Nicotinamide adenine dinucleotide (NAD+) is a cofactor in hydride transfer reactions and consumed substrate of several classes of glycohydrolyitc enzymes, including sirtuins. NAD+, its biosynthetic intermediates, breakdown products, and related nucleotides (the NAD metabolome) is altered in many metabolic disorders, such as aging and obesity. Supplementation with the novel NAD+ precursor, nicotinamide riboside (NR), ameliorates these alterations and opposes systemic metabolic dysfunctions in rodent models. Based on the hypothesis that perturbations of the NAD metabolome are both a symptom and cause of metabolic disease, accurate assessment of the abundance of these metabolites is expected to provide insight into the biology of diseases and the mechanism of action of NR in promoting metabolic health. Current quantitative methods, such as HPLC, lack specificity and sensitivity to detect distinct alterations to the NAD metabolome. In this thesis, I developed novel sensitive, accurate, robust liquid chromatography mass spectrometry methodologies to quantify the NAD metabolome and applied these methods to determine the effects of disease states and NR supplementation on NAD+ metabolism. My investigations indicate that NR robustly increases the NAD metabolome, especially NAD+ in a manner kinetically different than any other NAD+ precursor. I provide the first evidence of effective NAD+ supplementation from NR in a healthy, 52 year old human male, suggesting the metabolic promoting qualities of NR uncovered in rodent studies are translatable to humans. During my investigation of NR supplementation, my work establishes an unexpected robust, dramatic increase in deamino–NAD+, NAAD, directly from NR, which I argue could serve as an accessible biomarker for efficacious NAD+ supplementation and the effect of disease upon the NAD metabolome. Lastly, I further establish NR as a general therapeutic against metabolic disorder by detailing its ability to oppose aspects of chronic alcoholism and diabetes mellitus.

This thesis explores the potential impacts of the implementation of best management practices (BMPs) in Upper Roberts Creek (URC) watershed in northeast Iowa as part of the Iowa Nutrient Research Center (INRC). The INRC was formed in response to the United States Environmental Protection Agency (EPA) requirement that the states along the Mississippi River develop and implement strategies for reducing the nutrient load leaving their states and entering the Gulf of Mexico. The impacts of BMP implementation in URC were evaluated through the use of HydroGeoSphere which was used to develop a three dimensional, coupled surface/subsurface model of the watershed. The URC model was used to evaluate the hypothetical impacts of the widespread implementation of cover crops on agricultural land within the watershed, the construction of eight Iowa Conservation Enhancement Reserve Program (CREP) style wetlands, and the combination of these two BMPs. Through the comparison of these simplified, hypothetical scenarios to a baseline condition, potential nitrate load reduction estimates were made for each practice or combination of practices. These estimates indicate that neither of the individual practices would be likely to achieve the nitrogen reductions targeted by the EPA and in order to achieve these goals a combination of practices would likely be required.

This dissertation study explored women's labor in the beauty industries of the YouTube vlogosphere, specifically beauty video production on the ICON network, the beauty and lifestyle channel of YouTube entrepreneur Michelle Phan. Via a case study of ICON's YouTube creators and their video production, this dissertation explored female digital labor by interrogating gender, ethnicity, bodies, and power to address two interconnected elements situated particularly in the YouTube vlogosphere: beauty and entrepreneurship. The study's key research questions asked: In the transnational world of digital employment, what are the material and ideological complexities of beauty YouTubers' experiences? And how do YouTubers interpret their technical production, their beauty ideologies, their power, their authenticity, and the material outcomes of their production for themselves and others? Following an analysis of ICON as a company, interviews with its management and video creators, and its video products, the case study's findings reveal that while ICON recruits beauty creators to market on behalf of its retail partners, the creators see themselves as entrepreneurs who negotiate their own stances regarding their beauty ideals, user-generated content, (post)feminisms, and online authenticity.

Sulfur dioxide is a primary pollutant and a known respiratory irritant. While there is a small level of background SO2, elevated concentrations are caused by industrial emissions. Muscatine, IA was designated as an area of nonattainment due to the persistent elevated levels of SO2 in the area. There are currently no available methods for predicting potential SO2 violations in Muscatine, and very little research was found investigating predictive modeling efforts. This thesis examines atmospheric conditions in Muscatine caused by SO2 emissions from facilities near the city. The main goals were to examine the plume dispersion model AERMOD for its ability to accurately map pollution levels, and to determine whether AERMOD could be used to predict SO2 concentrations when using meteorological forecast models as weather inputs. An historical analysis was performed using meteorological records from 2007 and AERMOD. The maximum emission limit was used in AERMOD. The resulting predicted concentrations were compared with concentrations reported at a monitoring site within the city. A forecasting analysis was also completed using two weather model forecasts (WRF and NAM) from March 2012 as meteorological input for AERMOD. Accurate daily SO2 emissions were obtained from each facility, and the corresponding rates were used in AERMOD. The resulting predicted concentrations were compared with monitored concentrations during the same time period. Overall, the historical analysis showed AERMOD's tendency to overestimate SO2 concentrations, particularly on days that also resulted in high monitored levels. The forecasting analysis resulted in favorable results with respect to the WRF weather forecast, but the NAM forecast created concentrations in AERMOD that were poorly correlated with monitored values. AERMOD still was likely to overestimate concentrations, but these overestimations were lessened due to more accurate emission information. Further research will be needed to further advance the prediction of pollution levels.

Prevalence of childhood overweight and obesity has tripled in the United States in the last 30 years, resulting in 31.8% of youth (ages 2-19 years of age) classified as overweight or obese.1,2 To date many high-intensity and medium-intensity programs have been developed and tested in efforts to ameliorate the high prevalence of childhood obesity, however there is a gap in the testing and implementation of low-intensity family-based treatments.3–7The Traffic Light Program is the only childhood obesity program that has published long-term outcomes and was developed by Epstein et. al., however it only includes children from ages 6-12. We developed an 8-week family based childhood obesity program (Healthy Hawkeye Program) to test the feasibility and efficacy of an adapted version (light intensity) of the Traffic Light Program in families of overweight and obese children. To our knowledge, this is the first study to test the efficacy of a low-intensity (21 hours) comprehensive family-based intervention specifically tailored for overweight and obese children from 6 to 17 years of age. Measures include body composition (weight, fat mass, lean body mass, body fat %, BMI, waist circumference), sedentary, light and moderate levels of physical activity (wrist-worn Generative Accelerometer), dietary quality (caloric intake, fruit/vegetable daily servings), measures of nutritional and physical activity self-efficacy, Lifestyle Behavior Checklist (LBC), Family Nutrition and Physical activity (FNPA) survey, Satisfaction with Life Scale, and the Healthy Hawkeye Program Evaluation Survey. We hypothesize that participants will improve in selected (1) health measures (weight, caloric intake, daily fruit intake, daily vegetable intake, sedentary, light, and moderate physical activity levels), (2) improve in selected theoretical constructs (self-efficacy, behaviors, environments), and (3) will find the Healthy Hawkeye Program acceptable and helpful. A total of five families were recruited and only 3 families (3 mothers, 2 male children, and 1 female child) completed the program (attended 6 of 8 weekly meetings). The very low sample size of only 3 families limited the statistical analysis. The results showed parents reduced their absolute weight by 5.6 lbs and children slightly increased by 0.1 lbs. Both parents and children decreased their daily sedentary time as well as increased their daily moderate activity. Various measures of self-efficacy, behaviors, nutrition improved among parents and children. Parents and children found the program to be acceptable and helpful.

In the 1960s, Gustav Mahler's music received renewed interest in America. While certain champions of Mahler from this period, such as Leonard Bernstein and Bruno Walter, have attracted scholarly attention, other conductors have been largely overlooked, including Maurice Abravanel (1903–1993). During Abravanel's directorship of the Utah Symphony (1947–1979), he consistently programmed Mahler's music, making the orchestra the first American orchestra to record all of Mahler's symphonies. Although the concerts contributed meaningfully to Utah's musical life and some of the recordings were well-received by critics in and outside America, they remain marginalized in accounts of Mahler's music in America. To bridge this gap, the dissertation examines primary sources, including concert and record reviews, program notes, correspondence, and interview transcripts to present the history, reception, and influence of Abravanel's Mahler journey with the Utah Symphony. By examining the musical past of a Western city and considering musical and extramusical factors, this dissertation demonstrates that local and technological histories influenced musical decisions, all of which in turn played a role in the growth of the Utah Symphony and planted Mahler's music in the community. The examination reveals that Abravanel's Mahler carried different meanings for different parties. The recordings, with low prices and superior sound, were recommended by critics and welcomed by audiophiles and music lovers. Abravanel's interpretations were commonly criticized as dispassionate, yet were embraced by those who did not prefer Bernstein's more involved, dramatic readings. Through the recordings of Mahler's music, the Utah Symphony gained national and international acclaim. In Salt Lake City, Mahler became a familiar name, and his music remains integral to the city's music culture. As of the completion of this dissertation, the Utah Symphony is nearing the end a two-season (2014–2016) Mahler cycle and has recorded two symphonies by Mahler under music director Thierry Fischer. The McKay Music Library of the University of Utah is digitizing Abravanel's Mahler scores and documenting memories about Abravanel's endeavors with the Austrian composer's music. The concerts, recordings, and efforts to preserve history again bring the collective memories of Abravanel's Mahler back to the community.

Sustainable energy solutions are necessary in developing nations as current food preparation practices are becoming harmful to the environment, economic development and the overall health of the population. The purpose of this study was to create a Scheffler reflector-based system prototype, experimentally analyze the system and to predict its behavior when subjected to the solar conditions of Rajasthan, India. Former designs from India, the University of Iowa and several other institutions were consulted during the formulation of the prototype design. While consulting a specific set of design constraints, pertinent to developing counties, a Scheffler reflector and tracking stand were fabricated. Solutions for a thermal storage unit were investigated for eventual integration with the prototype. Solar flux data for Iowa and India was used to predict the amount of energy transmitted by the reflector. Experiments were designed and completed to observe the temperatures experienced at the focal point of the reflector and estimate the energy stored by a steel mass. A series of sun angles, monthly solar flux data and experimental data were used to predict the performance of the storage unit, over a three day span, in Rajasthan. Aspects of the system were then modified to investigate their effects on the temperature of the storage unit.

I create my artwork using a variety of media to explore and define my concepts. My concepts involve the body and are also integrated into a larger environment to tell a story.

Previous studies have shown that the experience of negative emotions is rarer, while experience of positive emotions is more frequent in the elderly, suggesting an overall improvement in emotional well-being as people age. However, most research did not account for the dynamic characteristics of emotions (e.g. peak intensity, latency, duration) and the levels of emotional challenges. In addition, since most previous studies have focused on studying the experience, expression, and psychophysiological response of emotion, it is still not fully understood how performance in cognitive or behavioral tasks (e.g., automobile driving) can be affected by emotions in older age. To address this gap, the current study examined the effect of normal aging on the dynamic processes of emotion during different levels of emotional challenge (aim 1), and the effect of emotion on driving in older adults as compared to middle-aged adults (aim 2). Parkinson’s disease (PD) is an age-related neurodegenerative disease that shares similar pathological characteristics with the process of normal aging (i.e., reduced dopamine), but to a much higher degree. In addition to investigating the effect of normal aging, the current study also examined the effect of “abnormal aging” on emotion and driving using PD as a model (aim 3). Participants included 16 older (65 - 79 years old), 16 middle-aged (38 - 55 years old) neurologically normal adults, and 16 patients with mild PD (56 - 80 years old). This study focused on fear and anger, the two negative emotions that are most likely to be elicited by driving experiences and to disrupt driving behaviors. Low-level and high-level fear and anger challenges were created using simulated driving scenarios: 1) Low fear task, participants drove in fog and frequently encountered static obstacles on the road; 2) High fear task, participants drove at nighttime and frequently encountered deer running across the road; 3) Low anger task, participants drove following a slow-moving vehicle; 4) High anger task, participants followed a slow vehicle and were honked at by a tailgating vehicle. Participants rated the intensity of fear and anger experiences at 1- minute intervals when they were driving. Comparing older adults against middle-aged adults, it was found that 1) fear intensity was lower in older adults in the low fear task. In contrast, latency and duration of fear were similar between groups in both fear tasks. 2) Anger intensity was lower in older adults in both anger tasks. Anger latency and duration were similar between groups in the high anger task, but anger took longer to develop and was of shorter duration in older adults in the low anger task. 3) In the low fear task, older adults exhibited more cautious driving behaviors (e.g., more frequent uses of brake). In the high anger task older adults were less able to control the acceleration and brake pedals smoothly (e.g., higher forces for brake and acceleration). These results suggest that age differences in the dynamic processes of emotion and the effect of emotion on driving may depend on the type of emotion and level of emotional challenge. When comparing PD patients against age- and education-matched neurologically normal participants (n = 18), it was found that the PD patients reported experiencing similar degrees of fear and anger as the normal comparisons. However, in the high fear task PD patients were less responsive to deer running across the road (e.g., mean and variation of force for brake was lower in PD patients). This finding suggests an impaired ability in PD patients to respond to the sudden appearance of driving hazards. Collectively, the findings of this study provide a window into how the moment-to-moment experience of negative emotions in response to environmental challenges may contribute to the overall emotional well-being of older adults. They also suggest that both the type of emotion and the level of challenge may be important factors in determining the experience of emotion and the effect of emotion on driving during “normal” and “abnormal” aging.

Diseases of the liver have a large impact on human health. Genetic disorders, metabolic disorders, alcoholism, cancer, or infections can all impair liver function. If serious enough, a liver transplant may be necessary, a major surgical procedure which requires life-long immune suppression and relies on the availability of donor livers. Gene therapy is being intensively studied as a potential method to treat many disorders, including disorders of the liver. While viral gene therapy has seen some success, possible side effects make it risky, so nonviral gene delivery vectors are being developed. Unfortunately, these nonviral vectors do not yet have the efficiency of the viral vectors. Nonviral gene delivery vectors face many chges in vivo. The vectors must protect DNA from nucleases while it moves through the bloodstream, they must avoid nonspecific uptake, they must be enter the correct cells, and must enter the nucleus before the DNA can be expressed. If any step of this process fails, there will be very little, if any, expression, and it may be impossible to determine what went wrong. One impediment to nonviral gene delivery research is the transition from in vitro studies to in vivo studies. The cancer derived cell lines most often used for in vitro transfections are rapidly dividing, which makes nuclear entry much easier than in the whole animal. While primary cells would be a more accurate model of the in vivo environment, the number of cells that can be obtained from tissues is small, and primary cells usually cannot be cultured for long. This limits the number of experiments that can be done with each preparation of cells. To overcome this, we have miniaturized transfection assays, including the transfection of mouse primary hepatocytes with luciferase in 384 well plates. Because fewer cells are needed, more experiments can be performed with each liver preparation. Another issue introduced by the differences between in vitro and in vivo research is circulatory stability. In vitro, large particles with strong positive charges are desired, because they sink down onto the cells and are attracted to the negatively charged cellular membranes. However, in vivo these particles will aggregate serum proteins and become lodged in narrow capillary beds in the lungs or other organs, often causing toxicity. While this behavior can usually be overcome through PEGylation, improving a particle's circulatory half-life will still improve its chances of finding the correct target. Scavenger receptors found on liver nonparenchymal cells are very efficient at removing negatively charged particles from the bloodstream. We have shown that dosing large amounts of PEGylated polyacridine DNA polyplex can saturate the scavenger receptors and improve circulatory half-life. We have also shown that large doses of PEGylated peptide with or without acridine groups can inhibit scavenger receptor uptake through the formation of peptide-protein nanoparticles. By inhibiting scavenger receptor uptake, DNA can be successfully hydrodynamically stimulated at times up to 12 hours post-delivery, demonstrating a longer circulatory half-life and suggesting a mechanism to explain how delayed hydrodynamic stimulation can achieve full level gene expression in the liver after the DNA has had time to circulate throughout the whole animal. Once a nonviral vector finds its target cell, it must still enter the cell through endocytosis and then escape the endosome before it becomes digested in the lysosome. Before the DNA cargo can be expressed, it must enter the nucleus. Nuclear entry in nondividing cells is a major barrier to efficient gene delivery. One method to over come this barrier is to avoid the need for nuclear entry altogether by delivering mRNA instead of DNA. mRNA can produce protein in the cytoplasm by finding a ribosome and initiating translation. However, it is even less stable in the bloodstream than DNA. We have produced an mRNA construct capable of high-level expression in the liver through hydrodynamic delivery. The PEGylated polyacridine peptides used to protect DNA were applied to mRNA and shown to enhance expression, allowing a 1μg dose of mRNA peptide polyplex to produce higher expression than an equal dose of DNA. The peptides were also shown to provide some protection against nuclease digestion in serum. This suggests that efficient, if transient, protein expression can be achieved through peptide protected mRNA delivery. However, DNA delivery is still desired for longer term expression, and the nuclear entry of DNA is still a problem. In an effort to help facilitate nuclear entry, the membrane disrupting enzyme phospholipase A2 was modified in several ways. The enzyme was conjugated with DNA binding peptides, nuclear localization peptides, and hepatocyte targeting oligosaccharides. Additionally, mutant forms of the enzyme were prepared in bacterial expression systems to achieve site-specific conjugation. Unfortunately, none of these efforts produced a useful tool for nuclear entry. The research presented in this thesis represents some progress toward the goal of nonviral gene delivery to the liver. Hopefully, some of this work will be useful in the development of new treatments and therapies to improve human health.