This project proposes a reactor-based instrument, which retains most of the above advantages of spallation source engineering instruments, while maintaining the advantages inherent to steady-state instruments. The main idea is to allow the entire white beam from the reactor onto the sample---no monochromation. Diffraction is then allowed at a fixed angle, and information from two sample directions can be obtained simultaneously. Since a white beam is incident onto the sample, the diffraction condition is satisfied for multiple sample planes in the fixed angle of diffraction. Multiple analyzer/detector pairs are placed downstream from the sample and tuned to scatter only one of the diffracted wavelength bands. Monte Carlo methods were used to create models of both a standard two-axis engineering diffractometer, found on current reactor sources, and the proposed white beam instrument. There models were validated by experiments performed on a standard two-axis instrument, which was also modified to operate in a white beam configuration, in which the position of the sample and monochromator were interchanged. Both the models and the experiments of the white beam instrument showed proof of concept for this design and identified areas of concern that required special attention. Upon a comparison on the results from the standard two-axis instrument to the results from the white beam instrument (both simulation and experimental), it was found that the standard diffractometer showed a better performance in all aspects. However, this project proposes numerous areas where the white beam design can be improved upon in order to enhance its performance as an engineering instrument. The most important of these is the design of an appropriate analyzer/detector system, as the results overwhelmingly show this to be the area of greatest concern. Ideas for a few such designs are also given. / Thesis (Master, Physics, Engineering Physics and Astronomy) -- Queen's University, 2009-04-23 17:46:59.419

Made available in DSpace on 2014-07-29T15:29:08Z (GMT). No. of bitstreams: 1 Marcelo de sousa Vieira.pdf: 1862129 bytes, checksum: 7cc8be40ceb11c75c5ec56b362ffec29 (MD5) Previous issue date: 2009-04-14 / The animal replacement in expirements has been very encouraged by government and other institutions. However, in drugs development the animal replacement is not yet a reality, like at oral acute systemic tests. The validation of in vitro protocols is necessary for data generation with reproducibility, repetability and accuracy. In this study was validated at the Laboratório de Farmacologia e Toxicologia Celular- Faculdade de Farmácia/Universidade Federal de Goiás the protocol already validated by three laboratories (two in the USA and one at United Kingdom) and coordinated by ICCVAM: In Vitro Cytotoxicity Methods for Estimating Starting Doses for Acute Systemic Toxicity Tests, using the neutral red uptake in BAL/c 3T3-A31 cell line. It was used the grandisine, a lignan, and its major metabolite taken by fungi biodegradation. Our research group has identified a potential anti-tumoral action of grandisine, data not yet published. After in house validation we estimated the LD50 of grandisin and 4-O-demethylgrandisin: 617.72 mg/kg and 429.95 mg/kg, respectively. Both were classified under the GSH category 4. / A substituição ou redução do uso de animais em experimentos para a avaliação de toxicidade tem sido bastante encorajada e tem recebido grandes incentivos, inclusive financeiros, governamentais e institucionais. No entanto, a substituição completa da maioria dos testes mandatórios por agências reguladoras do setor ainda não é realidade, a exemplo, o teste de toxicidade oral aguda sistêmica. Neste contexto, se aplica a validação de testes in vitro para estimar dados in vivo. No presente trabalho, realizamos a validação in house do protocolo internacional e multilaboratorial recomendado pelo Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): Utilização da Citotoxicidade In Vitro na Estimativa de Doses Iniciais para Testes de Toxicidade Oral Aguda Sistêmica. Para tal, utilizamos o método de captação do corante vermelho neutro e a linhagem celular fibroblástica de camundongos BALB/c 3T3-A31. Dentre as substâncias recomendadas pelo ICCVAM para a validação do método foram investigadas 9 substâncias. A metabolização de produtos pelo organismo vivo é uma grande limitação dos testes in vitro. Utilizamos a grandisina, um tipo de ligana com grande potencial antitumoral e seu metabólito majoritário como substâncias modelos. Com utilização do metabólito conseguimos transpor esta barreira dos testes in vitro. Os resultados demonstraram que os dados obtidos estão em consonância com os dados da literatura sendo possível classificar ambas as substâncias na categoria GHS 4: grandisina e 4-Odemetilgrandisina: 617,72 mg/kg and 429,95 mg/kg, respectivamente.