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
Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments in cell degeneration research with the four major chapters, I trace the emergence of the degenerating cell as a scientific object, describe the generations of a variety of concepts, interpretations and usages associated with cell death and aging, and analyze the transforming influences of the rising cell degeneration research. Particularly, the four chapters show how the changing scientific practices about cellular life in embryology, cell culture, aging research, and molecular biology of Caenorhabditis elegans shaped the interpretations about cell degeneration in the twentieth-century as life-shaping, limit-setting, complex, yet regulated. These events created and consolidated important concepts in life sciences such as programmed cell death, the Hayflick limit, apoptosis, and death genes. These cases also transformed the material and epistemic practices about the end of cellular life subsequently and led to the formations of new research communities. The four cases together show the ways cell degeneration became a shared subject between molecular cell biology, developmental biology, gerontology, oncology, and pathology of degenerative diseases. These practices and perspectives created a special kind of interconnectivity between different fields and led to a level of interdisciplinarity within cell degeneration research by the early 1990s.
ContributorsJiang, Lijing (Author) / Maienschein, Jane (Thesis advisor) / Laubichler, Manfred (Thesis advisor) / Hurlbut, James (Committee member) / Creath, Richard (Committee member) / White, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
Researchers in the twentieth and twenty-first centuries identify the study of the intrinsic and external factors that influence human aging as senescence. A commonly held belief in the year 2015 is that at least some kinds of cells can replicate over long periods or even indefinitely, thereby meaning the cell does not undergo senescence (also known as replicative senescence) and is considered immortal. This study aims to provide information to answer the following question: While some scientists claim they can indefinitely culture a stem cell line in vitro, what are the consequences of those culturing practices? An analysis of a cluster of articles from the Embryo Project Encyclopedia provides information to suggest possible solutions to some potential problems in cell culturing, recognition of benefits for existing or historical culturing practices, and identification of gaps in scientific knowledge that warrant further research. Recent research suggests that hESCs, and immortalized cell lines in general, do not escape the effects of senescence. While there exists a constant change in the practices of cell culturing, a large portion of scientists still rely on practices established before modern senescence research: research that seems to suggest that cultured hESCs, among other immortal cell lines, are not truly immortal.
ContributorsBartlett, Zane (Author) / Maienschein, Jane (Thesis advisor) / Ellison, Karin (Committee member) / Hurlbut, James (Committee member) / Arizona State University (Publisher)
Created2015
Description
Cell adhesion is an important aspect of many biological processes. The atomic force microscope (AFM) has made it possible to quantify the forces involved in cellular adhesion using a technique called single cell force spectroscopy (SCFS). AFM based SCFS offers versatile control over experimental conditions for probing directly the interaction between specific cell types and specific proteins, surfaces, or other cells. Transmembrane integrins are the primary proteins involved in cellular adhesion to the extra cellular matix (ECM). One of the chief integrins involved in the adhesion of leukocyte cells is αMβ2 (Mac-1). The experiments in this dissertation quantify the adhesion of Mac-1 expressing human embryonic kidney (HEK Mac-1), platelets, and neutrophils cells on substrates with different concentrations of fibrinogen and on fibrin gels and multi-layered fibrinogen coated fibrin gels. It was shown that multi-layered fibrinogen reduces the adhesion force of these cells considerably. A novel method was developed as part of this research combining total internal reflection microscopy (TIRFM) with SCFS allowing for optical microscopy of HEK Mac-1 cells interacting with bovine serum albumin (BSA) coated glass after interacting with multi-layered fibrinogen. HEK Mac-1 cells are able to remove fibrinogen molecules from the multi-layered fibrinogen matrix. An analysis methodology for quantifying the kinetic parameters of integrin-ligand interactions from SCFS experiments is proposed, and the kinetic parameters of the Mac-1 fibrinogen bond are quantified. Additional SCFS experiments quantify the adhesion of macrophages and HEK Mac-1 cells on functionalized glass surfaces and normal glass surfaces. Both cell types show highest adhesion on a novel functionalized glass surface that was prepared to induce macrophage fusion. These experiments demonstrate the versatility of AFM based SCFS, and how it can be applied to address many questions in cellular biology offering quantitative insights.
ContributorsChristenson, Wayne B (Author) / Ros, Robert (Thesis advisor) / Beckstein, Oliver (Committee member) / Lindsay, Stuart (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2016
Description
Writing speculative fiction is a valuable method for exploring the potential societal transformations elicited by advances in science and technology. The aim of this project is to use speculative fiction to explore the potential consequences of precision medicine for individuals’ daily lives. Precision medicine is a vision of the future in which medicine is about predicting, and ultimately preventing disease before symptoms arise. The idea is that identification of all the factors that influence health and contribute to disease development will translate to better and less expensive healthcare and empower individuals to take responsibility for maintaining their own health and wellness. That future, as envisioned by the leaders of the Human Genome Project, the Institute for Systems Biology, and the Obama administration’s Precision Medicine Initiative, is assumed to be a shared future, one that everyone desires and that is self-evidently “better” than the present. The aim of writing speculative fiction about a “precision medicine” future is to challenge that assumption, to make clear the values underpinning that vision of precision medicine, and to leave open the question of what other possible futures could be imagined instead.
ContributorsVenkatraman, Richa (Author) / Brian, Jennifer (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Hurlbut, James (Committee member) / Arizona State University (Publisher)
Created2022
Description
Emerging pathogens present several challenges to medical diagnostics. Primarily, the exponential spread of a novel pathogen through naïve populations require a rapid and overwhelming diagnostic response at the site of outbreak. While point-of-care (PoC) platforms have been developed for detection of antigens, serologic responses, and pathogenic genomes, only nucleic acid diagnostics currently have the potential to be developed and manufactured within weeks of an outbreak owing to the speed of next-generation sequencing and custom DNA synthesis. Among nucleic acid diagnostics, isothermal amplification strategies are uniquely suited for PoC implementation due to their simple instrumentation and lack of thermocycling requirement. Unfortunately, isothermal strategies are currently prone to spurious nonspecific amplification, hindering their specificity and necessitating extensive empirical design pipelines that are both time and resource intensive. In this work, isothermal amplification strategies are extensively compared for their feasibility of implementation in outbreak response scenarios. One such technology, Loop-mediated Amplification (LAMP), is identified as having high-potential for rapid development and PoC deployment. Various approaches to abrogating nonspecific amplification are described including a novel in silico design tool based on coarse-grained simulation of interactions between thermophilic DNA polymerase and DNA strands in isothermal reaction conditions. Nonspecific amplification is shown to be due to stabilization of primer secondary structures by high concentrations of Bst DNA polymerase and a mechanism of micro-complement-mediated cross-priming is demonstrated as causal via nanopore sequencing of nonspecific reaction products. The resulting computational model predicts primer set background in 64% of 67 test assays and its usefulness is illustrated further by determining problematic primers in a West Nile Virus-specific LAMP primer set and optimizing primer 3’ nucleotides to eliminate micro-complements within the reaction, resulting in inhibition of background accumulation. Finally, the emergence of Orthopox monkeypox (MPXV) as a recurring threat is discussed and SimCycle is utilized to develop a novel technique for clade-specific discrimination of MPXV based on bridging viral genomic rearrangements (Bridging LAMP). Bridging LAMP is implemented in a 4-plex microfluidic format and demonstrates 100% sensitivity in detection of 100 copies of viral lysates and 45 crude MPXV-positive patient samples collected during the 2022 Clade IIb outbreak.
ContributorsKnappenberger, Mark Daniel (Author) / Anderson, Karen S (Thesis advisor) / LaBaer, Joshua (Committee member) / Roberson, Robert (Committee member) / Lindsay, Stuart (Committee member) / Arizona State University (Publisher)
Created2023