. In this sense, the use of biosensors gains relevance because they are versatile devices, of easy construction and use, sensitive and selective. Combined with the use of transducing surface modifying polymers, which favors a stage of immobilization of the biomolecules, the biodevices constructed in this way are more sensitive due to the compatibility of the biological element characteristics and the polymer film. Thus, this work aimed to develop an impedimetric immunosensor to Dengue diagnose using screen-printed electrode (SPE) functionalized with polymer films derived from 4-aminophenylacetic acid (4-APA). The immunosensor was based on the specific interaction between Dengue antigen, NS1 protein, and anti-NS1 antibodies, IgG e IgM. In characterization study by cyclic voltammetry (CV) of the functionalized platform, it has been observed that the polymer film shown two oxidation peaks in +0.17 and +0.35 V in 0,5 M sulfuric acid solution medium, which shows its adsorption and electroactivity at the SPE surface. Electrochemical impedance spectroscopy (EIS) measurements has shown a higher charge transfer resistance to the polymer film modified SPE when compared to the non-modified SPE, corroborating the previous study. For the study of NS1 best concentration to immobilization, it has been verified that 1,00 ng/mL presented better analytical signal, due to the decrease of the interactions that occur between the antigens. Immunoreaction time between antigens (Ag) and antibody (Ab) has also been studied, in which it has been observed that the ideal time for immunocomplexation was 20 minutes. Afterwards, a positive and negative sera dilution study was carried out by EIE, in which it has been possible to observe, for the positive serum, that the more diluted the serum the greater the Rct found. The negative serum also presented analytical signal, probably due to the presence of non-specific antibodies, however, the generated signal presented values closer to the NS1 signal, showing the selectivity of the proposed platform. The study was repeated in electrode without modification in order to verify the importance of the polymeric film in the biosensor construction. It was observed that when NS1 is immobilized to the non-modified electrode, Rct increases very little when compared to the 4-AFA derived film modified electrode, which shows the efficiency and sensitivity of the proposed platform.

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-09-08T13:27:28Z No. of bitstreams: 1 Dissertação-Tâmara V. Reis 2010.pdf: 19348303 bytes, checksum: b427ed6600aabe45a3f60838670def9b (MD5) / Approved for entry into archive by Vanessa Reis (vanessa.jamile@ufba.br) on 2016-09-08T13:44:47Z (GMT) No. of bitstreams: 1 Dissertação-Tâmara V. Reis 2010.pdf: 19348303 bytes, checksum: b427ed6600aabe45a3f60838670def9b (MD5) / Made available in DSpace on 2016-09-08T13:44:47Z (GMT). No. of bitstreams: 1 Dissertação-Tâmara V. Reis 2010.pdf: 19348303 bytes, checksum: b427ed6600aabe45a3f60838670def9b (MD5) / CNPq / O presente trabalho descreve o isolamento e a identificação estrutural de metábolitos secundários do extrato hexânico obtido do caule da espécie de Kielmeyera coriacea Mart. (Clusiaceae) (pau-santo) - coletada na Chapada Diamantina, entre os municípios de Mucugê e João Correia (fevereiro de 2006) – bem como a avaliação antibacteriana dos extratos hexânico e acetato e, das substâncias isoladas; avaliação helminticida do extrato acetato e avaliação da citotoxicidade dos extratos hexânico e acetato. Os caules foram submetidos a extrações com hexano e em seguida com acetato de etila. O fracionamento do extrato hexânico e o isolamento das substâncias foram realizados através de cromatografia em coluna de sílica. As identificações das substâncias foram realizadas através de métodos espectrométricos, tais como Ressonância Magnética Nuclear de 1H e de 13C (incluindo DEPT 135° e NOEDIF). Os extratos hexânico e acetato do caule foram avaliados quanto às suas propriedades antibacterianas contra bactérias Gram-positivas Staphylococcus aureus, Bacillus subtillis, Streptococcus mutans, Micrococcus luteus e Gram-negativas Pseudomonas aeruginosa, Escherichia coli e Salmonella choleraesuis, e helminticida contra Schistosoma mansoni. Do extrato hexânico foram isoladas e identificadas as seguintes substâncias: os neoflavonóides ponalídeo, isomammeigina e isomesuagina; uma mistura contendo os neoflavonóides mammea A/AB ciclo D (MAB), mammeigina e mesuagina; as xantonas 6-desidroxiisojacareubina e nigrolinea F; o triterpeno lupenona e os esteróides β-sitosterol e β-sitostenona. Apenas os neoflavonóides mesuagina e ponalídeo ainda não tinham sido isolados no gênero Kielmeyera e, o neoflavonóide isomesuagina ainda não havia sido encontrado como produto natural, tendo sido relatado apenas como produto de síntese. Os extratos exibiram baixa atividade frente às bactérias Gram positivas e o extrato acetato exibiu alto efeito helminticida e baixo valor para a ED50. As substâncias isoladas não exibiram atividade antibacteriana nas concentrações testadas / This paper describes the isolation and structural identification of secondary metabolites present in hexane extract obtained from Kielmeyera coriacea Mart. (Clusiaceae) (pau-santo) stem species - collected in Chapada Diamantina, in between Mucugê and João Correia towns (February 2006) – as well as the antibacterial evaluation of acetate and hexane extracts and the isolated compounds; helminthicidal evaluation of acetate extract and cytotoxicity evaluation of hexane and acetate extracts. The stems underwent extraction with hexane followed by ethyl acetate. The hexane extract cracking and compounds isolation was achieved by means of column chromatography using silica as stationary phase. Identification of compounds was performed by the use of spectrometric methods such as NMR 1H and 13C (including DEPT 135° and NOEDIF). The hexane and acetate extracts were evaluated as to their antibacterial properties against Gram-positive Staphylococcus aureus, Bacillus subtilis, Streptococcus mutans, Micrococcus luteus as well as Gram- negative Pseudomonas aeruginosa, Escherichia coli, Salmonella choleraesuis and helminthicidal against Schistosoma mansoni. From hexane extract the following compounds were isolated and identified: the neoflavonoids ponnalide, isomammeigin and isomesuagin; a mixture containing mammea A / AB cyclo D (MAB), mammeigin and mesuagin neoflavonoids; the xanthones 6-desidroxiisojacareubin and nigrolinea F; lupenone triterpene and the steroids β-sitostenone and β-sitosterol. Mesuagin and ponnalide neoflavonoids were the only ones which had not been isolated in the genus Kielmeyera and isomesuagin neoflavonoids had not been found as natural products yet, which have been reported as a synthesis product, only. The extracts showed low activity against Gram positive bacteria while acetate extract showed high helminthicidal activity and low ED50 values. The compounds did not show any antibacterial activity for evaluation concentrations.

Lors de certains scénarios accidentels, percement de cuve de réacteur avec entrée d’air, dénoyage de piscinesde manutention, de stockage ou d’entreposage de combustibles usés, ou encore certains accidents de transport,les assemblages combustibles des Réacteurs à Eau Pressurisée (REP), peuvent se retrouver privés de leurrefroidissement et exposés à l’air. Dans ces conditions, la température des assemblages s’élève et les gaines descrayons combustibles, en alliage à base de zirconium, s’oxydent. Par rapport à une oxydation sous vapeur, lavitesse de dégradation des gaines est beaucoup plus élevée, d’une part à cause de l’enthalpie élevée de laréaction zirconium-oxygène, comparée à la réaction zirconium-vapeur d’eau, et d’autre part parce que l’azotecontribue à la dégradation. Des phénomènes d’emballement sont attendus qui peuvent rapidement conduire à laperte de la fonction de confinement assurée par les gaines.L’objectif de cette thèse a été d’affiner la compréhension des mécanismes d’oxydation sous air à hautetempérature des deux alliages de zirconium les plus utilisés dans les REP français, le Zircaloy-4 et le M5®, et depréciser le rôle de l’azote.Des tronçons de gaines vierges de Zircaloy-4 et M5® ont été oxydés dans une thermobalance sous air enconditions isothermes à des températures comprises entre 800°C et 1000°C. Plusieurs techniquesexpérimentales (spectroscopie micro-Raman, EPMA, DRX, microscopies optique et électronique à balayage…)ont été mises en oeuvre pour caractériser les couches d’oxyde. La formation et l’évolution des différentes phasesqui composent ces couches (zircone monoclinique, quadratique et cubique, oxynitrure de zirconium et ZrN) ontainsi pu être mises en évidence et analysées en fonction de l’avancement de l’oxydation. Des mécanismesd’oxydation ont été proposés, et la résistance à l’oxydation plus importante de l’alliage M5® par rapport auZircaloy-4 a été expliquée.Les informations recueillies permettront d’alimenter des modèles visant à prédire le comportement des gaineslors de l’oxydation en situation accidentelle avec entrée d’air (transitoire de température, composition évolutive dela phase gazeuse…). / In nuclear plants, some accidental situations can result in air exposure of Pressurized Water Reactor (PWR) fuelassemblies: air ingress following a breach in the reactor vessel, deflooding during handling, spent fuel storagepool deflooding. Deprived of cooling source, the assemblies temperature raises and the fuel cladding, made out ofzirconium based alloys, oxidize. Compared to a steam oxidation, the degradation kinetic of the cladding is higher,on the one hand because of the high enthalpy of the zirconium-oxygen reaction (compared to zirconium-steamreaction), on the other hand because of the nitrogen contribution to the degradation. Temperature escalation andreaction runaway are expected and can rapidly lead to the loss of integrity of the cladding tubes.The objective of this PhD thesis was to affine the understanding of the high temperature air oxidation mechanismsof the two mostly used zirconium alloys in French PWR, Zircaloy-4 and M5®. Special attention has been paid toclarify the role of nitrogen.As-received Zircaloy-4 and M5® claddings segments have been oxidized in a thermobalance in air in isothermalconditions at temperatures between 800°C and 1000°C. Several characterization techniques (micro-Ramanspectroscopy, EPMA, XRD, optical and scanning electron microcopies...) have been used to analyze the oxidelayers. Identification and evolution of the different phases (monoclinic, tetragonal and cubic zirconia, zirconiumoxynitride and ZrN) has been evidenced and analyzed at several step of the oxidation process. Oxidationmechanisms have been proposed and the better oxidation resistance of the M5® alloy, compared to Zircaloy-4alloy, has been explained.The collected information will allow improvement of modeling aiming to predict the behavior of the claddings invarious accidental situations with air ingress (temperature transients, evolution of the gas phase composition…).

Orientador: Luiz Claudio Di Stasi / Resumo: A Doença Inflamatória Intestinal é uma doença crônica, cuja patogênese envolve uma interação complexa de fatores múltiplos. Entre os novos compostos estudados para o tratamento da inflamação intestinal, a 4-metilesculetina (4-ME) apresentou potentes atividades antioxidante e anti-inflamatória intestinal, porém estudos mais detalhados sobre o mecanismo de ação das cumarinas são necessários. Neste trabalho, foram verificados que os tratamentos com a 4-ME preveniram a depleção dos níveis de glutationa total, diminuíram a atividade de mieloperoxidase e glutationa peroxidase (GPX), preveniram a diminuição da atividade de glutationa redutase (GSR) e glutationa S-transferase. Além disso, os tratamentos com a 4-ME preveniram a redução da abundância relativa de RNAm de γ-glutamil transferase 1, glutationa redutase e fator nuclear eritroide 2 relacionado ao fator 2 causada pela inflamação intestinal. A investigação da interação entre a 4-ME e GSR, GPX ou proteína inibitória κB (IkB) mostrou que a 4-ME interage com a GSR e IkB por um processo predominantemente estático, enquanto a interação entre a 4-ME e GPX ocorre por um processo dinâmico. As forças de van der Waals e as pontes de hidrogênio possuem papel fundamental na formação e na estabilização do complexo GSR/4-ME, por outro lado interações hidrofóbicas determinam as interações da 4-ME com a GPX e a IkB. Adicionalmente, os resultados indicam que o grupo metila do carbono C-4 é o segundo epítopo mais próximo na interação GSR/4-ME. ... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Made available in DSpace on 2014-12-17T14:08:49Z (GMT). No. of bitstreams: 1 VilmaAC_DISSERT_PARCIAL.pdf: 283414 bytes, checksum: 221724a56ff323c23efa132cc9f62484 (MD5) Previous issue date: 2011-02-03 / Crude oil has between 0.04 up to 5% of sulphur, the higher the oil the higher the sulphur levels. Sulphur usually gives problems such as corrosion in refinery, and once burnt produces SO2 that goes to atmosphere. This work aim to investigate the capacity of Rhodococcus rhodochrous (NRRL B-2149) to metabolize the model compound 4-methyldibenzotiophene (4-MDBT), to remove the sulphur and transform it in 2-hydroxybiphenyl (2-HBF) and sulphite using the 4S pathway. Kynetic runs were carried out in shaker at 120 rpm and 32?C. Samples were taken every 12h to assay substrate consume as well as cells production using HPLC. Results showed that R. rhodochrous NRRL B-2149 can use the 4S pathway in order to remove sulphur without change the carbon chain of the molecule as well as that cells and 4-MDBT affects the product formation. The production of 2-hydroxybiphenyl has interest for industry once it is a potent biocide. However, evaluation is necessary in order to obtain better results compatible with industry needs / O petr?leo bruto convencional cont?m entre 0,04 a 5% de enxofre, e em geral ?leos mais densos apresentam teores mais elevados. Embora pequena, esta fra??o ? importante e sua presen?a torna-se indesej?vel, tanto por promover a corros?o do equipamento da refinaria, como porque parte dela persiste na composi??o dos derivados, que, ao serem queimados, liberam di?xido de enxofre (SO2) para a atmosfera. Este ? um dos principais poluentes atmosf?ricos, respons?vel pelas chuvas ?cidas. O presente trabalho teve como objetivo avaliar a capacidade da cepa Rhodococcus rhodochrous (NRRL B-2149) em metabolizar o composto modelo 4-metildibenzotiofeno (4-MDBT), remover-lhe o ?tomo de enxofre e convert?-lo em 2-hidr?xibifenil (2-HBF) e sulfito utilizando a via sulf?xido-sulfona-sulfonato-sulfato ( 4S ), sem reduzir significativamente seu poder calor?fico. Para essa avalia??o foi realizado um estudo cin?tico em incubador rotativo sob agita??o de 120 rpm e 32?C. As amostras foram retiradas em intervalos de 12 h para an?lise da concentra??o celular e consumo de substrato e quantificadas por cromatografia l?quida. Os resultados mostraram que a cepa de R. rhodochrous NRRL B-2149 ? capaz de utilizar a Via 4S para remover o enxofre do composto sem contudo, alterar sua cadeia carb?nica e que a concentra??o de c?lulas e de 4-MDBT interferem na forma??o do produto 2-HBF. A produ??o do 2-hidroxibifenil detectada neste estudo ? de grande relev?ncia j? que ele ? um biocida potente de interesse industrial. No entanto, avalia-se condi??es dos ensaios visando obter concentra??es vi?veis para amplia??o industrial / 2020-01-01