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
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
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
With the advent of social media (like Twitter, Facebook etc.,) people are easily sharing their opinions, sentiments and enforcing their ideologies on others like never before. Even people who are otherwise socially inactive would like to share their thoughts on current affairs by tweeting and sharing news feeds with their friends and acquaintances. In this thesis study, we chose Twitter as our main data platform to analyze shifts and movements of 27 political organizations in Indonesia. So far, we have collected over 30 million tweets and 150,000 news articles from RSS feeds of the corresponding organizations for our analysis. For Twitter data extraction, we developed a multi-threaded application which seamlessly extracts, cleans and stores millions of tweets matching our keywords from Twitter Streaming API. For keyword extraction, we used topics and perspectives which were extracted using n-grams techniques and later approved by our social scientists. After the data is extracted, we aggregate the tweet contents that belong to every user on a weekly basis. Finally, we applied linear and logistic regression using SLEP, an open source sparse learning package to compute weekly score for users and mapping them to one of the 27 organizations on a radical or counter radical scale. Since, we are mapping users to organizations on a weekly basis, we are able to track user's behavior and important new events that triggered shifts among users between organizations. This thesis study can further be extended to identify topics and organization specific influential users and new users from various social media platforms like Facebook, YouTube etc. can easily be mapped to existing organizations on a radical or counter-radical scale.
ContributorsPoornachandran, Sathishkumar (Author) / Davulcu, Hasan (Thesis advisor) / Sen, Arunabha (Committee member) / Woodward, Mark (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
The pay-as-you-go economic model of cloud computing increases the visibility, traceability, and verifiability of software costs. Application developers must understand how their software uses resources when running in the cloud in order to stay within budgeted costs and/or produce expected profits. Cloud computing's unique economic model also leads naturally to an earn-as-you-go profit model for many cloud based applications. These applications can benefit from low level analyses for cost optimization and verification. Testing cloud applications to ensure they meet monetary cost objectives has not been well explored in the current literature. When considering revenues and costs for cloud applications, the resource economic model can be scaled down to the transaction level in order to associate source code with costs incurred while running in the cloud. Both static and dynamic analysis techniques can be developed and applied to understand how and where cloud applications incur costs. Such analyses can help optimize (i.e. minimize) costs and verify that they stay within expected tolerances. An adaptation of Worst Case Execution Time (WCET) analysis is presented here to statically determine worst case monetary costs of cloud applications. This analysis is used to produce an algorithm for determining control flow paths within an application that can exceed a given cost threshold. The corresponding results are used to identify path sections that contribute most to cost excess. A hybrid approach for determining cost excesses is also presented that is comprised mostly of dynamic measurements but that also incorporates calculations that are based on the static analysis approach. This approach uses operational profiles to increase the precision and usefulness of the calculations.
ContributorsBuell, Kevin, Ph.D (Author) / Collofello, James (Thesis advisor) / Davulcu, Hasan (Committee member) / Lindquist, Timothy (Committee member) / Sen, Arunabha (Committee member) / Arizona State University (Publisher)
Created2012
Description
The F1Fo ATP synthase is required for energy conversion in almost all living organisms. The F1 complex is a molecular motor that uses ATP hydrolysis to drive rotation of the γ–subunit. It has not been previously possible to resolve the speed and position of the γ–subunit of the F1–ATPase as it rotates during a power stroke. The single molecule experiments presented here measured light scattered from 45X91 nm gold nanorods attached to the γ–subunit that provide an unprecedented 5 μs resolution of rotational position as a function of time. The product of velocity and drag, which were both measured directly, resulted in an average torque of 63±8 pN nm for the Escherichia coli F1-ATPase that was determined to be independent of the load. The rotational velocity had an initial (I) acceleration phase 15° from the end of the catalytic dwell, a slow (S) acceleration phase during ATP binding/ADP release (15°–60°), and a fast (F) acceleration phase (60°–90°) containing an interim deceleration (ID) phase (75°–82°). High ADP concentrations decreased the velocity of the S phase proportional to 'ADP-release' dwells, and the F phase proportional to the free energy derived from the [ADP][Pi]/[ATP] chemical equilibrium. The decreased affinity for ITP increased ITP-binding dwells by 10%, but decreased velocity by 40% during the S phase. This is the first direct evidence that nucleotide binding contributes to F1–ATPase torque. Mutations that affect specific phases of rotation were identified, some in regions of F1 previously considered not to contribute to rotation. Mutations βD372V and γK9I increased the F phase velocity, and γK9I increased the depth of the ID phase. The conversion between S and F phases was specifically affected by γQ269L. While βT273D, βD305E, and αR283Q decreased the velocity of all phases, decreases in velocity due to βD302T, γR268L and γT82A were confined to the I and S phases. The correlations between the structural locations of these mutations and the phases of rotation they affect provide new insight into the molecular basis for F1–ATPase γ-subunit rotation.
ContributorsMartin, James (Author) / Frasch, Wayne D (Thesis advisor) / Chandler, Douglas (Committee member) / Gaxiola, Roberto (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2012
Description
Contention based IEEE 802.11MAC uses the binary exponential backoff algorithm (BEB) for the contention resolution. The protocol suffers poor performance in the heavily loaded networks and MANETs, high collision rate and packet drops, probabilistic delay guarantees, and unfairness. Many backoff strategies were proposed to improve the performance of IEEE 802.11 but all ignore the network topology and demand. Persistence is defined as the fraction of time a node is allowed to transmit, when this allowance should take into account topology and load, it is topology and load aware persistence (TLA). We develop a relation between contention window size and the TLA-persistence. We implement a new backoff strategy where the TLA-persistence is defined as the lexicographic max-min channel allocation. We use a centralized algorithm to calculate each node's TLApersistence and then convert it into a contention window size. The new backoff strategy is evaluated in simulation, comparing with that of the IEEE 802.11 using BEB. In most of the static scenarios like exposed terminal, flow in the middle, star topology, and heavy loaded multi-hop networks and in MANETs, through the simulation study, we show that the new backoff strategy achieves higher overall average throughput as compared to that of the IEEE 802.11 using BEB.
ContributorsBhyravajosyula, Sai Vishnu Kiran (Author) / Syrotiuk, Violet R. (Thesis advisor) / Sen, Arunabha (Committee member) / Richa, Andrea (Committee member) / Arizona State University (Publisher)
Created2013
Description
As networks are playing an increasingly prominent role in different aspects of our lives, there is a growing awareness that improving their performance is of significant importance. In order to enhance performance of networks, it is essential that scarce networking resources be allocated smartly to match the continuously changing network environment. This dissertation focuses on two different kinds of networks - communication and social, and studies resource allocation problems in these networks. The study on communication networks is further divided into different networking technologies - wired and wireless, optical and mobile, airborne and terrestrial. Since nodes in an airborne network (AN) are heterogeneous and mobile, the design of a reliable and robust AN is highly complex. The dissertation studies connectivity and fault-tolerance issues in ANs and proposes algorithms to compute the critical transmission range in fault free, faulty and delay tolerant scenarios. Just as in the case of ANs, power optimization and fault tolerance are important issues in wireless sensor networks (WSN). In a WSN, a tree structure is often used to deliver sensor data to a sink node. In a tree, failure of a node may disconnect the tree. The dissertation investigates the problem of enhancing the fault tolerance capability of data gathering trees in WSN. The advent of OFDM technology provides an opportunity for efficient resource utilization in optical networks and also introduces a set of novel problems, such as routing and spectrum allocation (RSA) problem. This dissertation proves that RSA problem is NP-complete even when the network topology is a chain, and proposes approximation algorithms. In the domain of social networks, the focus of this dissertation is study of influence propagation in presence of active adversaries. In a social network multiple vendors may attempt to influence the nodes in a competitive fashion. This dissertation investigates the scenario where the first vendor has already chosen a set of nodes and the second vendor, with the knowledge of the choice of the first, attempts to identify a smallest set of nodes so that after the influence propagation, the second vendor's market share is larger than the first.
ContributorsShirazipourazad, Shahrzad (Author) / Sen, Arunabha (Committee member) / Xue, Guoliang (Committee member) / Richa, Andrea (Committee member) / Saripalli, Srikanth (Committee member) / Arizona State University (Publisher)
Created2014