The role of redox signaling in the molecular mechanism of tamoxifen resistance in breast cancer.

The emergence of tamoxifen or aromatase inhibitor resistance is a major problem in the treatment of breast cancer. The molecular signaling mechanism of antiestrogen resistance is not clear. Understanding the mechanisms by which resistance to these agents arise could have major clinical implications for preventing or circumventing it. Therefore, in this dissertation we have investigated the molecular mechanisms underlying antiestrogen resistance by studying the contributions of reactive oxygen species (ROS)-induced redox signaling pathways in antiestrogen resistant breast cancer cells. Our hypothesis is that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with a progressive shift towards a pro-oxidant environment of cells as a result of oxidative stress. The hypothesis of this dissertation was tested in an in vitro 2-D cell culture model employing state of the art biochemical and molecular techniques, including gene overexpression, immunoprecipitation, Western blotting, confocal imaging, ChIP, Real-Time RT-PCR, and anchorage-independent cell growth assays. We observed that tamoxifen (TAM) acts like both an oxidant and an antioxidant. Exposure of tamoxifen resistant LCC2 cell to TAM or 17 beta-estradiol (E2) induced the formation of reactive oxidant species (ROS). The formation of E2-induced ROS was inhibited by co-treatment with TAM, similar to cells pretreated with antioxidants. In LCC2 cells, treatments with either E2 or TAM were capable of inducing cell proliferation which was then inhibited by biological and chemical antioxidants. Exposure of LCC2 cells to tamoxifen resulted in a decrease in p27 expression. The LCC2 cells exposed to TAM showed an increase in p27 phosphorylation on T157 and T187. Conversely, antioxidant treatment showed an increase in p27 expression and a decrease in p27 phosphorylation on T157 and T187 in TAM exposed cells which were similar to the effects of Fulvestrant. In line with previous studies, we showed an increase in the binding of cyclin E-Cdk2 and in the level of p27 in TAM exposed cells that overexpressed biological antioxidants. Together these findings highly suggest that lowering the oxidant state of antiestrogen resistant LCC2 cells, increases LCC2 susceptibility to tamoxifen via the cyclin dependent kinase inhibitor p27.

Pre-Disaster Risk Management in Post-Earthquake (1999) Turkey

This paper assesses the status of pre-disaster risk management in the case of Turkey. By focusing on the period following the catastrophic August 17, 1999 earthquake, the study benefits from USAID’s Disaster Risk Management Benchmarking Tool (DRMBT). In line with the benchmarking tool, the paper covers key developments in the four components of pre-disaster risk management, namely: risk identification, risk mitigation, risk transfer and disaster preparedness. In the end, it will present three major conclusions: (i) Although post-1999 Turkey has made some important progress in the pre-disaster phase of DRM, particularly with the enactment of obligatory earthquake insurance and tightened standards for building construction, the country is far away from substantial levels of success in DRM. (ii) In recent years, local governments have had been given more authority in the realm of DRM, however, Turkey’s approach to DRM is still predominantly centralized at the expense of successful DRM practices at the local level. (iii) While the devastating 1999 earthquake has resulted in advances in the pre-disaster components of DRM; progress has been mostly in the realm of earthquakes. Turkey’s other major disasters (landslides, floods, wild fires i.e.) also require similar attention by local and central authorities.

The World in Singing Made: David Markson's "Wittgenstein's Mistress"

In line with Wittgenstein's axiom that "what the solipsist means is quite correct; only it cannot be said, but makes itself manifest," this thesis aims to demonstrate how the gulf between analytic and continental philosophy can best be bridged through the mediation of art. The present thesis brings attention to Markson's work, lauded in the tradition of Faulkner, Joyce, and Lowry, as exemplary of the shift from modernity to postmodernity, wherein the human heart is not only in conflict with itself, but with the language out of which it is necessarily constituted. Markson limns the paradoxical condition of the subject severed from intersubjectivity, and affected not only by the grief of bereavement, which can be defined in Heideggarian terms as anxiety for the ontic negation of a being (i.e., death), but by loss, which I assert is the ontological ground for how Dasein encounters the nothing in anxiety proper.

Previous Holocaust Experiences Continue to Affect Food Attitudes in Survivors

A qualitative study was conducted to determine if Holocaust survivors’ food attitudes are influenced by their earlier experiences. The 25 survivor interviewees (14 males, 11 females) ranged in age from 71 to 85 years and resided in Miami-Dade and Broward, Florida counties. Most (56%) were interned in concentration camps during the Holocaust. Interviews were tape-recorded and later transcribed. Results showed earlier experiences influenced food attitudes. The most common themes were: 1) Difficulty throwing food away - even when spoiled; 2) Storing excess food; 3) Craving a certain food; 4) Difficulty standing in line for food; and 5) Anxiety when food is not readily available. Sub-themes included healthy eating and empathy for those currently suffering from hunger. Fourteen (56%) fast for religious holidays, but 7 (28%) said they already had “fasted enough.” Dietitians and others are encouraged to evaluate food service programs to minimize uncomfortable food-related situations for Holocaust survivors.

A study to identify the motivation compelling the business traveler to choose a specific airline in the Miami to Atlanta market and to develop a marketing strategy

The purpose of this study was to determine if the business traveler's behavior is influenced by brand loyalty. This brand loyalty, which became evident through the use of a survey, was then to be thoroughly evaluated. In order for this information to be best understood and utilized as the basis of future marketing strategies, much research was undertaken and its significance explained in relation to the airline industry as it exists at present. The results and conclusions of this study indicate that the airline industry is, for the most part, taking a successful approach in attracting business travelers. These travelers' business is highly valued due to the frequency with which they pay full-fare rates. The airlines view business travelers as a potential for great profit and their actions are in line with these philosophies.