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- Creators: Arizona State University
Description
Cancer is a leading cause of death worldwide. The traditional modalities for treating cancers include radiotherapy and chemotherapy, which are often non-curative, highly invasive, and disfiguring. Immunotherapies are a promising new form of cancer treatment with better therapeutic outcomes than traditional cancer treatments. Immunotherapies work by stimulating the host immune system to combat the diseases. Oncolytic viruses (OV) are cancer immunotherapies that infect, replicate, and kill cancer cells and, in the process, turn immunologically ‘cold’ tumors ‘hot.’ Despite the recent successes of OV, several fundamental experimental questions remain unanswered. What kind of immunological cell death is activated by the OV? Which virus and host proteins regulate optimal oncolytic virotherapy? This dissertation delves into some of these questions for myxoma virus (MYXV), a rabbit poxvirus currently being developed as an OV. The origins and structures of the E3-like proteins within poxviruses, particularly the Z-nucleic acids binding domain (Zα-BD) of the E3 proteins, dictate the poxvirus's potential to activate necroptosis. My research illustrates a higher degree of structural variability in the Zα-BD than in the dsRNA binding domain (dsRNA-BD) amongst poxvirus E3-like proteins. Furthermore, I show that unlike Orthopoxviruses (Cowpox and Vaccinia virus) that inhibit necroptosis, Leporipoxviruses (Myxoma virus Lausanne, Shope Fibroma Virus, and Myxoma virus Toledo) activate necroptosis in necroptosis competent human cancer cells, making MYXV a potential game-changer in cancer treatment. Secondly, I demonstrate that the MYXV M147 protein is a viral MLKL (mixed lineage kinase domain-like protein) required for optimal MYXV replication in all transformed and cancer cells that MYXV can permissively replicate. In addition, MYXV deficient in the M147 gene product sub-optimally spreads in human tumor murine models.
Furthermore, I show that M147 regulates cellular functions, at least in part, through host SCRIB (Scribble planar Cell Polarity Protein). Lastly, I provide evidence that DHX9, a member of the DExD/H-box family of helicases, promotes cancer cell epithelial-to-mesenchymal transition and inhibits MYXV replication in human-derived cancer cells.
My work demonstrates that MYXV activates necroptosis in cancer cells and that the MYXV M147 and host DHX9 modulate MYXV replication. These findings contribute to our understanding of virology and oncolytic virotherapy.
ContributorsAyuk Enow, Junior (Author) / Rahman, Masmudur (Thesis advisor) / Li, Yize (Thesis advisor) / McFadden, Grant (Committee member) / Jacobs, Bertram (Committee member) / Florsheim, Esther (Committee member) / Arizona State University (Publisher)
Created2024
Description
This dissertation delivers a timely scholarly conversation on differently imagined grassroots feminist politics in a non-Western neoliberal authoritarian context. The project pivots on a central inquiry: how do Chinese rural migrant women, whose lifetimes are cast under the shadows of “Made in China” global production and punctuated by multiple concurrent neoliberal crises, collectively give birth to community power for radical livability? Drawing from extensive ethnographic fieldnotes, six oral history interviews, and archival studies, the dissertation employs community-based participatory action research to document and advance community organizing efforts by Green Rose (hence GR), a migrant women-led grassroots collective in Shenzhen. Set against the historical backdrop of China’s post-socialist reform when South China emerged as the world’s factory for manufacturing globalization, my study traces the trajectories in which a group of migrant women, upon gaining exposure to transnational labor NGO activism in the early 2000s, asserted collective power at the frontline for intersectional gender and class struggles. In the aftermath of the 2008 global financial crisis, when economic downturns and welfare austerity measures entangled with the resurgence of state authoritarianism targeting civic actions, GR women temporarily transitioned to guerrilla activism to bring emancipatory cultural organizing and mutual aid into the social arena of a precarious migrant neighborhood. To survive welfare segregation and economic-political contingencies, GR women tactically established a social work service NGO to translate their depoliticized service labor into radical actions. They animate a sisterhood kinship system to liberate individual care capacity from the privatized household; they reorganize people, spaces, and resources to build a care safety net for all. By foregrounding migrant women as political protagonists in China’s precarious and fragmented civic landscape, my study problematizes both male-dominant labor politics embraced by orthodox Marxist scholars and the mainstream feminist movement sponsored by urban middle-class feminists, all the while exposing the state censorship that attempts and yet fails to erase the history of the marginalized gendered collective.
ContributorsDong, Anzi (Author) / Quan, H. L. T (Thesis advisor) / Fonow, Mary Margaret (Thesis advisor) / Linton, Mellissa (Committee member) / Arizona State University (Publisher)
Created2024
Description
Across the tree of life, rotary molecular motors like the F1FO ATP synthase utilize a transmembrane nonequilibrium proton gradient to synthesize adenosine triphosphate (ATP), the biological energy currency. The catalytic portion of rotary motors, such as the F1 complex from E. coli and the V1 complex from S. cerevisiae, was purified and studied during ATP hydrolysis. Single-molecule assays utilized gold nanorods to investigate the kinetics of the F1-ATPase catalytic dwell, the biophysics of V1-ATPase, and the kinematics of the F1-ATPase power stroke. Observation of oscillatory rotor motion during the F1 catalytic dwell provided new insight as to how energy from ATP binding is stored during its three stages. That motion indicated a ratchet mechanism, in which F1 changed states according to first-order kinetics with a time constant τ = 0.182, showing that Stage-1 represents a pre-hydrolysis state and Stage-2 represents a post-hydrolysis state. F1 was then observed to return to 0° prior to its next power stroke (Stage-3), which explained why the three catalytic dwells remain 120° apart after many revolutions. Analysis of the 120° power stroke following Stage-3 was conducted in both V1 and F1, allowing comparative biology to elucidate defects in the ATPase mechanism, such as ADP inhibition and faltering rotation. It is noteworthy that the V1 rotary positions of ADP release and ATP binding are the opposite of F1, and that less elastic energy is stored in the V1 rotor due to differences in its catch loop. In both rotary ATPases, energy contributed by binding and hydrolysis can dissipate at multiple points. When the F1 catch loop contact between F1 βD305 and γQ269 was mutated, the elastic energy stored in the rotor dissipated dramatically. Dissipation was clearly shown by sustained Phase-1 decelerations, the distribution of ATP-binding dwells, and high-amplitude oscillations in γQ269L. These findings clarify evolutionary similarities and differences between eukaryotic V1, which is exclusively a hydrolase, and F1, which can both hydrolyze and synthesize ATP.
ContributorsBukhari, Zain Aziz (Author) / Frasch, Wayne D (Thesis advisor) / Gaxiola, Roberto A (Committee member) / Presse, Steve (Committee member) / Wideman, Jeremy G (Committee member) / Arizona State University (Publisher)
Created2024
Description
The Studio Ghibli animated films have achieved international recognition for their cinematic quality and original soundtracks composed by Joe Hisaishi. The music from these films is so celebrated it is performed by symphony orchestras without the movie animations in concert halls worldwide. Film music originally scored for full-size orchestras can be arranged for smaller chamber ensembles and is a popular genre that makes performing these works more accessible. Arranging and rewriting orchestral reductions are skills collaborative pianists use every day when dealing with concertos or arias, and applying these skills to the music of Hisaishi was the foundation of this research. For this project, I created a medley of musical themes from three Studio Ghibli films: My Neighbor Totoro, Howl’s Moving Castle, and Spirited Away. The medley is written for traditional piano trio: violin, cello, and piano. This paper includes a brief history of the relationship between composer Joe Hisaishi and film director Hayao Miyazaki, one of the founders of Studio Ghibli, and explains the methods of creating this arrangement without access to the original orchestral score. Methods for creating transitions between different film themes, creation of countermelodies, and nuances of voicing are also presented, along with the score of the medley. I hope this project and these methods will inspire other collaborative pianists and musicians to create their own arrangements and medleys.
ContributorsTelling, Emily (Author) / Campbell, Andrew (Thesis advisor) / Aoki, Miki (Committee member) / Reymore, Lindsey (Committee member) / Arizona State University (Publisher)
Created2024
Description
How can we understand and pursue sustainability transitions that disrupt everyday practices and social norms? This dissertation finds potential answers to this fundamental sustainability governance question in Arizona utilities’ efforts to legitimate wastewater as a drinking water source. Due to widespread public concern regarding the direct potable reuse of wastewater (DPR), utilities and other stakeholders have developed innovative governance approaches. By offering tastings of DPR water (often in the form of beer), utilities create spaces for deliberation within a traditionally top-down policy planning paradigm, and furthermore, invite feelings—emotions and bodily sensations—into policymaking. This dissertation explores and advances Arizona's emerging transition to deliberative water governance through three distinct investigations. The first of these, an institutional analysis based on interviews with 34 regional stakeholders and observations at 56 water industry meetings, identifies direct experiences with DPR (e.g., tastings) as a pivotal strategy to institutionalize new wastewater practices. The second investigation examines utility-sponsored initiatives to promote DPR and finds that, instead of assuming that consumers behave as rational choice or bounded rationality would predict, water utilities’ use of drinking water tastings reflects a new normative assumption, termed embodied rationality. The third investigation applies embodied rationality in action research with skeptical consumers and reuse industry stakeholders to co-design an exhibit about DPR that engaged more than 1,100 people. Drawing insights from the literatures of embodied and enacted cognition, practice theory, organizational institutionalism, sustainability transitions management, and design research, this dissertation proposes an analytical approach, normative framework, and practical tools for collaboratively addressing real-world sustainability challenges.
ContributorsManheim, Marisa (Author) / White, Dave (Thesis advisor) / Spackman, Christy (Committee member) / Eakin, Hallie (Committee member) / Arizona State University (Publisher)
Created2024
Description
Nutritional supplement use by high school student athletes may pose risks of consuming prohibited or banned substances that can result in suspension of athletic participation. Currently, there is no peer-reviewed published data that exists on the use of supplements and use of third-party tested supplements for this population. When looking at supplement use, the Theory of Planned Behavior (TPB) can be utilized. This model was designed to determine if the intention of completing a behavior is based on three different constructs which include attitude, subjective norm, and perceived behavioral control. A pre- and post- test questionnaire was used to determine the effect of an educational intervention that was designed and developed. A total of 106 high school student athletes, ranging from 14-19 years of age from a private high school in the western US were included in the analysis of the study. The intention to use a good basic diet and intention to use nutritional supplements were both predicted by attitude, subjective norm, and perceived behavioral control and both resulted in a significant regression equation (p < .001). There was 95.3% (n=101) of athletes that reported use of at least one supplement in the last 12 months with reporting on average eight supplements ranging from 0-31 supplements. In conclusion, almost all high school student athletes reported using at least one nutritional supplement in the last 12 months, while roughly one-fourth consistently reported to use third-party tested nutritional supplements. The TPB based supplement education program resulted in the intention to change supplement behavior toward using safe third-party tested supplements more frequently at a group level.
ContributorsMorton, Lindsay (Author) / Wardenaar, Floris (Thesis advisor) / Wharton, Christopher (Committee member) / Levinson, Simin (Committee member) / Arizona State University (Publisher)
Created2024
Description
Background: Despite research aimed at understanding the mechanisms of metabolic syndrome (MetS), this prevalence continues to rise. Recent literature indicates that dietary fiber may offer prevention and management of MetS in various studies involving human and animal subjects. Objective: This six-week study aimed to test the efficacy of a novel fiber-rich complex in young male Sprague-Dawley rats by examining the effects on high-fat diet-induced weight gain, adiposity, high blood sugar, lipid imbalance, and oxidative stress.
Methods: 24 six-week-old male Sprague Dawley rats were randomly assigned into three diet groups (regular chow, high-fat, or high-fat + fiber) and fed for six weeks. Blood from the animals was collected at weeks 0, 3, and 6 for fasting blood glucose (FBG) analysis and at weeks 0 and 6 for lipid profile assessment. Body mass was weighed weekly. Organ mass, nasoanal, and tail length were measured at week 6. Findings were considered significant at p-value < 0.05. Data collected at week 6 were analyzed by one-way ANOVA, whereas data collected at multiple time points were analyzed by two-way ANOVA with diet and time as factors. Student-Newman-Keuls posthoc analyses were used to compare differences between and within groups.
Results: No significant differences were found in the size of rats fed each diet as measured by tail length (p = 0.599) or nasoanal length (p = 0.875). Abdominal circumference was not significantly different (p = 0.477). There were no significant differences between groups in fasting whole blood HDL cholesterol (p = 0.297), fasting whole blood HDL triglycerides (p = 0.624), plasma total triglycerides (p = 0.137), or beta-hydroxybutyrate (p=0.185) after six weeks of each dietary treatment. Similarly, plasma true triglycerides and free glycerol were not significantly different between groups (p = 0.148 and 0.529, respectively). Thiobarbituric acid reactive substances (TBARS) were also not significantly different between groups (p = 0.412).
Conclusion: The addition of the novel fiber-rich complex did not significantly affect high-fat diet-induced weight gain, adiposity, high blood sugar, lipid imbalance, or oxidative stress in this experimental design.
ContributorsLing, Jingyu (Author) / Sweazea, Karen (Thesis advisor) / Sears, Dorothy (Committee member) / Kim, Min-Hyun (Committee member) / Arizona State University (Publisher)
Created2024
Description
Obesity has consistently presented a significant challenge, with excess body fat contributing to the development of numerous severe conditions such as diabetes, cardiovascular disease, cancer, and various musculoskeletal disorders. In this study, different methods are proposed to study substrate utilization (carbohydrates, proteins, and fats) in the human body and validate the biomarkers enabling to investigation of weight management and monitor metabolic health. The first technique to study was Indirect calorimetry, which assessed Resting Energy Expenditure (REE) and measured parameters like oxygen consumption (VO2) and carbon dioxide production (VCO2). A validation study was conducted to study the effectiveness of the medical device Breezing Med determining REE, VO2, and VCO2. The results were compared with correlation slopes and regression coefficients close to 1. Indirect Calorimetry can be used to determine carbohydrate and fat utilization but it requires additional correction for protein utilization. Protein utilization can be studied by analyzing urinary nitrogen. Therefore, a secondary technique was studied for identifying urea and ammonia concentration in human urine samples. Along this line two methods for detecting urea were explored, a colorimetric technique and it was validated against the Ion-Selective method. The results were then compared by correlation analysis of urine samples measured with both methods simultaneously curves. The equations for fat, carb, and protein oxidation, involving VO2, VCO2 consumption, and urinary nitrogen were implemented and validated, using the above-described methods in a human subject study with 16 subjects. The measurements included diverse diets (normal vs. high fat/protein) in normal energy balance and pre-/post interventions of exercise, fasting, and a high-fat meal. It can be concluded that the indirect calorimetry portable method in conjunction with urine urea methods are important to help the understanding of substrate utilization in human subjects, and therefore, excellent tools to contribute to the treatments and interventions of obesity and overweighted populations.
ContributorsPradhan, Ayushi (Author) / Forzani, Erica (Thesis advisor) / Lind, Mary Laura (Committee member) / Wang, Shaopeng (Committee member) / Arizona State University (Publisher)
Created2023
Description
Mealworms (Tenebrio molitor), the larval stage of yellow mealworm beetles, are a popular feeder insect for birds, amphibians, reptiles, fish, and even human populations throughout the world. As such, the goal of this work was to understand how the diet of mealworms impacts their nutritional quality as variations in quality can impact the animals (and humans) that consume them. In this study, 500 mealworms were divided among each of the following substrates designed to model food sources available in urban versus rural, more natural areas: 100% wheat germ (control); 100% Styrofoam; mixture of soil, grasses, and leaves from urban lawns; a mixture of soil, grasses and leaves from rural lawns; 50% mixture of wheat germ + carrots; natural fertilizer; or fertilizer with weed killer. The mealworms were maintained at room temperature and the diets were replaced bi-weekly to prevent spoilage and to remove mealworm waste. Once a week for three weeks, mealworms were sampled from each substrate and frozen at -20°C. After 3 weeks, mealworms housed in wheat germ + carrots weighed significantly more than all other groups (p<0.05), whereas those housed in Styrofoam or urban lawn substrates weighed significantly less at week 3 as compared to week 1 (p<0.01). The urban lawn substrate resulted in greater molting and contained the highest number of pupae, but also the greatest mortality among the substrates. The Bradford method measured the total protein content of mealworms homogenized in phosphate-buffered saline. Mealworms maintained on wheat germ had significantly greater total protein content as compared to mealworms transitioned to any other diet (p<0.05). So, compared to wheat germ, urban foods generally reduced protein, total sugars, and crude fat, although they also decreased oxidized lipoproteins. Urban lawn had lower oxidized lipoprotein content than wheat germ, but levels were higher compared to wheat germ with carrots and natural fertilizer. In addition, urban foods generally increase the water content in mealworms. Urban foods were not much different from rural lawns as no there was difference between urban and rural lawns. Differences in body mass and total protein support the hypothesis that mealworms' nutritional quality is altered by ingesting urban substrates. These data suggest that mealworms (and potentially other insects) in cities may be exposed to food substrates that result in less nutritional value than those living in more natural areas as mimicked by the rural lawn substrates and wheat germ control, although they may be higher in water content.
ContributorsLockett, Rory Earle (Author) / Sweazea, Karen (Thesis advisor) / Deviche, Pierre (Committee member) / Senko, Jesse (Committee member) / Arizona State University (Publisher)
Created2024
Description
This dissertation examines the development of a singular ritual tradition—the “rites of summoning for interrogation” (kaozhao fa考召法)—from its earliest traces during the Han (2nd century CE) to its full-flowering as a ritual specialty by the end of the Tang (618–907) by drawing upon both esoteric Daoist texts as well as anecdotal materials from the period. Practitioners of this tradition, termed “Ritual Masters of Summoning for Interrogation” (kaozhao fashi), identified as constituents of a larger celestial surveillatory bureaucracy and drew upon its authority to cure disease, exorcize spirits, mend rifts in the community, and even determine marriage compatibility. They did so by utilizing a range of ritualistic practices drawn from the earlier Celestial Master (Zhengyi 正一) and Upper Purity (Shangqing 上清) traditions, such as visualizations, incantations, ritualized pacing, and the talismanic arts. Such practices became widespread in the Song dynasty (960–1279) and were broadly adapted by Daoist movements of the period such as the Orthodox Methods of the Celestial Heart (Tianxin zhengfa 天心正法. In Chapter 1, I trace the origins of kaozhao back to the Han, where they—along with similar exorcistic traditions—drew inspiration from the bureaucratic argot and juridical stylings of officialdom. In Chapter 2, I posit a timeline for the development of kaozhao through the examination of ritual registers and situate the practice in context of the ritual landscape of 8th century China. Chapter 3 details the construction of the kaozhao practitioner’s identity, lineage, and history in the pages of a Tang-era ritual manual, the Jinsuo liuzhu yin 金鎖流珠引. This text provides the earliest categorization of kaozhao—dividing it into a binary of “civil” (wen 文) and “martial” (wu 武) practices—the combination of which were required to attain a new form of communal transcendence called “raising the residence” (bazhai 拔宅). Finally, I demonstrate how the kaozhao rite of “patrolling” (xunyou 巡遊), located therein, recast practitioners as celestial equivalents of the itinerant surveillance commissioners of the Tang, broadening their mandate as ritual polymaths.
ContributorsWolf, Lucas A (Author) / Bokenkamp, Stephen R (Thesis advisor) / Ling, Xiaoqiao (Committee member) / Chen, Huaiyu (Committee member) / West, Stephen H (Committee member) / Arizona State University (Publisher)
Created2024