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 69
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 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
Doppler radar can be used to measure respiration and heart rate without contact and through obstacles. In this work, a Doppler radar architecture at 2.4 GHz and a new signal processing algorithm to estimate the respiration and heart rate are presented. The received signal is dominated by the transceiver noise, LO phase noise and clutter which reduces the signal-to-noise ratio of the desired signal. The proposed architecture and algorithm are used to mitigate these issues and obtain an accurate estimate of the heart and respiration rate. Quadrature low-IF transceiver architecture is adopted to resolve null point problem as well as avoid 1/f noise and DC offset due to mixer-LO coupling. Adaptive clutter cancellation algorithm is used to enhance receiver sensitivity coupled with a novel Pattern Search in Noise Subspace (PSNS) algorithm is used to estimate respiration and heart rate. PSNS is a modified MUSIC algorithm which uses the phase noise to enhance Doppler shift detection. A prototype system was implemented using off-the-shelf TI and RFMD transceiver and tests were conduct with eight individuals. The measured results shows accurate estimate of the cardio pulmonary signals in low-SNR conditions and have been tested up to a distance of 6 meters.
ContributorsKhunti, Hitesh Devshi (Author) / Kiaei, Sayfe (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Bliss, Daniel (Committee member) / Kitchen, Jennifer (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
Electrical neural activity detection and tracking have many applications in medical research and brain computer interface technologies. In this thesis, we focus on the development of advanced signal processing algorithms to track neural activity and on the mapping of these algorithms onto hardware to enable real-time tracking. At the heart of these algorithms is particle filtering (PF), a sequential Monte Carlo technique used to estimate the unknown parameters of dynamic systems. First, we analyze the bottlenecks in existing PF algorithms, and we propose a new parallel PF (PPF) algorithm based on the independent Metropolis-Hastings (IMH) algorithm. We show that the proposed PPF-IMH algorithm improves the root mean-squared error (RMSE) estimation performance, and we demonstrate that a parallel implementation of the algorithm results in significant reduction in inter-processor communication. We apply our implementation on a Xilinx Virtex-5 field programmable gate array (FPGA) platform to demonstrate that, for a one-dimensional problem, the PPF-IMH architecture with four processing elements and 1,000 particles can process input samples at 170 kHz by using less than 5% FPGA resources. We also apply the proposed PPF-IMH to waveform-agile sensing to achieve real-time tracking of dynamic targets with high RMSE tracking performance. We next integrate the PPF-IMH algorithm to track the dynamic parameters in neural sensing when the number of neural dipole sources is known. We analyze the computational complexity of a PF based method and propose the use of multiple particle filtering (MPF) to reduce the complexity. We demonstrate the improved performance of MPF using numerical simulations with both synthetic and real data. We also propose an FPGA implementation of the MPF algorithm and show that the implementation supports real-time tracking. For the more realistic scenario of automatically estimating an unknown number of time-varying neural dipole sources, we propose a new approach based on the probability hypothesis density filtering (PHDF) algorithm. The PHDF is implemented using particle filtering (PF-PHDF), and it is applied in a closed-loop to first estimate the number of dipole sources and then their corresponding amplitude, location and orientation parameters. We demonstrate the improved tracking performance of the proposed PF-PHDF algorithm and map it onto a Xilinx Virtex-5 FPGA platform to show its real-time implementation potential. Finally, we propose the use of sensor scheduling and compressive sensing techniques to reduce the number of active sensors, and thus overall power consumption, of electroencephalography (EEG) systems. We propose an efficient sensor scheduling algorithm which adaptively configures EEG sensors at each measurement time interval to reduce the number of sensors needed for accurate tracking. We combine the sensor scheduling method with PF-PHDF and implement the system on an FPGA platform to achieve real-time tracking. We also investigate the sparsity of EEG signals and integrate compressive sensing with PF to estimate neural activity. Simulation results show that both sensor scheduling and compressive sensing based methods achieve comparable tracking performance with significantly reduced number of sensors.
ContributorsMiao, Lifeng (Author) / Chakrabarti, Chaitali (Thesis advisor) / Papandreou-Suppappola, Antonia (Thesis advisor) / Zhang, Junshan (Committee member) / Bliss, Daniel (Committee member) / Kovvali, Narayan (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
Immunosignaturing is a medical test for assessing the health status of a patient by applying microarrays of random sequence peptides to determine the patient's immune fingerprint by associating antibodies from a biological sample to immune responses. The immunosignature measurements can potentially provide pre-symptomatic diagnosis for infectious diseases or detection of biological threats. Currently, traditional bioinformatics tools, such as data mining classification algorithms, are used to process the large amount of peptide microarray data. However, these methods generally require training data and do not adapt to changing immune conditions or additional patient information. This work proposes advanced processing techniques to improve the classification and identification of single and multiple underlying immune response states embedded in immunosignatures, making it possible to detect both known and previously unknown diseases or biothreat agents. Novel adaptive learning methodologies for un- supervised and semi-supervised clustering integrated with immunosignature feature extraction approaches are proposed. The techniques are based on extracting novel stochastic features from microarray binding intensities and use Dirichlet process Gaussian mixture models to adaptively cluster the immunosignatures in the feature space. This learning-while-clustering approach allows continuous discovery of antibody activity by adaptively detecting new disease states, with limited a priori disease or patient information. A beta process factor analysis model to determine underlying patient immune responses is also proposed to further improve the adaptive clustering performance by formatting new relationships between patients and antibody activity. In order to extend the clustering methods for diagnosing multiple states in a patient, the adaptive hierarchical Dirichlet process is integrated with modified beta process factor analysis latent feature modeling to identify relationships between patients and infectious agents. The use of Bayesian nonparametric adaptive learning techniques allows for further clustering if additional patient data is received. Significant improvements in feature identification and immune response clustering are demonstrated using samples from patients with different diseases.
ContributorsMalin, Anna (Author) / Papandreou-Suppappola, Antonia (Thesis advisor) / Bliss, Daniel (Committee member) / Chakrabarti, Chaitali (Committee member) / Kovvali, Narayan (Committee member) / Lacroix, Zoé (Committee member) / Arizona State University (Publisher)
Created2013
Description
This dissertation introduces stochastic ordering of instantaneous channel powers of fading channels as a general method to compare the performance of a communication system over two different channels, even when a closed-form expression for the metric may not be available. Such a comparison is with respect to a variety of performance metrics such as error rates, outage probability and ergodic capacity, which share common mathematical properties such as monotonicity, convexity or complete monotonicity. Complete monotonicity of a metric, such as the symbol error rate, in conjunction with the stochastic Laplace transform order between two fading channels implies the ordering of the two channels with respect to the metric. While it has been established previously that certain modulation schemes have convex symbol error rates, there is no study of the complete monotonicity of the same, which helps in establishing stronger channel ordering results. Toward this goal, the current research proves for the first time, that all 1-dimensional and 2-dimensional modulations have completely monotone symbol error rates. Furthermore, it is shown that the frequently used parametric fading distributions for modeling line of sight exhibit a monotonicity in the line of sight parameter with respect to the Laplace transform order. While the Laplace transform order can also be used to order fading distributions based on the ergodic capacity, there exist several distributions which are not Laplace transform ordered, although they have ordered ergodic capacities. To address this gap, a new stochastic order called the ergodic capacity order has been proposed herein, which can be used to compare channels based on the ergodic capacity. Using stochastic orders, average performance of systems involving multiple random variables are compared over two different channels. These systems include diversity combining schemes, relay networks, and signal detection over fading channels with non-Gaussian additive noise. This research also addresses the problem of unifying fading distributions. This unification is based on infinite divisibility, which subsumes almost all known fading distributions, and provides simplified expressions for performance metrics, in addition to enabling stochastic ordering.
ContributorsRajan, Adithya (Author) / Tepedelenlioğlu, Cihan (Thesis advisor) / Papandreou-Suppappola, Antonia (Committee member) / Bliss, Daniel (Committee member) / Kosut, Oliver (Committee member) / Arizona State University (Publisher)
Created2014