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The Teheran Conference, November 27- December 1, 1943, set the stage for the present-day Cold War. In that conference Sir Winston Churchill, Prime Minister of Great Britain, played a forceful, but unsuccessful, role.

Winter injury of bermudagrass (Cynodon spp.) continues to be a problem across the transition zone. In an attempt to delay or induce winter dormancy while maintaining cold hardiness, applications of seaweed extract (SWE) (0.54 kg ha-1), ethephon (16 L ha-1), Fe (1 kg ha-1), and N (49 kg ha-1) took place every three weeks during the fall of 2001 and 2002. Cultivars examined included 'Riviera', 'Midiron', 'Princess', and 'Tifway'. Tifway exhibited greatest fall color retention in both years of the study. Ethephon promoted early senescence and turfgrass quality during fall ratings in both years of the study while N, Fe, and SWE increased quality over the control in 2001 and only N showed better quality and color retention over the control in 2002. Samples removed from cold acclimated plots were artificially frozen as a measure of cold hardiness. Treatments did not have an effect on post freeze regrowth, however, cultivar was significant in both years. Midiron showed best regrowth followed by Riviera, Tifway, and Princess. In both years Riviera and Midiron displayed the quickest and greatest amount of spring greenup followed by Tifway and then Princess. Ethephon reduced greenup in both years and SWE, Fe, and N showed no differences from the control in 2001 and Fe showed significantly better greenup in 2002. Proline and Linolenic acid levels were highest in Midiron, followed by Riviera, Tifway, and Princess. Nitrogen, SWE, and Fe generally did not have an effect on linolenic acid and no consistent effects were noted on proline concentration. Ethephon treatments did not have an effect on linolenic acid levels, however, there was a negative effect on proline concentrations. The results of this study indicate that judicial N applications during the fall can promote color retention and do not have a negative effect on bermudagrass cold-tolerance. Linolenic acid and proline findings also help to explain differences in cold-tolerance between different bermudagrass cultivars. / Ph. D.

Introduction: Cold exposure is a challenging environmental stimulus for humans, particularly in vulnerable populations such as older adults. Decrements in cold tolerance observed in older adults may be mediated by an age-related reduction in the stress-induced cytoprotective mechanism of autophagy, which enhances cell survival by eliminating damaged cellular components. However, it is unknown how autophagy and accompanying cytoprotective pathways (i.e., heat shock proteins) respond to cold conditions in humans. Purpose: The purpose of this thesis was to evaluate the impact of aging on autophagic activity during cold exposure and assess strategies to reverse age-related autophagic dysfunction. Methods: We examined the influence of age on autophagy during acute cold exposure utilizing ex vivo, in vitro, and in vivo models in young (19-29 years) and older (54-76 years) adults. Autophagic activity in all investigations was assessed in peripheral blood mononuclear cells (i.e., immune cells) via Western blotting. Simulated hypothermic conditions (equivalent to 4-35°C core temperature) were evaluated using ex vivo whole-blood exposure. In vivo cold stress was achieved using cold-water immersions to elicit a physiologically relevant decrease in core temperature by 0.5 and 1.0°C. Techniques that potentially reversed autophagic impairments during cold exposure were assessed including, 1) an in vitro treatment of a known autophagic stimulator (rapamycin) in immune cells obtained from young and older males, and 2) an in vivo cold acclimation in young males with cold-water immersions (14°C for 60 min) repeated on 7 consecutive days. Results: Simulated hypothermia (4-35°C) induced autophagic dysfunction regardless of age or sex. Moderate cold stress (a 0.5°C reduction in core temperature) stimulated autophagy in young males. However, intense cold exposures (equivalent to ≥ 1.0°C decrease in core temperature) elicited signs of autophagic dysfunction and a shift towards apoptotic cell death. Additionally, older adults displayed evidence of autophagic dysfunction during each cold exposure, although age-related autophagic dysfunction was mitigated with acute rapamycin treatment. Further, cold acclimation robustly improved autophagic responses to cold exposure. Conclusion: Despite an observed age-related impairment in autophagic responses during cold exposure, this thesis provided the first evidence in humans that autophagic dysregulation during cold exposure can be reversed through the administration of autophagic stimulators and through cold acclimation.

The widespread emergence of antibiotic resistance determinants for nearly all drug classes threatens human health on a global scale. It is therefore essential to discover antibiotics with novel functions that are less likely to be influenced by pre-existing resistance mechanisms. An emerging approach to identify inhibitors of investigator-defined cellular processes involves screening compounds for antimicrobial activity under non-standard growth conditions. Indeed, by growing cells under conditions of stress, inhibitors of specific cellular targets can be enriched, thereby allowing for the identification of molecules with predictable activities in the complex environment of the cell. Here, I exploit cold stress in Escherichia coli to identify molecules targeting ribosome biogenesis and outer membrane biosynthesis. First, through a screen of 30,000 small molecules for growth inhibition exclusively at 15°C, I was able to identify the first small molecule inhibitor of bacterial ribosome biogenesis, lamotrigine. Second, by leveraging the idiosyncratic cold sensitivity of E. coli to vancomycin, I developed a novel screening technology designed to enrich for non-lethal inhibitors of Gram- negative outer membrane biosynthesis. From this platform, I identified pentamidine as an efficient outer membrane perturbant that was able to potentiate Gram-positive antibiotics against Gram-negative pathogens, similar to the polymyxins. Remarkably, however, this compound was able to overcome mcr-1 mediated polymyxin resistance. Together, this thesis highlights the utility of exploiting the bacterial cold stress response in antibiotic discovery. / Thesis / Doctor of Philosophy (PhD)

On the first day of August in 1961, the Health Ministry of the German Democratic Republic (GDR) announced the closure of the German-German border permanently, accusing the Federal Republic of Germany (FRG) of neglecting its citizens and failing to properly administer vaccinations against poliomyelitis.1 This accusation sparked the ire of the West German and United States media, and the Federal Republic denied that there were outbreaks. The episode raises questions about common perceptions of healthcare in East Germany. The thought that East Germany might have an epidemic disease under control, which still caused problems in West Germany, contradicts the perception that East Germany lagged behind its western neighbor in every realm. While recent histories of international relations and healthcare emphasize collaboration between the US and the USSR, and their Cold War allies in this period, this dissertation presents a less constructive relationship. Despite the shared goal of polio control and eradication, East and West Germany used epidemic control as evidence of the successes of one system of healthcare governance, or the faults of the opponent’s system. The Berlin Wall announcement was the culmination of almost 15 years of government competition, speckled with individual collaboration, in the field of healthcare. This dissertation contributes to literature on healthcare in divided Germany, narratives which present the history of polio as an “American story,” and scholarship on healthcare and international relations. It shows how two separate healthcare systems were 1 “East Germany Curbs Travel: Blames Polio,” Chicago Tribune, 1 August 1961, 11. v constructed by Soviet and American occupiers with German collaborators between 1945 and 1947. These separate systems, established before the official division of Germany, laid the foundation for two separate states. During the first postwar polio epidemic in 1947, the United States showed its affluence and experience with polio through a robust response centered on technological solutions. The USSR, conversely, could not match the United States’ response due to inexperience with polio and lack of economic resources, garnering criticism from German citizens and US occupiers. In 1955, the introduction of Jonas Salk’s injected polio vaccine gave doctors and civilians in the US hope that polio would soon be a memory, but European responses were much more ambiguous. Albert Sabin’s forthcoming oral polio vaccine appeared to be a much more promising option to many physicians due to its ease of administration and cost-effectiveness. When Sabin chose to field test his vaccine in the USSR, his decision to collaborate with the US’s Cold War opponent demonstrated significant potential for collaboration. Nonetheless, the Soviet connections of Sabin OPV led to a crisis in divided Berlin. The history of polio is not an American story and recognizing the ways in which the fight against this disease went beyond the national, complicated by political boundaries but involving recognizable collaboration across those boundaries, helps expand the historical narrative of poliomyelitis. While vaccine diplomacy was indeed a form of soft power used in the context of the Cold War, promises of vaccines were not always received without question, and incorporating a deeper examination of recipient countries’ discourses helps complicate our understandings of diplomacy and hesitancy. / Thesis / Candidate in Philosophy / This thesis outlines the ways in which an infectious disease, poliomyelitis, was treated and prevented in divided Germany between 1945 and 1965, contextualizing medical history with the political context of the Cold War. The first two chapters examine the period from 1945 to 1953, when no vaccines against polio were available and Germany was occupied by the Allied powers. The German healthcare system was reconstructed differently in the Soviet and American zones. The political beliefs of each occupying power shaped the resulting systems: socialized and centralized medicine was a hallmark of the Soviet zone’s healthcare, while the American zone pursued a free market approach. Chapters three and four explain the introduction of two different vaccines, both developed in the United States: an injected vaccine created by Jonas Salk, and an oral vaccine developed by Albert Sabin. The United States championed the Salk vaccine, while the USSR was an early adopter of the Sabin vaccine. These chapters explain how a vaccine created in the US became known as a Soviet vaccine, and how this reputation affected western countries’ adoption of the medical innovation. The thesis concludes that doctors are not separate from the political contexts in which they live and shows how political ideology and cross-border rivalry affect healthcare provision.

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