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
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
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
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
Principle-based ethical frameworks, which commonly make use of codes of ethics, have come to be the popular approach in guiding ethical behavior within scientific research. In this thesis project, I investigate the benefits and shortcomings of this approach, ultimately to argue that codes of ethics are valuable as an exercise in developing a reconciled value profile for a given research community, and also function well as an internal and external proclamation of values and norms. However, this approach results in technical adherence, at best, and given the extent to which scientific research now irreversibly shapes our experience as human beings, I argue for the importance of cultivating ethical virtues in scientific research. In the interest of doing so I explore concepts from Aristotelian virtue ethics, to consider how to ameliorate the shortcomings of principle-based approaches. This project was inspired by a call to research and develop an ethical framework upon which to found a cooperative research network that would be aimed at combating the spread of emerging and re-emerging infectious diseases in resource-restricted countries, specifically throughout Latin America. The desire to found this network on an ethics-based framework is to move beyond technical compliance and cultivate a research community committed to integrity, therefore establishing and maintaining trust and communication that will allow for unprecedented productive collaboration and meaningful outcomes. I demonstrate in this thesis that this requires more than a code of ethics, and use this initiative as a case study to exhibit the merit of integrating concepts from virtue ethics.
ContributorsCraer, Jennifer Ryan (Author) / Ellison, Karin (Thesis advisor) / Sarewitz, Daniel (Committee member) / Blattman, Joseph (Committee member) / Robert, Jason S (Committee member) / Arizona State University (Publisher)
Created2017
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
Description
Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The adaptive therapy model comes from the integrated pest management agricultural strategy, predator prey model, and the unique intra- and inter-tumor heterogeneity of tumors. The purpose of this thesis is to analyze and compare gemcitabine dose response on hormone refractory breast cancer cells retrieved from mice using an adaptive therapy strategy with standard therapy treatment. In this study, we compared intermittent (drug holiday) adaptive therapy with maximum tolerated dose therapy. The MCF7 resistant cell lines to both fulvestrant and palbociclib were injected into the mammary fat pads of 8 weeks old NOD/SCID gamma (NSG) mice which were then treated with gemcitabine. Tumor burden graphs were made to track tumor growth/decline during different treatments while Drug Dose Response (DDR) curves were made to test the sensitivity of the cell lines to the drug gemcitabine. The tumor burden graphs showed success in controlling the tumor burden with intermittent treatment. The DDR curves showed a positive result in using the adaptive therapy treatment method to treat mice with gemcitabine. Due to some fluctuating DDR results, the sensitivity of the cell lines to gemcitabine needs to be further studied by repeating the DDR experiment on the other mice cell lines for stronger results.
ContributorsConti, Aviona Christina (Author) / Maley, Carlo (Thesis advisor) / Blattman, Joseph (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2022