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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- Creators: Yan, Hao
- Creators: Chassin, Laurie
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
Research has shown that a developmental process of maturing out of alcohol involvement occurs during young adulthood, and that this process is related to both young adult role transitions (e.g., marriage) and personality developmental (e.g., decreased disinhibition and neuroticism). The current study extended past research by testing whether protective marriage and personality effects on maturing out were stronger among more severe late adolescent drinkers, and whether protective marriage effects were stronger among those who experienced more personality development. Parental alcoholism and gender were tested as moderators of marriage, personality, and late adolescent drinking effects on maturing out; and as distal predictors mediated by these effects. Participants were a subsample (N = 844; 51% children of alcoholics; 53% male, 71% non-Hispanic Caucasian, 27% Hispanic; Chassin, Barrera, Bech, & Kossak-Fuller, 1992) from a larger longitudinal study of familial alcoholism. Hypotheses were tested with latent growth models characterizing alcohol consumption and drinking consequence trajectories from late adolescence to adulthood (age 17-40). Past findings were replicated by showing protective effects of becoming married, sensation-seeking reductions, and neuroticism reductions on the drinking trajectories. Moderation tests showed that protective marriage effects on the drinking trajectories were stronger among those with higher pre-marriage drinking in late adolescence (i.e., higher growth intercepts). This might reflect role socialization mechanisms such that more severe drinking produces more conflict with the demands of new roles (i.e., role incompatibility), thus requiring greater drinking reductions to resolve this conflict. In contrast, little evidence was found for moderation of personality effects by late adolescent drinking or for moderation of marriage effects by personality. Parental alcoholism findings suggested complex moderated mediation pathways. Parental alcoholism predicted less drinking reduction through decreasing the likelihood of marriage (mediation) and muting marriage's effect on the drinking trajectories (moderation), but parental alcoholism also predicted more drinking reduction through increasing initial drinking in late adolescence (mediation). The current study provides new insights into naturally occurring processes of recovery during young adulthood and suggests that developmentally-tailored interventions for young adults could harness these natural recovery processes (e.g., by integrating role incompatibility themes and addressing factors that block role effects among those with familial alcoholism).
ContributorsLee, Matthew R. (Author) / Chassin, Laurie (Thesis advisor) / Corbin, William R. (Committee member) / Mackinnon, David P (Committee member) / Presson, Clark C. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Past literature has indicated that the majority of people with alcohol problems never seek treatment and that this is especially true of women. Relatively few studies have investigated how different types of alcohol-related consequences longitudinally predict men and women's perceived need for treatment and their utilization of treatment services. The current study sought to expand the literature by examining whether gender moderates the links between four frequently endorsed types of consequences and perceived need for or actual utilization of treatment. Two-hundred thirty-seven adults ages 21-36 completed a battery of questionnaires at two time points five years apart. Results indicated that there were four broad types of consequences endorsed by both men and women. Multiple-group models and Wald chi square tests indicated that there were no significant relationships between consequences and treatment outcomes. No gender moderation was found but post-hoc power analyses indicated that the study was underpowered to detect moderation. Researchers need to continue to study factors that predict utilization of alcohol treatment services and the process of recovery so that treatment providers can better address the needs of people with alcohol-related consequences in the areas of referral procedures, clinical assessment, and treatment service provision and planning.
ContributorsBeltran Gonzalez, Iris (Author) / Chassin, Laurie (Thesis advisor) / Tein, Jenn-Yun (Committee member) / Corbin, William (Committee member) / Barrera, Jr., Manuel (Committee member) / Arizona State University (Publisher)
Created2013
Description
Juvenile offenders suffer from substance use disorders at higher rates than adolescents in the general public. Substance use disorders also predict an increased risk for re-offending. Therefore, it is important that these juveniles, in particular, receive the appropriate substance use disorder treatment. The present study used logistic regression to test whether race/ethnicity would moderate the match between substance use disorder diagnosis and the receipt of a substance use disorder related service in a sample of male, serious juvenile offenders. Results showed that among those with a substance use disorder diagnosis, there were no race/ethnicity differences in the receipt of the appropriate service. However, among those without a substance use disorder diagnosis, non-Hispanic Caucasians were more likely to receive substance use service than were Hispanics or African-Americans. Post-hoc analyses revealed that when using a broader definition of substance use problems, significant differences by race/ethnicity in the prediction of service receipt were only observed at low levels of substance use problems. These findings shed light on how race/ethnicity may play a role in the recommendation of substance use disorder services in the juvenile justice system.
ContributorsMansion, Andre (Author) / Chassin, Laurie (Thesis advisor) / Dishion, Thomas (Committee member) / Knight, George (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
The biological and chemical diversity of protein structure and function can be greatly expanded by position-specific incorporation of non-natural amino acids bearing a variety of functional groups. Non-cognate amino acids can be incorporated into proteins at specific sites by using orthogonal aminoacyl-tRNA synthetase/tRNA pairs in conjunction with nonsense, rare, or 4-bp codons. There has been considerable progress in developing new types of amino acids, in identifying novel methods of tRNA aminoacylation, and in expanding the genetic code to direct their position. Chemical aminoacylation of tRNAs is accomplished by acylation and ligation of a dinucleotide (pdCpA) to the 3'-terminus of truncated tRNA. This strategy allows the incorporation of a wide range of natural and unnatural amino acids into pre-determined sites, thereby facilitating the study of structure-function relationships in proteins and allowing the investigation of their biological, biochemical and biophysical properties. Described in Chapter 1 is the current methodology for synthesizing aminoacylated suppressor tRNAs. Aminoacylated suppressor tRNACUAs are typically prepared by linking pre-aminoacylated dinucleotides (aminoacyl-pdCpAs) to 74 nucleotide (nt) truncated tRNAs (tRNA-COH) via a T4 RNA ligase mediated reaction. Alternatively, there is another route outlined in Chapter 1 that utilizes a different pre-aminoacylated dinucleotide, AppA. This dinucleotide has been shown to be a suitable substrate for T4 RNA ligase mediated coupling with abbreviated tRNA-COHs for production of 76 nt aminoacyl-tRNACUAs. The synthesized suppressor tRNAs have been shown to participate in protein synthesis in vitro, in an S30 (E. coli) coupled transcription-translation system in which there is a UAG codon in the mRNA at the position corresponding to Val10. Chapter 2 describes the synthesis of two non-proteinogenic amino acids, L-thiothreonine and L-allo-thiothreonine, and their incorporation into predetermined positions of a catalytically competent dihydrofolate reductase (DHFR) analogue lacking cysteine. Here, the elaborated proteins were site-specifically derivitized with a fluorophore at the thiothreonine residue. The synthesis and incorporation of phosphorotyrosine derivatives into DHFR is illustrated in Chapter 3. Three different phosphorylated tyrosine derivatives were prepared: bis-nitrobenzylphosphoro-L-tyrosine, nitrobenzylphosphoro-L-tyrosine, and phosphoro-L-tyrosine. Their ability to participate in a protein synthesis system was also evaluated.
ContributorsNangreave, Ryan Christopher (Author) / Hecht, Sidney M. (Thesis advisor) / Yan, Hao (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2013
Description
Solution conformations and dynamics of proteins and protein-DNA complexes are often difficult to predict from their crystal structures. The crystal structure only shows a snapshot of the different conformations these biological molecules can have in solution. Multiple different conformations can exist in solution and potentially have more importance in the biological activity. DNA sliding clamps are a family of proteins with known crystal structures. These clamps encircle the DNA and enable other proteins to interact more efficiently with the DNA. Eukaryotic PCNA and prokaryotic β clamp are two of these clamps, some of the most stable homo-oligomers known. However, their solution stability and conformational equilibrium have not been investigated in depth before. Presented here are the studies involving two sliding clamps: yeast PCNA and bacterial β clamp. These studies show that the β clamp has a very different solution stability than PCNA. These conclusions were reached through various different fluorescence-based experiments, including fluorescence correlation spectroscopy (FCS), Förster resonance energy transfer (FRET), single molecule fluorescence, and various time resolved fluorescence techniques. Interpretations of these, and all other, fluorescence-based experiments are often affected by the properties of the fluorophores employed. Often the fluorescence properties of these fluorophores are influenced by their microenvironments. Fluorophores are known to sometimes interact with biological molecules, and this can have pronounced effects on the rotational mobility and photophysical properties of the dye. Misunderstanding the effect of these photophysical and rotational properties can lead to a misinterpretation of the obtained data. In this thesis, photophysical behaviors of various organic dyes were studied in the presence of deoxymononucleotides to examine more closely how interactions between fluorophores and DNA bases can affect fluorescent properties. Furthermore, the properties of cyanine dyes when bound to DNA and the effect of restricted rotation on FRET are presented in this thesis. This thesis involves studying fluorophore photophysics in various microenvironments and then expanding into the solution stability and dynamics of the DNA sliding clamps.
ContributorsRanjit, Suman (Author) / Levitus, Marcia (Thesis advisor) / Lindsay, Stuart (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2013
Description
Single molecule DNA Sequencing technology has been a hot research topic in the recent decades because it holds the promise to sequence a human genome in a fast and affordable way, which will eventually make personalized medicine possible. Single molecule differentiation and DNA translocation control are the two main challenges in all single molecule DNA sequencing methods. In this thesis, I will first introduce DNA sequencing technology development and its application, and then explain the performance and limitation of prior art in detail. Following that, I will show a single molecule DNA base differentiation result obtained in recognition tunneling experiments. Furthermore, I will explain the assembly of a nanofluidic platform for single strand DNA translocation, which holds the promised to be integrated into a single molecule DNA sequencing instrument for DNA translocation control. Taken together, my dissertation research demonstrated the potential of using recognition tunneling techniques to serve as a general readout system for single molecule DNA sequencing application.
ContributorsLiu, Hao (Author) / Lindsay, Stuart M (Committee member) / Yan, Hao (Committee member) / Levitus, Marcia (Committee member) / Arizona State University (Publisher)
Created2013
Description
Levels of heavy episodic drinking peak during emerging adulthood and contribute to the experience of negative consequences. Previous research has identified a number of trait-like personality characteristics that are associated with drinking. Studies of the Acquired Preparedness Model have supported positive expectancies, and to a lesser extent negative expectancies, as mediators of the relation between trait-like characteristics and alcohol outcomes. However, expectancies measured via self-report may reflect differences in learned expectancies in spite of similar alcohol-related responses, or they may reflect true individual differences in subjective responses to alcohol. The current study addressed this gap in the literature by assessing the relative roles of expectancies and subjective response as mediators within the APM in a sample of 236 emerging adults (74.7% male) participating in a placebo-controlled alcohol challenge study. The study tested four mediation models collapsed across beverage condition as well as eight separate mediation models with four models (2 beverage by 2 expectancy/subjective response) for each outcome (alcohol use and alcohol-related problems). Consistent with previous studies, SS was positively associated with alcohol outcomes in models collapsed across beverage condition. SS was also associated with positive subjective response in collapsed models and in the alcohol models. The hypothesized negative relation between SS and sedation was not significant. In contrast to previous studies, neither stimulation nor sedation predicted either weekly drinking or alcohol-related problems. While stimulation and alcohol use appeared to have a positive and significant association, this relation did not hold when controlling for SS, suggesting that SS and stimulation account for shared variability in drinking behavior. Failure to find this association in the placebo group suggests that, while explicit positive expectancies are related to alcohol use after controlling for levels of sensation seeking, implicit expectancies (at least as assessed by a placebo manipulation) are not. That the relation between SS and stimulation held only in the alcohol condition in analyses separate by beverage condition indicates that sensation seeking is a significant predictor of positive subjective response to alcohol (stimulation), potentially above and beyond expectancies.
ContributorsScott, Caitlin (Author) / Corbin, William (Thesis advisor) / Shiota, Michelle (Committee member) / Chassin, Laurie (Committee member) / Arizona State University (Publisher)
Created2012
Description
As the genetic information storage vehicle, deoxyribonucleic acid (DNA) molecules are essential to all known living organisms and many viruses. It is amazing that such a large amount of information about how life develops can be stored in these tiny molecules. Countless scientists, especially some biologists, are trying to decipher the genetic information stored in these captivating molecules. Meanwhile, another group of researchers, nanotechnologists in particular, have discovered that the unique and concise structural features of DNA together with its information coding ability can be utilized for nano-construction efforts. This idea culminated in the birth of the field of DNA nanotechnology which is the main topic of this dissertation. The ability of rationally designed DNA strands to self-assemble into arbitrary nanostructures without external direction is the basis of this field. A series of novel design principles for DNA nanotechnology are presented here, from topological DNA nanostructures to complex and curved DNA nanostructures, from pure DNA nanostructures to hybrid RNA/DNA nanostructures. As one of the most important and pioneering fields in controlling the assembly of materials (both DNA and other materials) at the nanoscale, DNA nanotechnology is developing at a dramatic speed and as more and more construction approaches are invented, exciting advances will emerge in ways that we may or may not predict.
ContributorsHan, Dongran (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Ros, Anexandra (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2012