Search

Orientador: Prof. Dr. Cícero Ribeiro de Lima Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Engenharia Mecânica, Santo André, 2022. O domínio do tempo é a alternativa mais amplamente escolhida em testes de fadiga mecânica para representar completamente eventos aleatórios em vários canais simultâneos, como uma interação entre a suspensão do veículo e o solo. A razão para isso é a possibilidade de uma reprodução completa desses eventos físicos em uma bancada de teste, sem nenhuma matemática adicional, simplificação e/ou pós-processamento. Ou seja, o conjunto de entrada de cargas/deslocamentos obtido em ensaio de campo é o mesmo executado em equipamento de teste de laboratório. A principal desvantagem dessa abordagem é a longa duração de teste e o alto custo do equipamento. Os hardwares necessários para esses testes são complexos, compostos por servo atuadores, a fim de incitar uma determinada quantidade de carga em uma janela de tempo. O tempo necessário para completar o teste também é longo, pois consiste na mesma duração da prova multiplicada pelo número de repetições para atingir o desempenho de fadiga. Os testes de bancada de fadiga no domínio da frequência, por outro lado, são alternativas potenciais para superar essas desvantagens. Ou seja, requerem equipamentos menos sofisticados, uma vez que exigem apenas atuadores simples em vez de servos atuadores e a duração do teste é reduzida, pois o comprimento total do evento é substituído por repetições constantes e dano constante. Este trabalho propõe e explora um novo método que utiliza o resultado estimado da fadiga estrutural como ponto de partida e, através da solução de um problema de otimização, determina quais cargas/deslocamentos as causaram no domínio da frequência. O objetivo é auxiliar futuros desenvolvimentos em testes de fadiga, suplantando os testes no domínio do tempo sem perder a correlação com eventos físicos. The time domain is the most widely chosen alternative in mechanical fatigue tests to completely represent random events across multiple simultaneous channels, such as an interaction between vehicle suspension and the ground. The reason for this is the possibility of a complete reproduction of these physical events on a test bench, without any additional math, simplification and / or post-processing. That is, the load/displacement input set obtained in the field test is the same as that performed in laboratory test equipment. The main disadvantage of this approach is the long test duration and the high cost of the equipment. The hardware required for these tests is complex, composed of servo actuators, in order to incite a certain amount of charge in a window of time. The time required to complete the test is also long, as it consists of the same duration of the test multiplied by the number of repetitions to achieve fatigue performance. Frequency fatigue bench tests, on the other hand, are potential alternatives to overcome these disadvantages. That is, they require less sophisticated equipment, since they require only simple actuators instead of servo actuators and the test duration is reduced, as the total length of the event is replaced by constant repetitions and constant damage. This work proposes and explores a new method that uses the result of structural fatigue as a starting point and, through the solution of an optimization problem, it determines which loads/displacements caused them in the frequency domain. The objective is to assist future developments in fatigue tests, supplanting tests in the time domain without losing the correlation with physical events.

Purpose: To investigate the effects and mechanisms of atorvastatin and celecoxib administered individually or in combination on human prostate cancer PC-3 cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. Experimental Design: Human prostate cancer PC-3 cells in culture were treated with atorvastatin and celecoxib alone or in combination. Severe combined immunodeficient (SCID) mice were injected s.c. with PC-3 cells. The mice received daily i.p injections starting 2 days before tumor cell inoculation and continuing during the course of treatment with atorvastatin (10 μg/g body weight/d), celecoxib (10 μg/g/d), a combination of atorvastatin (10 μg/g/d) and celecoxib (10 μg/g/d), or a combination of atorvastatin (5 μg/g/d) and celecoxib (5 μg/g/d). Results: Atorvastatin in combination with celecoxib had stronger effects on growth inhibition and apoptosis of PC-3 cells than either agent used individually. Atorvastatin and celecoxib in combination also had a stronger inhibitory effect on activation of nuclear factor-κB and extracellular signal-regulated kinase 1/2 in PC-3 cells than either agent alone. Treatment of SCID mice with combinations of atorvastatin and celecoxib more effectively inhibited the formation and growth of PC-3 tumors in the mice than either agent administered alone. Conclusions: A combination of atorvastatin and celecoxib had a more potent inhibitory effect on the growth of PC-3 cells cultured in vitro or grown in SCID mice than either agent alone. A combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer.

Epidemiological studies indicate that statins and non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of prostate cancer. In the present study, we assessed the effects of Lipitor and Celebrex alone or in combination on androgen-independent growth of human prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. In the in vitro studies, LNCaP cells were cultured in medium supplemented with charcoal-stripped fetal bovine serum to mimic androgen-deprivation treatment. We found that treatment of LNCaP cells cultured in androgen-depleted medium with Lipitor or Celebrex alone resulted in growth inhibition and apoptosis. A combination of Lipitor and Celebrex had more potent effects on growth inhibition and apoptosis than either agent alone. In animal studies, severe combined immunodeficient (SCID) mice were injected subcutaneously with LNCaP cells in Matrigel. After 4-6 weeks, mice with LNCaP tumors (about 0.6 cm wide and 0.6 cm long) were surgically castrated and received daily i.p injections with vehicle, Lipitor (10 μg/g body weight/day), Celebrex (10 μg/g/day) or a combination of Lipitor (5 μg/g/day) and Celebrex (5 μg/g/day) for 42 days. In the vehicle control group, LNCaP tumors regressed initially in response to castration and then re-grew in 2 weeks after castration to develop androgen-independent tumors. Treatment of the mice with Lipitor or Celebrex alone suppressed the re-growth of LNCaP tumors after castration. A combination of low doses of Lipitor and Celebrex had a more potent effect for inhibiting the androgen-independent growth of LNCaP tumors than a higher dose of either agent alone. The results from our study indicate that a combination of Lipitor and Celebrex may be an effective strategy for the prevention of prostate cancer progression from androgen-dependence to an androgen-independent stage.