ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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Description
Infertility has become an increasing problem in developed countries and in many cases can be attributed to compromised sperm quality. Assessment of male fertility typically utilizes semen analysis which mainly examines sperm morphology, however many males whose sperm appear normal are sub- or infertile, suggesting that sperm from these males may be deficient in a protein or suite of proteins. To date, very little is known about the composition of sperm or the complex maturation process that confers motility and fertilization competency to sperm. Chapter 1 discusses the use of whole cell mass spectrometry to identify 1247 proteins comprising the Rhesus macaque (Macaca mulatta) sperm proteome, a commonly used model of human reproduction. This study provides a more robust proxy of human sperm composition than was previously available and facilitates studies of sperm using the rhesus macaque as a model. Chapters 2 & 3 provide a systems level overview of changes in sperm proteome composition that occurs during epididymal transit. Chapter 2 reports the proteomes of sperm collected from the caput, corpus and cauda segments of the mouse epididymis, identifying 1536, 1720 and 1234 proteins respectively. Chapter 3 reports the sperm proteome from four distinct segments of the Rhesus macaque epididymis, including the caput, proximal corpus, distal corpus and cauda, identifying 1951, 2014, 1764 and 1423 proteins respectively. These studies identify a number of proteins that are added and removed from sperm during epididymal transit which likely play an important role in the sperm maturation process. To date no comparative evolutionary studies of sperm proteomes have been undertaken. Chapter 4 compares four mammalian sperm proteomes including the human, macaque, mouse and rat. This study identified 98 proteins common to all four sperm proteomes, 82 primate and 90 rodent lineage-specific proteins and 494, 467, 566, and 193 species specific proteins in the human, macaque, mouse and rat sperm proteomes respectively and discusses how differences in sperm composition may ultimately lead to functional differences across species. Finally, chapter 5 uses sperm proteome data to inform the preliminary design of a rodent contraceptive vaccine delivered orally using recombinant attenuated Salmonella vaccine vectors.
ContributorsSkerget, Sheri Jo (Author) / Karr, Timothy L. (Thesis advisor) / Lake, Douglas (Committee member) / Petritis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Corporations in biomedicine hold significant power and influence, in both political and personal spheres. The decisions these companies make about ethics are critically important, as they help determine what products are developed, how they are developed, how they are promoted, and potentially even how they are regulated. In the last fifteen years, for-profit private companies have been assembling bioethics committees to help resolve dilemmas that require informed deliberation about ethical, legal, scientific, and economic considerations. Private sector bioethics committees represent an important innovation in the governance of emerging technologies, with corporations taking a lead role in deciding what is ethically appropriate or problematic. And yet, we know very little about these committees, including their structures, memberships, mandates, authority, and impact. Drawing on an extensive literature review and qualitative analysis of semi-structured interviews with executives, scientists and board members, this dissertation provides an in-depth analysis of the Ethics and Public Policy Board at SmithKline Beecham, the Ethics Advisory Board at Advanced Cell Technology, and the Bioethics Committee at Eli Lilly and offers insights about how ideas of bioethics and governance are currently imagined and enacted within corporations. The SmithKline Beecham board was the first private sector bioethics committee; its mandate was to explore, in a comprehensive and balanced analysis, the ethics of macro trends in science and technology. The Advanced Cell Technology board was created to be like a watchdog for the company, to prevent them from making major errors. The Eli Lilly board is different than the others in that it is made up mostly of internal employees and does research ethics consultations within the company. These private sector bioethics committees evaluate and construct new boundaries between their private interests and the public values they claim to promote. Findings from this dissertation show that criticisms of private sector bioethics that focus narrowly on financial conflicts of interest and a lack of transparency obscure analysis of the ideas about governance (about expertise, credibility and authority) that emerge from these structures and hamper serious debate about the possible impacts of moving ethical deliberation from the public to the private sector.
ContributorsBrian, Jennifer (Author) / Robert, Jason S (Thesis advisor) / Maienschein, Jane (Committee member) / Hurlbut, James B (Committee member) / Sarewitz, Daniel (Committee member) / Brown, Mark B. (Committee member) / Moreno, Jonathan D. (Committee member) / Arizona State University (Publisher)
Created2012
Description
Despite the minor differences in the inclusiveness of the word, there is a general assumption among the scientific community that the 'pursuit of knowledge' is the most fundamental element in defining the word 'science'. However, a closer examination of how science is being conducted in modern-day South Korea reveals a value system starkly different from the value of knowledge. By analyzing the political discourse of the South Korean policymakers, mass media, and government documents, this study examines the definition of science in South Korea. The analysis revealed that the Korean science, informed by the cultural, historical, and societal contexts, is largely focused on the values of national economic prosperity, international competitiveness, and international reputation of the country, overshadowing other values like the pursuit of knowledge or even individual rights. The identification of the new value system in South Korean science deviating from the traditional definition of science implies that there must be other definitions of science that also deviates, and that even in the Western world, the definition of science may yield similar deviations upon closer examination. The compatibility of the South Korean brand of science to the international scientific community also implies that a categorical quality is encompassing these different contextual definitions of science.
ContributorsHyun, Byunghun (Author) / Hurlbut, Ben (Thesis advisor) / Maienschein, Jane (Committee member) / Ellison, Karin (Committee member) / Arizona State University (Publisher)
Created2011
Description
Evolution is the foundation of biology, yet it remains controversial even among college biology students. Acceptance of evolution is important for students if we want them to incorporate evolution into their scientific thinking. However, students’ religious beliefs are a consistent barrier to their acceptance of evolution due to a perceived conflict between religion and evolution. Using pre-post instructional surveys of students in introductory college biology, Study 1 establishes instructional strategies that can be effective for reducing students' perceived conflict between religion and evolution. Through interviews and qualitative analyses, Study 2 documents how instructors teaching evolution at public universities may be resistant towards implementing strategies that can reduce students' perceived conflict, perhaps because of their own lack of religious beliefs and lack of training and awareness about students' conflict with evolution. Interviews with religious students in Study 3 reveals that religious college biology students can perceive their instructors as unfriendly towards religion which can negatively impact these students' perceived conflict between religion and evolution. Study 4 explores how instructors at Christian universities, who share the same Christian backgrounds as their students, do not struggle with implementing strategies that reduce students' perceived conflict between religion and evolution. Cumulatively, these studies reveal a need for a new instructional framework for evolution education that takes into account the religious cultural difference between instructors who are teaching evolution and students who are learning evolution. As such, a new instructional framework is then described, Religious Cultural Competence in Evolution Education (ReCCEE), that can help instructors teach evolution in a way that can reduce students' perceived conflict between religion and evolution, increase student acceptance of evolution, and create more inclusive college biology classrooms for religious students.
ContributorsBarnes, Maryann Elizabeth (Author) / Brownell, Sara (Thesis advisor) / Nesse, Randolph (Committee member) / Collins, James (Committee member) / Husman, Jenefer (Committee member) / Maienschein, Jane (Committee member) / Arizona State University (Publisher)
Created2018
Description
Antibodies are naturally occurring proteins that protect a host during infection through direct neutralization and/or recruitment of the innate immune system. Unfortunately, in some infections, antibodies present unique hurdles that must be overcome for a safer and more efficacious antibody-based therapeutic (e.g., antibody dependent viral enhancement (ADE) and inflammatory pathology). This dissertation describes the utilization of plant expression systems to produce N-glycan specific antibody-based therapeutics for Dengue Virus (DENV) and Chikungunya Virus (CHIKV). The Fc region of an antibody interacts with Fcγ Receptors (FcγRs) on immune cells and components of the innate immune system. Each class of immune cells has a distinct action of neutralization (e.g., antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP)). Therefore, structural alteration of the Fc region results in novel immune pathways of protection. One approach is to modulate the N-glycosylation in the Fc region of the antibody. Of scientific significance, is the plant’s capacity to express human antibodies with homogenous plant and humanized N-glycosylation (WT and GnGn, respectively). This allows to study how specific glycovariants interact with other components of the immune system to clear an infection, producing a tailor-made antibody for distinct diseases. In the first section, plant-produced glycovariants were explored for reduced interactions with specific FcγRs for the overall reduction in ADE for DENV infections. The results demonstrate a reduction in ADE of our plant-produced monoclonal antibodies in in vitro experiments, which led to a greater survival in vivo of immunodeficient mice challenged with lethal doses of DENV and a sub-lethal dose of DENV in ADE conditions. In the second section, plant-produced glycovariants were explored for increased interaction with specific FcγRs to improve ADCC in the treatment of the highly inflammatory CHIKV. The results demonstrate an increase ADCC activity in in vitro experiments and a reduction in CHIKV-associated inflammation in in vivo mouse models. Overall, the significance of this dissertation is that it can provide a treatment for DENV and CHIKV; but equally importantly, give insight to the role of N-glycosylation in antibody effector functions, which has a broader implication for therapeutic development for other viral infections.
ContributorsHurtado, Jonathan (Author) / Chen, Qiang (Thesis advisor) / Arntzen, Charles (Committee member) / Borges, Chad (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2019
Description
Measles is a contagious, vaccine-preventable disease that continues to be the leading
cause of death in children younger than the age of 5 years. While the introduction of the Measles, Mumps, and Rubella vaccine (MMR) has significantly decreased morbidity and mortality rates worldwide, vaccine coverage is highly variable across global regions. Current diagnostic methods rely on enzyme immunoassays (EIA) to detect IgM or IgG Abs in serum. Commercially available Diamedix Immunosimplicity® Measles IgG test kit has been shown to have 91.1% sensitivity and 93.8% specificity, with a positive predictive value of 88.7% and a negative predictive value of 90.9% on the basis of a PRN titer of 120. There is an increasing need for rapid screening for measles specific immunity in outbreak settings. This study aims to develop a rapid molecular diagnostic assay to detect IgG reactive to three individual measles virus (MeV) proteins.
Measles virus (MeV) genes were subcloned into the pJFT7_nGST vector to generate N- terminal GST fusion proteins. Single MeV cistrons were expressed using in vitro transcription/translation (IVTT) with human cell lysate. Expression of GST-tagged proteins was measured with mouse anti-GST mAb and sheep anti-mouse IgG. Relative light units (RLUs) as luminescence was measured. Antibodies to MeV antigens were measured in 40 serum samples from healthy subjects.
Protein expression of three MeV genes of interest was measured in comparison with vector control and statistical significance was determined using the Student’s t-test (p<0.05). N expressed at the highest level with an average RLU value of 3.01 x 109 (p<0.001) and all proteins were expressed at least 50% greater than vector control (4.56 x 106 RLU). 36/40 serum samples had IgG to N (Ag:GST ratio>1.21), F (Ag:GST ratio>1.92), or H (Ag:GST ratio> 1.23).
These data indicate that the in vitro expression of MeV antigens, N, F, and H, were markedly improved by subcloning into pJFT7_nGST vector to generate N-terminal GST fusion proteins. The expression of single MeV genes N, F and H, are suitable antigens for serologic capture analysis of measles-specific antibodies. These preliminary data can be used to design a more intensive study to explore the possibilities of using these MeV antigens as a diagnostic marker.
cause of death in children younger than the age of 5 years. While the introduction of the Measles, Mumps, and Rubella vaccine (MMR) has significantly decreased morbidity and mortality rates worldwide, vaccine coverage is highly variable across global regions. Current diagnostic methods rely on enzyme immunoassays (EIA) to detect IgM or IgG Abs in serum. Commercially available Diamedix Immunosimplicity® Measles IgG test kit has been shown to have 91.1% sensitivity and 93.8% specificity, with a positive predictive value of 88.7% and a negative predictive value of 90.9% on the basis of a PRN titer of 120. There is an increasing need for rapid screening for measles specific immunity in outbreak settings. This study aims to develop a rapid molecular diagnostic assay to detect IgG reactive to three individual measles virus (MeV) proteins.
Measles virus (MeV) genes were subcloned into the pJFT7_nGST vector to generate N- terminal GST fusion proteins. Single MeV cistrons were expressed using in vitro transcription/translation (IVTT) with human cell lysate. Expression of GST-tagged proteins was measured with mouse anti-GST mAb and sheep anti-mouse IgG. Relative light units (RLUs) as luminescence was measured. Antibodies to MeV antigens were measured in 40 serum samples from healthy subjects.
Protein expression of three MeV genes of interest was measured in comparison with vector control and statistical significance was determined using the Student’s t-test (p<0.05). N expressed at the highest level with an average RLU value of 3.01 x 109 (p<0.001) and all proteins were expressed at least 50% greater than vector control (4.56 x 106 RLU). 36/40 serum samples had IgG to N (Ag:GST ratio>1.21), F (Ag:GST ratio>1.92), or H (Ag:GST ratio> 1.23).
These data indicate that the in vitro expression of MeV antigens, N, F, and H, were markedly improved by subcloning into pJFT7_nGST vector to generate N-terminal GST fusion proteins. The expression of single MeV genes N, F and H, are suitable antigens for serologic capture analysis of measles-specific antibodies. These preliminary data can be used to design a more intensive study to explore the possibilities of using these MeV antigens as a diagnostic marker.
ContributorsMushtaq, Zuena (Author) / Anderson, Karen (Thesis advisor) / Blattman, Joseph (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2016
Description
This thesis explores concept of "global bioethics" in both its development as well as its current state in an effort to understand exactly where it fits into the larger field of bioethics. Further, the analysis poses specific questions regarding what it may contribute to this field and related fields, and the possibility and scope associated with the continued development of global bioethics as its own discipline. To achieve this, the piece addresses questions regarding current opinions on the subject, the authorities and their associated publications related to global bioethics, and what the aims of the subject should be given its current state. "Global Bioethics" is a term that, while seen frequently in bioethics literature, is difficult to define succinctly. While many opinions are provided on the concept, little consensus exists regarding its application and possible contributions and, in some cases, even its very possibility. Applying ethical principles of health and medicine globally is undoubtedly complicated by the cultural, social, and geographical considerations associated with understanding health and medicine in different populations, leading to a dichotomy between two schools of thought in relation to global bioethics. These two sides consist of those who think that universality of bioethics is possible whereas the opposing viewpoint holds that relativism is the key to applying ethics on a global scale. Despite the aforementioned dichotomy in addressing applications of global bioethics, this analysis shows that the goals of the subject should be more focused on contributing to ethical frameworks and valuable types of thinking related to the ethics health and medicine on a global scale. This is achieved through an exploration of bioethics in general, health as a function of society and culture, the history and development of global bioethics itself, and an exploration of pertinent global health topics. While primarily descriptive in nature, this analysis critiques some of the current discussions and purported goals surrounding global bioethics, recommending that the field focus on fostering valuable discussion and framing of issues rather than the pursuit of concrete judgments on moral issues in global health and medicine.
ContributorsRuffenach, Stephen Charles (Author) / Robert, Jason S (Thesis advisor) / Maienschein, Jane (Committee member) / Hruschka, Daniel J (Committee member) / Arizona State University (Publisher)
Created2011
Climate Sensitivity in Mature Versus Pre-Reproductive Saguaro Determined from Spine Isotopic Signals
Description
The saguaro cactus is vital to the unique biodiversity of the Sonoran Desert. Many animals rely on it for survival and shelter. Due to its thick waxy exterior, it is able to retain a massive amount of water in its succulent stems, making it an ideal habitat for many birds that are native to the region. It also holds a large cultural significance for many native tribes of this region. Thus, it is important to understand how these magnificent plants are affected by changing environmental conditions in order to protect them in the future. Measurements of carbon isotope (13C) signals in saguaros spine tissues have been shown to be a robust approach for evaluating plant responses to climate variation over multiple seasons and years. This study investigated growth and 13C signals in young saguaros (< 2.5 m tall) at a location north of Phoenix to compare with large saguaros (> 4 m tall) that actively flower in the spring. Adolescent saguaros were examined to determine how they responded to variation in moisture between the years 2012 through 2016. As with a previous study by Hultine et al. (2018), this research demonstrated a strong relationship between height growth and precipitation. Stem growth was also highly correlated with the number of areoles produced across both young and old plants. Winter and late summer moisture from the previous year had a significant effect on stem growth, and a legacy effect could be seen in the low growth rates in 2014 which may be a result of low precipitation during the previous fall and winter. This study also established that the adolescent saguaro may be less sensitive to seasonal changes than the mature saguaro. When comparing the large plants with the adolescent plants, spine 13C values were similar between mature and adolescent plants, indicating that perhaps flower does not impose a significant added cost to saguaro water budgets. However, identifying the cost of flowering requires more investigation than that from only spine carbon isotope measurements and coarse measurements of plant productivity.
ContributorsDe Leon, Isabella (Author) / Hultine, Kevin (Thesis advisor) / Pigg, Kathleen (Thesis advisor) / Maienschein, Jane (Committee member) / Arizona State University (Publisher)
Created2021
Exploring the Relationship Between Depression and Graduate School Among Life Sciences Ph.D. Students
Description
Depression is one of the top mental health concerns among biology graduate students and has contributed to the “graduate student mental health crisis” declared in 2018. Prominent science outlets have called for interventions to improve graduate student mental health, but few studies have examined the relationship between depression and graduate school among life sciences Ph.D. students. In this coupled set of qualitative interview studies, 50 life sciences Ph.D. students from 28 institutions across the United States were interviewed. The first study explored how research and teaching affect depression in Ph.D. students and how depression in turn also affects students’ experiences in graduate school. Using inductive coding, four overarching aspects of graduate school that influenced student depression were highlighted, (1) structure in teaching and research, (2) positive and negative reinforcement, (3) success and failure, and (4) social support and isolation. The second study explored depression as a concealable stigmatized identity (CSI) by examining (1) to what extent and why graduate students revealed their depression to faculty advisors, graduate students, and undergraduate researchers, and (2) the consequences or benefits that they perceive are associated with revealing one’s depression through a hybrid approach of deductive and inductive coding. Graduate students most commonly revealed their depression to other graduate students; however, most were reluctant to share their depression with undergraduate researchers. These qualitative interview studies provide insights into creating more inclusive life science graduate programs for students with depression.
ContributorsWiesenthal, Nicholas John (Author) / Cooper, Katelyn M (Thesis advisor) / Brownell, Sara E (Committee member) / Maienschein, Jane (Committee member) / Arizona State University (Publisher)
Created2022
Description
Adoptive transfer of T cells engineered to express synthetic antigen-specific T cell receptors (TCRs) has provocative therapeutic applications for treating cancer. However, expressing these synthetic TCRs in a CD4+ T cell line is a challenge. The CD4+ Jurkat T cell line expresses endogenous TCRs that compete for space, accessory proteins, and proliferative signaling, and there is the potential for mixed dimer formation between the α and β chains of the endogenous receptor and that of the synthetic cancer-specific TCRs. To prevent hybridization between the receptors and to ensure the binding affinity measured with flow cytometry analysis is between the tetramer and the TCR construct, a CRISPR-Cas9 gene editing pipeline was developed. The guide RNAs (gRNAs) within the complex were designed to target the constant region of the α and β chains, as they are conserved between TCR clonotypes. To minimize further interference and confer cytotoxic capabilities, gRNAs were designed to target the CD4 coreceptor, and the CD8 coreceptor was delivered in a mammalian expression vector. Further, Golden Gate cloning methods were validated in integrating the gRNAs into a CRISPR-compatible mammalian expression vector. These constructs were transfected via electroporation into CD4+ Jurkat T cells to create a CD8+ knockout TCR Jurkat cell line for broadly applicable uses in T cell immunotherapies.
ContributorsHirneise, Gabrielle Rachel (Author) / Anderson, Karen (Thesis advisor) / Mason, Hugh (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2020