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 102
Description
In the 1970s James Watson recognized the inability of conventional DNA replication machinery to replicate the extreme termini of chromosomes known as telomeres. This inability is due to the requirement of a building block primer and was termed the end replication problem. Telomerase is nature's answer to the end replication problem. Telomerase is a ribonucleoprotein which extends telomeres through reverse transcriptase activity by reiteratively copying a short intrinsic RNA sequence to generate 3' telomeric extensions. Telomeres protect chromosomes from erosion of coding genes during replication, as well as differentiate native chromosome ends from double stranded breaks. However, controlled erosion of telomeres functions as a naturally occurring molecular clock limiting the replicative capacity of cells. Telomerase is over activated in many cancers, while inactivation leads to multiple lifespan limiting human diseases. In order to further study the interaction between telomerase RNA (TR) and telomerase reverse transcriptase protein (TERT), vertebrate TERT fragments were screened for solubility and purity following bacterial expression. Soluble fragments of medaka TERT including the RNA binding domain (TRBD) were identified. Recombinant medaka TRBD binds specifically to telomerase RNA CR4/CR5 region. Ribonucleotide and amino acid pairs in close proximity within the medaka telomerase RNA-protein complex were identified using photo-activated cross-linking in conjunction with mass spectrometry. The identified cross-linking amino acids were mapped on known crystal structures of TERTs to reveal the RNA interaction interface of TRBD. The identification of this RNA TERT interaction interface furthers the understanding of the telomerase complex at a molecular level and could be used for the targeted interruption of the telomerase complex as a potential cancer treatment.
ContributorsBley, Christopher James (Author) / Chen, Julian (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase ribonucleoprotein is a unique reverse transcriptase that adds telomeric DNA repeats to chromosome ends. Telomerase RNA (TER) is extremely divergent in size, sequence and has to date only been identified in vertebrate, yeast, ciliate and plant species. Herein, the identification and characterization of TERs from an evolutionarily distinct group, filamentous fungi, is presented. Based on phylogenetic analysis of 69 TER sequences and mutagenesis analysis of in vitro reconstituted Neurospora telomerase, we discovered a conserved functional core in filamentous fungal TERs sharing homologous structural features with vertebrate TERs. This core contains the template-pseudoknot and P6/P6.1 domains, essential for enzymatic activity, which retain function in trans. The in vitro reconstituted Neurospora telomerase is highly processive, synthesizing canonical TTAGGG repeats. Similar to Schizosaccharomycetes pombe, filamentous fungal TERs utilize the spliceosomal splicing machinery for 3' processing. Neurospora telomerase, while associating with the Est1 protein in vivo, does not bind homologous Ku or Sm proteins found in both budding and fission yeast telomerase holoenzyme, suggesting a unique biogenesis pathway. The development of Neurospora as a model organism to study telomeres and telomerase may shed light upon the evolution of the canonical TTAGGG telomeric repeat and telomerase processivity within fungal species.
ContributorsQi, Xiaodong (Author) / Chen, Julian (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Chaput, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex.
ContributorsLi, Yang (Author) / Chen, Julian Jl (Thesis advisor) / Yan, Hao (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
It is estimated that wind induced soil transports more than 500 x 106 metric tons of fugitive dust annually. Soil erosion has negative effects on human health, the productivity of farms, and the quality of surface waters. A variety of different polymer stabilizers are available on the market for fugitive dust control. Most of these polymer stabilizers are expensive synthetic polymer products. Their adverse effects and expense usually limits their use. Biopolymers provide a potential alternative to synthetic polymers. They can provide dust abatement by encapsulating soil particles and creating a binding network throughout the treated area. This research into the effectiveness of biopolymers for fugitive dust control involved three phases. Phase I included proof of concept tests. Phase II included carrying out the tests in a wind tunnel. Phase III consisted of conducting the experiments in the field. Proof of concept tests showed that biopolymers have the potential to reduce soil erosion and fugitive dust transport. Wind tunnel tests on two candidate biopolymers, xanthan and chitosan, showed that there is a proportional relationship between biopolymer application rates and threshold wind velocities. The wind tunnel tests also showed that xanthan gum is more successful in the field than chitosan. The field tests showed that xanthan gum was effective at controlling soil erosion. However, the chitosan field data was inconsistent with the xanthan data and field data on bare soil.
ContributorsAlsanad, Abdullah (Author) / Kavazanjian, Edward (Thesis advisor) / Edwards, David (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2011
Description
A method for evaluating the integrity of geosynthetic elements of a waste containment system subject to seismic loading is developed using a large strain finite difference numerical computer program. The method accounts for the effect of interaction between the geosynthetic elements and the overlying waste on seismic response and allows for explicit calculation of forces and strains in the geosynthetic elements. Based upon comparison of numerical results to experimental data, an elastic-perfectly plastic interface model is demonstrated to adequately reproduce the cyclic behavior of typical geomembrane-geotextile and geomembrane-geomembrane interfaces provided the appropriate interface properties are used. New constitutive models are developed for the in-plane cyclic shear behavior of textured geomembrane/geosynthetic clay liner (GMX/GCL) interfaces and GCLs. The GMX/GCL model is an empirical model and the GCL model is a kinematic hardening, isotropic softening multi yield surface plasticity model. Both new models allows for degradation in the cyclic shear resistance from a peak to a large displacement shear strength. The ability of the finite difference model to predict forces and strains in a geosynthetic element modeled as a beam element with zero moment of inertia sandwiched between two interface elements is demonstrated using hypothetical models of a heap leach pad and two typical landfill configurations. The numerical model is then used to conduct back analyses of the performance of two lined municipal solid waste (MSW) landfills subjected to strong ground motions in the Northridge earthquake. The modulus reduction "backbone curve" employed with the Masing criterion and 2% Rayleigh damping to model the cyclic behavior of MSW was established by back-analysis of the response of the Operating Industries Inc. landfill to five different earthquakes, three small magnitude nearby events and two larger magnitude distant events. The numerical back analysis was able to predict the tears observed in the Chiquita Canyon Landfill liner system after the earthquake if strain concentrations due to seams and scratches in the geomembrane are taken into account. The apparent good performance of the Lopez Canyon landfill geomembrane and the observed tension in the overlying geotextile after the Northridge event was also successfully predicted using the numerical model.
ContributorsArab, Mohamed G (Author) / Kavazanjian, Edward (Thesis advisor) / Zapata, Claudia (Committee member) / Houston, Sandra (Committee member) / Arizona State University (Publisher)
Created2011
Description
Natural products that target the DNA of cancer cells have been an important source of knowledge and understanding in the development of anticancer chemotherapeutic agents. Bleomycin (BLM) exemplifies this class of DNA damaging agent. The ability of BLM to chelate metal ions and effect oxidative damage of the deoxyribose sugar moiety of DNA has been studied extensively for four decades. Here, the study of BLM A5 was conducted using a previously isolated library of hairpin DNAs found to bind strongly to metal free BLM. The ability of BLM to effect single-stranded was then extensively characterized on both the 3′ and 5′-arms of the hairpin DNAs. The strongly bound DNAs were found to be efficient substrates for Fe·BLM A5-mediated cleavage. Surprisingly, the most prevalent site of damage by BLM was found to be a 5′-AT-3′ dinucleotide sequence. This dinucleotide sequence and others generally not cleaved by BLM when examined using arbitrarily chosen DNA substrate were found in examining the library of ten hairpin DNAs. In total, 111 sites of DNA damage were found to be produced by exposure of the hairpin DNA library to Fe·BLM A5. Also, an assay was developed with which to test the propensity of the hairpin DNAs to undergo double stranded DNA damage. Adapting methods previously described by the Povirk laboratory, one hairpin was characterized using this method. The results were in accordance with those previously reported.
ContributorsSegerman, Zachary (Author) / Hecht, Sidney M. (Thesis advisor) / Levitus, Marcia (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
The properties of materials depend heavily on the spatial distribution and connectivity of their constituent parts. This applies equally to materials such as diamond and glasses as it does to biomolecules that are the product of billions of years of evolution. In science, insight is often gained through simple models with characteristics that are the result of the few features that have purposely been retained. Common to all research within in this thesis is the use of network-based models to describe the properties of materials. This work begins with the description of a technique for decoupling boundary effects from intrinsic properties of nanomaterials that maps the atomic distribution of nanomaterials of diverse shape and size but common atomic geometry onto a universal curve. This is followed by an investigation of correlated density fluctuations in the large length scale limit in amorphous materials through the analysis of large continuous random network models. The difficulty of estimating this limit from finite models is overcome by the development of a technique that uses the variance in the number of atoms in finite subregions to perform the extrapolation to large length scales. The technique is applied to models of amorphous silicon and vitreous silica and compared with results from recent experiments. The latter part this work applies network-based models to biological systems. The first application models force-induced protein unfolding as crack propagation on a constraint network consisting of interactions such as hydrogen bonds that cross-link and stabilize a folded polypeptide chain. Unfolding pathways generated by the model are compared with molecular dynamics simulation and experiment for a diverse set of proteins, demonstrating that the model is able to capture not only native state behavior but also partially unfolded intermediates far from the native state. This study concludes with the extension of the latter model in the development of an efficient algorithm for predicting protein structure through the flexible fitting of atomic models to low-resolution cryo-electron microscopy data. By optimizing the fit to synthetic data through directed sampling and context-dependent constraint removal, predictions are made with accuracies within the expected variability of the native state.
ContributorsDe Graff, Adam (Author) / Thorpe, Michael F. (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Matyushov, Dmitry (Committee member) / Ozkan, Sefika B. (Committee member) / Treacy, Michael M. J. (Committee member) / Arizona State University (Publisher)
Created2011
Description
A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable helical structures with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Another alternative genetic system, glycerol nucleic acid (GNA) undergoes intrasystem pairing with superior thermalstability compared to that of DNA. Inspired by this property, I demonstrated a minimal nanostructure composed of both left- and right-handed mirro image GNA. This work suggested that GNA could be useful as promising orthogonal material in structural DNA nanotechnology.
ContributorsZhang, Su (Author) / Chaut, John C (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2011
Description
This dissertation describes development of a procedure for obtaining high quality, optical grade sand coupons from frozen sand specimens of Ottawa 20/30 sand for image processing and analysis to quantify soil structure along with a methodology for quantifying the microstructure from the images. A technique for thawing and stabilizing frozen core samples was developed using optical grade Buehler® Epo-Tek® epoxy resin, a modified triaxial cell, a vacuum/reservoir chamber, a desiccator, and a moisture gauge. The uniform epoxy resin impregnation required proper drying of the soil specimen, application of appropriate confining pressure and vacuum levels, and epoxy mixing, de-airing and curing. The resulting stabilized sand specimen was sectioned into 10 mm thick coupons that were planed, ground, and polished with progressively finer diamond abrasive grit levels using the modified Allied HTP Inc. polishing method so that the soil structure could be accurately quantified using images obtained with the use of an optical microscopy technique. Illumination via Bright Field Microscopy was used to capture the images for subsequent image processing and sand microstructure analysis. The quality of resulting images and the validity of the subsequent image morphology analysis hinged largely on employment of a polishing and grinding technique that resulted in a flat, scratch free, reflective coupon surface characterized by minimal microstructure relief and good contrast between the sand particles and the surrounding epoxy resin. Subsequent image processing involved conversion of the color images first to gray scale images and then to binary images with the use of contrast and image adjustments, removal of noise and image artifacts, image filtering, and image segmentation. Mathematical morphology algorithms were used on the resulting binary images to further enhance image quality. The binary images were then used to calculate soil structure parameters that included particle roundness and sphericity, particle orientation variability represented by rose diagrams, statistics on the local void ratio variability as a function of the sample size, and the local void ratio distribution histograms using Oda's method and Voronoi tessellation method, including the skewness, kurtosis, and entropy of a gamma cumulative probability distribution fit to the local void ratio distribution.
ContributorsCzupak, Zbigniew David (Author) / Kavazanjian, Edward (Thesis advisor) / Zapata, Claudia (Committee member) / Houston, Sandra (Committee member) / Arizona State University (Publisher)
Created2011
Description
As a prelude to a study on the post-liquefaction properties and structure of soil, an investigation of ground freezing as an undisturbed sampling technique was conducted to investigate the ability of this sampling technique to preserve soil structure and properties. Freezing the ground is widely regarded as an appropriate technique to recover undisturbed samples of saturated cohesionless soil for laboratory testing, despite the fact that water increases in volume when frozen. The explanation generally given for the preservation of soil structure using the freezing technique was that, as long as the freezing front advanced uni-directionally, the expanding pore water is expelled ahead of the freezing front as the front advances. However, a literature review on the transition of water to ice shows that the volume of ice expands approximately nine percent after freezing, bringing into question the hypothesized mechanism and the ability of a frozen and then thawed specimen to retain the properties and structure of the soil in situ. Bench-top models were created by pluviation of sand. The soil in the model was then saturated and subsequently frozen. Freezing was accomplished using a pan filled with alcohol and dry ice placed on the surface of the sand layer to induce a unidirectional freezing front in the sample container. Coring was used to recover frozen samples from model containers. Recovered cores were then placed in a triaxial cell, thawed, and subjected to consolidated undrained loading. The stress-strain-strength behavior of the thawed cores was compared to the behavior of specimens created in a split mold by pluviation and then saturated and sheared without freezing and thawing. The laboratory testing provide insight to the impact of freezing and thawing on the properties of cohesionless soil.
ContributorsKatapa, Kanyembo (Author) / Kavazanjian, Edward (Thesis advisor) / Houston, Sandra (Committee member) / Zapata, Claudia (Committee member) / Arizona State University (Publisher)
Created2011