Matching Items (143)
Description
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
Description
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
Description
Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges. Vulnerability assessment (VA) examines the potential consequences a system is likely to experience due to exposure to perturbation or stressors and lack of the capacity to adapt. Post-fire debris flow and heat represent particularly challenging problems for infrastructure and users in the arid U.S. West. Post-fire debris flow, which is manifested with heat and drought, produces powerful runoff threatening physical transportation infrastructures. And heat waves have devastating health effects on transportation infrastructure users, including increased mortality rates. VA anticipates the potential consequences of these perturbations and enables infrastructure stakeholders to improve the system's resilience. The current transportation climate VA—which only considers a single direct climate stressor on the infrastructure—falls short of addressing the wildfire and heat challenges. This work proposes advanced transportation climate VA methods to address the complex and multiple climate stressors and the vulnerability of infrastructure users. Two specific regions were chosen to carry out the progressive transportation climate VA: 1) the California transportation networks’ vulnerability to post-fire debris flows, and 2) the transportation infrastructure user’s vulnerability to heat exposure in Phoenix.
ContributorsLi, Rui (Author) / Chester, Mikhail V. (Thesis advisor) / Middel, Ariane (Committee member) / Hondula, David M. (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2022
Description
Weight stigma is a prevalent issue that has detrimental effects on health for both adolescents and parents. Adolescents are in a formative stage of life, so it is important to understand how parents may impact adolescents’ own experience with weight stigma. Past research has examined adolescent coping, body image, and associated stigma in the context of the parent-child relationship. This cross-sectional study examined self-reported weight stigma experience and internalization within 42 parent/adolescent dyads to provide greater understanding of how adolescents and parents are experiencing and internalizing weight stigma independently and transversely.
ContributorsMillett, Emma (Author) / McEntee, Mindy (Thesis director) / Adams, Marc (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-12
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 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
Description
Machine learning (ML) and deep learning (DL) has become an intrinsic part of multiple fields. The ability to solve complex problems makes machine learning a panacea. In the last few years, there has been an explosion of data generation, which has greatly improvised machine learning models. But this comes with a cost of high computation, which invariably increases power usage and cost of the hardware. In this thesis we explore applications of ML techniques, applied to two completely different fields - arts, media and theater and urban climate research using low-cost and low-powered edge devices. The multi-modal chatbot uses different machine learning techniques: natural language processing (NLP) and computer vision (CV) to understand inputs of the user and accordingly perform in the play and interact with the audience. This system is also equipped with other interactive hardware setups like movable LED systems, together they provide an experiential theatrical play tailored to each user. I will discuss how I used edge devices to achieve this AI system which has created a new genre in theatrical play. I will then discuss MaRTiny, which is an AI-based bio-meteorological system that calculates mean radiant temperature (MRT), which is an important parameter for urban climate research. It is also equipped with a vision system that performs different machine learning tasks like pedestrian and shade detection. The entire system costs around $200 which can potentially replace the existing setup worth $20,000. I will further discuss how I overcame the inaccuracies in MRT value caused by the system, using machine learning methods. These projects although belonging to two very different fields, are implemented using edge devices and use similar ML techniques. In this thesis I will detail out different techniques that are shared between these two projects and how they can be used in several other applications using edge devices.
ContributorsKulkarni, Karthik Kashinath (Author) / Jayasuriya, Suren (Thesis advisor) / Middel, Ariane (Thesis advisor) / Yu, Hongbin (Committee member) / Arizona State University (Publisher)
Created2021
Description
Heart disease is the leading cause of death in the developed world and often occurs following myocardial infarction. Apelin is an endogenous prepropeptide that has been studied for its role in improving cardiac contractility and vasodilation but suffers from a short half-life in the body. By encasing apelin in a nanoparticle patch, we were able to slowly release apelin to cardiac tissue and observe its effects for one month following induced myocardial infarction surgery in mice. This study demonstrates that the apelin nanoparticles can protect the heart from myocardial-induced heart failure, observing overall improved cardiac function and reduction of fibrotic scarring associated with post-myocardial infarction compared to a nontreated group.
ContributorsHenderson, Adam (Author) / Chen, Qiang (Thesis director) / Zhu, Wuqiang (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor)
Created2022-05
Description
Weight stigma is present in many aspects of society, and especially in medicine. Weight stigma has detrimental effects on individuals physical and mental health, as well as patient-physician interactions. Application of weight-neutral healthcare ideologies such as Health at Every Size (HAES) are promising ways of decreasing weight stigma within the medical field without reducing the focus on improving patient health. Most widely applicable interventions include changing the focus of interactions from weight to health-promoting behaviors and lab values, improving provider education, and improving the general population's awareness of the problem.
ContributorsBrouhard, Mya (Author) / Chen, Qiang (Thesis director) / Parker, Lynn (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2024-05
Description
Platelet Rich Plasma (PRP) is an emerging procedure in regenerative medicine that offers a non-surgical minimally invasive way for tissue repair and regeneration. PRP has many different bioactive molecules that are able to influence and help achieve greater recovery and regenerative outcomes. Diet has many effects on platelets and looking at the mechanism in which platelet function and aggregation are affected with different diets shows how they are able to affect PRP therapy. Looking at these mechanisms allows for better physician recommendations for preprocedural diets to optimize efficacy. This paper conducts a systematic review to investigate the influence that diet can have on PRP outcomes. It was shown that high fat diets lower the efficacy of treatment while the Mediterranean diet helps promote platelet function and help efficacy. The future is to look at more diets while also integrating lifestyle choice before treatment for optimal outcomes.
ContributorsLaguna, Sebastian (Author) / Chen, Qiang (Thesis director) / Goyle, Ashu (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor)
Created2024-05
The Association Between Time to Eat and Students Fruit & Vegetable Consumption, Selection, and Waste
Description
Background: Studies have examined student fruit/vegetable (FV) consumption, selection, and waste related to lunch duration and found that longer duration at lunch was associated with greater consumption, selection, and reduced waste. However, few studies have investigated the relationship between time to eat and FVs. The aim of this research is to analyze the relationship between objective time to students took to eat (“time to eat”) as it relates to their fruit and vegetable consumption, selection, and plate waste.in elementary, middle, and high schools. Methods: A secondary analysis of cross-sectional study of 37 Arizona schools to discover the differences in the selection, consumption, and waste of FVs from students (Full N = 2226, Elementary N = 630, Middle School N = 699, High School N = 897) using objective time to eat measures. Zero-inflated negative binomial regressions examined differences in FV grams selected, consumed, and wasted adjusted for sociodemographics including race, ethnicity, eligibility for free or reduced lunch, academic year, and sex and clustering for students within schools. Results are presented across school level (elementary, middle, and high school).
Results: The average time taken to eat ranged from 10-12 minutes for all students. The association of time to eat and lunch duration were not closely related (r=0.03, p = 0.172). In the count model for every additional minute spent, there was a 0.5% greater likelihood of selecting FVs for elementary kids among those who took any FVs. In the zero-inflated model, it was found that there was a statistically significant relationship between time spent eating and the selection of fruits and vegetables. For the total sample and high schoolers, a minute more of eating time was associated with a 4.3% and 8.8% greater odds of selecting FV. This means that longer eating time increased the likelihood of choosing fruits and vegetables. The results indicated that the longer students took to eat, the higher the likelihood of consuming more of FVs. Each 10 more minutes spent eating (i.e., time to eat) is associated with a 5% increase in grams of FV selected relative to mean (for those that chose FV) over 1 week this equates to 32 g increase of FV selected. However, for middle schoolers, the time to eat was not found to be significant in relation to the grams of fruits and vegetables consumed. There was some significance in the sociodemographic factors such as gender (all) and other (middle school). There was a relationship between time taken to eat and waste as a proportion for fruits and vegetables. For example, among those among the students who wasted something (as a proportion of selection), each additional 10 minutes of eating time was associated with a .6% decrease in waste relative to the mean (for those who chose fruits and vegetables) over a week, resulting in a decrease in waste percentage of 16.5%. Among high schoolers, males had a slightly higher odds of wasting a proportion of fruits and vegetables.
Conclusions: This study aimed to examine the association between the time students take to eat during lunch and their fruit and vegetable (FV) consumption, selection, and plate waste. The findings revealed that the time to eat was related to FV consumption, depending on the school level. However, it was not significantly associated with FV selection or waste. The study emphasized the need for further research on time to eat, distinguishing it from the duration of lunch. Longer lunch periods and adequate time could influence better food choices, increased FV consumption, and reduced waste. The study highlighted the importance of interventions and school policies promoting healthier food choices and providing sufficient time for students to eat. Future research should validate these findings and explore the impact of socialization opportunities on promoting healthier eating habits. Understanding the relationship between lunch duration, time to eat, and students' dietary behaviors can contribute to improved health outcomes and inform effective strategies in school settings.
ContributorsDandridge, Christina Marie (Author) / Adams, Marc (Thesis advisor) / Whisner, Corrie (Committee member) / Bruening, Meg (Committee member) / Arizona State University (Publisher)
Created2023