Exposure of cells to hydrogen peroxide can cause oxidative damage to cellular constituents including lipids, protein, and DNA. At elevated concentrations, hydrogen peroxide can trigger cell death by apoptosis or necrosis. Apoptotic cell death can be prevented by overexpression of the oncoprotein Bcl-2. The exact mechanism by which Bcl-2 blocks cell death is controversial. Some researchers believe that Bcl-2 possesses antioxidant properties that protect cells from apoptosis. The purpose of this thesis was to assess oxidative stress and apoptosis following hydrogen peroxide exposure in Jurkat T cells overexpressing Bcl-2. One of the major objectives was to ascertain whether or not Bcl-2 overexpression elevated the antioxidant capacity of Jurkat T cells to provide protection from oxidant-induced cell death. Hydrogen peroxide treated Jurkat cells became apoptotic at moderate levels of oxidant (25-100 uM H2O2), and necrotic at higher doses (greater than 200 uM H2O2). Bcl-2 overexpression prevented caspase activation and cell death at the apoptotic doses of H2O2, but not the necrotic doses. Caspase inhibition studies demonstrated that Bcl-2 overexpression provided a greater level of resistance from H2O2-induced cell death than the broad-spectrum caspase inhibitor z-VAD.fmk. A systematic study was carried out examining the antioxidant status of Jurkat cells overexpressing Bcl-2. Several Bcl-2 transfectants were utilised for the study, so that any differences seen could be correlated to the level of Bcl-2 expression. Surprisingly, there were no statistically significant differences among the Bcl-2 transfectants for any of the antioxidant enzymes. Jurkat cells overexpressing Bcl-2 exhibited the same level of oxidative damage to lipids and protein in response to H2O2 exposure as the parental Jurkat cells. Interestingly, Jurkat cells overexpressing Bcl-2 continued to grow in culture after H2O2 exposure, despite harboring damage to cellular constituents. Consistent with these results, H2O2 treated Jurkat cells overexpressing Bcl-2, which failed to undergo apoptosis, were more prone to genomic instability. Together, these findings suggest that Bcl-2 overexpression protects Jurkat cells from H2O2-induced cell death by blocking apoptosis. Jurkat cells overexpressing Bcl-2 were no better at detoxifying oxidants and showed the same level of oxidative damage following H2O2 exposure. As a result, the overexpression of Bcl-2 considerably enhanced the mutagenicity of H2O2.

Doctor of Philosophy / We investigate the linear growth and vertical structure of the magnetorotational instability (MRI) in weakly ionised, stratified accretion discs. The magnetic field is initially vertical and perturbations have vertical wavevectors only. Solutions are obtained at representative radial locations from the central protostar for different choices of the initial magnetic field strength, sources of ionisation, disc structure and configuration of the conductivity tensor. The MRI is active over a wide range of magnetic field strengths and fluid conditions in low conductivity discs. For the minimum-mass solar nebula model, incorporating cosmic ray and x-ray ionisation and assuming that charges are carried by ions and electrons only, perturbations grow at 1 AU for B < 8G. For a significant subset of these strengths (200mG < B < 5 G), the growth rate is of order the ideal MHD rate (0.75 Omega). Hall conductivity modifies the structure and growth rate of global unstable modes at 1 AU for all magnetic field strengths that support MRI. As a result, at this radius, modes obtained with a full conductivity tensor grow faster and are active over a more extended cross-section of the disc, than perturbations in the ambipolar diffusion limit. For relatively strong fields (e.g. B > 200 mG), ambipolar diffusion alters the envelope shapes of the unstable modes, which peak at an intermediate height, instead of being mostly flat as modes in the Hall limit are in this region of parameter space. Similarly, when cosmic rays are assumed to be excluded from the disc by the winds emitted by the magnetically active protostar, unstable modes grow at this radius for B < 2 G. For strong fields, perturbations exhibit a kink at the height where x-ray ionisation becomes active. Finally, for R = 5 AU (10 AU), unstable modes exist for B < 800 mG (B < 250 mG) and the maximum growth rate is close to the ideal-MHD rate for 20 mG < B < 500 mG (2 mG < B < 50 mG). Similarly, perturbations incorporating Hall conductivity have a higher wavenumber and grow faster than solutions in the ambipolar diffusion limit for B < 100 mG (B < 10 mG). Unstable modes grow even at the midplane for B > 100 mG (B ~ 1 mG), but for weaker fields, a small dead region exists. When a population of 0.1 um grains is assumed to be present, perturbations grow at 10 AU for B < 10 mG. We estimate that the figure for R = 1 AU would be of order 400 mG. We conclude that, despite the low magnetic coupling, the magnetic field is dynamically important for a large range of fluid conditions and field strengths in protostellar discs. An example of such magnetic activity is the generation of MRI unstable modes, which are supported at 1 AU for field strengths up to a few gauss. Hall diffusion largely determines the structure and growth rate of these perturbations for all studied radii. At radii of order 1 AU, in particular, it is crucial to incorporate the full conductivity tensor in the analysis of this instability, and more generally, in studies of the dynamics of astrophysical discs.

No description available.

No description available.

Diss. (sammanfattning) Göteborg : Univ. , 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

Όταν ένα εναλλασσόμενο ηλεκτρικό πεδίο, χαμηλής συχνότητας, εφαρμόζεται κάθετα σε ένα στρώμα νηματικού υγρού κρυστάλλου, με πάχος της τάξης από 10 μm έως 100 μm, παρατηρείται ένας αναπροσανατολισμός του πεδίου του κατευθυντή. Πρόκειται για την περίπτωση της μονοδιάστατης μετάβασης Freedericsz, όπως επίσης και για τη δισδιάστατη ή τρισδιάστατη περίπτωση της ηλεκτροϋδροδυναμικής αστάθειας. Λόγω της διπλοθλαστικότητας των νηματικών υγρών κρυστάλλων, η έναρξη της αστάθειας, και στις δύο περιπτώσεις, προκαλεί σε μονοχρωματική φωτεινή δέσμη, που προσπίπτει στο νηματικό στρώμα, αλλαγή στην ένταση ή/και στη φάση της, με επακόλουθο ιδιαίτερα οπτικά αποτελέσματα. Οι αστάθειες παρατηρούνται όταν η εξωτερικά εφαρμοζόμενη εναλλασσόμενη τάση είναι υψηλότερη από μία τιμή κατωφλίου, ο προσδιορισμός της οποίας έχει ιδιαίτερη σημασία σε πιθανές ηλεκτροοπτικές εφαρμογές των νηματικών υγρών κρυστάλλων. Το κατώφλι της αστάθειας καθορίζεται μέσω της παρατήρησης του οπτικού αποτελέσματος, καθώς η φωτεινή δέσμη προσπίπτει στο νηματικό στρώμα. Όταν η εξωτερικά εφαρμοζόμενη τάση είναι χαμηλότερη ή ίση με την τιμή κατωφλίου, το οπτικό αποτέλεσμα είναι μηδενικό. Καθώς η τιμή της τάσης αυξάνει, σταδιακά εμφανίζεται, όλο και πιο έντονα, το ιδιαίτερο οπτικό αποτέλεσμα της αστάθειας. Έχοντας υπόψη την παραπάνω πειραματική συμπεριφορά, μπορεί κανείς να υπολογίσει την τάση κατωφλίου αρκεί να καθορίσει, μέσω οπτικής παρατήρησης, το σημείο έναρξης της αστάθειας. Στην παρούσα εργασία παρουσιάζεται μία αντικειμενική μέθοδος πειραματικού προσδιορισμού της ηλεκτροϋδροδυναμικής αστάθειας, βασισμένη στην εξάρτηση του χρόνου αποκατάστασης του κατευθυντή, Τ, από την τιμή του εξωτερικά εφαρμοζόμενου ηλεκτρικού πεδίου. Όταν η εφαρμοζόμενη τάση τείνει στην τιμή κατωφλίου, ο ρυθμός εξασθένισης, 1/Τ, του πεδίου του κατευθυντή τείνει στο μηδέν. Επομένως, η γραφική παράσταση του 1/Τ σε συνάρτηση με την εξωτερικά εφαρμοζόμενη τάση καθιστά δυνατό τον προσδιορισμό της τάσης κατωφλίου της αστάθειας. / When an AC electric field in the acoustic frequency range is applied perpendicularly to a nematic liquid crystal layer, with a thickness of the order of 10μm to 100μm, a reorientation of the director of the nematic layer is observed. This is the case of the one dimensional Freedericsz instability, as well as of the two or three dimensional electrohydrodynamic instability. Due to the birefringence of any nematic material, the onset of the instability in both cases causes a monochromatic light beam illuminating the nematic layer, to change its intensity and/or its phase, resulting in spectacular optical effects. On the other hand, the instabilities are observed when the applied AC voltage is larger than a threshold value, the determination of which is of major importance for the potential electro-optical applications of nematic liquid crystals. As a rule, the instability threshold is determined by observing its optical effect on the incident of the monochromatic light beam : When the applied voltage is lower than or equal to its threshold value, the optical effect is zero. Upon further increasing of the applied voltage, the optical effect increases gradually. The measurement of the threshold voltage, based on the above experimental behavior, leads to a subjective estimation of the experimental result. One has to decide which optical result has to be considered to mark the onset of the instability. In what follows, we present a completely objective method for the experimental determination of the instability threshold, based on the dependence of the decay time, T, of the director field on the value of the electric field applied across the nematic layer. When the applied voltage tends to its threshold value, the decay rate, 1/T, of the director field tends to zero. Thus, plotting 1/T as a function of the applied voltage, enables us to graphically determine the threshold value of the latter.

Submitted by Eduardo Felipe de Campos null (eduardo81010@aluno.feis.unesp.br) on 2018-01-11T17:05:53Z No. of bitstreams: 1 DISSERTACAO.pdf: 18831766 bytes, checksum: c62a5bf82a73cc4a7517b74b6a078fb4 (MD5) / Approved for entry into archive by Cristina Alexandra de Godoy null (cristina@adm.feis.unesp.br) on 2018-01-11T18:55:13Z (GMT) No. of bitstreams: 1 campos_ef_me_ilha.pdf: 18831766 bytes, checksum: c62a5bf82a73cc4a7517b74b6a078fb4 (MD5) / Made available in DSpace on 2018-01-11T18:55:13Z (GMT). No. of bitstreams: 1 campos_ef_me_ilha.pdf: 18831766 bytes, checksum: c62a5bf82a73cc4a7517b74b6a078fb4 (MD5) Previous issue date: 2017-08-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Estruturas de paredes finas são muito utilizadas na engenharia moderna devido sua boa relação entre peso e resistência. Sua aplicação vai desde obras civis, como cúpulas em edifícios e pontes, até estruturas aeronáuticas e equipamentos industriais. Uma geometria que é muito comum de ser encontrada nas estruturas de paredes finas são os cilindros, como pode ser observado no corpo dos aviões, tubulações e vasos de pressão. Submetidas a esforços compressivos, essas estruturas ficam suscetíveis ao fenômeno de instabilidade ou flambagem, podendo entrar em colapso repentinamente, mesmo antes de apresentar altas tensões. Assim, compreender o comportamento da instabilidade se torna crucial em um projeto de estruturas de paredes finas. Um dos fatores que influenciam no comportamento da instabilidade é a imperfeição geométrica da estrutura, e qualquer processo de fabricação possui erros associados ao processo. Para iniciar o estudo foi necessário medir os defeitos devido ao processo de fabricação do cilindro. Duas alternativas para realizar as medidas foram propostas, a primeira utilizando LVDTs, que medem a variação do raio do cilindro ao longo de toda sua extensão, e a segunda o fotoprocessamento. Ambos os métodos nos deram uma nuvem de pontos que foram processadas para obter a estrutura 3D CAD, possibilitando sua análise pelo método de elementos finitos e obtenção das respectivas cargas de flambagem numéricas. Além do método numérico foi realizado um ensaio experimental visando validar a análise numérica. O cilindro foi fechado com duas tampas e montado em uma bancada experimental, instrumentado com LVDTs, manômetro e por fim, uma bomba de vácuo foi ligada a uma das tampas. A bomba criou vácuo dentro do cilindro até o mesmo sofrer colapso. As cargas de flambagem numéricas foram superiores a encontrada experimentalmente em 14,48% a geometria foto, 11,72% da geometria LVDT e 39,98% a do cilindro referência. Os resultados mostram que as imperfeições geométricas são de grande relevância na resistência a instabilidade de uma estrutura, e também que grandes imperfeições geométricas tendem a ser o local onde ocorrem as ondas de flambagem. Em relação ao método de medição por fotoprocessamento os resultados mostram que é interessante estudar a técnica para aplicações na área de instabilidade. / Thin-walled structures are widely used in modern engineering because of their good weight-to-strength ratio. Its application ranges from civil works, such as domes in buildings and bridges, to aeronautical structures and industrial equipment. One geometry that is very common to be found in thin-walled structures is the cylinder, as can be seen in the body of airplanes, pipes and pressure vessels. Under compressive stresses, these structures are susceptible to the buckling phenomenon, which can suddenly collapse, even before presenting high stresses. Therefore, understanding the behavior of instability becomes crucial in designing thin-walled structures. One of the factors influencing the behavior of instability is the geometric imperfection of the structure, and any manufacturing process has errors associated with the process. To begin the study it was necessary to measure the defects due to the cylinder manufacturing process. Two alternatives to carry out the measurements were proposed, the first using LVDTs, which measure the variation of the cylinder radius along its length, and the second the photoprocessing. Both methods gave us a point cloud that were processed to obtain the 3D CAD structure, allowing its analysis by the finite element method and obtaining the respective numerical buckling loads. In addition to the numerical method, an experimental test was carried out to validate the numerical analysis. The cylinder was closed with two flat heads and mounted on an experimental bench, instrumented with LVDTs, manometer and finally, a vacuum pump was attached to one of the flat heads. The pump has created a vacuum inside the cylinder until it collapses. Numerical buckling loads were greater than that found experimentally at 14.48 % photo geometry, 11.72 % LVDT geometry and 39.98 % a reference cylinder. The results show that the geometric imperfections are of great relevance in the resistance to buckling of a structure, and also that great geometric imperfections tend to be the place where the buckling waves occur. Regarding the method of measurement by photoprocessing the results show that it is interesting to study the technique for applications in the area of instability. / CAPES: 1544963

Orientador: Amarildo Tabone Paschoalini / Resumo: Estruturas de paredes finas são muito utilizadas na engenharia moderna devido sua boa relação entre peso e resistência. Sua aplicação vai desde obras civis, como cúpulas em edifícios e pontes, até estruturas aeronáuticas e equipamentos industriais. Uma geometria que é muito comum de ser encontrada nas estruturas de paredes finas são os cilindros, como pode ser observado no corpo dos aviões, tubulações e vasos de pressão. Submetidas a esforços compressivos, essas estruturas ficam suscetíveis ao fenômeno de instabilidade ou flambagem, podendo entrar em colapso repentinamente, mesmo antes de apresentar altas tensões. Assim, compreender o comportamento da instabilidade se torna crucial em um projeto de estruturas de paredes finas. Um dos fatores que influenciam no comportamento da instabilidade é a imperfeição geométrica da estrutura, e qualquer processo de fabricação possui erros associados ao processo. Para iniciar o estudo foi necessário medir os defeitos devido ao processo de fabricação do cilindro. Duas alternativas para realizar as medidas foram propostas, a primeira utilizando LVDTs, que medem a variação do raio do cilindro ao longo de toda sua extensão, e a segunda o fotoprocessamento. Ambos os métodos nos deram uma nuvem de pontos que foram processadas para obter a estrutura 3D CAD, possibilitando sua análise pelo método de elementos finitos e obtenção das respectivas cargas de flambagem numéricas. Além do método numérico foi realizado um ensaio experimental visando vali... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Thin-walled structures are widely used in modern engineering because of their good weight-to-strength ratio. Its application ranges from civil works, such as domes in buildings and bridges, to aeronautical structures and industrial equipment. One geometry that is very common to be found in thin-walled structures is the cylinder, as can be seen in the body of airplanes, pipes and pressure vessels. Under compressive stresses, these structures are susceptible to the buckling phenomenon, which can suddenly collapse, even before presenting high stresses. Therefore, understanding the behavior of instability becomes crucial in designing thin-walled structures. One of the factors influencing the behavior of instability is the geometric imperfection of the structure, and any manufacturing process has errors associated with the process. To begin the study it was necessary to measure the defects due to the cylinder manufacturing process. Two alternatives to carry out the measurements were proposed, the first using LVDTs, which measure the variation of the cylinder radius along its length, and the second the photoprocessing. Both methods gave us a point cloud that were processed to obtain the 3D CAD structure, allowing its analysis by the finite element method and obtaining the respective numerical buckling loads. In addition to the numerical method, an experimental test was carried out to validate the numerical analysis. The cylinder was closed with two flat heads and mounted on an expe... (Complete abstract click electronic access below) / Mestre