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Vaccines are one of the most effective ways of combating infectious diseases and developing vaccine platforms that can be used to produce vaccines can greatly assist in combating global public health threats. This dissertation focuses on the development and pre-clinical testing of vaccine platforms that are highly immunogenic, easily modifiable,

Vaccines are one of the most effective ways of combating infectious diseases and developing vaccine platforms that can be used to produce vaccines can greatly assist in combating global public health threats. This dissertation focuses on the development and pre-clinical testing of vaccine platforms that are highly immunogenic, easily modifiable, economically viable to produce, and stable. These criteria are met by the recombinant immune complex (RIC) universal vaccine platform when produced in plants. The RIC platform is modeled after naturally occurring immune complexes that form when an antibody, a component of the immune system that recognizes protein structures or sequences, binds to its specific antigen, a molecule that causes an immune response. In the RIC platform, a well-characterized antibody is linked via its heavy chain, to an antigen tagged with the antibody-specific epitope. The RIC antibody binds to the epitope tags on other RIC molecules and forms highly immunogenic complexes. My research has primarily focused on the optimization of the RIC platform. First, I altered the RIC platform to enable an N-terminal antigenic fusion instead of the previous C-terminal fusion strategy. This allowed the platform to be used with antigens that require an accessible N-terminus. A mouse immunization study with a model antigen showed that the fusion location, either N-terminal or C-terminal, did not impact the immune response. Next, I studied a synergistic response that was seen upon co-delivery of RIC with virus-like particles (VLP) and showed that the synergistic response could be produced with either N-terminal or C-terminal RIC co-delivered with VLP. Since RICs are inherently insoluble due to their ability to form complexes, I also examined ways to increase RIC solubility by characterizing a panel of modified RICs and antibody-fusions. The outcome was the identification of a modified RIC that had increased solubility while retaining high immunogenicity. Finally, I modified the RIC platform to contain multiple antigenic insertion sites and explored the use of bioinformatic tools to guide the design of a broadly protective vaccine.

ContributorsPardhe, Mary (Author) / Mason, Hugh S (Thesis advisor) / Chen, Qiang (Committee member) / Mor, Tsafrir (Committee member) / Wilson, Melissa (Committee member) / Arizona State University (Publisher)
Created2021
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Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination

Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
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The Hong Kong-born Canadian photographer and performance artist Tseng Kwong Chi mostly worked in the United States until the year he died in 1990. Upon arriving in New York in 1979, he started his career with a new name. By dropping his anglicized name Joseph and replacing it with his

The Hong Kong-born Canadian photographer and performance artist Tseng Kwong Chi mostly worked in the United States until the year he died in 1990. Upon arriving in New York in 1979, he started his career with a new name. By dropping his anglicized name Joseph and replacing it with his Chinese given name Kwong Chi, Tseng made a clear statement: this is my staged persona who refuses to assimilate to Western culture. This thesis deconstructs Tseng’s key works, including his party-crashing Met series, the decade-long East Meets West series, and the extended Expeditionary series. With his persona disguised by wearing a Mao suit and a pair of sunglasses, I argue that Tseng was a pioneer in the genre of Asian American performance photography and that his work foreshadowed the cultural jamming movement in his innovative use of détournement while it also critically comments on orientalism, cultural fetish, and Asian identity politics. Additionally, Tseng’s work served as a bridge, connecting art history with issues of Asian American identity. As a gay artist who worked mostly in the United States, his work was an early example of what Jachinson Chan has suggested as an alternative model of masculinity for Asian American men: that Asian American men can be free, independent, expressive, and willing to embrace femininity with their masculinity. As David Eng has argued, Tseng also bridged the fields of Asian American queer studies and diaspora studies. Moreover, Tseng carried the legacy of the first-generation Chinese American artists in the medium of photography and inspired the next generation of diasporic artists to explore Asian identity, and to contest the image of Mao and the power dynamics between East and West.
ContributorsWei, Xin (Author) / Mesch, Claudia (Thesis advisor) / Hoy, Meredith (Committee member) / Kuo, Karen (Committee member) / Arizona State University (Publisher)
Created2022
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This dissertation consists of three chapters that investigate the rapid adoption and complex implementation of city commitments to transition to 100% renewable energy (100RE). The first paper uses a two-stage, mixed methods approach to examine 100RE commitments across the US, combining a multivariate regression of demographic, institutional, and policy factors

This dissertation consists of three chapters that investigate the rapid adoption and complex implementation of city commitments to transition to 100% renewable energy (100RE). The first paper uses a two-stage, mixed methods approach to examine 100RE commitments across the US, combining a multivariate regression of demographic, institutional, and policy factors in adoption and six interview-based state case studies to discuss implementation. Adoption of this non-binding commitment progressed rapidly for city councils around the US. Results show that many cities passed 100RE commitments with no implementation plan and minimal understanding of implementation challenges. This analysis highlights that many cities will need new institutions and administrative capacities for successful implementation of these ambitious new policies. While many cities abandoned the commitment soon after adoption, collaboration allowed cities in a few states to break through and pursue implementation, examined further in the next two studies. The second paper is a qualitative case study examining policymaking for the Utah Community Renewable Energy Act. Process tracing methods are used to identify causal factors in enacting this legislation at the state level and complementary resolutions at the local level. This Act was passed through the leadership and financial backing of major cities and committed the investor-owned utility to fulfill any city 100RE resolutions passed through 2019. Finally, the third paper is a mixed-methods, descriptive case study of the benefits of Community Choice Aggregation (CCA) in California, which many cities are using to fulfill their 100RE commitments. Cities have adopted CCAs to increase their local voice in the energy process, while fulfilling climate and energy goals. Overall, this research shows that change in the investor-owned utility electricity system is in fact possible from the city scale, though many cities will need institutional innovation to implement these policies and achieve the change they desire. While cities with greater resources are better positioned to make an impact, smaller cities can collaborate to similarly influence the energy system. Communities are interested in lowering energy costs for customers where possible, but the central motivations in these cases were the pursuit of sustainability and increasing local voice in energy decision-making.
ContributorsKunkel, Leah Christine (Author) / Breetz, Hanna L (Thesis advisor) / Parker, Nathan (Committee member) / Salon, Deborah (Committee member) / Arizona State University (Publisher)
Created2022
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that emerged from a zoonotic host at the end of 2019 and caused a public health crisis. In this collection of studies, Nicotiana benthamiana plants are used to set the foundation for producing monoclonal

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) that emerged from a zoonotic host at the end of 2019 and caused a public health crisis. In this collection of studies, Nicotiana benthamiana plants are used to set the foundation for producing monoclonal antibodies (mAbs) with homogeneous glycosylation to neutralize SARS-CoV-2 and potentially address the immunopathology often observed with severe COVID-19. Specifically, a mAb against the human interleukin (IL)-6 receptor (sarilumab) was generated and evaluated in vitro for its potential to reduce IL-6 signaling that has been shown to be associated with more severe cases of COVID-19. Furthermore, multiple mAbs that bind to the receptor-binding domain (RBD) of SARS-CoV-2 and efficiently neutralize the virus were developed using plant-based expression. Several of these mAbs are from different classes of RBD-binding mAbs that have distinct binding sites from one another. Several mAbs from different classes showed synergy in neutralizing the ancestral strain of SARS-CoV-2 and a smaller subset showed synergy when tested against the highly mutated Omicron (B.1.1.529) variant. Of interest, a novel RBD-binding mAb, termed 11D7, that was raised against the ancestral strain and derived from a hybridoma, appears to have an epitope on the RBD that contributes more synergy to a mAb combination that efficiently neutralizes the B.1.1.529 variant of SARS-CoV-2. This epitope was partially mapped by competitive binding and shows that it overlaps with another known antibody that binds a cryptic, distal epitope, away from the receptor binding site, giving insight into the potential mechanism by which 11D7 neutralizes SARS-CoV-2, as well as potentially allowing it to resist SARS-CoV-2 immune evasion more efficiently. Furthermore, this mAb carries a highly homogeneous glycan pattern when expressed in N. benthamiana, that may contribute to enhanced effector function and provides a tool to elucidate the precise role of crystallizable fragment (Fc)-mediated protection in SARS-CoV-2 infection. Ultimately, these studies provide evidence of the utility of plant-made mAbs to be used as cocktail members, giving clarity to the use of less potent mAbs as valuable cocktail components which will spur further investigations into how mAbs with unique epitopes work together to efficiently neutralize SARS-CoV-2.
ContributorsJugler, Collin (Author) / Chen, Qiang (Thesis advisor) / Lake, Douglas (Committee member) / Steele, Kelly (Committee member) / Mason, Hugh (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Tire blowout often occurs during driving, which can suddenly disturb vehicle motions and seriously threaten road safety. Currently, there is still a lack of effective methods to mitigate tire blowout risks in everyday traffic, even for automated vehicles. To fundamentally study and systematically resolve the tire blowout issue for automated

Tire blowout often occurs during driving, which can suddenly disturb vehicle motions and seriously threaten road safety. Currently, there is still a lack of effective methods to mitigate tire blowout risks in everyday traffic, even for automated vehicles. To fundamentally study and systematically resolve the tire blowout issue for automated vehicles, a collaborative project between General Motors (GM) and Arizona State University (ASU) has been conducted since 2018. In this dissertation, three main contributions of this project will be presented. First, to explore vehicle dynamics with tire blowout impacts and establish an effective simulation platform for close-loop control performance evaluation, high-fidelity tire blowout models are thoroughly developed by explicitly considering important vehicle parameters and variables. Second, since human cooperation is required to control Level 2/3 partially automated vehicles (PAVs), novel shared steering control schemes are specifically proposed for tire blowout to ensure safe vehicle stabilization via cooperative driving. Third, for Level 4/5 highly automated vehicles (HAVs) without human control, the development of control-oriented vehicle models, controllability study, and automatic control designs are performed based on impulsive differential systems (IDS) theories. Co-simulations Matlab/Simulink® and CarSim® are conducted to validate performances of all models and control designs proposed in this dissertation. Moreover, a scaled test vehicle at ASU and a full-size test vehicle at GM are well instrumented for data collection and control implementation. Various tire blowout experiments for different scenarios are conducted for more rigorous validations. Consequently, the proposed high-fidelity tire blowout models can correctly and more accurately describe vehicle motions upon tire blowout. The developed shared steering control schemes for PAVs and automatic control designs for HAVs can effectively stabilize a vehicle to maintain path following performance in the driving lane after tire blowout. In addition to new research findings and developments in this dissertation, a pending patent for tire blowout detection is also generated in the tire blowout project. The obtained research results have attracted interest from automotive manufacturers and could have a significant impact on driving safety enhancement for automated vehicles upon tire blowout.
ContributorsLi, Ao (Author) / Chen, Yan (Thesis advisor) / Berman, Spring (Committee member) / Kannan, Arunachala Mada (Committee member) / Liu, Yongming (Committee member) / Lin, Wen-Chiao (Committee member) / Marvi, Hamidreza (Committee member) / Arizona State University (Publisher)
Created2023
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Description
With rapid advances in technology development and public adoption, it is crucial to understand how these services will shape the future of travel depending on the extent to which people will use these services; impact the transportation and infrastructure systems such as changes in the use of transit and active

With rapid advances in technology development and public adoption, it is crucial to understand how these services will shape the future of travel depending on the extent to which people will use these services; impact the transportation and infrastructure systems such as changes in the use of transit and active modes of travel; and influence how technology developers create and update these transportation technologies to better serve people’s mobility needs. This dissertation explores how two major emerging services, namely ridehailing services and autonomous vehicles (AVs), will be used in the future when they are widely available and vastly used, and how they may impact the transportation infrastructure and societal travel patterns. The four proposed chapters use comprehensive quantitative and qualitative methods to explore the status of these technologies from theory, through robust modeling frameworks, to practice, by investigating the recent AV pilot deployments in real-world settings. In the second chapter, it was found that increased frequency of ridehailing use is significantly associated with a decrease in bus usage, suggesting that ridehailing functions more as a substitute for buses than as a complement and implying that transit agencies should explore ways to incorporate ridehailing services in their plans to enhance transit usage. Next, the third chapter showed that interest in using AVs for running errands had a positive and significant effect on AV ownership intent, even after accounting for a host of variables. The fourth chapter depicted how ridehailing experiences have a considerable effect on the willingness to ride AV-based services in both private and shared modes, suggesting that experience is crucial for future adoption of these services. Then, two recent real-world AV experiences are explored in the fifth chapter. Lessons learned from these experiments reinforced the importance of first-hand experiences in promoting AV awareness and trustworthiness, potentially leading to greater degrees of adoption. Finally, the results and discussions presented in this dissertation strengthen the body of literature on key emerging transportation technologies and inform policymakers and stakeholders to properly prepare cities and the public to welcome these technologies into our transportation system in an efficient, equitable, and complementary way.
ContributorsMagassy, Tassio Bezerra (Author) / Pendyala, Ram M (Thesis advisor) / Khoeini, Sara (Committee member) / Polzin, Steven E (Committee member) / Salon, Deborah (Committee member) / Arizona State University (Publisher)
Created2023
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Description

Recently the domestic aviation industry has been influenced by rapidly growing ultra low-cost carriers (ULCCs). The pattern of airport markets served by ULCCs is incongruous with legacy carriers and low-cost airlines alike. Existing literature, however, is limited for North American ULCCs: research has only recently begun to identify them separately

Recently the domestic aviation industry has been influenced by rapidly growing ultra low-cost carriers (ULCCs). The pattern of airport markets served by ULCCs is incongruous with legacy carriers and low-cost airlines alike. Existing literature, however, is limited for North American ULCCs: research has only recently begun to identify them separately from mainstream low-cost carriers. This study sought to understand the market factors that influence ULCC service decisions. The relationship between ULCC operations and airport market factors was analyzed using three methods: mapping 2019 flight data for four ULCCs combined, two regression analyses to evaluate variables, and three case studies examining distinct scenarios through interviews with airport managers. Enplanement data were assembled for every domestic airport offering scheduled service in 2019. Independent variables were collected for each Part 139 airport. The first model estimated an ordinary least squares regression model to analyze ULCC enplanements. The second model estimated a binary logistic equation for presence of ULCC service. Case studies for Bellingham, Waco, and Lincoln were selected using compelling airport factors and relevant ULCC experience. Maps of ULCC enplanements revealed concentrations of operations on the East Coast. Both regression analyses showed strong relationships between population and non-ULCC enplanements (two measures of airport market size) and ULCC operations. A significant relationship also existed between tourism and enplanements. In the logit model, distance and competition variables were associated with ULCC presence. Case studies emphasized the importance of airport fees and competition in ULCC preferences, although aeronautical costs were generally not significant in the regressions.

ContributorsTaplin, Drew (Author) / Kuby, Michael (Author) / Salon, Deborah (Author) / King, David A. (Author)
Created2023-01-31
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Description
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically

Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Public transportation is considered a solution to congestion and a tool for reducing greenhouse gas emissions. It is becoming popular even in cities with the harshest climate conditions as these cities grow rapidly and are trying to provide sustainable alternatives for their vehicle-oriented communities. A lot must be taken into

Public transportation is considered a solution to congestion and a tool for reducing greenhouse gas emissions. It is becoming popular even in cities with the harshest climate conditions as these cities grow rapidly and are trying to provide sustainable alternatives for their vehicle-oriented communities. A lot must be taken into consideration whendesigning transit systems to reduce riders' vulnerability to heat in cities with high temperatures averaging 40°C during the summer and humidity levels reaching 90 percent. Using transit systems in Dubai, United Arab Emirates, and Phoenix Metropolitan, United States, as case studies, this paper focuses on both qualitative and quantitative research methods to observe the built environment around public transit stations and measure the temperatures and humidity levels to compare with the experienced temperatures and the built environment observations. The results show that the design of transit stations and the public realm significantly impacts a rider's experience. The findings show that passive cooling, shading, and vegetation as the best practices in the two case studies. Both transit systems have certain elements that work efficiently and other elements that need improvement to provide a better rider experience. Identifying these best practices helps develop recommendations for the future of designing transit systems in desert cities worldwide.
ContributorsAlbastaki, Mohamed (Author) / King, David (Thesis advisor) / Salon, Deborah (Committee member) / Kelley, Jason (Committee member) / Arizona State University (Publisher)
Created2022