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.
Displaying 1 - 10 of 68
Description
The effect of earthquake-induced liquefaction on the local void ratio distribution of cohesionless soil is evaluated using x-ray computed tomography (CT) and an advanced image processing software package. Intact, relatively undisturbed specimens of cohesionless soil were recovered before and after liquefaction by freezing and coring soil deposits created by pluviation and by sedimentation through water. Pluviated soil deposits were liquefied in the small geotechnical centrifuge at the University of California at Davis shared-use National Science Foundation (NSF)-supported Network for Earthquake Engineering Simulation (NEES) facility. A soil deposit created by sedimentation through water was liquefied on a small shake table in the Arizona State University geotechnical laboratory. Initial centrifuge tests employed Ottawa 20-30 sand but this material proved to be too coarse to liquefy in the centrifuge. Therefore, subsequent centrifuge tests employed Ottawa F60 sand. The shake table test employed Ottawa 20-30 sand. Recovered cores were stabilized by impregnation with optical grade epoxy and sent to the University of Texas at Austin NSF-supported facility at the University of Texas at Austin for high-resolution CT scanning of geologic media. The local void ratio distribution of a CT-scanned core of Ottawa 20-30 sand evaluated using Avizo® Fire, a commercially available advanced program for image analysis, was compared to the local void ratio distribution established on the same core by analysis of optical images to demonstrate that analysis of the CT scans gave similar results to optical methods. CT scans were subsequently conducted on liquefied and not-liquefied specimens of Ottawa 20-30 sand and Ottawa F60 sand. The resolution of F60 specimens was inadequate to establish the local void ratio distribution. Results of the analysis of the Ottawa 20-30 specimens recovered from the model built for the shake table test showed that liquefaction can substantially influence the variability in local void ratio, increasing the degree of non-homogeneity in the specimen.
ContributorsGutierrez, Angel (Author) / Kavazanjian, Edward (Thesis advisor) / Houston, Sandra (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2013
Description
Heating of asphalt during production and construction causes the volatilization and oxidation of binders used in mixes. Volatilization and oxidation causes degradation of asphalt pavements by increasing the stiffness of the binders, increasing susceptibility to cracking and negatively affecting the functional and structural performance of the pavements. Degradation of asphalt binders by volatilization and oxidation due to high production temperature occur during early stages of pavement life and are known as Short Term Aging (STA). Elevated temperatures and increased exposure time to elevated temperatures causes increased STA of asphalt. The objective of this research was to investigate how elevated mixing temperatures and exposure time to elevated temperatures affect aging and stiffening of binders, thus influencing properties of the asphalt mixtures. The study was conducted in two stages. The first stage evaluated STA effect of asphalt binders. It involved aging two Performance Graded (PG) virgin asphalt binders, PG 76-16 and PG 64-22 at two different temperatures and durations, then measuring their viscosities. The second stage involved evaluating the effects of elevated STA temperature and time on properties of the asphalt mixtures. It involved STA of asphalt mixtures produced in the laboratory with the PG 64-22 binder at mixing temperatures elevated 25OF above standard practice; STA times at 2 and 4 hours longer than standard practices, and then compacted in a gyratory compactor. Dynamic modulus (E*) and Indirect Tensile Strength (IDT) were measured for the aged mixtures for each temperature and duration to determine the effect of different aging times and temperatures on the stiffness and fatigue properties of the aged asphalt mixtures. The binder test results showed that in all cases, there was increased viscosity. The results showed the highest increase in viscosity resulted from increased aging time. The results also indicated that PG 64-22 was more susceptible to elevated STA temperature and extended time than the PG 76-16 binders. The asphalt mixture test results confirmed the expected outcome that increasing the STA and mixing temperature by 25oF alters the stiffness of mixtures. Significant change in the dynamic modulus mostly occurred at four hour increase in STA time regardless of temperature.
ContributorsLolly, Rubben (Author) / Kaloush, Kamil (Thesis advisor) / Bearup, Wylie (Committee member) / Zapata, Claudia (Committee member) / Mamlouk, Michael (Committee member) / Arizona State University (Publisher)
Created2013
Description
Unsaturated soil mechanics is becoming a part of geotechnical engineering practice, particularly in applications to moisture sensitive soils such as expansive and collapsible soils and in geoenvironmental applications. The soil water characteristic curve, which describes the amount of water in a soil versus soil suction, is perhaps the most important soil property function for application of unsaturated soil mechanics. The soil water characteristic curve has been used extensively for estimating unsaturated soil properties, and a number of fitting equations for development of soil water characteristic curves from laboratory data have been proposed by researchers. Although not always mentioned, the underlying assumption of soil water characteristic curve fitting equations is that the soil is sufficiently stiff so that there is no change in total volume of the soil while measuring the soil water characteristic curve in the laboratory, and researchers rarely take volume change of soils into account when generating or using the soil water characteristic curve. Further, there has been little attention to the applied net normal stress during laboratory soil water characteristic curve measurement, and often zero to only token net normal stress is applied. The applied net normal stress also affects the volume change of the specimen during soil suction change. When a soil changes volume in response to suction change, failure to consider the volume change of the soil leads to errors in the estimated air-entry value and the slope of the soil water characteristic curve between the air-entry value and the residual moisture state. Inaccuracies in the soil water characteristic curve may lead to inaccuracies in estimated soil property functions such as unsaturated hydraulic conductivity. A number of researchers have recently recognized the importance of considering soil volume change in soil water characteristic curves. The study of correct methods of soil water characteristic curve measurement and determination considering soil volume change, and impacts on the unsaturated hydraulic conductivity function was of the primary focus of this study. Emphasis was placed upon study of the effect of volume change consideration on soil water characteristic curves, for expansive clays and other high volume change soils. The research involved extensive literature review and laboratory soil water characteristic curve testing on expansive soils. The effect of the initial state of the specimen (i.e. slurry versus compacted) on soil water characteristic curves, with regard to volume change effects, and effect of net normal stress on volume change for determination of these curves, was studied for expansive clays. Hysteresis effects were included in laboratory measurements of soil water characteristic curves as both wetting and drying paths were used. Impacts of soil water characteristic curve volume change considerations on fluid flow computations and associated suction-change induced soil deformations were studied through numerical simulations. The study includes both coupled and uncoupled flow and stress-deformation analyses, demonstrating that the impact of volume change consideration on the soil water characteristic curve and the estimated unsaturated hydraulic conductivity function can be quite substantial for high volume change soils.
ContributorsBani Hashem, Elham (Author) / Houston, Sandra L. (Thesis advisor) / Kavazanjian, Edward (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2013
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in the loss of lower body muscle function. SMA is the second leading genetic cause of death in infants and arises from the loss of the Survival of Motor Neuron (SMN) protein. SMN is produced by two genes, smn1 and smn2, that are identical with the exception of a C to T conversion in exon 7 of the smn2 gene. SMA patients lacking the smn1 gene, rely on smn2 for production of SMN. Due to an alternative splicing event, smn2 primarily encodes a non-functional SMN lacking exon 7 (SMN D7) as well as a low amount of functional full-length SMN (SMN WT). SMN WT is ubiquitously expressed in all cell types, and it remains unclear how low levels of SMN WT in motor neurons lead to motor neuron degradation and SMA. SMN and its associated proteins, Gemin2-8 and Unrip, make up a large dynamic complex that functions to assemble ribonucleoproteins. The aim of this project was to characterize the interactions of the core SMN-Gemin2 complex, and to identify differences between SMN WT and SMN D7. SMN and Gemin2 proteins were expressed, purified and characterized via size exclusion chromatography. A stable N-terminal deleted Gemin2 protein (N45-G2) was characterized. The SMN WT expression system was optimized resulting in a 10-fold increase of protein expression. Lastly, the oligomeric states of SMN and SMN bound to Gemin2 were determined. SMN WT formed a mixture of oligomeric states, while SMN D7 did not. Both SMN WT and D7 bound to Gemin2 with a one-to-one ratio forming a heterodimer and several higher-order oligomeric states. The SMN WT-Gemin2 complex favored high molecular weight oligomers whereas the SMN D7-Gemin2 complex formed low molecular weight oligomers. These results indicate that the SMA mutant protein, SMN D7, was still able to associate with Gemin2, but was not able to form higher-order oligomeric complexes. The observed multiple oligomerization states of SMN and SMN bound to Gemin2 may play a crucial role in regulating one or several functions of the SMN protein. The inability of SMN D7 to form higher-order oligomers may inhibit or alter those functions leading to the SMA disease phenotype.
ContributorsNiday, Tracy (Author) / Allen, James P. (Thesis advisor) / Wachter, Rebekka (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2012
Description
This thesis presents a probabilistic evaluation of multiple laterally loaded drilled pier foundation design approaches using extensive data from a geotechnical investigation for a high voltage electric transmission line. A series of Monte Carlo simulations provide insight about the computed level of reliability considering site standard penetration test blow count value variability alone (i.e., assuming all other aspects of the design problem do not contribute error or bias). Evaluated methods include Eurocode 7 Geotechnical Design procedures, the Federal Highway Administration drilled shaft LRFD design method, the Electric Power Research Institute transmission foundation design procedure and a site specific variability based approach previously suggested by the author of this thesis and others. The analysis method is defined by three phases: a) Evaluate the spatial variability of an existing subsurface database. b) Derive theoretical foundation designs from the database in accordance with the various design methods identified. c) Conduct Monti Carlo Simulations to compute the reliability of the theoretical foundation designs. Over several decades, reliability-based foundation design (RBD) methods have been developed and implemented to varying degrees for buildings, bridges, electric systems and other structures. In recent years, an effort has been made by researchers, professional societies and other standard-developing organizations to publish design guidelines, manuals and standards concerning RBD for foundations. Most of these approaches rely on statistical methods for quantifying load and resistance probability distribution functions with defined reliability levels. However, each varies with regard to the influence of site-specific variability on resistance. An examination of the influence of site-specific variability is required to provide direction for incorporating the concept into practical RBD design methods. Recent surveys of transmission line engineers by the Electric Power Research Institute (EPRI) demonstrate RBD methods for the design of transmission line foundations have not been widely adopted. In the absence of a unifying design document with established reliability goals, transmission line foundations have historically performed very well, with relatively few failures. However, such a track record with no set reliability goals suggests, at least in some cases, a financial premium has likely been paid.
ContributorsHeim, Zackary (Author) / Houston, Sandra (Thesis advisor) / Witczak, Matthew (Committee member) / Kavazanjian, Edward (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2014
Description
This thesis explores a wide array of topics related to the protein folding problem, ranging from the folding mechanism, ab initio structure prediction and protein design, to the mechanism of protein functional evolution, using multi-scale approaches. To investigate the role of native topology on folding mechanism, the native topology is dissected into non-local and local contacts. The number of non-local contacts and non-local contact orders are both negatively correlated with folding rates, suggesting that the non-local contacts dominate the barrier-crossing process. However, local contact orders show positive correlation with folding rates, indicating the role of a diffusive search in the denatured basin. Additionally, the folding rate distribution of E. coli and Yeast proteomes are predicted from native topology. The distribution is fitted well by a diffusion-drift population model and also directly compared with experimentally measured half life. The results indicate that proteome folding kinetics is limited by protein half life. The crucial role of local contacts in protein folding is further explored by the simulations of WW domains using Zipping and Assembly Method. The correct formation of N-terminal β-turn turns out important for the folding of WW domains. A classification model based on contact probabilities of five critical local contacts is constructed to predict the foldability of WW domains with 81% accuracy. By introducing mutations to stabilize those critical local contacts, a new protein design approach is developed to re-design the unfoldable WW domains and make them foldable. After folding, proteins exhibit inherent conformational dynamics to be functional. Using molecular dynamics simulations in conjunction with Perturbation Response Scanning, it is demonstrated that the divergence of functions can occur through the modification of conformational dynamics within existing fold for β-lactmases and GFP-like proteins: i) the modern TEM-1 lactamase shows a comparatively rigid active-site region, likely reflecting adaptation for efficient degradation of a specific substrate, while the resurrected ancient lactamases indicate enhanced active-site flexibility, which likely allows for the binding and subsequent degradation of different antibiotic molecules; ii) the chromophore and attached peptides of photocoversion-competent GFP-like protein exhibits higher flexibility than the photocoversion-incompetent one, consistent with the evolution of photocoversion capacity.
ContributorsZou, Taisong (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Woodbury, Neal W (Committee member) / Vaiana, Sara M (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Interactions driving the collapse of islet amyloid polypeptide: implications for amyloid aggregation
Description
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-residue intrinsically disordered hormone involved in glucose regulation and gastric emptying. The aggregation of hIAPP into amyloid fibrils is believed to play a causal role in type 2 diabetes. To date, not much is known about the monomeric state of hIAPP or how it undergoes an irreversible transformation from disordered peptide to insoluble aggregate. IAPP contains a highly conserved disulfide bond that restricts hIAPP(1-8) into a short ring-like structure: N_loop. Removal or chemical reduction of N_loop not only prevents cell response upon binding to the CGRP receptor, but also alters the mass per length distribution of hIAPP fibers and the kinetics of fibril formation. The mechanism by which N_loop affects hIAPP aggregation is not yet understood, but is important for rationalizing kinetics and developing potential inhibitors. By measuring end-to-end contact formation rates, Vaiana et al. showed that N_loop induces collapsed states in IAPP monomers, implying attractive interactions between N_loop and other regions of the disordered polypeptide chain . We show that in addition to being involved in intra-protein interactions, the N_loop is involved in inter-protein interactions, which lead to the formation of extremely long and stable β-turn fibers. These non-amyloid fibers are present in the 10 μM concentration range, under the same solution conditions in which hIAPP forms amyloid fibers. We discuss the effect of peptide cyclization on both intra- and inter-protein interactions, and its possible implications for aggregation. Our findings indicate a potential role of N_loop-N_loop interactions in hIAPP aggregation, which has not previously been explored. Though our findings suggest that N_loop plays an important role in the pathway of amyloid formation, other naturally occurring IAPP variants that contain this structural feature are incapable of forming amyloids. For example, hIAPP readily forms amyloid fibrils in vitro, whereas the rat variant (rIAPP), differing by six amino acids, does not. In addition to being highly soluble, rIAPP is an effective inhibitor of hIAPP fibril formation . Both of these properties have been attributed to rIAPP's three proline residues: A25P, S28P and S29P. Single proline mutants of hIAPP have also been shown to kinetically inhibit hIAPP fibril formation. Because of their intrinsic dihedral angle preferences, prolines are expected to affect conformational ensembles of intrinsically disordered proteins. The specific effect of proline substitutions on IAPP structure and dynamics has not yet been explored, as the detection of such properties is experimentally challenging due to the low molecular weight, fast reconfiguration times, and very low solubility of IAPP peptides. High-resolution techniques able to measure tertiary contact formations are needed to address this issue. We employ a nanosecond laser spectroscopy technique to measure end-to-end contact formation rates in IAPP mutants. We explore the proline substitutions in IAPP and quantify their effects in terms of intrinsic chain stiffness. We find that the three proline mutations found in rIAPP increase chain stiffness. Interestingly, we also find that residue R18 plays an important role in rIAPP's unique chain stiffness and, together with the proline residues, is a determinant for its non-amyloidogenic properties. We discuss the implications of our findings on the role of prolines in IDPs.
ContributorsCope, Stephanie M (Author) / Vaiana, Sara M (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Ros, Robert (Committee member) / Lindsay, Stuart M (Committee member) / Ozkan, Sefika B (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT Enzyme-Induced Carbonate Precipitation (EICP) using a plant-derived form of the urease enzyme to induce the precipitation of calcium carbonate (CaCO3) shows promise as a method of stabilizing soil for the mitigation of fugitive dust. Fugitive dust is a significant problem in Arizona, particularly in Maricopa County. Maricopa County is an EPA air quality non-attainment zone, due primarily to fugitive dust, which presents a significant health risk to local residents. Conventional methods for fugitive dust control, including the application of water, are either ineffective in arid climates, very expensive, or limited to short term stabilization. Due to these limitations, engineers are searching for new and more effective ways to stabilize the soil and reduce wind erosion. EICP employs urea hydrolysis, a process in which carbonate precipitation is catalyzed by the urease enzyme, a widely occurring protein found in many plants and microorganisms. Wind tunnel experiments were conducted in the ASU/NASA Planetary Wind Tunnel to evaluate the use of EICP as a means to stabilize soil against fugitive dust emission. Three different soils were tested, including a native Arizona silty-sand, a uniform fine to medium grained silica sand, and mine tailings from a mine in southern Arizona. The test soil was loosely placed in specimen container and the surface was sprayed with an aqueous solution containing urea, calcium chloride, and urease enzyme. After a short period of time to allow for CaCO3 precipitation, the specimens were tested in the wind tunnel. The completed tests show that EICP can increase the detachment velocity compared to bare or wetted soil and thus holds promise as a means of mitigating fugitive dust emissions.
ContributorsKnorr, Brian (Author) / Kavazanjian, Edward (Thesis advisor) / Houston, Sandra (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2014
Description
Telomerase is a unique reverse transcriptase that has evolved specifically to extend the single stranded DNA at the 3' ends of chromosomes. To achieve this, telomerase uses a small section of its integral RNA subunit (TR) to reiteratively copy a short, canonically 6-nt, sequence repeatedly in a processive manner using a complex and currently poorly understood mechanism of template translocation to stop nucleotide addition, regenerate its template, and then synthesize a new repeat. In this study, several novel interactions between the telomerase protein and RNA components along with the DNA substrate are identified and characterized which come together to allow active telomerase repeat addition. First, this study shows that the sequence of the RNA/DNA duplex holds a unique, single nucleotide signal which pauses DNA synthesis at the end of the canonical template sequence. Further characterization of this sequence dependent pause signal reveals that the template sequence alone can produce telomerase products with the characteristic 6-nt pattern, but also works cooperatively with another RNA structural element for proper template boundary definition. Finally, mutational analysis is used on several regions of the protein and RNA components of telomerase to identify crucial determinates of telomerase assembly and processive repeat synthesis. Together, these results shed new light on how telomerase coordinates its complex catalytic cycle.
ContributorsBrown, Andrew F (Author) / Chen, Julian J. L. (Thesis advisor) / Jones, Anne (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014
Description
ABSTRACT
Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.
In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.
In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.
Post Translational Modifications (PTMs) are a series of chemical modifications with the capacity to expand the structural and functional repertoire of proteins. PTMs can regulate protein-protein interaction, localization, protein turn-over, the active state of the protein, and much more. This can dramatically affect cell processes as relevant as gene expression, cell-cell recognition, and cell signaling. Along these lines, this Ph.D. thesis examines the role of two of the most important PTMs: glycosylation and phosphorylation.
In chapters 2, 3 and 4, a 10,000 peptide microarray is used to analyze the glycan variations in a series lipopolysaccharides (LPS) from Gram negative bacteria. This research was the first to demonstrate that using a small subset of random sequence peptides, it was possible to identify a small subset with the capacity to bind to the LPS of bacteria. These peptides bound to LPS not only in the solid surface of the array but also in solution as demonstrated with surface plasmon resonance (SPR), isothermal titration calorimetry (ITC) and flow cytometry. Interestingly, some of the LPS binding peptides also exhibit antimicrobial activity, a property that is also analyzed in this work.
In chapters 5 and 6, the role of protein phosphorylation, another PTM, is analyzed in the context of human cancer. High risk neuroblastoma, a very aggressive pediatric cancer, was studied with emphasis on the phosphorylations of two selected oncoproteins: the transcription factor NMYC and the adaptor protein ShcC. Both proteins were isolated from high risk neuroblastoma cells, and a targeted-directed tandem mass spectrometry (LC-MS/MS) methodology was used to identify the phosphorylation sites in each protein. Using this method dramatically improved the phosphorylation site detection and increased the number of sites detected up to 250% in comparison with previous studies. Several of the novel identified sites were located in functional domain of the proteins and that some of them are homologous to known active sites in other proteins of the same family. The chapter concludes with a computational prediction of the kinases that potentially phosphorylate those sites and a series of assays to show this phosphorylation occurred in vitro.
ContributorsMorales Betanzos, Carlos (Author) / LaBaer, Joshua (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2014