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In 2004, President Bush addressed the nation and presented NASA's new vision for space exploration. This vision included the completion of the International Space Station, the retirement of the Space Shuttle, the development of a new crew exploration vehicle, and the return of humans to the moon by 2020. NASA's Exploration Systems Architecture Study (ESAS) produced a transportation architecture for returning humans to the moon affordably and safely. This architecture requires the development of two new Shuttle-derived launch vehicles, an in-space transportation vehicle, a lunar descent and landing vehicle, and a crew exploration vehicle for human transportation. The development of an in-space propellant transfer capability could greatly improve the performance, cost, mission success, and mission extensibility of the overall lunar architecture, providing a more optimal solution for future exploration missions. The work done in this thesis will analyze how this new capability could affect the current NASA lunar architecture, and will outline the value proposition of propellant refueling to NASA. A value proposition for propellant refueling will be provided to establish why an architecture that utilizes propellant refueling is better equipped to meet the goals of the Vision for Space Exploration than the current baseline design. The primary goal addressed in this research is the development of a sustainable and affordable exploration program. The value proposition will outline various refueling strategies that can be used to improve each of the architecture Figures of Merit. These include a decrease in the Life Cycle Cost of both the lunar and Mars exploration campaigns, the ability to more than double the mission payload that can be delivered to the lunar surface during cargo missions, improving the probability of successfully completing each lunar mission, decreasing the uncertainty, and therefore risk, experienced during the development process, and improving the extensibility of the exploration architecture by utilizing a greater portion of the lunar program for future crewed mission. The ability to improve these Figures of Merit provides NASA with a more valuable architecture because NASA is able to achieve a greater return on its large initial investment.

Thesis--Auburn University, 2009. / Abstract. Vita. Includes bibliographical references (p. 95-101).

Visceral adipose tissue (AT) mass increases risk for cardiovascular disease and diabetes. Glucocorticoids (GCs) cause preferential expansion of visceral compared to subcutaneous AT through poorly understood mechanisms. GCs are necessary for adipogenesis, the differentiation of adipose stem cells (ASCs) to mature adipocytes. However, this process may be impaired in visceral depots. Insufficient adipogenesis can lead to excessive hypertrophy of existing adipocytes. This hypertrophic expansion increases cell death and inflammation, driving AT dysfunction. To better understand the genes and pathways by which high GCs cause preferential expansion of visceral fat we performed transcriptomic profiling (microarray) on paired samples of visceral (Omental, Om) and abdominal subcutaneous (Abdsc) AT explants cultured with the GC receptor agonist, dexamethasone (Dex), for 7 days. Gene set enrichment analysis showed the transforming growth factor beta (TGFβ) signaling pathway, most notably the secreted anti-adipogenic factors, TGFβ and activin A, was highly enriched in Om and suppressed less by Dex. We hypothesized that Om AT and ASCs secrete factors that inhibit adipogenesis in an autocrine/paracrine manner. Conditioned media (CM) from Om tissue and ASCs suppressed differentiation by 70-80% compared to control; Dex attenuated this anti-adipogenic effect. Both TGFβ and activin A levels were 4-5 fold higher in CM from Om compared to Abdsc ASCs. Both factors signal via cell surface receptors that increase SMAD2 phosphorylation (P-SMAD2), basal levels of which were 3-4 fold higher in Om ASCs. Additionally, CM from Om ASCs increased P-SMAD2. siRNA mediated knockdown of activin A improved differentiation of Om ASCs, but did not reach levels observed in Abdsc. Blocking TGFβ and activin A signaling using SB431542 robustly increased adipogenesis of Om ASCs and prevented the anti-adipogenic effect of CM. GCs decreased production of TGFβ and activin A, but both remained higher in OmCM. Overnight Dex treatment decreased P-SMAD2 and increased the expression of the TGFβ co-receptor, TGFBR3, which decreases TGFβ signaling, in Abdsc ASCs. GCs failed to decrease P-SMAD2 and increased TGFBR3 in Om ASCs only at high concentrations. Taken together, these data implicate GC-TGFβ crosstalk as a determinant of depot differences in adipogenic capacity and hypertrophic vs. healthy hyperplastic expansion of AT. / 2019-11-01T00:00:00Z

Background: HSV-2 was estimated to infect 491 million people worldwide, with women disproportionately affected by HSV-2. Understanding factors that influence susceptibility to HSV-2 in women is important in preventing infections. Through various studies, the progestin-based contraceptive DMPA exhibited immunosuppressive effects, and has shown increased susceptibility to HIV and HSV-2. Studies comparing DMPA to other contraceptives like NET suggest that NET may be safer. In vivo NET effects have not been characterized thoroughly to better understand the effect of NET on susceptibility to HSV-2. Therefore, this study aimed to compare the effects of NET and DMPA in mouse models that affect susceptibility to HSV-2. We hypothesized that NET treated mice will have decreased susceptibility to HSV-2 compared to DMPA but elevated compared to normal mice. Method of study: Ovariectomized mice were treated with DMPA (2mg) and NET (2 mg injections, 2.5 mg pellets or 5 mg pellets) for 10 days and intravaginally immunized with HSV-2 TK-, then intravaginally challenged with WT HSV-2 ~4-7 weeks later. Primary intravaginal WT HSV-2 challenges were conducted in ovariectomized and normal mice after 10 days of DMPA and NET treatment. Viral titers, pathology and survival were examined. Mucus production in the vagina was investigated through immunohistology. Effects of hormones on immune cells were explored in the lymph nodes, spleens, and vaginal tracts through flow cytometry. Results: Increased mucus was consistently observed in the vaginal tracts of mice after treatment with NET 2.5 mg and 5 mg treated mice, but not with DMPA Therefore, NET treated mice displayed reduced viral shedding and delayed pathology compared to DMPA treated mice. No significant changes occurred in immune cells analyzed post DMPA and NET treatment, although there were trends of increased T cells in progestin treated mice. However, more experiments need to be conducted to confirm observed trends. Conclusion: NET treatment in mice results in mucus production in the vaginal tract, a potential mechanism impeding intravaginal HSV-2 infection and could be applied to other STIs. This provides insight into protective effects of NET compared to DMPA allowing women to make informed decisions regarding hormonal contraceptives. / Thesis / Master of Science in Medical Sciences (MSMS)

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No description available.

<p>Neuroinflammation associated with lumbar radiculopathy and peripheral nerve injury is characterized by locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF&alpha;). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in local delivery of anti-inflammatory drugs to treat this pathology, as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNF&alpha; in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. </p><p>ELPs are biopolymers capable of thermally-triggered in situ depot formation and have been successfully employed as drug carriers and biomaterials in several applications. A library of ELP-curcumin conjugates were synthesized and characterized. One lead conjugate was shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNF&alpha; and NF-&kappa;B with near-equivalent potency compared to free curcumin. When injected into the perineural space via intramuscular (i.m.) injection proximal to the sciatic nerve in mice, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4 days post-injection and decreased systemic exposure of curcumin 3-fold. </p><p>The results of this dissertation support the use of ELP as a drug carrier for local perineural drug delivery, and the strategy presented here for drug conjugate development and use of depot-forming ELP-curcumin conjugates represents a novel means of providing sustained treatment of neuroinflammation and pain associated with radiculopathy and peripheral nerve injury.</p> / Dissertation

Approved for public release; distribution in unlimited. / In a warehouse, a fast-pick-area is a region containing many items that can be retrieved quickly and inexpensively to fulfill customer orders. The Defense Distribution Center San Joaquin (DDJC) implements a similar strategy on a wider scale by designating one of many warehouses as a "fast-pick-area." We develop a plan to optimally slot the fast-pick area at DDJC using a computer model that captures the tradeo.s of storage space versus cost of replenishment from bulk storage. Our results suggest that defense distribution centers should consider implementing a fast pick area as a means of reducing operating costs. / Lieutenant Commander, United States Navy

Nesta tese, nós apresentamos uma compilação de três artigos de otimização aplicados no contexto de transporte urbano de ônibus. O principal objetivo foi estudar e implementar heurísticas com base em Pesquisa Operacional para otimizar problemas de (re)escalonamento de veículos off-line e on-line considerando várias garagens e frota heterogênea. No primeiro artigo, foi proposta uma abordagem heurística para o problema de escalonamento de veículos múltiplas garagens. Acreditamos que as principais contribuições são o método de geração de colunas para grandes instâncias e as técnicas de redução do espaço de estados para acelerar as soluções. No segundo artigo, adicionamos complexidade ao considerar a frota heterogênea, denotada como multiple depot vehicle type scheduling problem (MDVTSP). Embora a importância e a aplicabilidade do MDVTSP, formulações matemáticas e métodos de solução para isso ainda sejam relativamente inexplorados. A principal contribuição desse trabalho foi o método de geração de colunas para o problema com frota heterogênea, já que nenhuma outra proposta na literatura foi identificada no momento pelos autores. Na terceira parte desta tese, no entanto, nos concentramos no reescalonamento em tempo real para o caso de quebras definitivas de veículos. A principal contribuição é a abordagem eficiente do reescalonamento sob uma quebra. A abordagem com redução de espaço de estados, solução inicial e método de geração de colunas possibilitou uma ação realmente em tempo real. Em menos de cinco minutos, reescalonando todas as viagens restantes. / In this dissetation we presented a three articles compilation in urban bus transportation optimization. The main objective was to study and implement heuristic solutions method based on Operations Research to optimizing offline and online vehicle (re)scheduling problems considering multiple depots and heterogeneous fleet. In the first paper, a fast heuristic approach to deal with the multiple depot vehicle scheduling problem was proposed. We think the main contributions are the column generation framework for large instances and the state-space reduction techniques for accelerating the solutions. In the second paper, we added complexity when considering the heterogeneous fleet, denoted as "the multiple-depot vehicle-type scheduling problem" (MDVTSP). Although the MDVTSP importance and applicability, mathematical formulations and solution methods for it are still relatively unexplored. We think the main contribution is the column generation framework for instances with heterogeneous fleet since no other proposal in the literature has been identified at moment by the authors. In the third part of this dissertation, however, we focused on the real-time schedule recovery for the case of serious vehicle failures. Such vehicle breakdowns require that the remaining passengers from the disabled vehicle, and those expected to become part of the trip, to be picked up. In addition, since the disabled vehicle may have future trips assigned to it, the given schedule may be deteriorated to the extent where the fleet plan may need to be adjusted in real-time depending on the current state of what is certainly a dynamic system. Usually, without the help of a rescheduling algorithm, the dispatcher either cancels the trips that are initially scheduled to be implemented by the disabled vehicle (when there are upcoming future trips planned that could soon serve the expected demand for the canceled trips), or simply dispatches an available vehicle from a depot. In both cases, there may be considerable delays introduced. This manual approach may result in a poor solution. The implementation of new technologies (e.g., automatic vehicle locators, the global positioning system, geographical information systems, and wireless communication) in public transit systems makes it possible to implement real-time vehicle rescheduling algorithms at low cost. The main contribution is the efficient approach to rescheduling under a disruption. The approach with integrated state-space reduction, initial solution, and column generation framework enable a really real-time action. In less than five minutes rescheduling all trips remaining.