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<p>Detta är en studie med en kvalitativ ansats som syftar till att undersöka bonusföräldrars behov av riktat stöd i föräldraskapet. Den ombildade familjen består av vuxna som har barn sedan tidigare och denna studie behandlar ombildade familjer där enbart en av de vuxna har barn sedan tidigare. Vidare läggs fokus på bonusförälderns upplevelse av att bli en del i en sådan familj. Studien har genomförts med hjälp av semistrukturerade intervjuer med sju bonusföräldrar. De intervjuade bonusföräldrarnas familjesituationer skilde sig åt på många sätt vilket ger en nyanserad bild av hur en bonusförälder kan uppleva sin situation. Studiens teoretiska utgångspunkt utgörs av rollteori och generell systemteori. I resultatet framkommer att bonusföräldrarna upplever en övergripande tillfredställelse med sin roll inom familjen och även utåt mot skola, myndigheter m.m. De har givits utrymme att själva utveckla sin roll även om de inte reflekterat över det. De har haft möjlighet att söka stöd hos sin partner, sin familj och sina vänner. De flesta problem som bonusföräldrarna upplever är förknippade med den externa föräldern och rör sällan bonusföräldern personligen även om denne påverkas.</p> / <p>This is a study with a qualitative approach, with the purpose of examining bonus parents need of certain support in the parenthood. The reconstructed family consists of adults who have children from before and this research concerns reconstructed families where only one of the adults have children from before. Focus is placed on the bonus parents experiences of becoming a part of that type of family. The research has been conducted through semi structured interviews with seven bonus parents who where recruited through criterion sampling. The family situations of the interviewed bonus parents differed in many ways which offers a diverse picture of how a bonus parent can experience his or her situation. The theoretical basis used in the research is role theory and general system theory. The result shows that the bonus parents experience a general satisfaction with his or her role in the family and also outwards towards school, authorities etc. They have been given the space to develop their role even though they haven’t thought so much about it. They have had the opportunity to seek support through their partner, and among their family and friends. Most of the problems experienced by the bonus parents are associated with the external parent and do seldom concerns the bonus parent in person even if he or she is affected by it.</p>

Detta är en studie med en kvalitativ ansats som syftar till att undersöka bonusföräldrars behov av riktat stöd i föräldraskapet. Den ombildade familjen består av vuxna som har barn sedan tidigare och denna studie behandlar ombildade familjer där enbart en av de vuxna har barn sedan tidigare. Vidare läggs fokus på bonusförälderns upplevelse av att bli en del i en sådan familj. Studien har genomförts med hjälp av semistrukturerade intervjuer med sju bonusföräldrar. De intervjuade bonusföräldrarnas familjesituationer skilde sig åt på många sätt vilket ger en nyanserad bild av hur en bonusförälder kan uppleva sin situation. Studiens teoretiska utgångspunkt utgörs av rollteori och generell systemteori. I resultatet framkommer att bonusföräldrarna upplever en övergripande tillfredställelse med sin roll inom familjen och även utåt mot skola, myndigheter m.m. De har givits utrymme att själva utveckla sin roll även om de inte reflekterat över det. De har haft möjlighet att söka stöd hos sin partner, sin familj och sina vänner. De flesta problem som bonusföräldrarna upplever är förknippade med den externa föräldern och rör sällan bonusföräldern personligen även om denne påverkas. / This is a study with a qualitative approach, with the purpose of examining bonus parents need of certain support in the parenthood. The reconstructed family consists of adults who have children from before and this research concerns reconstructed families where only one of the adults have children from before. Focus is placed on the bonus parents experiences of becoming a part of that type of family. The research has been conducted through semi structured interviews with seven bonus parents who where recruited through criterion sampling. The family situations of the interviewed bonus parents differed in many ways which offers a diverse picture of how a bonus parent can experience his or her situation. The theoretical basis used in the research is role theory and general system theory. The result shows that the bonus parents experience a general satisfaction with his or her role in the family and also outwards towards school, authorities etc. They have been given the space to develop their role even though they haven’t thought so much about it. They have had the opportunity to seek support through their partner, and among their family and friends. Most of the problems experienced by the bonus parents are associated with the external parent and do seldom concerns the bonus parent in person even if he or she is affected by it.

Modern image guided radiation therapy involves the use of an isocentrically mounted imaging system to take radiographs of a patient's position before the start of each treatment. Image guidance helps to minimize errors associated with a patients setup, but the radiation dose received by patients from imaging must be managed to ensure no additional risks. The Varian On-Board Imager (OBI) (Varian Medical Systems, Inc., Palo Alto, CA) does not have an automatic exposure control system and therefore requires exposure factors to be manually selected. Without patient specific exposure factors, images may become saturated and require multiple unnecessary exposures. A software based automatic exposure control system has been developed to predict optimal, patient specific exposure factors. The OBI system was modelled in terms of the x-ray tube output and detector response in order to calculate the level of detector saturation for any exposure situation. Digitally reconstructed radiographs are produced via ray-tracing through the patients' volumetric datasets that are acquired for treatment planning. The ray-trace determines the attenuation of the patient and subsequent x-ray spectra incident on the imaging detector. The resulting spectra are used in the detector response model to determine the exposure levels required to minimize detector saturation. Images calculated for various phantoms showed good agreement with the images that were acquired on the OBI. Overall, regions of detector saturation were accurately predicted and the detector response for non-saturated regions in images of an anthropomorphic phantom were calculated to generally be within 5 to 10 % of the measured values. Calculations were performed on patient data and found similar results as the phantom images, with the calculated images being able to determine detector saturation with close agreement to images that were acquired during treatment. Overall, it was shown that the system model and calculation method could potentially be used to predict patients' exposure factors before their treatment begins, thus preventing the need for multiple exposures. / Graduate / 0760 / 0574 / 0756

L'allergie de contact est une pathologie en constante augmentation et particulièrement répandue dans les pays industrialisés. Aucune thérapie n'existe actuellement et seule l'éviction totale de l'allergène permet d'éviter toute nouvelle réaction d'allergie. La base de l'allergie de contact est la formation d'une liaison entre l'allergène et les protéines épidermiques. C'est cette étape chimique clé qu' il est important de comprendre afin de développer de nouvelles méthodes dites« alternatives» dans le cadre de l'actuelle législation sur les cosmétiques. Le but de ce travail de thèse a été d'étudier la réactivité de différents allergènes connus face aux acides aminés et protéines d'épidermes reconstruits de type SkinEthic® par la technique RMN HRMAS dérivée de la RMN du solide. Six allergènes ont ainsi été étudiés et leur réactivité a été comparée a celle observée en solution face à une protéine modèle. / Contact dermatitis is one of the most common health problem and highly prevalent in industrialized countries. No therapy currently exists and only the total eviction of the allergen can prevent further allergie reaction.The key molecular event in skin sensitization is the formation of a bond between the allergen and the epidermal proteins. Due to the recent legislation on cosmetic and to help avoid the inappropriate use of new allergens, the understanding of this key step has to be expanded in order to develop new alternative metbods.The aim of this PhD work is to study the reactivity of some allergens towards amino acids and proteins presents in reconstructed human epidermis like SkinEthic® using the HRMAS NMR technique. Six allergens have been studied and their reactivity was compared to that observed ln solution with a model protein.

Submitted by Valquíria Barbieri (kikibarbi@hotmail.com) on 2018-04-12T21:31:08Z No. of bitstreams: 1 DISS_2014_Hozana Silva.pdf: 2930112 bytes, checksum: a448b201c517d606857386ff862f0a41 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2018-04-27T14:49:19Z (GMT) No. of bitstreams: 1 DISS_2014_Hozana Silva.pdf: 2930112 bytes, checksum: a448b201c517d606857386ff862f0a41 (MD5) / Made available in DSpace on 2018-04-27T14:49:19Z (GMT). No. of bitstreams: 1 DISS_2014_Hozana Silva.pdf: 2930112 bytes, checksum: a448b201c517d606857386ff862f0a41 (MD5) Previous issue date: 2014-02-25 / CAPES / O objetivo do trabalho foi analisar a temperatura do ar utilizando a teoria da complexidade em floresta de transição no Norte Mato Grosso. Avaliar a relação entre os atratores reconstruídos e as estações do ano, a influência de frentes frias e posteriores variáveis que modificam os padrões da temperatura do ar. Os dados abrangem os anos 2001, 2002, 2003 e 2007, a análise estatística foi realizada com o teste de Qui-Quadrado (X2), verificando que os valores médios horários representam os dados experimentais para os meses considerados. Logo, a Floresta Amazônica tem sido considerada um importante ecossistema no controle do clima local. Com o desmatamento em grande escala, poderão se perceber mudanças no clima local. Por isso, a Teoria da Complexidade é necessária para entender a floresta amazônica por se tratar de um ambiente complexo, onde suas variáveis se influenciam mutuamente não obedecendo a uma linearidade, por consequência levando à incerteza e imprevisibilidade intrínsecas. Com essa condição, torna-se necessário um estudo que aprofunde no comportamento dos ecossistemas da Floresta Amazônica. Para um melhor entendimento da previsibilidade das variáveis ambientais com a temperatura do ar, faz-se necessário um estudo sobre essa variável em certos períodos, verificando, assim, as dificuldades em prevê-las e um possível efeito da sazonalidade. Uma maneira de conduzir esse estudo é a reconstrução de atratores, tendo como base a Teoria da Complexidade. / The aim of study was to study the air temperature behavior using complexity theory in transition forest in Sinop Mato Grosso State. Evaluate the relationship between the attractors reconstructed and the seasons, influence of cold fronts and subsequent variables that modify the patterns of air temperature. The data include the years 2001, 2002, 2003 and 2007. The statistical analysis was performed with chi - square test (x2) checking the hourly average values represent the experimental data for months. Soon the Amazon rainforest has been considered important ecosystem in control of the local climate. With the large-scale deforestation, may notice changes in the local climate. Therefore, Complexity Theory is needed to understand the Amazon rainforest because it is a complex environment where your variables influence each other not obeying a linearity thus transmitting to the inherent uncertainty and unpredictability. With this condition, it is necessary a study more dup that this ecosystems behavior of the Amazon rainforest. For a better understanding of the environmental variables predictability, likes air temperature, it is necessary a study of this variable in certain periods, thus verifying the difficulties in providing for them and a possible effect of seasonality. One way to conduct this study is the reconstruction of attractors, based on the Theory of Complexity.

Le facteur de transcription HIF-1 est un hétérodimère composé d’une sous-unité α et d’une sous-unité ß. HIF-1 est capable de reconnaître une séquence consensus appelée HRE (HIF Response Element) et de réguler l’expression de plus de 200 gènes cibles impliqués dans divers mécanismes cellulaires. Nous nous intéressons à étudier le rôle de HIF-1α dans la peau, d’une part dans la régulation des enzymes de la réparation de l’ADN suite à l’irradiation UVB, d’autre part dans la physiologie cutanée.Nos résultats montrent bien que HIF-1α régule l’expression des gènes participant à la réparation de l’ADN (XPC et XPD). Ces gènes contiennent dans leurs régions promotrices des HRE de HIF-1α. La quantification de l’immunoprécipitation de chromatine révèle des HRE putatifs dans les gènes codant pour d'autres protéines de la réparation de l'ADN (XPB, XPG, CSA et CSB), ce qui suggère que HIF-1α est un régulateur clé de la machinerie de réparation de l'ADN. Nous avons prouvé que HIF-1α est indispensable à l’adhésion des kératinocytes par sa régulation exercée sur la laminine-332 et les intégrines (α6 et ß1). L’absence de l’expression de HIF-1α empêche aussi la reconstruction des épidermes à partir des kératinocytes humains. Nos résultats ont montré que les souris invalidées pour HIF-1α développent avec l’âge un phénotype d’inflammation dans plusieurs régions. Ces souris sont très sensibles au moindre stress consécutif à une blessure et une irradiation UVB. L’induction de l’inhibition de HIF-1α dans des souris inductibles avec le tamoxifène indique un détachement de l’épiderme au niveau des couches supra-basales. Ces souris meurent deux semaines après injection du tamoxifène / The transcription factor HIF-1 is a heterodimer composed of an α and ß subunit. HIF-1 is capable of recognizing a consensus sequence called HRE (hypoxia Response Element) and regulate the expression of more than 200 target genes involved in various cellular mechanisms. We are interested in studying the role of HIF-1α in the skin physiology.Our results show that HIF-1α regulates the expression of two main factors (XPC and XPD) involved in nucleotide excision repair through binding on HRE in their promoter regions. Quantitative chromatin immunoprecipitation assays further revealed putative HREs in the genes encoding other DNA repair proteins (XPB, XPG, CSA and CSB), suggesting that HIF-1α is a key regulator of the DNA repair machinery. We proved that HIF-1α is essential for keratinocyte adhesion through its regulation exerted on laminin-332 and integrins (α6, ß1). The lack of HIF-1α expression also prevents the reconstruction of epidermis by human keratinocytes. Our results showed that mice constitutively depleted for HIF-1α in their epidermis develop with age a phenotype of inflammation in several regions. These mice are very sensitive to the stress resulting from wound injury and UVB irradiation. HIF-1α depletion in the epidermis of inducible mice using tamoxifen results in a detachment of the epidermis in suprabasal layers. These mice die within two weeks after injection of tamoxifen

Magister Artium - MA / The focus on space and spatiality is relatively new in literary studies and also not unproblematic. Problems arise from the way in which these concepts are constructed, described, defined and interpret~. It is possible to derive numerous kinds of space, such as historical space, physical space, metaphysical space and religious space, to name a few, from the structure or thematics of a novel. This in itself presents a problem, since the literary scholar must differentiate between these spaces in order to determine which will be most useful for study of a particular aspect. There does not seem to be a coherent theoretical position in literary scholar regarding space, and thus various views of theorists will be considered. Gullon (1975:21), in a seminal article on space entitled On Space in the Novel provides a possible definition of space, with reference to another seminal article, this time by Joseph Frank when he states that "Frank calls 'spatial' the form of those works that at a given instant in time concentrate actions that can be perceived, but not related, simultaneously". This definition denotes a further complication engendered by space, namely the notion that different spaces intersect and interrelate with each other, and consequently that it is very difficult - if not impossible - to separate the various kinds of literary spaces in order to analyse the occurrence of a single space in a text. It also seems bound to time, but in a sense bridges the temporal gaps in a novel since it brings together parts that are not necessarily adjacent to each other temporally. Time becomes spatialized by treating events in the novel as separate chunks which can be rearranged and linked to each other. 1bis creates a more coherent and comprehensive picture of events in a text. namely the notion that different spaces intersect and interrelate with each other, and consequently that it is very difficult - if not impossible - to separate the various kinds of literary spaces in order to analyse the occurrence of a single space in a text. The main point in this regard seems to be creating patterns. This brings together more elements for the reader to be viewed at once, allowing him or her to attain a broader perspective on the text.

La lysyl oxydase (LOX) est une enzyme extracellulaire dont le rôle canonique est de catalyser la réticulation des fibres de collagènes et de l’élastine, assurant ainsi l’intégrité des tissus conjonctifs. La LOX agit également dans plusieurs types cellulaires comme régulateur de différents processus biologiques, soulignant des fonctions à la fois extra et intracellulaires. Ces travaux de thèse ont contribué à améliorer la compréhension du rôle de LOX dans l’épiderme, et plus précisément au cours de la différenciation des kératinocytes. Le développement d’un modèle de culture en monocouche à confluence, et d’un modèle tridimensionnel d’épiderme reconstruit ont permis d’aborder l’étude de LOX au cours de l’induction du programme de différenciation des kératinocytes et du processus de différenciation terminale conduisant à la formation d’un épiderme pluristratifié, cornifié et fonctionnel. L’expression de LOX est induite au cours des premières étapes de la différenciation de kératinocytes primaires ainsi que d’une lignée de kératinocytes immortalisés. Grâce à l’établissement de lignées de kératinocytes éteignant l’expression de LOX de façon stable, nous avons mis en évidence l’implication de la protéine LOX, indépendamment de son activité enzymatique, dans la régulation des premières étapes de différenciation des kératinocytes. En absence de LOX, l’initiation du programme de différenciation est perturbée, affectant la différenciation terminale et fonctionnelle des épidermes reconstruits. Ainsi, une régulation fine de l’expression de LOX est nécessaire au déroulement normal du processus de différenciation des kératinocytes, et donc au maintien de l’homéostasie épidermique / Lysyl oxidase (LOX) is an extracellular enzyme that catalyzes the cross-linking of fibrillar collagens or elastin, thereby regulating the structural integrity of connective tissues. Moreover, LOX displays multiple roles in different cell types, acting as a regulator of various biological processes at both extra and intracellular levels. The aim of the present work was to shed light on LOX functions in the epidermis, especially during keratinocyte differentiation. The development of culture models, consisting of confluent monolayers or reconstructed-epidermis allowed us to study LOX functions during the induction of the differentiation program, and furthermore during the terminal differentiation process leading to the formation of a pluristratified, cornified and functional epidermis. LOX expression is induced at the onset of the commitment to differentiation, both in primary and immortalized keratinocytes. Stable silencing of LOX expression affects the induction of the differentiation program and strongly impairs terminal and functional epidermal differentiation in reconstructed-epidermis. Therefore, LOX protein acts during the first steps of keratinocyte differentiation, independently of its enzymatic activity, and is implied for subsequent commitment into terminal differentiation. Taken together, these results suggest that a finely regulated expression of LOX is required for normal keratinocyte differentiation, and thus for maintenance of epidermal

O presente trabalho teve o objetivo de desenvolver uma formulação tópica contendo os filtros solares benzofenona-3 e avobenzona microencapsulados em associação com filtro solar não encapsulado octocrileno e nanoparticulas lipídicas sólidas contendo rutina (formulação completa) e avaliar a eficácia fotoquimiopreventiva dessa formulação usando biópsias de pele humana e pele reconstruída in vitro. Microparticulas lipídicas sólidas contendo grandes quantidades de filtros solares, benzofenona-3 e avobenzona foram obtidas pela técnica do spray congealing com propriedades adequadas para aplicação tópica. Além disso, o processo de microencapsulação foi capaz de diminuir a penetração de benzofenona-3 na pele, aumentar a estabilidade da avobenzona frente à radiação ultravioleta A e a capacidade fotoprotetora desses filtros microencapsulados em formulações tópicas quando expostos a radiação ultravioleta. Nanopartículas lipídicas sólidas contendo o flavonóide rutina foram produzidas pelo processo de homogeneização a alta pressão e suas condições foram otimizadas pelo método da desejabilidade rendendo nanopartículas lipídicas sólidas com tamanho médio de 74,22 ±2,77 nm, índice de polispersividade de 0,161±0,03 e eficiência de encapsulação de 98,90 ±0,25 %. Em adição, as nanopartículas mostraram serem capazes de proteger a viabilidade celular de fibroblastos de ratos L929 irradiados com radiação ultravioleta A e B. Para a eficácia fotoquimiopreventiva a formulação completa foi capaz de evitar/diminuir a formação de células apoptóticas, caspase-3, dímeros de ciclobutanodipirimidina, metaloproteinases e peroxidação lipídica em pele humana e pele reconstruída expostos a UVB. O processo tecnológico de microencapsulação e nanoencapsulação dos ativos avaliados mostrou ser eficaz, não comprometendo as propriedades de fotoproteção dos filtros solares e rutina, apresentando resultados similares ou melhores do que as formulações contendo os ativos na forma livre. Portanto, o desenvolvimento de formulações contendo ativos microencapsulados e nanoencapsulados é uma alternativa interessante para o emprego em produtos comerciais para proteção solar, por diminuir as características indesejáveis como penetração e instabilidade, melhorando as propriedades fotoprotetoras e evitando a necessidade de desenvolver novos compostos com propriedades fotoprotetoras. / This study aimed the pharmaceutical development of a topical formulation containing an association of microencapsulated sunscreens benzophenone-3 and avobenzone, free sunscreen octocrylene and rutin flavonol solid lipid nanoparticles (complete formulation). This formulation was assessed for photochemoprotective ability using human skin obtained surgically and reconstructed human skin. Solid lipid microparticles containing large amounts of sunscreens benzophenone-3 and avobenzone were obtained by the spray congealing technique under conditions that allowed the manufacture of microparticles with suitable properties for topical application. The microencapsulation conditions were also able to reduce the penetration of benzophenone-3 through the skin, enhanced the stability of avobenzone against the ultraviolet radiation (UVR) and increased the photoprotective ability of both filters in topical formulations exposed to UVR. Solid lipid nanoparticles containing rutin were produced by the high pressure homogenization process whose conditions were optimized using the desirability method, yielding nanoparticles with size of 74.22 ± 2.77 nm, polispersivity index of 0.161 ± 0.03 and encapsulation efficiency of 98.90 ± 0.25%. In addition, the nanoparticles were able to avoid the death of L929 mice fibroblasts exposed to UVR A and B. For the photochemopreventive ability studies, the complete formulation was able to reduce/avoid the induction of apoptotic cells, caspase-3, CPDs, metalloproteinases and lipid peroxides in human skin obtained surgically and reconstructed human skin in vitro exposed to UVB.Thus, the micro and nanoencapsulation solved some intrinsic problems related to sunscreens and rutin without, however, compromising their photohemoprotective ability, since the results showed similar or better efficacy when compared to the formulations containing actives in free form. Therefore, the development of formulations containing microencapsulated and nanoencapsulated compounds is an interesting alternative for employment in commercial products for sun protection by decreasing the undesirable characteristics, such as penetration and instability, improving the photoprotective properties and avoiding the need to develop new compounds with photoprotective characteristics.