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
Endocrine disruptors are chemicals that interact with the hormone system to negative effect. They ‘disrupt’ normal processes to cause diseases like vaginal cancer and obesity, reproductive issues like t-shaped uteri and infertility, and developmental abnormalities like spina bifida and cleft palate. These chemicals are ubiquitous in our daily lives, components in everything from toothpaste to microwave popcorn to plastic water bottles. My dissertation looks at the history, science, and regulation of these impactful substances in order to answer the question of how endocrine disruptors appeared, got interpreted by different groups, and what role science played in the process. My analysis reveals that endocrine disruptors followed a unique science policy trajectory in the US, rapidly going from their proposal in 1991 to their federal regulation in 1996, even amid intense and majority scientific disagreement over whether the substances existed at all. That trajectory resulted from the work of a small number of scientist-activists who constructed a concept and category as scientific, social, and regulatory. By playing actors from each sphere against each other and advancing a very specific scientific narrative that fit into a regulatory and social window of opportunity in the 1990s, those scientist-activists made endocrine disruptors a national issue that few could ignore. Those actions resulted in the Endocrine Disruptor Screening Program, a heavily-criticized and ineffective regulatory program. My dissertation tells a story of the past that informs the present. In 2018, the work of researchers, public media, and policymakers in the 1990s continues to play out, evident in the deep scientific division over endocrine disrupting effects and the inability of the European Union to settle on even a definition of endocrine disruptors for regulation purposes.
ContributorsAbboud, Alexis J (Author) / Maienschein, Jane A (Thesis advisor) / Crow, Michael M. (Committee member) / Hurlbut, J. Benjamin (Committee member) / Marchant, Gary E (Committee member) / Arizona State University (Publisher)
Created2018
Description
Resistance to existing anti-cancer drugs poses a key challenge in the field of medical oncology, in that it results in the tumor not responding to treatment using the same medications to which it responded previously, leading to treatment failure. Adaptive therapy utilizes evolutionary principles of competitive suppression, leveraging competition between drug resistant and drug sensitive cells, to keep the population of drug resistant cells under control, thereby extending time to progression (TTP), relative to standard treatment using maximum tolerated dose (MTD). Development of adaptive therapy protocols is challenging, as it involves many parameters, and the number of parameters increase exponentially for each additional drug. Furthermore, the drugs could have a cytotoxic (killing cells directly), or a cytostatic (inhibiting cell division) mechanism of action, which could affect treatment outcome in important ways. I have implemented hybrid agent-based computational models to investigate adaptive therapy, using either a single drug (cytotoxic or cytostatic), or two drugs (cytotoxic or cytostatic), simulating three different adaptive therapy protocols for treatment using a single drug (dose modulation, intermittent, dose-skipping), and seven different treatment protocols for treatment using two drugs: three dose modulation (DM) protocols (DM Cocktail Tandem, DM Ping-Pong Alternate Every Cycle, DM Ping-Pong on Progression), and four fixed-dose (FD) protocols (FD Cocktail Intermittent, FD Ping-Pong Intermittent, FD Cocktail Dose-Skipping, FD Ping-Pong Dose-Skipping). The results indicate a Goldilocks level of drug exposure to be optimum, with both too little and too much drug having adverse effects. Adaptive therapy works best under conditions of strong cellular competition, such as high fitness costs, high replacement rates, or high turnover. Clonal competition is an important determinant of treatment outcome, and as such treatment using two drugs leads to more favorable outcome than treatment using a single drug. Switching drugs every treatment cycle (ping-pong) protocols work particularly well, as well as cocktail dose modulation, particularly when it is feasible to have a highly sensitive measurement of tumor burden. In general, overtreating seems to have adverse survival outcome, and triggering a treatment vacation, or stopping treatment sooner when the tumor is shrinking seems to work well.
ContributorsSaha, Kaushik (Author) / Maley, Carlo C (Thesis advisor) / Forrest, Stephanie (Committee member) / Anderson, Karen S (Committee member) / Cisneros, Luis H (Committee member) / Arizona State University (Publisher)
Created2023
Description
This dissertation investigates how ideas of the right relationships among science, the public, and collective decision-making about science and technology come to be envisioned in constructions of public engagement. In particular, it explores how public engagement has come to be constructed in discourse around gene editing to better understand how it holds together with visions for good, democratic governance of those technologies and with what effects. Using a conceptual idiom of the co-production of science and the social order, I investigate the mutual formation of scientific expertise, responsibility, and democracy through constructions of public engagement. I begin by tracing dominant historical narratives of contemporary public engagement as a continuation of public understanding of science’s projects of social ordering for democratic society. I then analyze collections of prominent expert meetings, publications, discussions, and interventions about development, governance, and societal implications human heritable germline gene editing and gene drives that developed in tandem with commitments to public engagement around those technologies. Synthesizing the evidence from across gene editing discourse, I offer a constructive critique of constructions of public engagement as expressions and evidence of scientific responsibility as ultimately reasserting and reinforcing of scientific experts' authority in gene editing decision-making, despite intentions for public engagement to extend decision-making participation and power to publics. Such constructions of public engagement go unrecognized in gene editing discourse and thereby subtly reinforce broader visions of scientific expertise as essential to good governance by underwriting the legitimacy and authority of scientific experts to act on behalf of public interests. I further argue that the reinforcement of scientific expert authority in gene editing discourse through public engagement also centers scientific experts in a sociotechnical imaginary that I call “not for science alone.” This sociotechnical imaginary envisions scientific experts as guardians and guarantors of good, democratic governance. I then propose a possible alternatives to public engagement alone to improve gene editing governance by orienting discourse around notions of public accountability for potential shared benefits and collective harms of gene editing.
ContributorsRoss, Christian (Author) / Hurlbut, James B. (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Collins, James P. (Committee member) / Crow, Michael M. (Committee member) / Sarewitz, Daniel R. (Committee member) / Arizona State University (Publisher)
Created2021
Cancer autoantibody biomarker discovery and validation using nucleic acid programmable protein array
Description
Currently in the US, many patients with cancer do not benefit from the population-based screening, due to challenges associated with the existing cancer screening scheme. Blood-based diagnostic assays have the potential to detect diseases in a non-invasive way. Proteins released from small early tumors may only be present intermittently and get diluted to tiny concentrations in the blood, making them difficult to use as biomarkers. However, they can induce autoantibody (AAb) responses, which can amplify the signal and persist in the blood even if the antigen is gone. Circulating autoantibodies is a promising class of molecules that have potential to serve as early detection biomarkers for cancers. This Ph.D thesis aims to screen for autoantibody biomarkers for the early detection of two deadly cancer, basal-like breast cancer and lung adenocarcinoma. First, a method was developed to display proteins in both native and denatured conformation on protein array. This method adopted a novel protein tag technology, called HaloTag, to covalently immobilize proteins on glass slide surface. The covalent attachment allowed these proteins to endure harsh treatment without getting dissociated from slide surface, which enabled the profiling of antibody responses against both conformational and linear epitopes. Next, a plasma screening protocol was optimized to significantly increase signal to noise ratio of protein array based AAb detection. Following this, the AAb responses in basal-like breast cancer were explored using nucleic acid programmable protein arrays (NAPPA) containing 10,000 full-length human proteins in 45 cases and 45 controls. After verification in a large sample set (145 basal-like breast cancer cases / 145 controls / 70 non-basal breast cancer) by ELISA, a 13-AAb classifier was developed to differentiate patients from controls with a sensitivity of 33% at 98% specificity. Similar approach was also applied to the lung cancer study to identify AAbs that distinguished lung cancer patients from computed-tomography positive benign pulmonary nodules (137 lung cancer cases, 127 smoker controls, 170 benign controls). In this study, two panels of AAbs were discovered that showed promising sensitivity and specificity. Six out of eight AAb targets were also found to have elevated mRNA level in lung adenocarcinoma patients using TCGA data. These projects as a whole provide novel insights on the association between AAbs and cancer, as well as general B cell antigenicity against self-proteins.
ContributorsWang, Jie (Author) / LaBaer, Joshua (Thesis advisor) / Anderson, Karen S (Committee member) / Lake, Douglas F (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2015