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 85
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
The rapid advancement of wireless technology has instigated the broad deployment of wireless networks. Different types of networks have been developed, including wireless sensor networks, mobile ad hoc networks, wireless local area networks, and cellular networks. These networks have different structures and applications, and require different control algorithms. The focus of this thesis is to design scheduling and power control algorithms in wireless networks, and analyze their performances. In this thesis, we first study the multicast capacity of wireless ad hoc networks. Gupta and Kumar studied the scaling law of the unicast capacity of wireless ad hoc networks. They derived the order of the unicast throughput, as the number of nodes in the network goes to infinity. In our work, we characterize the scaling of the multicast capacity of large-scale MANETs under a delay constraint D. We first derive an upper bound on the multicast throughput, and then propose a lower bound on the multicast capacity by proposing a joint coding-scheduling algorithm that achieves a throughput within logarithmic factor of the upper bound. We then study the power control problem in ad-hoc wireless networks. We propose a distributed power control algorithm based on the Gibbs sampler, and prove that the algorithm is throughput optimal. Finally, we consider the scheduling algorithm in collocated wireless networks with flow-level dynamics. Specifically, we study the delay performance of workload-based scheduling algorithm with SRPT as a tie-breaking rule. We demonstrate the superior flow-level delay performance of the proposed algorithm using simulations.
ContributorsZhou, Shan (Author) / Ying, Lei (Thesis advisor) / Zhang, Yanchao (Committee member) / Zhang, Junshan (Committee member) / Xue, Guoliang (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 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
The cyber-physical systems (CPS) are emerging as the underpinning technology for major industries in the 21-th century. This dissertation is focused on two fundamental issues in cyber-physical systems: network interdependence and information dynamics. It consists of the following two main thrusts. The first thrust is targeted at understanding the impact of network interdependence. It is shown that a cyber-physical system built upon multiple interdependent networks are more vulnerable to attacks since node failures in one network may result in failures in the other network, causing a cascade of failures that would potentially lead to the collapse of the entire infrastructure. There is thus a need to develop a new network science for modeling and quantifying cascading failures in multiple interdependent networks, and to develop network management algorithms that improve network robustness and ensure overall network reliability against cascading failures. To enhance the system robustness, a "regular" allocation strategy is proposed that yields better resistance against cascading failures compared to all possible existing strategies. Furthermore, in view of the load redistribution feature in many physical infrastructure networks, e.g., power grids, a CPS model is developed where the threshold model and the giant connected component model are used to capture the node failures in the physical infrastructure network and the cyber network, respectively. The second thrust is centered around the information dynamics in the CPS. One speculation is that the interconnections over multiple networks can facilitate information diffusion since information propagation in one network can trigger further spread in the other network. With this insight, a theoretical framework is developed to analyze information epidemic across multiple interconnecting networks. It is shown that the conjoining among networks can dramatically speed up message diffusion. Along a different avenue, many cyber-physical systems rely on wireless networks which offer platforms for information exchanges. To optimize the QoS of wireless networks, there is a need to develop a high-throughput and low-complexity scheduling algorithm to control link dynamics. To that end, distributed link scheduling algorithms are explored for multi-hop MIMO networks and two CSMA algorithms under the continuous-time model and the discrete-time model are devised, respectively.
ContributorsQian, Dajun (Author) / Zhang, Junshan (Thesis advisor) / Ying, Lei (Committee member) / Zhang, Yanchao (Committee member) / Cochran, Douglas (Committee member) / Arizona State University (Publisher)
Created2012
Description
The purpose of this paper is to introduce a new method of dividing wireless communication (such as the 802.11a/b/g
and cellular UMTS MAC protocols) across multiple unreliable communication links (such as Ethernet). The purpose is to introduce the appropriate hardware, software, and system architecture required to provide the basis for a wireless system (using a 802.11a/b/g
and cellular protocols as a model) that can scale to support thousands of users simultaneously (say in a large office building, super chain store, etc.) or in a small, but very dense communication RF region. Elements of communication between a base station and a Mobile Station will be analyzed statistically to demonstrate higher throughput, fewer collisions and lower bit error rates (BER) with the given bandwidth defined by the 802.11n wireless specification (use of MIMO channels will be evaluated). A new network nodal paradigm will be presented. Alternative link layer communication techniques will be recommended and analyzed for the affect on mobile devices. The analysis will describe how the algorithms used by state machines implemented on Mobile Stations and Wi-Fi client devices will be influenced by new base station transmission behavior. New hardware design techniques that can be used to optimize this architecture as well as hardware design principles in regard to the minimal hardware functional blocks required to support such a system design will be described. Hardware design and verification simulation techniques to prove the hardware design will accommodate an acceptable level of performance to meet the strict timing as it relates to this new system architecture.
and cellular UMTS MAC protocols) across multiple unreliable communication links (such as Ethernet). The purpose is to introduce the appropriate hardware, software, and system architecture required to provide the basis for a wireless system (using a 802.11a/b/g
and cellular protocols as a model) that can scale to support thousands of users simultaneously (say in a large office building, super chain store, etc.) or in a small, but very dense communication RF region. Elements of communication between a base station and a Mobile Station will be analyzed statistically to demonstrate higher throughput, fewer collisions and lower bit error rates (BER) with the given bandwidth defined by the 802.11n wireless specification (use of MIMO channels will be evaluated). A new network nodal paradigm will be presented. Alternative link layer communication techniques will be recommended and analyzed for the affect on mobile devices. The analysis will describe how the algorithms used by state machines implemented on Mobile Stations and Wi-Fi client devices will be influenced by new base station transmission behavior. New hardware design techniques that can be used to optimize this architecture as well as hardware design principles in regard to the minimal hardware functional blocks required to support such a system design will be described. Hardware design and verification simulation techniques to prove the hardware design will accommodate an acceptable level of performance to meet the strict timing as it relates to this new system architecture.
ContributorsJames, Frank (Author) / Reisslein, Martin (Thesis advisor) / Ying, Lei (Committee member) / Zhang, Yanchao (Committee member) / Arizona State University (Publisher)
Created2014
Description
Data centers connect a larger number of servers requiring IO and switches with low power and delay. Virtualization of IO and network is crucial for these servers, which run virtual processes for computing, storage, and apps. We propose using the PCI Express (PCIe) protocol and a new PCIe switch fabric for IO and switch virtualization. The switch fabric has little data buffering, allowing up to 512 physical 10 Gb/s PCIe2.0 lanes to be connected via a switch fabric. The switch is scalable with adapters running multiple adaptation protocols, such as Ethernet over PCIe, PCIe over Internet, or FibreChannel over Ethernet. Such adaptation protocols allow integration of IO often required for disjoint datacenter applications such as storage and networking. The novel switch fabric based on space-time carrier sensing facilitates high bandwidth, low power, and low delay multi-protocol switching. To achieve Terabit switching, both time (high transmission speed) and space (multi-stage interconnection network) technologies are required. In this paper, we present the design of an up to 256 lanes Clos-network of multistage crossbar switch fabric for PCIe system. The switch core consists of 48 16x16 crossbar sub-switches. We also propose a new output contention resolution algorithm utilizing an out-of-band protocol of Request-To-Send (RTS), Clear-To-Send (CTS) before sending PCIe packets through the switch fabric. Preliminary power and delay estimates are provided.
ContributorsLuo, Haojun (Author) / Hui, Joseph (Thesis advisor) / Song, Hongjiang (Committee member) / Reisslein, Martin (Committee member) / Zhang, Yanchao (Committee member) / Arizona State University (Publisher)
Created2013