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The synergistic effects between Vorinostat and Tamoxifen observed through a phase II study on breast cancer patients resistant to hormone therapy may involve more than the modulation of ER-alpha to reverse Tamoxifen resistance in ERBC cells. RT-qPCR of genes expressed in Tamoxifen resistant cells, trefoil factor 1(TFF1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC), were evaluated along with ESR1 and Diablo as a control. MYC was observed to have increased expression in the treated cells, whereas the other genes had a decrease in their expression levels after the cells were treated for 3 days with Vorinostat IC30 of 1 µM. As for targeting the AR, MCF7 Tamoxifen sensitive and resistant cells were not affected by the AR antagonists to determine an IC50. The cell viability for all MCF7 sub-clones only decreased for high concentrations of 5.56 µM - 50 µM in Bicalutamide and 16.67 µM – 50 µM of MDV1300. Furthermore, hormone depletion of MCF7 G11 Tamoxifen resistant sub-clones did not show a great response to DHT stimulation or the AR antagonists. In the RT-qPCR, the MCF7 G11 cells showed an increase in mRNA expression for ER, AR, and PR after 4 hours of treatment with estradiol. As for the DHT treatment, ER, AR, PR, and PSA had a minimal increase in the fold change, but the fold change in AR was less than in the estradiol treatment. The Mayo Clinic will investigate the possible usage of AR as a biomarker through immunohistochemistry.
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The potential empowerment of the UN System as a result of the Responsibility to Protect doctrine requires an examination of what it could mean for both state sovereignty and the authority of the UN Security Council. I argue that the Security Council is already a sovereign body within the international system that would be greatly empowered by the implementation of the Responsibility to Protect doctrine and the veto reform efforts of the Accountability, Transparency and Coherence (ACT) Group. I rely on Carl Schmitt’s influential definition of sovereignty and his key takeaways regarding the 1919 German constitution to illustrate the existence of two distinct levels of Schmittian-like sovereigns in the international system: state sovereigns and representative sovereigns. I will then describe the authority and structure of the Security Council followed by a brief case study of the North Atlantic Treaty Organization’s (NATO) intervention in Kosovo as an example of how real-life situations challenge the Security Council’s ability to exercise its role as a representative sovereign, including a discussion about how it can either fail to act or choose not to act and the difference between them. Afterwards, I will discuss the Responsibility to Protect doctrine and how it expands the relative power of representative sovereignty at the cost of reducing the relative power of state sovereignty, culminating in a discussion of what attempts to reform the veto power on the Security Council may do to the Council’s sovereignty. Finally, I will conclude with a discussion of the key takeaways of this paper and some further considerations.
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The United States’ War on Drugs declared in 1971 by President Richard Nixon and revamped by President Reagan in the 1980s has been an objectively failed initiative with origins based in racism and oppression. After exploring the repercussions of this endeavor for societies and individuals around the world, global researchers and policymakers have declared that the policies and institutions created to fight the battle have left devastation in their wake. Despite high economic and social costs, missed opportunities in public health and criminal justice sectors, and increasing limits on our personal freedoms, all the measures taken to eradicate drug abuse and trafficking have been unsuccessful. Not only that, but militarized police tactics, mass incarceration, and harsh penalties that stifle opportunities for rehabilitation, growth, and change disproportionately harm poor and minority communities. <br/>Because reform in U.S. drug policy is badly needed, the goals of America’s longest war need to be reevaluated, implications of the initiative reexamined, and alternative strategies reconsidered. Solutions must be propagated from a diverse spectrum of contributors and holistic understanding through scientific research, empirical evidence, innovation, public health, social wellbeing, and measurable outcomes. But before we can know where we should be headed, we need to appreciate how we got to where we are. This preliminary expository investigation will explore and outline the history of drug use and prohibition in the United States before the War on Drugs was officially declared. Through an examination of the different patterns of substance use, evolving civil tolerance of users, racially-charged anti-drug misinformation/propaganda campaigns, and increasingly restrictive drug control policies, a foundation for developing solutions and strengths-based strategies for drug reform will emerge.
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I conducted a literature review of articles pertaining to the history and treatment of rats. After outlining all of the relevant connections, I argue that as a result of people's conceptions about rats, rats do not receive the same respect and protections afforded other animals, such as cats and dogs, in the laboratory and beyond. I present both negative and positive conceptions about rats and the realities of these conceptions. Finally, I talk about the changes that need to take place in laboratory research, why animals are still used in research today, and the alternatives that exist to animal models.
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Urban encroachment into traditional snake territories has long been underway; likely increasing snake sightings in urban neighborhoods. With increasing overlap, I ask if the perceptions of snakes are actually influencing urban residents to say that snakes are a significant problem in their neighborhood today? I was interested in finding out whether or not there would be a positive correlation between the perception of snakes being a problem within a neighborhood and the actual number of sightings recorded. To address this, I used survey responses from 2017 regarding the risk perception of snakes from twelve neighborhoods within Maricopa County. These responses were then compared to the number of snake sightings within those same neighborhoods over a span of ten years using community science data from iNaturalist. The average results of the people who took the survey perceived that snakes were not a problem in their neighborhood. It was also found that in the outlying areas closer to natural snake habitat (desert preserves), a positive correlation between a higher survey response and a higher number of snake sightings could be seen. Overall, the conclusion of the data revealed that the perceptions of residents did not align with the actual number of snake sightings.