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: Davulcu, Hasan
- Creators: Yan, Hao
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 increasing popularity of Twitter renders improved trustworthiness and relevance assessment of tweets much more important for search. However, given the limitations on the size of tweets, it is hard to extract measures for ranking from the tweet's content alone. I propose a method of ranking tweets by generating a reputation score for each tweet that is based not just on content, but also additional information from the Twitter ecosystem that consists of users, tweets, and the web pages that tweets link to. This information is obtained by modeling the Twitter ecosystem as a three-layer graph. The reputation score is used to power two novel methods of ranking tweets by propagating the reputation over an agreement graph based on tweets' content similarity. Additionally, I show how the agreement graph helps counter tweet spam. An evaluation of my method on 16~million tweets from the TREC 2011 Microblog Dataset shows that it doubles the precision over baseline Twitter Search and achieves higher precision than current state of the art method. I present a detailed internal empirical evaluation of RAProp in comparison to several alternative approaches proposed by me, as well as external evaluation in comparison to the current state of the art method.
ContributorsRavikumar, Srijith (Author) / Kambhampati, Subbarao (Thesis advisor) / Davulcu, Hasan (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2013
Description
Continuous Delivery, as one of the youngest and most popular member of agile model family, has become a popular concept and method in software development industry recently. Instead of the traditional software development method, which requirements and solutions must be fixed before starting software developing, it promotes adaptive planning, evolutionary development and delivery, and encourages rapid and flexible response to change. However, several problems prevent Continuous Delivery to be introduced into education world. Taking into the consideration of the barriers, we propose a new Cloud based Continuous Delivery Software Developing System. This system is designed to fully utilize the whole life circle of software developing according to Continuous Delivery concepts in a virtualized environment in Vlab platform.
ContributorsDeng, Yuli (Author) / Huang, Dijiang (Thesis advisor) / Davulcu, Hasan (Committee member) / Chen, Yinong (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
Our research focuses on finding answers through decentralized search, for complex, imprecise queries (such as "Which is the best hair salon nearby?") in situations where there is a spatiotemporal constraint (say answer needs to be found within 15 minutes) associated with the query. In general, human networks are good in answering imprecise queries. We try to use the social network of a person to answer his query. Our research aims at designing a framework that exploits the user's social network in order to maximize the answers for a given query. Exploiting an user's social network has several challenges. The major challenge is that the user's immediate social circle may not possess the answer for the given query, and hence the framework designed needs to carry out the query diffusion process across the network. The next challenge involves in finding the right set of seeds to pass the query to in the user's social circle. One other challenge is to incentivize people in the social network to respond to the query and thereby maximize the quality and quantity of replies. Our proposed framework is a mobile application where an individual can either respond to the query or forward it to his friends. We simulated the query diffusion process in three types of graphs: Small World, Random and Preferential Attachment. Given a type of network and a particular query, we carried out the query diffusion by selecting seeds based on attributes of the seed. The main attributes are Topic relevance, Replying or Forwarding probability and Time to Respond. We found that there is a considerable increase in the number of replies attained, even without saturating the user's network, if we adopt an optimal seed selection process. We found the output of the optimal algorithm to be satisfactory as the number of replies received at the interrogator's end was close to three times the number of neighbors an interrogator has. We addressed the challenge of incentivizing people to respond by associating a particular amount of points for each query asked, and awarding the same to people involved in answering the query. Thus, we aim to design a mobile application based on our proposed framework so that it helps in maximizing the replies for the interrogator's query by diffusing the query across his/her social network.
ContributorsSwaminathan, Neelakantan (Author) / Sundaram, Hari (Thesis advisor) / Davulcu, Hasan (Thesis advisor) / Turaga, Pavan (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
This dissertation presents the Temporal Event Query Language (TEQL), a new language for querying event streams. Event Stream Processing enables online querying of streams of events to extract relevant data in a timely manner. TEQL enables querying of interval-based event streams using temporal database operators. Temporal databases and temporal query languages have been a subject of research for more than 30 years and are a natural fit for expressing queries that involve a temporal dimension. However, operators developed in this context cannot be directly applied to event streams. The research extends a preexisting relational framework for event stream processing to support temporal queries. The language features and formal semantic extensions to extend the relational framework are identified. The extended framework supports continuous, step-wise evaluation of temporal queries. The incremental evaluation of TEQL operators is formalized to avoid re-computation of previous results. The research includes the development of a prototype that supports the integrated event and temporal query processing framework, with support for incremental evaluation and materialization of intermediate results. TEQL enables reporting temporal data in the output, direct specification of conditions over timestamps, and specification of temporal relational operators. Through the integration of temporal database operators with event languages, a new class of temporal queries is made possible for querying event streams. New features include semantic aggregation, extraction of temporal patterns using set operators, and a more accurate specification of event co-occurrence.
ContributorsShiva, Foruhar Ali (Author) / Urban, Susan D (Thesis advisor) / Chen, Yi (Thesis advisor) / Davulcu, Hasan (Committee member) / Sarjoughian, Hessam S. (Committee member) / Arizona State University (Publisher)
Created2012