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 110
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
ABSTRACT Developing new non-traditional device models is gaining popularity as the silicon-based electrical device approaches its limitation when it scales down. Membrane systems, also called P systems, are a new class of biological computation model inspired by the way cells process chemical signals. Spiking Neural P systems (SNP systems), a certain kind of membrane systems, is inspired by the way the neurons in brain interact using electrical spikes. Compared to the traditional Boolean logic, SNP systems not only perform similar functions but also provide a more promising solution for reliable computation. Two basic neuron types, Low Pass (LP) neurons and High Pass (HP) neurons, are introduced. These two basic types of neurons are capable to build an arbitrary SNP neuron. This leads to the conclusion that these two basic neuron types are Turing complete since SNP systems has been proved Turing complete. These two basic types of neurons are further used as the elements to construct general-purpose arithmetic circuits, such as adder, subtractor and comparator. In this thesis, erroneous behaviors of neurons are discussed. Transmission error (spike loss) is proved to be equivalent to threshold error, which makes threshold error discussion more universal. To improve the reliability, a new structure called motif is proposed. Compared to Triple Modular Redundancy improvement, motif design presents its efficiency and effectiveness in both single neuron and arithmetic circuit analysis. DRAM-based CMOS circuits are used to implement the two basic types of neurons. Functionality of basic type neurons is proved using the SPICE simulations. The motif improved adder and the comparator, as compared to conventional Boolean logic design, are much more reliable with lower leakage, and smaller silicon area. This leads to the conclusion that SNP system could provide a more promising solution for reliable computation than the conventional Boolean logic.
ContributorsAn, Pei (Author) / Cao, Yu (Thesis advisor) / Barnaby, Hugh (Committee member) / Chakrabarti, Chaitali (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 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
With increasing transistor volume and reducing feature size, it has become a major design constraint to reduce power consumption also. This has given rise to aggressive architectural changes for on-chip power management and rapid development to energy efficient hardware accelerators. Accordingly, the objective of this research work is to facilitate software developers to leverage these hardware techniques and improve energy efficiency of the system. To achieve this, I propose two solutions for Linux kernel: Optimal use of these architectural enhancements to achieve greater energy efficiency requires accurate modeling of processor power consumption. Though there are many models available in literature to model processor power consumption, there is a lack of such models to capture power consumption at the task-level. Task-level energy models are a requirement for an operating system (OS) to perform real-time power management as OS time multiplexes tasks to enable sharing of hardware resources. I propose a detailed design methodology for constructing an architecture agnostic task-level power model and incorporating it into a modern operating system to build an online task-level power profiler. The profiler is implemented inside the latest Linux kernel and validated for Intel Sandy Bridge processor. It has a negligible overhead of less than 1\% hardware resource consumption. The profiler power prediction was demonstrated for various application benchmarks from SPEC to PARSEC with less than 4\% error. I also demonstrate the importance of the proposed profiler for emerging architectural techniques through use case scenarios, which include heterogeneous computing and fine grained per-core DVFS. Along with architectural enhancement in general purpose processors to improve energy efficiency, hardware accelerators like Coarse Grain reconfigurable architecture (CGRA) are gaining popularity. Unlike vector processors, which rely on data parallelism, CGRA can provide greater flexibility and compiler level control making it more suitable for present SoC environment. To provide streamline development environment for CGRA, I propose a flexible framework in Linux to do design space exploration for CGRA. With accurate and flexible hardware models, fine grained integration with accurate architectural simulator, and Linux memory management and DMA support, a user can carry out limitless experiments on CGRA in full system environment.
ContributorsDesai, Digant Pareshkumar (Author) / Vrudhula, Sarma (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Wu, Carole-Jean (Committee member) / Arizona State University (Publisher)
Created2013
Description
Multicore processors have proliferated in nearly all forms of computing, from servers, desktop, to smartphones. The primary reason for this large adoption of multicore processors is due to its ability to overcome the power-wall by providing higher performance at a lower power consumption rate. With multi-cores, there is increased need for dynamic energy management (DEM), much more than for single-core processors, as DEM for multi-cores is no more a mechanism just to ensure that a processor is kept under specified temperature limits, but also a set of techniques that manage various processor controls like dynamic voltage and frequency scaling (DVFS), task migration, fan speed, etc. to achieve a stated objective. The objectives span a wide range from maximizing throughput, minimizing power consumption, reducing peak temperature, maximizing energy efficiency, maximizing processor reliability, and so on, along with much more wider constraints of temperature, power, timing, and reliability constraints. Thus DEM can be very complex and challenging to achieve. Since often times many DEMs operate together on a single processor, there is a need to unify various DEM techniques. This dissertation address such a need. In this work, a framework for DEM is proposed that provides a unifying processor model that includes processor power, thermal, timing, and reliability models, supports various DEM control mechanisms, many different objective functions along with equally diverse constraint specifications. Using the framework, a range of novel solutions is derived for instances of DEM problems, that include maximizing processor performance, energy efficiency, or minimizing power consumption, peak temperature under constraints of maximum temperature, memory reliability and task deadlines. Finally, a robust closed-loop controller to implement the above solutions on a real processor platform with a very low operational overhead is proposed. Along with the controller design, a model identification methodology for obtaining the required power and thermal models for the controller is also discussed. The controller is architecture independent and hence easily portable across many platforms. The controller has been successfully deployed on Intel Sandy Bridge processor and the use of the controller has increased the energy efficiency of the processor by over 30%
ContributorsHanumaiah, Vinay (Author) / Vrudhula, Sarma (Thesis advisor) / Chatha, Karamvir (Committee member) / Chakrabarti, Chaitali (Committee member) / Rodriguez, Armando (Committee member) / Askin, Ronald (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
Adaptive processing and classification of electrocardiogram (ECG) signals are important in eliminating the strenuous process of manually annotating ECG recordings for clinical use. Such algorithms require robust models whose parameters can adequately describe the ECG signals. Although different dynamic statistical models describing ECG signals currently exist, they depend considerably on a priori information and user-specified model parameters. Also, ECG beat morphologies, which vary greatly across patients and disease states, cannot be uniquely characterized by a single model. In this work, sequential Bayesian based methods are used to appropriately model and adaptively select the corresponding model parameters of ECG signals. An adaptive framework based on a sequential Bayesian tracking method is proposed to adaptively select the cardiac parameters that minimize the estimation error, thus precluding the need for pre-processing. Simulations using real ECG data from the online Physionet database demonstrate the improvement in performance of the proposed algorithm in accurately estimating critical heart disease parameters. In addition, two new approaches to ECG modeling are presented using the interacting multiple model and the sequential Markov chain Monte Carlo technique with adaptive model selection. Both these methods can adaptively choose between different models for various ECG beat morphologies without requiring prior ECG information, as demonstrated by using real ECG signals. A supervised Bayesian maximum-likelihood (ML) based classifier uses the estimated model parameters to classify different types of cardiac arrhythmias. However, the non-availability of sufficient amounts of representative training data and the large inter-patient variability pose a challenge to the existing supervised learning algorithms, resulting in a poor classification performance. In addition, recently developed unsupervised learning methods require a priori knowledge on the number of diseases to cluster the ECG data, which often evolves over time. In order to address these issues, an adaptive learning ECG classification method that uses Dirichlet process Gaussian mixture models is proposed. This approach does not place any restriction on the number of disease classes, nor does it require any training data. This algorithm is adapted to be patient-specific by labeling or identifying the generated mixtures using the Bayesian ML method, assuming the availability of labeled training data.
ContributorsEdla, Shwetha Reddy (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Chakrabarti, Chaitali (Committee member) / Kovvali, Narayan (Committee member) / Tepedelenlioğlu, Cihan (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