Thesis (M.Eng.). / Written for the Dept. of Electrical and Computer Engineering. Title from title page of PDF (viewed 2009/06/17). Includes bibliographical references.

Thesis (M.S.)--Ohio University, June, 2004. / Includes bibliographical references (p. 99-100).

Thesis (M.S.)--Ohio University, June, 2004. / Title from PDF t.p. Includes bibliographical references (p. 99-100)

Thesis (Ph. D.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 79-82). Also available on the World Wide Web.

CAPES / Este trabalho descreve a caracterização de ondas acústicas flexurais que se propagam em fibras de cristal fotônico, nas quais estão gravadas Redes de Bragg, e que são excitadas com auxílio de um modulador acusto-óptico. Para sua medida foi desenvolvido um sistema óptico interferométrico, que permitiu a detecção das deflexões mecânicas do transdutor piezoelétrico e da fibra. Medidas da frequência e do período permitiram estimar a velocidade de fase das ondas acústicas flexurais. As ressonâncias do transdutor são verificadas até uma frequência de excitação de 1 MHz. Resultados de medidas realizadas em fibras monomodo convencionais também são apresentados, e as velocidades de fase estimadas são comparadas entre os dois tipos de fibra. / This work describes the characterization of flexural acoustic waves propagating in Photonic Crystal Fibers with inscribed Bragg gratings, which are excited by means of an acoustic-optic modulator. An interferometric optical system was developed in order to measure the flexural deformations of the piezoelectric transducer and of the fiber. Measurements of the excitation frequency and period allowed the phase velocity estimation of the flexural acoustic waves. The transducer resonances are checked up to an excitation frequency of 1 MHz. Measured values obtained in standard single mode fibers are also presented and the estimated phase velocities between both types of fibers are compared.

La résistance aux agents chimiothérapeutiques (Multidrug Resistance ou MDR) est caractérisée par la surexpression de différentes protéines membranaires de type ABC, parmi lesquelles, MRP1 et ABCG2 sont largement impliquées. Ces transporteurs diminuent les concentrations intracellulaires des agents chimiothérapeutiques en augmentant leur efflux de la cellule cancéreuse. Dans le but de contrecarrer cette chimiorésistance, nous avons conçu, synthétisé et étudié des activateurs de MRP1 et des inhibiteurs d'ABCG2. Les activateurs de MRP1 sont des dérivés de flavonoïdes et de vérapamil. Ces activateurs sont capables d'induire un efflux rapide et massif de glutathion cellulaire via MRP1 qui entraîne l'apoptose des cellules cancéreuses. Nous avons également conçu et synthétisé de nouveaux composés, dérivés de chromone, inhibiteurs sélectifs d'ABCG2, afin de restaurer la sensibilité des cellules cancéreuses aux agents chimiothérapeutiques. Mots clés : MRP1, ABCG2, flavonoïdes, analogues de vérapamil, chromones, inhibiteurs, activateurs / Resistance to chemotherapeutic agents (Multidrug Resistance or MDR) is characterized by the overexpression of membrane ABC proteins, such as MRP1 and ABCG2. These transporters decrease intracellular concentrations of chemotherapeutic agents by increasing their efflux from the cancer cell. In order to find effective modulators of drug resistance, we have designed, synthesized and investigated MRP1 activators and ABCG2 inhibitors. We designed and synthesized new derivatives of flavonoids and verapamil as activators of MRP1. These activators are capable of inducing a rapid and massive efflux of intracellular glutathione via MRP1 and causing cells death by apoptosis. We have also designed and synthesized new compounds, derivatives of chromone, as selective inhibitors of ABCG2, to restore sensitivity of cancer cells to chemotherapeutic agents. The biological evaluation of investigated compounds enabled us to identify new activators of MRP1 as well as potent and selective inhibitors of ABCG2. Keywords: MRP1, ABCG2, flavonoids, verapamil analogs, chromone, inhibitors, activators

This thesis is concerned with the guiding of cold atoms using optical forces, which is of great importance in the field of atom optics. Atomic beams can be used for precision sensor equipment, building nano-scale structures, construction of quantum computers and to further the understanding of the properties of atoms. Atoms are guided along light beams using the dipole force; there are two regimes under which this force works. Typically red-detuned guides are used (atoms are attracted towards the light) such guides, however, require large detuning and high powers. In this thesis we investigate the use of blue-detuned (atoms are repelled from the light) hollow light beams of moderate power (a few hundred mW) and confine atoms in the dark centre of the beams. Several magneto-optical traps (MOTs) have been constructed to exploit different guiding geometries. Hollow beams have been generated using a variety of methods; in particular the use of a computer controlled spatial light modulator (SLM) has provided great versatility and simplicity to the experimental arrangements. First, experiments were performed with a low-velocity intense source (LVIS) of atoms. A co-linear LG beam significantly enhances the observed flux, however, considerable difficulties are encountered loading atoms into oblique guides. Imaging a hole in the walls of the light tube was used to improve the loading efficiency. Second, guiding a free-falling atom cloud is performed using a non-diffracting Bessel beam. It is found that while the potential of the Bessel beam is steeper than equivalent LG beams the power distribution across the beam severely limits its usefulness. The next study investigated higher-order LG guide beams generated with an SLM. High order modes have a narrower profile so confine the atoms with less interaction with the guide beam, leading to a more natural guide (as opposed to a pushing force). Finally the SLM was used to create non-trivial beam shapes for beam splitters and interferometers.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In this study, a new modulator that is simple, robust and presents low operation costs was developed. This modulator uses compressed air to cool two small portions of the second chromatographic column of a GC×GC system. To evaluate the modulation process, solutions of alkanes C7 to C29, and pesticides (bifenthrin, cyfluthrin, cypermethrin, esfenvalerate, fenitrotion, fipronil, trifloxystrobin and trifluralin) were analyzed by GC×GC-FID. The results showed small variations of the peaks areas, between 0.67 and 2.80% for alkanes and between 0.24 and 5.34% for pesticides. The standard deviation (SD) for the retention time in the first column (1tR) was around 0.05 min, for alkanes and pesticides. For retention times in the second column (2tR), the SD was 0.04 s for the majority of the compounds, except for cyfluthrin and permethrin (0.08 s). The linear range was between 0.1 and 5.0 mg L-1 with a coefficient of determination (r2) greater than 0.9945 for pesticides analyzed by GC×GC-FID. The GC×GC system proposed was applied in the determination of pyrethroid pesticides (bifenthrin, cypermethrin, deltamethrin, fenvalerate and esfenvalerate and permethrin cis and trans) in grape samples Italy cultivar spiked at 3 levels (0.02, 0.05 and 0.5 mg kg- 1). Samples were extracted by the mini-Luke modified method (acetone method) and pesticides were quantified by GC×GC-μECD. The parameters evaluated in the validation of the method were: analytical curve, linearity, limit of detection (LOD), limit of quantification (LOQ), precision (in terms of repetitivity and intermediate precision) and accuracy (recovery), as well as the matrix effect on the chromatographic response. All analytical curves showed a linear range between 0.02 and 0.5 mg L-1 with r2 greater than 0.9956 and 0.9994 for the curves prepared in solvent (ethyl acetate) and matrix extract (grape), respectively. From the results obtained by calculation of the matrix effect percentage it can be concluded that the pyrethroid pesticides showed a considerable negative matrix effect. The values of method LOQ were 0.01 to 0.02 mg kg-1 for all pyrethroids. The values of recovery for the 3 spiked levels were between 94.3 and 115.2%, with good precision (RSD<18.4%), demonstrating that the performance of the mini-Luke modified method employed for the extractions is satisfactory. This study also showed that the GC×GC-μECD system using a modulator with a double jet of compressed air has potential for application in the analysis of pyrethroid pesticide residues in grapes, since it supplies low values of LOD and LOQ, and good accuracy in the analytical response. / Neste trabalho foi desenvolvido um novo modulador, simples, robusto e de baixo custo de operação. Este modulador utiliza ar comprimido para resfriar duas pequenas porções da segunda coluna cromatográfica de um sistema GC×GC. Para avaliar o processo de modulação utilizaram-se soluções de alcanos C7 a C29 e pesticidas (bifentrina, ciflutrina, cipermetrina, esfenvalerato, fenitrotiona, fipronil, trifloxistrobina e trifluralina) e análise por GC×GC-FID. Os resultados mostraram pequenas variações das áreas dos picos, entre 0,67 e 2,80% para alcanos e entre 0,24 e 5,34% para pesticidas. O desvio padrão (SD) para o tempo de retenção na primeira coluna (1tR) de alcanos e pesticidas foi em torno de 0,05 min. Para o tempo de retenção na segunda coluna (2tR), o SD foi de 0,04 s para a maioria dos compostos, exceto para ciflutrina e permetrina (0,08 s). A faixa linear situou-se entre 0,1 e 5,0 mg L-1 com coeficiente de determinação (r2) maior que 0,9945 para os pesticidas analisados por GC×GC-FID. O sistema GC×GC proposto foi aplicado na determinação de pesticidas piretróides (bifentrina, cipermetrina, deltametrina, fenvalerato e esfenvalerato, e permetrina cis e trans) em amostras de uva cultivar Itália fortificadas em 3 níveis (0,02; 0,05 e 0,5 mg kg-1). As amostras foram extraídas pelo método de mini-Luke modificado (método da acetona) e os pesticidas quantificados por GC×GC-μECD. Os parâmetros avaliados de validação do método foram: curva analítica, linearidade, limite de detecção (LOD), limite de quantificação (LOQ), precisão (em termos de repetitividade e precisão intermediária) e exatidão (recuperação), bem como o efeito matriz na resposta cromatográfica. Todas as curvas analíticas apresentaram faixa linear entre 0,02 e 0,5 mg L-1 com valores de r2 maiores que 0,9956 e 0,9994 para as curvas preparadas em solvente (acetato de etila) e extrato da matriz (uva), respectivamente. A partir dos resultados obtidos através do cálculo do efeito matriz percentual concluiu-se que os pesticidas piretróides avaliados apresentaram considerável efeito matriz negativo. Os valores de LOQ do método foram de 0,01 a 0,02 mg kg-1 para todos os piretróides. A recuperação para os 3 níveis de fortificação ficou entre 94,3 e 115,2%, com boa precisão (RSD<18,4%), o que mostrou que o desempenho do método mini-Luke modificado empregado para as extrações é satisfatório. Este estudo mostrou também, que o sistema GC×GC-μECD com modulador de duplo jato de ar comprimido tem potencial para aplicação nas análises de resíduos de pesticidas piretróides em uva, uma vez que fornece baixos valores de LOD e LOQ, e boa precisão da resposta analítica.

Apoptosis is the mechanism by which complex multicellular organisms induce the programmed death of damaged cells, thus maintaining tissue homeostasis. One of the main hallmarks of cancer, apoptosis is tightly regulated by pro- and anti-apoptotic factors whose equilibrium will decide of the fate of the cell. Among these factors, the cellular inhibitor of apoptosis cIAP1 is a key regulator of nuclear factor-κB dependent signaling and of caspase-8 mediated apoptosis. cIAP1 expression is controlled primarily at the translational level through an internal ribosome entry site (IRES) that facilitates the recruitment of the ribosome to the translation initiation start independently of the 5’ cap. We have previously identified four putative IRES trans-acting factors (ITAFs) that bind specifically to the cIAP1 IRES, namely NF45, NF90, IGF2BP1 and RH1. My research project characterised NF45 as an ITAF that positively regulates the IRES-mediated translation of cIAP1 and of the Xlinked inhibitor of apoptosis, XIAP. This regulation is important for maintaining Survivin and Cyclin E protein levels and insuring proper cell division. Furthermore, I showed that IGF2BP1 is another ITAF that is overexpressed in rhabdomyosarcoma cancer (RMS) and positively regulates cIAP1 translation, thus leading to apoptotic resistance in these cells. Importantly, the use of Smac mimetics, chemical compounds that cause cIAP1 proteasomal degradation, induces TNFα-mediated apoptosis of RMS cells and leads to growth inhibition of RMS xenograft tumors as well as significantly improved survival. Finally, I show that certain modulators of innate immunity synergize with Smac mimetics to improve the killing of RMS cancer cells. Hence, cIAP1 translation regulation by NF45 and IGF2BP1 is highly important for maintaining proper functioning of the cell and dysregulation of these ITAFs can lead to carcinogenesis.

Orientador: Claudio Kitano / Resumo: Sistemas ópticos operando em altas frequências utilizam modulação externa do laser, em especial através de moduladores baseados no efeito eletroóptico linear, onde se aplicam guias de ondas de dimensões reduzidas com eletrodos planares. Assim, é importante e conveniente determinar as propriedades e a distribuição do campo elétrico modulador de modo a conhecer outras características da estrutura, como resposta em frequência e potência de modulação. Neste trabalho, isto foi feito através do método de abordagem de domínio espectral. Contudo, este método apresenta imprecisões em estruturas com assimetria de eletrodos, aplicando-se então o método das imagens, clássico no eletromagnetismo, aliado à técnica de abordagem de domínio espectral. Esta nova abordagem permite a obtenção de funções de base adequadas à análise de parâmetros como o campo elétrico, assim como os demais parâmetros característicos dos guias de ondas planos. Este trabalho apresenta esta abordagem e seus resultados comparando-os à simples translação das funções de base para estruturas simétricas, validando a técnica proposta, bem como se propõe a desenvolver um conjunto de rotinas numéricas utilizando para isso o software Matlab. Através do processo de desenvolvimento das rotinas numéricas são apresentadas as dificuldades e metodologias de solução para implementação do método automatizado. Além de permitir a automatização de todo o processo de cálculo, minimizando a interferência humana, neste trabalho também é de... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor