The investigation of reactor pressure vessel (RPV) material from the decommissioned Greifswald nuclear power plant representing the first generation of Russian-type WWER-440/V-230 reactors offers the opportunity to evaluate the real toughness response. The Greifswald RPVs of 4 units represent different material conditions as follows: • Irradiated (Unit 4), • irradiated and recovery annealed (Units 2 and 3), and • irradiated, recovery annealed and re-irradiated (Unit1). The recovery annealing of the RPV was performed at a temperature of 475° for about 152 hours and included a region covering ±0.70 m above and below the core beltline welding seam. Material samples of a diameter of 119 mm called trepans were extracted from the RPV walls. The research program is focused on the characterisation of the RPV steels (base and weld metal) across the thickness of the RPV wall. This report presents test results measured on the trepans from the beltline welding seam No. SN0.1.4. and forged base metal ring No. 0.3.1. of the Units 1 2 and 4 RPVs. The key part of the testing is focussed on the determination of the reference temperature T0 of the Master Curve (MC) approach following the ASTM standard E1921 to determine the facture toughness, and how it degrades under neutron irradiation and is recovered by thermal annealing. Other than that the mentioned test results include Charpy-V and tensile test results. Following results have been determined: • The mitigation of the neutron embrittlement of the weld and base metal by recovery annealing could be confirmed. • KJc values of the weld metals generally followed the course of the MC though with a large scatter. • There was a large variation in the T0 values evaluated across the thickness of the multilayered welding seams. • The T0 measured on T-S oriented SE(B) specimens from different thickness locations of the welding seams strongly depended on the intrinsic structure along the crack front. • The reference temperature RT0 determined according to the “Unified Procedure for Lifetime Assessment of Components and Piping in WWER NPPs - VERLIFE” and the fracture toughness lower bound curve based thereon are applicable on the investigated weld metals. • A strong scatter of the fracture toughness KJc values of the recovery annealed and re-irradiated and the irradiated base metal of Unit 1 and 4, respectively is observed with clearly more than 2% of the values below the MC for 2% fracture probability. The application of the multimodal MC-based approach was more suitable and described the temperature dependence of the KJc values in a satisfactory manner. • It was demonstrated that T0 evaluated according to the SINTAP MC extension represented the brittle fraction of the data sets and is therefore suitable for the nonhomogeneous base metal. • The efficiency of the large-scale thermal annealing of the Greifswald WWER 440/V230 Unit 1 and 2 RPVs could be confirmed.

In this thesis, a general methodology for generating representative load cycles for arbitrary monohull surface vessels is developed. The proposed methodology takes a hull geometry and propeller placement, vessel loading condition, vessel mission, and weather data (wind, waves, currents) and, from that, generates the propeller states (torque, speed, power) and steering gear states (torque, speed, power) necessary to accomplish the given mission. The propeller states, together with the steering gear states, thus define the load cycle corresponding to the given inputs (vessel, mission, weather). Some key aspects of the proposed methodology include the use of a surge-sway-yaw model for vessel dynamics as well as the use of surrogate geometries for both the hull and propeller(s). What results is a methodology that is lean (that is, it requires only sparse input), fast, easy to generalize, and reasonably accurate. The proposed methodology is validated by way of two separate case studies, case A and case B (both involving distinct car-deck ferries), with case A being a more ideal case, and case B being a less ideal case given the methodology proposed. In both cases, the load cycle generation process completed in greater than real time, achieving time ratios (simulated time to execution time) of 3.3:1 and 12.8:1 for cases A and B respectively. The generated propeller and steering gear states were then compared to data collected either at sea or from the vessels' documentation. For case A, the propeller speed, torque, and power values generated were all accurate to within +/- 3%, +/- 7%, and +/- 10% of the true values, respectively, while cruising, and accurate to within +/- 14%, +/- 36%, and +/- 42% of the true values, respectively, while maneuvering. In addition, the steering gear powers generated in case A were consistent with the capabilities of the equipment actually installed on board. For case B, the propeller speed, torque, and power values generated were all accurate to within +/- 2%, +/- 8%, and +/- 9% of the true values, respectively, while cruising, and accurate to within +/- 28%, +/- 45%, and +/- 66% of the true values, respectively, while maneuvering. In case B, however, the steering gear powers generated were questionable. Considering the results of the validation, together with the rapid process runtimes achieved and sparse inputs given, one may conclude that the methodology proposed in this thesis shows promise in terms of being able to generate representative load cycles for arbitrary monohull surface vessels. / Graduate

Cerebral small vessel disease (SVD) is associated with increased risks of stroke and dementia, however the mechanisms remain unclear. Low cerebral blood flow (CBF) has long been suggested and accepted, but clinical evidence is conflicting. On the other hand, growing evidence suggests that increased intracranial pulsatility due to vascular stiffening might be an alternative mechanism. Pulse-gated phase-contrast MRI is an imaging technique that allows measuring of CBF contemporaneously with pulsatility in multiple vessels and cerebrospinal fluid (CSF) spaces. The overall aim of this thesis was to provide an overview of existing clinical evidence on both hypotheses, to test the reproducibility of CBF and pulsatility measures in phase-contrast MRI, and to explore the relationship between CBF and intracranial pulsatility and SVD features in a group of patients with minor stroke and SVD changes on brain imaging. I first systematically reviewed and meta-analysed clinical studies that have assessed CBF or intracranial pulsatility in SVD patients. There were 38 studies (n=4006) on CBF and 27 (n=3356) on intracranial pulsatility. Most were cross-sectional, and longitudinal studies were scarce. There were large heterogeneities in patient characteristics and indices used particularly for measuring and calculating pulsatility. Methods to reduce bias such as blinding and the expertise of structural image readers were generally poorly reported, and many studies did not account for the impact of confounding factors (e.g. age, vascular risk factors and disease severity) on CBF or pulsatility. Evidence for falling CBF predating SVD was not supported by longitudinal studies; high pulsatility in one large artery such as internal carotid arteries (ICA) or middle cerebral arteries might be related to SVD, but studies that measured arteries, veins and CSF in the same patients were very limited and the reliability of some pulsatility measures, especially in CSF, needs to be tested. In order to test the reproducibility of the CBF and intracranial pulsatility measures, I repeated 2D phase-contrast MRI scans of vessels and CSF on healthy volunteers during two visits. I also compared the ICA pulsatility index derived from the MRI flow waveform to that from the Doppler ultrasound velocity waveform in patients with minor stroke and SVD features. In 10 heathy volunteers (age 35.2±9.78 years), the reproducibility of CBF and vascular pulsatility indices was good, with within-subject coefficients of variability (CV) less than 10%; whereas CSF flow and pulsatility measures were generally less reproducible (CV > 20%). In 56 patients (age 67.8±8.27 years), the ICA pulsatility indices in Doppler ultrasound and MRI were acceptably well-correlated (r=0.5, p < 0.001) considering the differences in the two techniques. We carried out a cross-sectional study aiming to recruit 60 patients with minor stroke and SVD features. We measured CBF and intracranial pulsatility using phase-contrast MRI, as well as aortic augmentation index (AIx) using a SphygmoCor device. I first investigated the relationship between intracranial measures, and systemic blood pressure or aortic AIx, and then focused on how the intracranial haemodynamic measures related to two main SVD features (white matter hyperintensities (WMH) and perivascular spaces (PVS)). We obtained usable data from 56/60 patients (age 67.8±8.27 years), reflecting a range of SVD burdens. After the adjustment for age, gender, and history of hypertension, higher pulsatility in the venous sinuses was associated with lower diastolic blood pressure and lower mean arterial pressure (e.g. diastolic blood pressure on straight sinus pulsatility index (PI): β=-0.005, P=0.029), but not with aortic AIx. Higher aortic AIx was associated with low ICA PI (β=-0.011, P=0.040). Increased pulsatility in the venous sinuses, not low CBF, was associated with greater WMH volume (e.g. superior sagittal sinus PI: β=1.29, P=0.005) and more basal ganglia PVS (e.g. odds ratio=1.379 per 0.1 increase in superior sagittal sinus PI) after the adjustment for age, gender and blood pressure. The thesis is the first to summarise the literature on CBF and intracranial pulsatility in SVD patients, addressed the major limitations of current clinical studies of SVD, and also assessed CBF and intracranial pulsatility contemporaneously in well-characterised patients with SVD features. The overall results of the thesis challenge the traditional hypothesis of the cause and effect between low CBF and SVD, and suggest that increased cerebrovascular pulsatility, which might be due to intrinsic cerebral small vessel pathologies rather than just aortic stiffness, is important for SVD. More importantly, this pilot study also provides a reliable methodology for measuring intracranial pulsatility using phase-contrast MRI for future longitudinal or larger multicentre studies, and shows that intracranial pulsatility could be used as a secondary outcome in clinical trials of SVD. However, future research is required to elucidate the implication of venous pulsatility and to fully explore the passage of pulse wave transmission in the brain. Overall, this thesis advances knowledge and suggest potential targets for future SVD studies in terms of mechanisms, prevention and treatment.

[pt] O presente trabalho tem por objetivo o estudo de tensões críticas em bocais cilíndricos soldados a vasos de pressão, também cilíndricos, com tampas de geometria cônica submetidos a pressão interna e a um carregamento axial externo. O problema é atacado analiticamente através da teoria de cascas de revolução, particularizada para cascas finas axissimétricas. É utilizado o método de flexibilidade para imposição da continuidade dos esforços e deslocamentos nas junções bocal/tampa e tampa/vaso. Foi desenvolvido um programa de computador que fornece as tensões máximas que ocorrem no bocal, bem como as resultantes de tensão, momentos, deslocamentos e rotações ao longo da estrutura. Observou-se que para uma dada configuração do sistema (diâmetros do bocal e vaso, e ângulos da tampa cônica) existe uma relação ótima entre as espessuras do bocal e da tampa, para a qual o fator de concentração de tensões é mínimo. Esta relação é independente da rasão entre os carregamentos axial e a pressão. / [en] The present work is concerned whit critical stresses due to the combined affect of axial loads and intornal pressure in nossles welded to cilindrical pressure vessels whit conical hoads. The problem is treatod analytically through, axisimetric, thin ahell theory. The method of flexibility is employed to enforce the continuity of loads, moments, displacements and rotations at the junctions. A computer code has been developed for the calculation of the critical atresses in the nozzle, as well as the stresses resultants, moments, displacements, and the rotations along the atracture. It has been observed that for a griven configuration (nozzle and vessel diameters and angle of the conical head), there is an optimum between the nozzle and head thickness for which the stress concentration factor is minimum. This ratio is independent of the relation between the axial hoad and internal pressure.

A hiperplasia intimal é uma complicação comum após o implante de stent em artérias periféricas e a influência da homocisteína neste processo ainda é desconhecida. O objetivo deste estudo é comparar o espessamento intimal em aorta de suínos submetidos à hiper-homocisteinemia induzida com suínos normais, após implante de stents auto-expansíveis de nitinol. Foram utilizados 18 suínos da raça Macau, com peso médio de 30 kg. Os animais foram divididos aleatoriamente em dois grupos: o primeiro, grupo C (controle), foi alimentado com dieta normal e o outro, grupo M (metionina), recebeu dieta rica em metionina para induzir hiper-homocisteinemia durante 30 dias. Os stents utilizados para o experimento foram os auto-expansíveis, de nitinol, com 25 milímetros de comprimento e diâmetro final de oito milímetros. Foram realizadas dosagens de colesterol, triglicerídeos, colesterol HDL e homocisteína plasmática em ambos os grupos. A adequação das medidas do stent em relação às dimensões da artéria aorta dos suínos e a sua perviedade, após o implante, foram confirmadas mediante realização de arteriografias seletivas. Trinta dias após o implante do stent, os animais foram submetidos à eutanásia e as peças enviadas para exame anatomopatológico. O exame histológico mostrou intensa hiperplasia intimal no grupo controle e placas formadas por macrófagos espumosos com pouca hiperplasia intimal no grupo metionina. A análise morfométrica digital revelou maior hiperplasia intimal no grupo C em relação ao grupo M. Não ocorreram mudanças significativas nas dosagens de colesterol, triglicerídeos e colesterol HDL, em ambos os grupos. Não ocorreram variações significativas nos níveis de homocisteína plasmática dos suínos do grupo controle e, nos animais do grupo metionina, os níveis plasmáticos de homocisteína aumentaram de 17,47 para 58,90 μmol/l após 30 dias de administração de dieta rica em metionina. Concluindo, em aorta abdominal de suínos, alimentados com dieta rica em metionina por 30 dias, ocorreu uma hiperplasia intimal menor após o implante de stent auto-expansível de nitinol em comparação ao grupo controle. / Intimal hyperplasia is a common complication after stent placement in peripheral arteries and the influence of homocysteine in this process is still unknown. The purpose of this study is to compare the intimal thickening in the aorta of normal and induced hyperhomocysteinemic pigs following placement of self-expanding nitinol stents. The animals used were 18 pigs from the Macau specimen. They were over eight weeks old and average weight of 30 kg. Nitinol stents were self-expandable, 25 mm lenght and expanded diameters of 8 mm. The pigs were divided in two groups, the first (group C) was fed with a normal diet and the second group was fed with methionine rich diet to induce hyperhomocysteinemia (group M) during 30 days. Blood samples were collected for analyses of total cholesterol, triglycerides, and HDL and homocysteine concentrations. Assessment was done by angiography. After 30 days of the procedure, the animals where sacrificed and the abdominal aorta segment was removed for histological and digital morphometry analysis. Microscopic examinations of the aortas of the control group had a significant thicker intima compared with methionin group. In the comparison among groups, intimal thickening of the vessel wall at digital morphometric analysis was higher in group C than group M. There was no significant change in total cholesterol, triglycerides, and HDL concentrations in either group. There was no change in plasma homocysteine levels in group C; and in group M plasma homocysteine levels ranged from 17,47 to 59,80 μmol/l after 30 days with a methionine-rich diet. In conclusion, insertion of self-expandable nitinol stent in pig’s abdominal aorta after 30 days with a methionine-rich diet results in less intimal hyperplasia as compared to normal pigs.

[pt] Neste trabalho, apresenta-se uma nova proposta para forma de bocais radicais de vasos esféricos tal que as tensões de flexão devidas a um carregamento axial sejam as mínimas possíveis. Investigam-se os esforços de flexão oriundos da compatibilização entre o bocal e o vaso utilizando a técnina dos elementos finitos com um elemento curvílineo com três nós e um campo de deslocamentos com quatro variáveis. Obtem-se, também, a distribuição de tensões proveniente da pressão interna para o bocal ótimo para esforço axial. Considera-se a união tubulação-vaso esférico com espessuras diferentes utilizando um local com a mesma forma de meridiano dos bocais ótimos, tendo, porém, espessura de parede variável. Tendo como objetivo a comparação com os bocais ótimos, anali sam-se, também, os bocais tradicionais. A nova geometria mostrou-se, para os casos usuais de carga, superior á convecional, no que se refere aos níveis de tensão alcançados. / [en] A new shape of radial nozzles for spherical shells is presented in this paper. The geometry is obtained imposing a bending-free condition for the transition between a cylinder and sheperical shell. The soltion is exact for ideal boundary conditions, and under the action of axisymetric axial load. In order to examine the load effects introduced by the spherical an cylindrical shells at the ends of the nozzle, it was performed a stress analysis of the whole structure, using the finite element technique with a curvilinear element. Two load cases were considered: axial load and internal pressure, for constant thickness nozzles and nozzles with variable thickness, the results were compared with the stress distribuition for a conventional nozzle under the same loading conditions. The new geometry proved to be superior as compared with the conventional one as far a stress instensities are taken into account, for the usual loading conditions.

[pt] Neste trabalho são estudados diferentes tipos de estruturas sujeitas a carregamentos térmicos e sob condições de apoio distintas, com o objetivo de analisar o mecanismo de Thermical Ratchet. Tal fenômeno é previsto no aspecto de segurança de usinas nucleares, uma vez que vasos de pressão e tubulações podem sofrer deformações permanentes devido a diferenças térmicas. Um primeiro modelo estuda o comportamento de um conjunto de dois tubos ligados por suas extremidades e sujeitos a variações lineares de temperatura ao longo de suas seções transversais. Também são determinadas condições para que ocorra acúmulo de deformações plásticas. O terceiro modelo simula um vaso cilíndrico livre ou ligado à um flange a variações térmicas lineares na espessura, através do estudo de vigas sobre base elástica. Neste caso não se admite a estrutura sofrendo ciclos de temperatura e apenas o comportamento para o caso de aquecimento ou resfriamento é estudado. / [en] Different types of structures submitted to thermal loadings under different conditions of support are studied in this work, with the purpose of analysing the thermal Ratchet Mechanism. This phenomena is na important criteria of safety of nuclear power systems. A first model was used to simulate the bahavior of a structure free of bending, submitted to temperature fluctuation. The conditions for Ratcheting are determined. A second model was used to simulate the behavior of two tubes joinned at theirs ends, and submitted to a linear profile of temperature in its cross-section. A third model was used to beams on elastic foundation. This may be used to simulate the behavior of a cilindrical vessels submitted to thermal loadings.

Submitted by ALAN LIMA VIEIRA null (alan.vieira@hotmail.com) on 2016-03-23T00:12:16Z No. of bitstreams: 1 Dissertação ALAN LIMA VIEIRA.pdf: 3306402 bytes, checksum: bb2ced7b7ded44be46ee02b3cbf5db60 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-23T13:36:36Z (GMT) No. of bitstreams: 1 vieira_al_me_araiq.pdf: 3306402 bytes, checksum: bb2ced7b7ded44be46ee02b3cbf5db60 (MD5) / Made available in DSpace on 2016-03-23T13:36:36Z (GMT). No. of bitstreams: 1 vieira_al_me_araiq.pdf: 3306402 bytes, checksum: bb2ced7b7ded44be46ee02b3cbf5db60 (MD5) Previous issue date: 2016-03-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Estabelecer procedimentos simples, rápidos, eficientes e com preparo de amostras de baixo custo para determinar elementos em amostras de carne é um aspecto relevante para fins nutricionais e de saúde. Por esta razão, um sistema de digestão com aquecimento condutivo em frasco fechado (CHDS), foi avaliado recentemente para a decomposição de amostras “in natura” de músculo, fígado e rim (bovino, suíno e frango) visando a determinação de macronutrientes (Ca, Mg, Na, K, S e P), micronutrientes (Cu, Fe, Mn, Mo, Se e Zn) e contaminantes inorgânicos (As, Cd, Cr e Pb) por espectrometria de emissão óptica com plasma acoplado indutivamente (ICP OES) e espectrometria de massas com plasma acoplado indutivamente (ICP-MS). O aperfeiçoamento feito no CHDS foi planejado para melhorar a segurança, a praticidade e a robustez do sistema. Entre elas destaca-se a adaptação de um pistão a gás na tampa do gabinete de digestão; isolamento dos frascos no interior do gabinete de digestão; tampa de Teflon com sistema simples de alívio de pressão ao fim da decomposição sem manuseio do frasco. A precisão foi avaliada analisando três materiais de referência certificados digeridos pelo CHDS. As recuperações para Ca, Cu, Fe, Mg, Mn, Na, K, S, P e Zn determinados por ICP OES, variaram entre 85 a 106%. Para As, Cd, Cr, Mo, Pb e Se determinados por ICP-MS, foram obtidas recuperações entre 92 a 110%. A eficiência da digestão também foi avaliada pela determinação do teor de carbono residual, que variou de 10 a 12% m m-1. Quando as amostras de carne foram digeridas usando o CHDS, os resultados para Ca, Cu, Fe, Mg, Mn, Na, K, S, P e Zn determinados por ICP OES e para As, Cd, Cr, Mo, Pb e Se determinados por ICP-MS foram concordantes com aqueles obtidos após digestão ácida assistida por radiação micro-ondas em frasco fechado (MW-AD). Ao utilizar o CHDS, os limites de quantificação foram similares aos obtidos com a MW-AD para todos os analitos. O CHDS é capaz de digerir 800 mg de amostra de carne “in natura” utilizando 2 mL de HNO3 e 1 mL H2O2. O procedimento proposto foi capaz de atender a Instrução Normativa da Secretária de Defesa Agropecuária (SDA) nº 13 que trata do monitoramento de resíduos e contaminantes em carnes para As, Cd e Pb. Os resultados obtidos neste estudo estendem as aplicações do CHDS para amostras com maior teor de gordura, tais como músculo, fígado e rim. Este sistema de digestão simples e de baixo custo pode ser utilizado para preparar amostras para determinação subsequente de um grande número de elementos por espectrometria de ICP, incluindo espécies voláteis, tais como, As, Cd e Se. / Establishing simple, fast, efficient and low-cost sample preparation procedures to determine elements in meat samples is a relevant aspect for nutritional and health purposes. For this reason, the recently proposed closed-vessel conductivelyheated digestion system (CHDS) was evaluated for the decomposition of muscle, liver and kidney (cattle, pigs and chickens) samples fresh aiming for the determination of macronutrients (Ca, Mg, Na, K, S and P), micronutrients (Cu, Fe, Mn, Mo, Se and Zn) and inorganic contaminants (As, Cd, Cr and Pb) by inductively coupled plasma optical emission spectrometry (ICP OES) and inductively coupled plasma mass spectrometry (ICP-MS). The optimization of the CHDS was planned to improve safety, practicality and robustness such as adaptation of a gas piston in the digestion cabinet cover, isolation of vessels inside the digestion cabinet and a Teflon cap with a simple pressure relief system in the end of the decomposition without handling the vessel. The accuracy was evaluated by analyzing three certified reference materials digested by the CHDS. Recoveries for Ca, Cu, Fe, Mg, Mn, Na, K, S, P and Zn determinations by ICP OES varied from 85 to 106%. For As, Cd, Cr, Mo, Pb and Se determinations by ICP-MS, recoveries within the 92-110% were obtained. The digestion efficiency was also evaluated by determining the residual carbon content, which varied from 10 to 12% m m-1. When fresh meat samples were digested using the CHDS, results for Ca, Cu, Fe, Mg, Mn, Na, K, S, P and Zn determinations by ICP OES and for As, Cd, Cr, Mo, Pb and Se determinations by ICP-MS were in agreement with those obtained after closed-vessel microwave-acid digestion (MW-AD). When using the CHDS, limits of quantification were similar to those obtained with the MW-AD for all analytes. The CHDS enabled the digestion of 800 mg of fresh meat with 2 mL of HNO3 and 1 ml of H2O2. The proposed procedure was able to attend the normative instruction of agricultural defense secretary SDA N°. 13 for As, Cd and Pb. The results obtained in this study extend the applications of the CHDS to samples with higher contents of fat such as muscle, liver and kidney. This simple and low-cost digestion system can be used to prepare samples for subsequent determination of a large number of elements by ICP spectrometry, including volatile species such as As, Cd and Se.

A hiperplasia intimal é uma complicação comum após o implante de stent em artérias periféricas e a influência da homocisteína neste processo ainda é desconhecida. O objetivo deste estudo é comparar o espessamento intimal em aorta de suínos submetidos à hiper-homocisteinemia induzida com suínos normais, após implante de stents auto-expansíveis de nitinol. Foram utilizados 18 suínos da raça Macau, com peso médio de 30 kg. Os animais foram divididos aleatoriamente em dois grupos: o primeiro, grupo C (controle), foi alimentado com dieta normal e o outro, grupo M (metionina), recebeu dieta rica em metionina para induzir hiper-homocisteinemia durante 30 dias. Os stents utilizados para o experimento foram os auto-expansíveis, de nitinol, com 25 milímetros de comprimento e diâmetro final de oito milímetros. Foram realizadas dosagens de colesterol, triglicerídeos, colesterol HDL e homocisteína plasmática em ambos os grupos. A adequação das medidas do stent em relação às dimensões da artéria aorta dos suínos e a sua perviedade, após o implante, foram confirmadas mediante realização de arteriografias seletivas. Trinta dias após o implante do stent, os animais foram submetidos à eutanásia e as peças enviadas para exame anatomopatológico. O exame histológico mostrou intensa hiperplasia intimal no grupo controle e placas formadas por macrófagos espumosos com pouca hiperplasia intimal no grupo metionina. A análise morfométrica digital revelou maior hiperplasia intimal no grupo C em relação ao grupo M. Não ocorreram mudanças significativas nas dosagens de colesterol, triglicerídeos e colesterol HDL, em ambos os grupos. Não ocorreram variações significativas nos níveis de homocisteína plasmática dos suínos do grupo controle e, nos animais do grupo metionina, os níveis plasmáticos de homocisteína aumentaram de 17,47 para 58,90 μmol/l após 30 dias de administração de dieta rica em metionina. Concluindo, em aorta abdominal de suínos, alimentados com dieta rica em metionina por 30 dias, ocorreu uma hiperplasia intimal menor após o implante de stent auto-expansível de nitinol em comparação ao grupo controle. / Intimal hyperplasia is a common complication after stent placement in peripheral arteries and the influence of homocysteine in this process is still unknown. The purpose of this study is to compare the intimal thickening in the aorta of normal and induced hyperhomocysteinemic pigs following placement of self-expanding nitinol stents. The animals used were 18 pigs from the Macau specimen. They were over eight weeks old and average weight of 30 kg. Nitinol stents were self-expandable, 25 mm lenght and expanded diameters of 8 mm. The pigs were divided in two groups, the first (group C) was fed with a normal diet and the second group was fed with methionine rich diet to induce hyperhomocysteinemia (group M) during 30 days. Blood samples were collected for analyses of total cholesterol, triglycerides, and HDL and homocysteine concentrations. Assessment was done by angiography. After 30 days of the procedure, the animals where sacrificed and the abdominal aorta segment was removed for histological and digital morphometry analysis. Microscopic examinations of the aortas of the control group had a significant thicker intima compared with methionin group. In the comparison among groups, intimal thickening of the vessel wall at digital morphometric analysis was higher in group C than group M. There was no significant change in total cholesterol, triglycerides, and HDL concentrations in either group. There was no change in plasma homocysteine levels in group C; and in group M plasma homocysteine levels ranged from 17,47 to 59,80 μmol/l after 30 days with a methionine-rich diet. In conclusion, insertion of self-expandable nitinol stent in pig’s abdominal aorta after 30 days with a methionine-rich diet results in less intimal hyperplasia as compared to normal pigs.

abstract: The emergence of invasive non-Typhoidal Salmonella (iNTS) infections belonging to sequence type (ST) 313 are associated with severe bacteremia and high mortality in sub-Saharan Africa. Distinct features of ST313 strains include resistance to multiple antibiotics, extensive genomic degradation, and atypical clinical diagnosis including bloodstream infections, respiratory symptoms, and fever. Herein, I report the use of dynamic bioreactor technology to profile the impact of physiological fluid shear levels on the pathogenesis-related responses of ST313 pathovar, 5579. I show that culture of 5579 under these conditions induces profoundly different pathogenesis-related phenotypes than those normally observed when cultures are grown conventionally. Surprisingly, in response to physiological fluid shear, 5579 exhibited positive swimming motility, which was unexpected, since this strain was initially thought to be non-motile. Moreover, fluid shear altered the resistance of 5579 to acid, oxidative and bile stress, as well as its ability to colonize human colonic epithelial cells. This work leverages from and advances studies over the past 16 years in the Nickerson lab, which are at the forefront of bacterial mechanosensation and further demonstrates that bacterial pathogens are “hardwired” to respond to the force of fluid shear in ways that are not observed during conventional culture, and stresses the importance of mimicking the dynamic physical force microenvironment when studying host-pathogen interactions. The results from this study lay the foundation for future work to determine the underlying mechanisms operative in 5579 that are responsible for these phenotypic observations. / Dissertation/Thesis / Masters Thesis Biology 2016