Background: Esophageal adenocarcinoma (EAC) is one of the only malignancies whose incidence is rising in the United States. Current multidrug treatment for EAC has considerable toxic side effects that necessitate the development of less toxic, more specific target drugs. Recent large scale genomic analysis reveals that TP53 is the most frequently inactivated gene in EAC. One of the primary functions of TP53 and its gene product, the tumor suppressor p53, is in regulation of DNA repair in response to DNA damage. Inactivation of TP53 results in loss of the G1/S cell cycle checkpoint, and dependence on the G2/M checkpoint for DNA repair. Activity of cyclin-dependent kinase 1 (CDK1) is necessary for cells to exit the G2/M checkpoint and enter mitosis. Phosphorylation of CDK1 by the wee1 kinase inhibits CDK1 in response to DNA damage, allowing cells to maintain G2 arrest and repair the damaged DNA. Active in normal cells, wee1 kinase is critical in cancer cells to promote DNA repair and cell survival in response to DNA damage, particularly from commonly used DNA damaging therapies. AZD1775 is a small molecule inhibitor of wee1 kinase, currently under investigation in clinical trials. AZD1775 differentially targets cancer cells by blocking wee1 mediated inhibition of CDK1 and consequently preventing G2/M arrest in response to DNA damage. Combination of AZD1775 with DNA damaging agents is thought to push cancer cells with damaged DNA through to mitosis and initiate apoptosis instead of G2/M arrest and DNA repair. Based upon the incidence of TP53 mutation in EAC, we hypothesize that treatment with a DNA damaging agent in combination with AZD1775 will be as effective at eliciting DNA damage and cell death as the more toxic current standard of care, which is comprised of treatment with cisplatin, docetaxel, and radiation. Methods: p53 mutant EAC cell lines were dosed with cisplatin, AZD1775, and the combination of cisplatin and AZD1775, and then assayed for viability. Nude mice were implanted with p53 mutant patient derived xenograft esophageal adenocarcinoma tumors and randomized for treatment with AZD1775 alone, cisplatin and AZD1775, radiation and AZD1775, cisplatin, docetaxel, and radiation or vehicle (control). Tumor volume was measured over the five week treatment course. Results: In vitro and in vivo assays reveal a potent synergistic effect between AZD1775 and DNA damaging agents that is as efficacious as the standard of care therapy. The difference in AZD1775 sensitivity among TP53 mutant EAC cell lines indicates that TP53 alone may not be an adequate biomarker to assess for AZD1775- mediated toxicity.

This thesis examines the problems that occur when the politics and practices of social services, specifically maternal and prenatal care, are guided by a distorted understanding of immigration. It compares the politics and practice of this care across two international borders: the U.S.-Mexico and that within Hispaniola. In an ideal world, care would be extended to all individuals regardless of citizenship. However, since every welfare state has its limits at the national border, citizenship matters to both federal governments and medical professionals. Government-provided resources play an integral role in the current immigration debate, as these programs are a collective investment in which all individuals contribute in order to sustain it. The United States developed the welfare state in order to provide necessary resources to those who could not afford it. Its creators did not view these services as a handout, rather as a support for the future workforce of the country. However, health care was and still is not provided on this model of economic and social citizenship. Current U.S. healthcare policy dictates that no one can be turned away in an emergency situation because someone cannot pay their medical bill, including undocumented immigrants. But for immigrant mothers carrying children across the border, maternal and prenatal care does not qualify as an emergency and the federal government aid typically does not extend to them them as citizens. When care is extended to undocumented immigrants in the United States at all, it typically is provided to the child through Medicaid, who is by dint of the Fourteenth Amendment considered a citizen after birth. The relation between the Dominican Republic and Haiti offers a more complex situation, as the idea of birthright citizenship has recently been revoked. Following the Haitian Earthquake in 2010, the only healthcare to which many Haitians had access was across the Hispaniola border. Haitian women who give birth to children in the Dominican Republic are often not evaluated by a doctor until they are entering the delivery process, and even then health-care is complicated by or denied because of racial prejudice and unclear legal situation. In September of 2013, the Constitutional Court of the Dominican Republic issues a new ruling which declared that any immigrant born between 1929 and 2010 without documentation of their own or of their ancestors does not have citizenship, rendering many Haitians born in the Dominican Republic essentially stateless. To be born to a non-citizen mother typically means the child will likely be born with little or no prenatal care, and the mother will receive poor or inadequate care. Prenatal care is one of the most inexpensive elements of a care-model that carries huge returns relative to its costs. All governments would benefit from improved access to maternal and prenatal care because its future citizens who receive such care would be born healthier and have fewer expensive chronic illnesses. Fewer chronic illness among a population would have huge returns on the welfare state because fewer people would be utilizing it for expensive medical treatments. Though most medical professionals condemn the extreme act of denying care to pregnant women or infants (documented or not), the Dominican Republic and the United States have a popular politics that embraces this cruelty, despite the fact that both pride themselves on a multi-ethnic population. It is easy for policymakers to incriminate undocumented immigrants and claim that they are responsible for an illegitimate share of the consumption of the country's resources. Therefore, it seems likely that the host country's perceptions of immigrant natality and maternity help construct a negative image of the immigration "problem" in such a way that laws and policies are designed without accurate rationale. This thesis examines how the United States and the Dominican Republic might improve the relationship between the culture of healthcare and the role of the legal system for immigrants and their children. It seeks to understand the reasons, motivations, and consequences for denying immigrants services on the account of their citizenship status. The social, economic, and health consequences of being an undocumented citizen will be examined. Current legal policy and what political roadblocks and cultural prejudices must be overcome in order to implement a successful policy will be reviewed. Finally, the best practices prenatal care as a national investment will be discussed, as will the problem of cross-cultural perception of natality, maternity, and immigration.

The 1878 Treaty of Berlin sought to address the issue of minority rights in order to stabilize the interests of the Great Powers and the international order; however, in their formulation of a treaty intended to save the imperial component of the system, the European imperial powers not only gave one of their official acknowledgments to nationalist principles, but articulated a critique of the existing notion of state protection for ethnic minorities. This tentative but landmark modification of the imperial model of legitimacy suggested Europe or the world could consist of a host of sovereign nations. In so doing, it recognized the political, and ideological changes that nationalism demanded, changes that would reshape how national groups organize politically, culturally, and militarily. The logic of nationalism demanded that new boundaries, conceived on national lines be drawn, and they were drawn, both within the Austro-Hungarian and Ottoman Empires. The Treaty of Berlin led to the formation of Greater Bulgaria and Albania, and these new nationalities formed a initial answer to the European question of minority groups. The Treaty of Berlin is useful to examine in relation to its better-known and much more radical offspring, the Treaty of Versailles. Differences in the approach of either treaty provide a study in the lasting effects of soft power to resolve international conflict. The Great Powers met in Berlin to address a developing crisis in an attempt to avoid a destabilizing regional conflict through diplomatic and legal means, whereas the Paris Peace Conference met at Versailles to develop new order across Europe in the wake of the Great War. The Treaty of Versailles, sharply chiding the Central Powers as it promulgated a victor's peace, hoped to prevent future war by placing economic burdens on Germany. While the conference at Paris acknowledged the minority position, the overwhelming legal focus went to addressing developing nations and nationalisms in a way that was consistent with the beliefs of old imperial rule. The earlier Treaty of Berlin's relative emphasis on minority questions as logically antecedent to the disposition of nationalism becomes of highest significance in retrospect. It is this focused approach to addressing developing nationalism that makes the Treaty of Berlin an important point of discussion. It provides a precedent for how questions of minority rights should be addressed, and where it falls short of an answer on how conflict might be prevented, it explores how the tensions within the international system can exacerbate one another, as they did in the breakdown of diplomacy and law that to the First World War . This thesis aims to address how the triumph of nationalism as a model of state legitimacy almost immediately gave rise to the question of legal protection of minorities. The minority question only became more urgent as nationalists developed policies that practiced first passive, and then active exclusion of minority groups. While nationalism's relation to democratic rule seemed to solve the problems of representative government, it quickly forced the question of how legitimate representation was determined. Shifting notions of political legitimacy, unworkable empires, and heightened international rivalry formed a widening spiral of crisis that eclipsed the minority question, but this thesis supports the belief that the centrifugal force of conflict came out of the avoidance of addressing minority rights completely. Attempts were made through the twentieth century to mitigate conflict between people groups, but many failed to produce fully developed solutions, while many others favored the status quo, seemingly hoping that the question would answer itself. A study of the early history of the minority rights question helps us understand the national question in the old-new light of the international order and questions of international law. Given the conflicts that have arisen out of the relations between nations and the question of minority rights, the minority question is present in much of today's thinking about human rights and the maintenance of international order. Understanding the origins of minority rights and the factors considered in the early negotiations set to address the problem helps develop a deeper understanding of the of the interactions between nations and people today.

There are problems in the breeding practices of miniature horses. This study seeks to determine the source of these detrimental outcomes based on an evaluation of primary attributes selected for by breeders and the lack of genetic information and understanding of these attributes. In order to do this a program model was created to test the effects of selection criteria on breeder behavior and the resultant foals of these crosses. Moving forwards this program will evolve into a database of the equine genome for different horses. This will allow breeders to input their horses and do faux crosses in order to decrease the incidence of negative and detrimental outcomes.

The Barrett Poly Writing Colloquium is a dedicated group of students and faculty that come together to provide Freshmen in the Human Event with an impactful tutoring experience that enriches their Human Event papers and reading responses. There were, however, a few major issues with the way in which tutoring sessions were recorded, archived, and maintained. We set out to clean up the process and provide a more positive experience for all involved. Starting out, we searched to find a way to electronically archive tutoring receipts that students receive at the end of a tutoring session. In the beginning of the project, we were sporting experience with front-end coding languages such as HTML and CSS, with a minuscule amount of experience using JavaScript. By diving in and closing the gaps in our knowledge of JavaScript, we were able to build a web form that would suit the needs of the tutors and administrators, while still offering students the feedback that they needed to improve their writing, in a personal way that preserves the quality of the core service provided by the colloquium. Our primary objective was to build a system that moved the reporting of tutoring sessions online, while maintaining a way to generate a receipt for distribution to the students and tutors. We delivered on that, and then some, by building an automated system using Google's developer tools to automatically write all tutoring session data to a Google Sheet, and send an automated email with all relevant information to both the student and tutor. We then dedicated the time we had remaining to adding additional features. It is here that we began to run into problems that unfortunately proved to be technological constraints of the platforms we were developing on, and the languages we were using. By this point, it was too late for us to pivot, but we were still able to achieve many of our goals. For example, we successfully implemented a feature that automatically archives the entire year's worth of data and creates a new, clean Google Sheet at the beginning of each school year. If we were to continue our project, with more time, we would use different development tools and systems so that we could have more flexibility. However, using the Google API provided us with many benefits that allowed us to jump right in to building our program, without having to struggle with building a whole database with accounts and permissions.

The purpose of this thesis is to develop an aptitude test to administer to shelter dogs in order to determine which dogs could be adopted and trained for Search and Rescue (SAR) work. SAR is an essential field made up primarily of volunteers that search for people who have gotten lost. Many SAR teams work with the police force to locate missing persons. There are various types of SAR work, such as urban SAR, ground SAR, mountain rescue, and cadaver SAR, among others. The tasks of hiking, climbing, crawling, and various other methods of maneuvering are required from the SAR dogs and their handlers, so physical fitness is necessary in all SAR dogs. A stable, confident demeanor is also crucial for the overall effectiveness of the canine. The availability of a standardized aptitude test could prove beneficial for SAR dog handlers seeking dogs to train for work in the SAR field. This also presents the opportunity for increased adoption of shelter dogs, provided SAR dog handlers decide to work with homeless adult dogs. The aptitude test encompasses the critical qualities necessary for SAR dogs to possess. Physical suitability, temperament, aptitude, object focus, and emotional suitability have been implemented and defined in the test, based on the desired traits described by various SAR organizations and evaluations for puppies and working dogs. Though there are multiple variations of aptitude and temperament tests, these evaluations do not incorporate the administration to shelter dogs in order to determine their potential for working in a special field particularly the field of Search and Rescue. The qualities for SAR dogs described in this thesis were utilized to create ideal typologies of SAR dogs. This provides a theoretical idea of realistic dogs suitable for SAR work. These ideal typologies were scored against the aptitude test based on their characteristics described in order to determine consistent implementation of the test by multiple users. The aptitude test was also implemented on two real dogs to discern the effectiveness of the test. Although neither dog displayed the proper characteristics to become SAR dogs, the results from the trials demonstrated an overall efficacy of the test.

This project charts the development of autobiography as a genre through two pairs of writers: Benjamin Franklin and Jean-Jacques Rousseau of the Enlightenment, and Oscar Wilde and James Weldon Johnson of the fin de siècle, leading into the twentieth century. The Enlightenment thinkers took an Augustinian confessional approach to the autobiography as a genre, revealing their flawed selves to the public in order to make themselves both authentic and virtuous. Through both these writers, autobiography became a way to replace the religious precepts of the Middle Ages, as the flawed self could be redeemed through society in its current historical moment rather than God. Franklin’s autobiography shows how self-making through economic credit is conducive to virtue, while Rousseau turned inward toward a natural goodness lacking in corrupt social relations. Despite their differences, both furthered the development of autobiography as an account of authentic self-making.

The fin de siècle writers fictionalized the autobiography and derived a concept of authenticity that develops from the suffering of social otherness. Wilde praised the poor over the bourgeois in a British Philistine society, while Johnson’s narrator argued for the authenticity of an African-American class striving for economic and social justice. Both writers redeemed suffering through the ideals of the subjective self, a turn inward that resembles Rousseau’s own look into his natural, innermost self. Overall, this project focuses on how the development of the genre between these two pairs of thinkers gives multiple accounts of self-making leading to the social Other becoming an agent for authenticity; how is the self to be read, understood, and made authentic through its imperfections and sufferings? The fictionality of the later works casts an overarching question: is attaining authenticity through autobiography merely fictional?