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
Since Darwin popularized the evolution theory in 1895, it has been completed and studied through the years. Starting in 1990s, evolution at molecular level has been used to discover functional molecules while studying the origin of functional molecules in nature by mimicing the natural selection process in laboratory. Along this line, my Ph.D. dissertation focuses on the in vitro selection of two important biomolecules, deoxynucleotide acid (DNA) and protein with binding properties. Chapter two focuses on in vitro selection of DNA. Aptamers are single-stranded nucleic acids that generated from a random pool and fold into stable three-dimensional structures with ligand binding sites that are complementary in shape and charge to a desired target. While aptamers have been selected to bind a wide range of targets, it is generally thought that these molecules are incapable of discriminating strongly alkaline proteins due to the attractive forces that govern oppositely charged polymers. By employing negative selection step to eliminate aptamers that bind with off-target through charge unselectively, an aptamer that binds with histone H4 protein with high specificity (>100 fold)was generated. Chapter four focuses on another functional molecule: protein. It is long believed that complex molecules with different function originated from simple progenitor proteins, but very little is known about this process. By employing a previously selected protein that binds and catalyzes ATP, which is the first and only protein that was evolved completely from random pool and has a unique α/β-fold protein scaffold, I fused random library to the C-terminus of this protein and evolved a multi-domain protein with decent properties. Also, in chapter 3, a unique bivalent molecule was generated by conjugating peptides that bind different sites on the protein with nucleic acids. By using the ligand interactions by nucleotide conjugates technique, off-the shelf peptide was transferred into high affinity protein capture reagents that mimic the recognition properties of natural antibodies. The designer synthetic antibody amplifies the binding affinity of the individual peptides by ∼1000-fold to bind Grb2 with a Kd of 2 nM, and functions with high selectivity in conventional pull-down assays from HeLa cell lysates.
ContributorsJiang, Bing (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Liu, Yan (Committee member) / Arizona State University (Publisher)
Created2013
Description
The principle of Darwinian evolution has been applied in the laboratory to nucleic acid molecules since 1990, and led to the emergence of in vitro evolution technique. The methodology of in vitro evolution surveys a large number of different molecules simultaneously for a pre-defined chemical property, and enrich for molecules with the particular property. DNA and RNA sequences with versatile functions have been identified by in vitro selection experiments, but many basic questions remain to be answered about how these molecules achieve their functions. This dissertation first focuses on addressing a fundamental question regarding the molecular recognition properties of in vitro selected DNA sequences, namely whether negatively charged DNA sequences can be evolved to bind alkaline proteins with high specificity. We showed that DNA binders could be made, through carefully designed stringent in vitro selection, to discriminate different alkaline proteins. The focus of this dissertation is then shifted to in vitro evolution of an artificial genetic polymer called threose nucleic acid (TNA). TNA has been considered a potential RNA progenitor during early evolution of life on Earth. However, further experimental evidence to support TNA as a primordial genetic material is lacking. In this dissertation we demonstrated the capacity of TNA to form stable tertiary structure with specific ligand binding property, which suggests a possible role of TNA as a pre-RNA genetic polymer. Additionally, we discussed the challenges in in vitro evolution for TNA enzymes and developed the necessary methodology for future TNA enzyme evolution.
ContributorsYu, Hanyang (Author) / Chaput, John C (Thesis advisor) / Chen, Julian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
In the last years of the twentieth century, while the narrative of women in other Latin American countries has received critical attention, Bolivian women's narrative has been widely ignored. The fact that the voice of Bolivian women in Latin American feminist discourse is rarely discussed in Latin American criticism is enough to justify the present study. This work focuses on three prominent Bolivian writers: Gaby Vallejos, Giovanna Rivero Santa Cruz, and Erika Bruzonic. The short stories of these three authors are characterized by accentuating certain telluric features revealed in the background of their feminine/feminist narratives. At the same time, based on the American and European feminist literary critique, this work analyzes the feminine/feminist themes mounted in the narrative of these authors. Gaby Vallejos, with a cinematic style, chronicles the life and customs of the "valluno" context, building a mosaic of different voices in dialogue. Her topics revolve around binaries: life-death, and pain and pleasure, voicing condemnation for a patriarchal society. Ericka Bruzonic deals with women and identity, memory and the breaking of lineage as an imposing structure. Her themes are built around the cosmopolitism of "paceña" urban life, and her voice transgresses the binomials established by a patriarchal society. Finally Giovanna Rivero Santa Cruz takes the life and customs of the Santa Cruz and the Guarani culture and her plots weave these elements reaching for myths and taboos, involving the reader into her stories. In this manner, her narrative makes an incursion into the conscious and unconscious realm of the readers questioning their wealth of moral and social values, their notions of heterosexuality, and sexual taboos. The three writers, with different narrative styles yet dialogical, narrate various experiences of women from different regions, social classes, ages, education, and sexual orientations. Our authors give high value to the word and the body embedded in the culture, thereby affirming their woman's voice as Bolivians and their literary presence in the context of Latin American literature.
ContributorsLopez, Norma (Author) / Urioste-Ascorra, Carmen (Thesis advisor) / Tompkins, Cynthia (Committee member) / Rosales, Jesus (Committee member) / Arizona State University (Publisher)
Created2013
Description
Cyanovirin-N (CV-N) is a naturally occurring lectin originally isolated from the cyanobacteria Nostoc ellipsosporum. This 11 kDa lectin is 101 amino acids long with two binding sites, one at each end of the protein. CV-N specifically binds to terminal Manα1-2Manα motifs on the branched, high mannose Man9 and Man8 glycosylations found on enveloped viruses including Ebola, Influenza, and HIV. wt-CVN has micromolar binding to soluble Manα1-2Manα and also inhibits HIV entry at low nanomolar concentrations. CV-N's high affinity and specificity for Manα1-2Manα makes it an excellent lectin to study for its glycan-specific properties. The long-term aim of this project is to make a variety of mutant CV-Ns to specifically bind other glycan targets. Such a set of lectins may be used as screening reagents to identify biomarkers and other glycan motifs of interest. As proof of concept, a T7 phage display library was constructed using P51G-m4-CVN genes mutated at positions 41, 44, 52, 53, 56, 74, and 76 in binding Domain B. Five CV-N mutants were selected from the library and expressed in BL21(DE3) E. coli. Two of the mutants, SSDGLQQ-P51Gm4-CVN and AAGRLSK-P51Gm4-CVN, were sufficiently stable for characterization and were examined by CD, Tm, ELISA, and glycan array. Both proteins have CD minima at approximately 213 nm, indicating largely β-sheet structure, and have Tm values greater than 40°C. ELISA against gp120 and RNase B demonstrate both proteins' ability to bind high mannose glycans. To more specifically determine the binding specificity of each protein, AAGRLSK-P51Gm4-CVN, SSDGLQQ-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN were sent to the Consortium for Functional Glycomics (CFG) for glycan array analysis. AAGRLSK-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN, have identical specificities for high mannose glycans containing terminal Manα1-2Manα. SSDGLQQ-P51Gm4-CVN binds to terminal GlcNAcα1-4Gal motifs and a subgroup of high mannose glycans bound by P51G-m4-CVN. SSDGLQQ-wt-CVN was produced to restore anti-HIV activity and has a high nanomolar EC50 value compared to wt-CVN's low nanomolar activity. Overall, these experiments show that CV-N Domain B can be mutated and retain specificity identical to wt-CVN or acquire new glycan specificities. This first generation information can be used to produce glycan-specific lectins for a variety of applications.
ContributorsRuben, Melissa (Author) / Ghirlanda, Giovanna (Thesis advisor) / Allen, James (Committee member) / Wachter, Rebekka (Committee member) / Arizona State University (Publisher)
Created2013
Description
There is a critical need for the development of clean and efficient energy sources. Hydrogen is being explored as a viable alternative to fuels in current use, many of which have limited availability and detrimental byproducts. Biological photo-production of H2 could provide a potential energy source directly manufactured from water and sunlight. As a part of the photosynthetic electron transport chain (PETC) of the green algae Chlamydomonas reinhardtii, water is split via Photosystem II (PSII) and the electrons flow through a series of electron transfer cofactors in cytochrome b6f, plastocyanin and Photosystem I (PSI). The terminal electron acceptor of PSI is ferredoxin, from which electrons may be used to reduce NADP+ for metabolic purposes. Concomitant production of a H+ gradient allows production of energy for the cell. Under certain conditions and using the endogenous hydrogenase, excess protons and electrons from ferredoxin may be converted to molecular hydrogen. In this work it is demonstrated both that certain mutations near the quinone electron transfer cofactor in PSI can speed up electron transfer through the PETC, and also that a native [FeFe]-hydrogenase can be expressed in the C. reinhardtii chloroplast. Taken together, these research findings form the foundation for the design of a PSI-hydrogenase fusion for the direct and continuous photo-production of hydrogen in vivo.
ContributorsReifschneider, Kiera (Author) / Redding, Kevin (Thesis advisor) / Fromme, Petra (Committee member) / Jones, Anne (Committee member) / Arizona State University (Publisher)
Created2013
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Community-based development: scaling up the correct use of misoprostol at home births in Afghanistan
Description
Globally, more than 350 000 women die annually from complications during pregnancy and childbirth (UNFPA, 2011). Nearly 99% of these, according to World Health Organization (WHO) trends (2010) occur in the developing world outside of a hospital setting with limited resources including emergency care (WHO, 2012; UNFPA, 2011). The most prevalent cause of death is postpartum hemorrhage (PPH), accounting for 25% of deaths according to WHO statistics (2012). Conditions in Afghanistan are reflective of the scope and magnitude of the problem. In Afghanistan, maternal mortality is thought to be among the highest in the world. The Afghan Mortality Survey (AMS) data implies that one Afghan woman dies about every 2 hours from pregnancy-related causes (AMS, 2010). Lack of empowerment, education and access to health care resources increase a woman's risk of dying during pregnancy (AMS, 2010). This project aims to investigate the prospects of scaling-up the correct use of misoprostol, a prostaglandin E1 analogue, to treat PPH in developing countries where skilled assistance and resources are scant. As there has been little published on the lessons learned from programs already in place, this study is experience-driven, based on the knowledge of industry experts. This study employs a concurrent triangulation approach to synthesize quantitative data obtained from previous studies with qualitative information gathered through the testimonies of key personnel who participated in pilot programs involving misoprostol. There are many obstacles to scaling-up training initiatives in Afghanistan and other low-resource areas. The analysis concludes that the most crucial factors for scaling-up community-based programs include: more studies analyzing lessons learns from community driven approaches; stronger partnerships with community health care workers; overcoming barriers like association with abortion, misuse and product issues; and a heightened global and community awareness of the severity of PPH without treatment. These results have implications for those who actively work in Afghanistan to promote maternal health and other countries that may use Afghanistan's work as a blueprint for reducing maternal mortality through community-based approaches. Keywords: Afghanistan, community-based interventions, community-driven, maternal mortality, MDG5, misoprostol, postpartum hemorrhage, reproduction, scale-up
ContributorsCristy, Candice (Author) / Grossman, Gary (Thesis advisor) / Parmentier, Mary-Jane (Committee member) / Byrd, Denise (Committee member) / Arizona State University (Publisher)
Created2013
Description
The ribosome is a ribozyme and central to the biosynthesis of proteins in all organisms. It has a strong bias against non-alpha-L-amino acids, such as alpha-D-amino acids and beta-amino acids. Additionally, the ribosome is only able to incorporate one amino acid in response to one codon. It has been demonstrated that reengineering of the peptidyltransferase center (PTC) of the ribosome enabled the incorporation of both alpha-D-amino acids and beta-amino acids into full length protein. Described in Chapter 2 are five modified ribosomes having modifications in the peptidyltrasnferase center in the 23S rRNA. These modified ribosomes successfully incorporated five different beta-amino acids (2.1 - 2.5) into E. coli dihydrofolate reductase (DHFR). The second project (Chapter 3) focused on the study of the modified ribosomes facilitating the incorporation of the dipeptide glycylphenylalanine (3.25) and fluorescent dipeptidomimetic 3.26 into DHFR. These ribosomes also had modifications in the peptidyltransferase center in the 23S rRNA of the 50S ribosomal subunit. The modified DHFRs having beta-amino acids 2.3 and 2.5, dipeptide glycylphenylalanine (3.25) and dipeptidomimetic 3.26 were successfully characterized by the MALDI-MS analysis of the peptide fragments produced by "in-gel" trypsin digestion of the modified proteins. The fluorescent spectra of the dipeptidomimetic 3.26 and modified DHFR having fluorescent dipeptidomimetic 3.26 were also measured. The type I and II DNA topoisomerases have been firmly established as effective molecular targets for many antitumor drugs. A "classical" topoisomerase I or II poison acts by misaligning the free hydroxyl group of the sugar moiety of DNA and preventing the reverse transesterfication reaction to religate DNA. There have been only two classes of compounds, saintopin and topopyrones, reported as dual topoisomerase I and II poisons. Chapter 4 describes the synthesis and biological evaluation of topopyrones. Compound 4.10, employed at 20 µM, was as efficient as 0.5 uM camptothecin, a potent topoisomerase I poison, in stabilizing the covalent binary complex (~30%). When compared with a known topoisomerase II poison, etoposide (at 0.5 uM), topopyorone 4.10 produced similar levels of stabilized DNA-enzyme binary complex (~34%) at 5 uM concentration.
ContributorsMaini, Rumit (Author) / Hecht, Sidney M. (Thesis advisor) / Gould, Ian (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation integrates humanities with social science methodologies within a critical framework, seeking to explore the relationship between the neoliberal restructuring and the intersection of gender, class and heteronormativity in contemporary China. In this project, neoliberalism is conceptualized as an art of governance centering on the intersection of race, gender, class and sexuality to create market subjects and sustain market competition. Focusing on China's recent socio-economic and cultural upheavals, this dissertation tries to address these questions: 1. How have class inequalities, binaristic gender and heteronormative discourses been employed intersectionally by the Chinese state to facilitate China's social transformation? 2. How has this process been justified and consolidated through the intersection of gender, class, sexuality and race? 3. How do the marginalized groups respond to these material and cultural practices? Building on the discursive analysis of China's televised 60th anniversary ceremony and If You Are the One, a popular Chinese reality show, as well as the data from the interview, focus group and participant observation of more than 100 informants, it is found that the intersection of gender, class and heteronormativity is central to China's neoliberal transition. A group of flexible and cheap laborers have been disarticulated and rearticulated from the population as the voluntary servitude to China's marketization and re-integration with the global economy. New controlling images, such as the bourgeois nucleus family, are created to legitimize this process. However, these disparate material and discursive practices have entailed contradictions and conflicts within the intersectional biopolitical system, and created contingent spaces of ungovernability for the marginalized groups. Building on these discursive analyses and empirical data, I reconceptualize intersectionality as a multi-dimensional-and-directional network to regulate and manage power for social organization and regulation, which grounds the biopolitical basics for the neoliberal economy. Thus I argue that we need to engage with the dynamics between the intersectional biopolitical structure and people's emerging experiences to construct a grounded utopia alternative to the neoliberal dominance for substantive social changes.
ContributorsZhang, Charlie Yi (Author) / Quan, H. L. T. (Thesis advisor) / Fonow, Mary Margaret (Thesis advisor) / Martinez, Jacqueline M. (Committee member) / Lee, Charles T. (Committee member) / Arizona State University (Publisher)
Created2013
Description
The purpose of my dissertation project is to understand how Same-Gender Loving (SGL) Black Christian men negotiate their sexuality and spirituality in spaces that are not always accepting of SGL people, by examining on how Black SGL men perform their sexual identities within hegemonic institutions that often deny their existence or outwardly seek to exclude them from their communities. I have identified three scripts that Black SGL men often follow within Black religious settings. The first script that SGL people often follow in the church is that of deliverance-- confessing their same-gender desires and maintaining that they have been delivered from those desires The second is "don't ask don't tell" performed by men who many believe and suspect of being SGL; so long as they do not publicly affirm these beliefs they are able to hold a variety of positions in their religious communities.. The last script involves accepting one's same-gender desires and also affirming one's Christian beliefs, proclaiming that the two are not at odds with one another. I examine how these scripts and/or others are performed by and on the bodies of Black SGL males in two distinct sites. The first is the career and music of former gospel star Anthony Charles Williams II (Tonex / B. Slade), who has utilized the three scripts at various times in his career. The next site is that of theatre, where I explore how these scripts have been employed in dramatic texts. By reading Christian Black SGL performance through its theological parameters, I aim to discern the avenues in which Black people in the United States are able to perform same-gender sexual identities in spaces that are constructed as "homophobic," and in so doing combat the narrative of hyper-homophobia in Black communities.
ContributorsChester, Tabitha Jamie Mary (Author) / Anderson, Lisa (Thesis advisor) / Leong, Karen J (Committee member) / Honegger, Gitta (Committee member) / Arizona State University (Publisher)
Created2013