Made available in DSpace on 2017-07-24T19:38:04Z (GMT). No. of bitstreams: 1 Mariana Negrelli.pdf: 2632259 bytes, checksum: 8ffb18e87e90aff84b82a1268dc4596f (MD5) Previous issue date: 2011-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work describes the conformational analysis of cis/trans ethyl-2 hydroxycyclohexanecarboxylate. For this, were analyzed data obtained by ab initio theoretical calculations, the nuclear magnetic resonance spectroscopy (coupling constants 3JHH) and infrared (carbonyl stretch). Were performed calculations for the isolated molecule and calculations with solvation routines to assess the conformational preference in different ways. With the aid of maps of electrostatic potential, was possible to observe the main negative centers where are located the reactive sites involved in organic synthesis. According to the calculations of NBO was analyzed how interactions affect the stability of each conformation. The compounds cis/trans ethyl-2-hydroxycyclohexanecarboxylate presented each, two preferred conformers, which were observed by both theoretical calculations and IR. The NMR spectroscopy was very useful because with the use of the same was possible to characterize the majority conformer of each equilibrium. / Neste trabalho é apresentado o estudo conformacional do cis/trans-2-hidroxicicloexanocarboxilato de etila. Para tanto, foram realizadas análises a partir de dados obtidos pelos cálculos teóricos ab initio e pelas espectroscopias de ressonância magnética nuclear (constantes de acoplamento 3JHH) e na região do infravermelho (estiramento da carbonila). Foram realizados cálculos para a molécula isolada bem como cálculos com rotinas de solvatação, para avaliar a preferência conformacional em diferentes meios. Com o auxílio de mapas de potencial eletrostático, foi possível observar os principais centros negativos onde estão localizados os sítios reativos envolvidos em sínteses orgânicas. Pelos cálculos de NBO, foi analisado como as interações afetam a estabilidade de cada conformação. Os compostos cis/trans-2-hidroxicicloexanocarboxilato de etila apresentaram cada um, dois confôrmeros preferenciais, os quais foram observados tanto pelos cálculos teóricos como por IV. A espectroscopia de RMN foi muito útil, pois com o emprego da mesma foi possível caracterizar o confôrmero majoritário de cada equilíbrio.

A Mucopolissacaridose tipo IVA (MPS IVA), é uma doença lisossômica de depósito ocasionada pela degradação deficiente dos glicosaminoglicanos (GAG) queratan sulfato e condroitin-6-sulfato devido à deficiência da enzima N-acetilgalactosamina 6-sulfatase. Como a fisiopatologia desta doença ainda não está totalmente elucidada e muitos estudos vêm demonstrando o envolvimento do estresse oxidativo e inflamação na patogênese de outros tipos de mucopolissacaridoses, o objetivo principal deste trabalho foi investigar os parâmetros de estresse oxidativo e mediadores inflamatórios em pacientes MPS IVA sob terapia de reposição enzimática (TRE). Foram analisadas amostras de urina e sangue de pacientes MPS IVA sob TRE (n=17) e controles saudáveis pareados por idade (n=10-14). Os pacientes apresentaram diminuição significativa nos níveis de defesas antioxidantes, medida através dos níveis de glutationa reduzida (GSH), e aumento da enzima superóxido dismutase (SOD) em eritrócitos. Em relação ao dano a biomoléculas, foi observado nos pacientes um aumento de lipoperoxidação (aumento dos níveis de isoprostanos urinários) e de dano oxidativo a proteínas (aumento dos níveis urinários de di-tirosina e diminuição dos grupamentos sulfidrila no plasma) comparativamente aos controles. Nossos resultados também mostraram que os pacientes MPS IVA sob TRE apresentaram maior dano ao DNA, sendo este dano de origem oxidativa e atingindo bases purínicas e pirimidínicas. Além disso, os pacientes apresentaram níveis significativamente aumentados de interleucina-6 e esta, por sua vez, apresentou correlação negativa com GSH, mostrando uma possível relação entre inflamação e estresse oxidativo nesta doença. Considerando que os níveis de GAG urinários ainda se encontravam elevados nos pacientes em comparação com o grupo controle, pode-se supor que os mesmos estejam, pelo menos em parte, correlacionados com os danos oxidativos encontrados nestes pacientes. Os dados encontrados no presente trabalho sugerem que pacientes MPS IVA sob TRE apresentam uma condição pró-inflamatória e oxidativa e que a suplementação com antioxidantes em combinação com a TRE deve ser investigada com o intuito de melhorar a qualidade de vida dos pacientes. Cabe ressaltar que este é o primeiro estudo em pacientes que relaciona MPS IVA com estresse oxidativo e inflamação. / The Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease caused by impaired degradation of keratan sulfate and chondroitin-6-sulfate glycosaminoglycans (GAG), due to a deficiency on the enzyme N-acetylgalactosamine-6-sulfatase. Since the pathophysiology of this disease is still not totally elucidated and many studies demonstrated the involvement of oxidative stress and inflammation in the pathogenesis of other mucopolysaccharidoses types, the principal objective of this study was to investigate oxidative stress parameters and inflammatory mediators in MPS IVA patients under enzyme replacement therapy (ERT). Urine anda blood samples of MPS IVA patients under ERT (n= 17) and healthy age-matched controls (n= 10-14) were evaluated. Patients presented a significant decrease in antioxidant defenses levels, assessed by reduced glutathione (GSH), and increased superoxide dismutase (SOD) activity in erythrocytes. With regard to the biomolecules damage, was observed that patients presented lipid peroxidation (increase of isoprostanes urinary levels) and protein damage (increase of di-tyrosine urinary levels and decrease of sulfhydryl groups in plasma), when compared to controls. Our results showed higher DNA damage levels in MPS IVA patients compared to control group, in both pyrimidines and purines bases. The pro-inflammatory cytokine interleukin 6 (IL-6) was significantly increased in patients and showed an inverse correlation with GSH levels, showing a possible link between inflammation and oxidative stress in MPS IVA disease. Considering that GAG urinary level were still high in ERT patients compared to the control group, we propose that GAG are, at least in part, related with oxidative damage found in MPS IVA patients. The data presented suggest that pro-inflammatory and pro-oxidant states occur in MPS IVA patients under ERT, and the supplementation of antioxidants in combination with ERT can be investigated with the purpose of improving the patient’s life quality. To the best of our knowledge, this is the first study in patients relating MPS IVA with oxidative stress and inflammation.

Currently organic-inorganic hybrid perovskite solar cells (PSCs) is one kind of promising photovoltaic technology due to low production cost, easy fabrication method and high power conversion efficiency. Charge transport layers are found to be critical for device performance and stability. A traditional electron transport layer (ETL), such as TiO2 (Titanium dioxide), is not very efficient for charge extraction at the interface. Compared with TiO2, SnO2 (Tin (IV) Oxide) possesses several advantages such as higher mobility and better energy level alignment. In addition, PSCs with planar structure can be processed at lower temperature compared to PSCs with other structures. In this thesis, planar-structure perovskite solar cells with SnO2 as the electron transport layer are fabricated. The one-step spin-coating method is employed for the fabrication. Several issues are studied such as annealing the samples in ambient air or glovebox, different concentration of solution used for the samples, the impact of using filter for solutions on samples. Finally, a reproducible fabrication procedure for planer-structure perovskite solar cells with an average power conversion efficiency of 16.8%, and a maximum power conversion efficiency of 18.1% is provided.

The new millennium has seen revolutionary advances in photonsource technology. As the newly constructed synchrotron facilityMAX IV in Lund, Sweden, pushes brilliance toward what isphysically possible, low-yield spectroscopic techniques, such asresonant inelastic X-ray scattering (RIXS), open new doors inmolecular and condensed matter research. The VERITAS beamline atMAX IV is designed for high-resolution vibrational RIXS on gases.X-rays interact with flowing molecules inside a window-cappedcell, but the radiation intensity is expected to be large enoughto damage the windows, and cause build-up of photochemicalproducts, which lowers transmission. To address these issues, anovel gas cell design is presented, wherein the distance betweensample gas and window is increased by using a flowing heliumbuffer. The main challenge is maintaining a steep sample gasconcentration gradient within the cell, and to that end, gas flowswere simulated on various geometries by using the finite elementmethod to solve the Navier-Stokes equations. Results were used toconstruct a prototype, and confocal Raman microscopy was used forconcentration characterization. Preliminary measurements revealeda uniform sample gas distribution, and the technique proved to beinefficient for wide scanning of parameter values. This suggeststhat a supplementary experiment is required to find roughestimates of good parameter values, which can then be followed upwith new Raman measurements for fine-tuning of the properparameter space. Real-time visualization of the sample gas flow,using a visible gas under an optical microscope, is one candidatefor this supplementary experiment.

L'exposition du public au gaz radon 222Rn fait l'objet d'une attention croissante. Les méthodes traditionnelles de détection de radon étant soit peu flexibles, soit très chères, cette thèse présente le développement d'un dispositif électronique compact et autonome qui s'appuie sur les progrès récents en microélectronique pour la physique des particules. Le coeur du dispositif est un circuit intégré CMOS original (basse tension, faible consommation) qui assure à la fois les fonctions de capteur et de traitement. Les premiers tests, d'efficacité et en sources de particules alpha, s'appuient sur des simulations détaillées (TRIM, GEANT IV). Différents prototypes de cartes électroniques ont été développés pour d'une part la détection passive de radon à différentes concentrations et d'autre part la détection supplémentaire des descendants sur aérosols 218Po et 214Po qui contribuent de façon importante à l'irradiation α interne".Le système final est une carte miniaturisée au format CB, qui comprend quatre circuits pour la détection simultanée de radon et de ses descendants solides. Une excellente linéarité a été obtenue jusqu'à 80 kBq.m-3 sur le banc de test BACCARA au Laboratoire de Mesure des Aérosols de l‘IRSN à Saclay. Un circuit de deuxième génération est également proposé

Wolbachia est une bactérie Gram(-) intracellulaire symbiote de nombreux arthropodes. Chez A. vulgare, elle entraîne la féminisation des mâles (souche wVul). Nous avons caractérisé le chromosome de wVul (ADN circulaire de 1.75 Mb) qui semble comporter de façon atypique plusieurs opéron rrn et dont les profils de restriction sont différents de ceux des autres souches de Wolbachia. La purification de l'ADN bactérien a permis d'amorcer le séquençage de ce génome. Un système de sécrétion de type IV caractérisé par deux opérons vir a été mis en évidence. L'expression de ces gènes dans les ovocytes et l'étude des protéines impliquées révèlent que ce système pourrait être fonctionnel. Des cartographies bidimensionnelles de profils protéiques de tissus d'individus infectés ou non indiquent des différences d'expression correspondant à des protéines du métabolisme et du cytosquelette de l'hôte surexprimées, et à une RNA hélicase qui pourrait interagir avec le déterminisme du sexe de l'hôte.

Le recours à l'énergie électronucléaire pour diminuer les émissions anthropiques de CO2 nécessite des avancées technologiques majeures. Les réacteurs nucléaires de IVe génération doivent répondre à plusieurs contraintes, telles qu'une sûreté améliorée, la régénération du combustible et la minimisation de la production de déchets radioactifs. De ce point de vue, l'utilisation du Cycle Thorium en Réacteurs à Sel Fondu semble prometteuse. Cet axe de recherche, étudié dans le passé, avait cependant débouché sur un concept dont les défauts ont empêché la réalisation. Une nouvelle réflexion est menée afin de trouver des solutions et d'aboutir au concept de Thorium Molten Salt Reactor. Le couplage d'un code de transport de neutrons avec un code d'évolution des matériaux permet de simuler le comportement d'un coeur nucléaire, et de suivre son évolution tout au long de sa vie. Par cette méthode, nous avons étudié un large éventail de configurations de réacteurs. Les performances de ces systèmes ont été évaluées, grâce à un jeu de contraintes qu'ils doivent satisfaire au mieux. Ce travail a permis de comprendre bon nombre de phénomènes physiques régissant le comportement de ces réacteurs. Grâce à cette nouvelle compréhension, la recherche de configurations acceptables a pu aboutir à des solutions satisfaisantes, apportant un souffle nouveau dans le domaine des Réacteurs à Sel Fondu.

<p>Årligen slutar 30 procent av eleverna gymnasieskolan utan betygsbehörighet. På individuella program (IV) är siffran 85 procent. För att kartlägga skolsituationen för en elevgrupp på IV-programmet intervjuades 24 elever. Utöver detta gjordes en kognitiv bedömning samt en självskattning av upplevd psykisk hälsa. Huvuddelen av eleverna presterade på en ojämn kognitiv nivå, inom normalvariationen. Arton elever bearbetade information långsamt. Eleverna skattade att de mådde psykiskt sämre än normgruppen. De rapporterade tidiga skolsvårigheter som i vissa fall uppmärksammats,men lämnats utan adekvat åtgärd. Elever med långvariga skolproblem,försvårande additiva faktorer kombinerat med ett begåvningsvärde i normalvariationens nedre spann samt långsamhet vid informationsbearbetning upplever negativa individuella konsekvenser. De negativa effekterna kan mildras med tidiga interventioner på en för eleverna adekvat nivå och beaktat elevernas relativa kognitiva styrkor.</p>

This book is an attempt to formulate a sociological theory of the phenomena which is otherwise known as substance abuse and substance dependency in the medical field. The first step toward such a theory is a critique of how DSM-IV presents diagnostic criteria for substance abuse and substance dependency as if these criteria are valid and reliable ways of measuring mental illness and bodily dysfunction. I point to the fact that these criteria neither are valid or reliable variables for measurement nor theoretically grounded defi nitions of the phenomena. My point is that diagnosis is an elaborate way of disguising moral judgments as medical assessments of illness or dysfunction. The second step towards the formulation of my theory goes via my empirical study of nine men and women who call themselves sex and love addicts. By conducting deep interviews with them I conclude that it is impossible to talk about sex and love addiction without constantly referring to stereotypes and widely held assumptions of alcoholics and drug addicts. Moreover it is apparent that these men and women are making moral judgments about themselves rather than pointing to some form of genuine disruption which they cannot control. From my critique and my empirical study I am able to identify a number of areas that a theory of addiction, as opposed to the medical view where this phenomena are being broken down in two sub categories (abuse and dependency), must be able to handle to explain addiction generally and specifically in relation to alcohol, drugs, sex and other forms of social deviance. A number of philosophical hallmarks of medicine is also identifi ed and seen as part of the problem, therefore I mean that a successful theory of addiction must transcend the mind body dualism of Descartes as it is a cornerstone in the medical view upon and understanding of humans. By reconstructing the habitus and field concepts in Pierre Bourdieus theory of practice I mean that it is possible to understand addiction from an action theory point of view. This discussion is also broadened by a pragmatist discussion of the mind and a neo meadian theory of the emotional self. My conclusion is that addiction can be understood and explained within an action theory which focus upon individual as well as collective action and understand this as habitual practice that is partly embodied and therefore not discursive – habits of which we cannot easily speak is seen as one of the compelling components in addiction rather than a mythical loss of control which is nowhere to be found but as a rhetoric grip stemming from the AA view upon addiction as a disease.

This thesis is focused on the development of new pincer complex-catalyzed transformations. Optimization of the catalytic properties (fine-tuning) was directed to increase the catalytic activity as well as the chemo-, stereo- and enantioselectivity of the complexes. This was achieved by varying the heteroatoms in the terdentate pincer ligand, by changing the electronic properties of the coordinated aryl moiety and by implementing chiral functionalities in the pincer complexes. In the cross-coupling reaction of vinyl epoxides and aziridines with organoboronic acids the chemoselectivity of the reaction could be increased by employment of pincer complexes instead of commonly used Pd(0) catalysts. Furthermore, the introduction of a methoxy substituent in the aromatic subunit of the complex considerably increased the activity of the pincer complex catalyst. Fine-tuning of the enantioselectivity in electrophilic allylation reactions was achieved by using a wide variety of new BINOL- and biphenanthrol-based pincer complexes. The highest enantioselectivity (85% ee) was obtained by applying biphenanthrol-based pincer complexes. Stereoselective pincer complex-catalyzed condensation of sulfonylimines with isocyanoacetate could be achieved under mild reaction conditions. By application of chiral PCP catalysts, 2-imidazolines could be obtained with up to 86% ee. A new pincer complex-catalyzed C-H bond functionalization based reaction between organonitriles and sulfonylimines affords homoallylic amines and beta-aminonitriles in high yields. The asymmetric version of this process affords beta-aminonitriles with up to 71% ee. In the last chapter, a pincer complex-catalyzed redox coupling reaction is described. In this highly regio- and stereoselective process the integrity of the pincer catalysts is fully retained. This catalytic reaction proceeds with a high level of functional group tolerance, as allylic acetate and aryl halide functionalities are retained.