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
Understanding changes and trends in biomedical knowledge is crucial for individuals, groups, and institutions as biomedicine improves people’s lives, supports national economies, and facilitates innovation. However, as knowledge changes what evidence illustrates knowledge changes? In the case of microbiome, a multi-dimensional concept from biomedicine, there are significant increases in publications, citations, funding, collaborations, and other explanatory variables or contextual factors. What is observed in the microbiome, or any historical evolution of a scientific field or scientific knowledge, is that these changes are related to changes in knowledge, but what is not understood is how to measure and track changes in knowledge. This investigation highlights how contextual factors from the language and social context of the microbiome are related to changes in the usage, meaning, and scientific knowledge on the microbiome. Two interconnected studies integrating qualitative and quantitative evidence examine the variation and change of the microbiome evidence are presented. First, the concepts microbiome, metagenome, and metabolome are compared to determine the boundaries of the microbiome concept in relation to other concepts where the conceptual boundaries have been cited as overlapping. A collection of publications for each concept or corpus is presented, with a focus on how to create, collect, curate, and analyze large data collections. This study concludes with suggestions on how to analyze biomedical concepts using a hybrid approach that combines results from the larger language context and individual words. Second, the results of a systematic review that describes the variation and change of microbiome research, funding, and knowledge are examined. A corpus of approximately 28,000 articles on the microbiome are characterized, and a spectrum of microbiome interpretations are suggested based on differences related to context. The collective results suggest the microbiome is a separate concept from the metagenome and metabolome, and the variation and change to the microbiome concept was influenced by contextual factors. These results provide insight into how concepts with extensive resources behave within biomedicine and suggest the microbiome is possibly representative of conceptual change or a preview of new dynamics within science that are expected in the future.
ContributorsAiello, Kenneth (Author) / Laubichler, Manfred D (Thesis advisor) / Simeone, Michael (Committee member) / Buetow, Kenneth (Committee member) / Walker, Sara I (Committee member) / Arizona State University (Publisher)
Created2018
Description
In most diploid cells, autosomal genes are equally expressed from the paternal and maternal alleles resulting in biallelic expression. However, as an exception, there exists a small number of genes that show a pattern of monoallelic or biased-allele expression based on the allele’s parent-of-origin. This phenomenon is termed genomic imprinting and is an evolutionary paradox. The best explanation for imprinting is David Haig's kinship theory, which hypothesizes that monoallelic gene expression is largely the result of evolutionary conflict between males and females over maternal involvement in their offspring. One previous RNAseq study has investigated the presence of parent-of-origin effects, or imprinting, in the parasitic jewel wasp Nasonia vitripennis (N. vitripennis) and its sister species Nasonia giraulti (N. giraulti) to test the predictions of kinship theory in a non-eusocial species for comparison to a eusocial one. In order to continue to tease apart the connection between social and eusocial Hymenoptera, this study proposed a similar RNAseq study that attempted to reproduce these results in unique samples of reciprocal F1 Nasonia hybrids. Building a pseudo N. giraulti reference genome, differences were observed when aligning RNAseq reads to a N. vitripennis reference genome compared to aligning reads to a pseudo N. giraulti reference. As well, no evidence for parent-of-origin or imprinting patterns in adult Nasonia were found. These results demonstrated a species-of-origin effect. Importantly, the study continued to build a repository of support with the aim to elucidate the mechanisms behind imprinting in an excellent epigenetic model species, as it can also help with understanding the phenomenon of imprinting in complex human diseases.
ContributorsUnderwood, Avery Elizabeth (Author) / Wilson, Melissa (Thesis advisor) / Buetow, Kenneth (Committee member) / Gile, Gillian (Committee member) / Arizona State University (Publisher)
Created2019
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
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
Description
Evolutionary theory provides a rich framework for understanding cancer dynamics across scales of biological organization. The field of cancer evolution has largely been divided into two domains, comparative oncology - the study of cancer across the tree of life, and tumor evolution. This work provides a theoretical framework to unify these subfields with the intent that an understanding of the evolutionary dynamics driving cancer risk at one scale can inform the understanding of the dynamics on another scale. The evolution of multicellular life and the unique vulnerabilities in the cellular mechanisms that underpin it explain the ubiquity of cancer prevalence across the tree of life. The breakdown in cellular cooperation and communication that were required for multicellular life define the hallmarks of cancer. As divergent life histories drove speciation events, it similarly drove divergences in fundamental cancer risk across species. An understanding of the impact that species’ life history theory has on the underlying network of multicellular cooperation and somatic evolution allows for robust predictions on cross-species cancer risk. A large-scale veterinary cancer database is utilized to validate many of the predictions on cancer risk made from life history evolution. Changing scales to the cellular level, it lays predictions on the fate of somatic mutations and the fitness benefits they confer to neoplastic cells compared to their healthy counterparts. The cancer hallmarks, far more than just a way to unify the many seemingly unique pathologies defined as cancer, is a powerful toolset to understand how specific mutations may change the fitness of somatic cells throughout carcinogenesis and tumor progression. Alongside highlighting the significant advances in evolutionary approaches to cancer across scales, this work provides a lucid confirmation that an understanding of both scales provides the most complete portrait of evolutionary cancer dynamics.
ContributorsCompton, Zachary Taylor (Author) / Maley, Carlo C. (Thesis advisor) / Aktipis, Athena (Committee member) / Buetow, Kenneth (Committee member) / Nedelcu, Aurora (Committee member) / Compton, Carolyn (Committee member) / Arizona State University (Publisher)
Created2023