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 89
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
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
Today, the electric power system faces new challenges from rapid developing technology and the growing concern about environmental problems. The future of the power system under these new challenges needs to be planned and studied. However, due to the high degree of computational complexity of the optimization problem, conducting a system planning study which takes into account the market structure and environmental constraints on a large-scale power system is computationally taxing. To improve the execution time of large system simulations, such as the system planning study, two possible strategies are proposed in this thesis. The first one is to implement a relative new factorization method, known as the multifrontal method, to speed up the solution of the sparse linear matrix equations within the large system simulations. The performance of the multifrontal method implemented by UMFAPACK is compared with traditional LU factorization on a wide range of power-system matrices. The results show that the multifrontal method is superior to traditional LU factorization on relatively denser matrices found in other specialty areas, but has poor performance on the more sparse matrices that occur in power-system applications. This result suggests that multifrontal methods may not be an effective way to improve execution time for large system simulation and power system engineers should evaluate the performance of the multifrontal method before applying it to their applications. The second strategy is to develop a small dc equivalent of the large-scale network with satisfactory accuracy for the large-scale system simulations. In this thesis, a modified Ward equivalent is generated for a large-scale power system, such as the full Electric Reliability Council of Texas (ERCOT) system. In this equivalent, all the generators in the full model are retained integrally. The accuracy of the modified Ward equivalent is validated and the equivalent is used to conduct the optimal generation investment planning study. By using the dc equivalent, the execution time for optimal generation investment planning is greatly reduced. Different scenarios are modeled to study the impact of fuel prices, environmental constraints and incentives for renewable energy on future investment and retirement in generation.
ContributorsLi, Nan (Author) / Tylavsky, Daniel J (Thesis advisor) / Vittal, Vijay (Committee member) / Hedman, Kory W (Committee member) / Arizona State University (Publisher)
Created2012
Description
A distributed-parameter model is developed for a pressurized water reactor (PWR) in order to analyze the frequency behavior of the nuclear reactor. The model is built based upon the partial differential equations describing heat transfer and fluid flow in the reactor core. As a comparison, a multi-lump reactor core model with five fuel lumps and ten coolant lumps using Mann's model is employed. The derivations of the different transfer functions in both models are also presented with emphasis on the distributed parameter. In order to contrast the two models, Bode plots of the transfer functions are generated using data from the Palo Verde Nuclear Generating Station. Further, a detailed contradistinction between these two models is presented. From the comparison, the features of both models are presented. The distributed parameter model has the ability to offer an accurate transfer function at any location throughout the reactor core. In contrast, the multi-lump parameter model can only provide the average value in a given region (lump). Also, in the distributed parameter model only the feedback according to the specific location under study is incorporated into the transfer function; whereas the transfer functions derived from the multi-lump model contain the average feedback effects happening all over the reactor core.
ContributorsZhang, Taipeng (Author) / Holbert, Keith E. (Thesis advisor) / Vittal, Vijay (Committee member) / Tylavsky, Daniel (Committee member) / Arizona State University (Publisher)
Created2012
Description
The F1Fo ATP synthase is required for energy conversion in almost all living organisms. The F1 complex is a molecular motor that uses ATP hydrolysis to drive rotation of the γ–subunit. It has not been previously possible to resolve the speed and position of the γ–subunit of the F1–ATPase as it rotates during a power stroke. The single molecule experiments presented here measured light scattered from 45X91 nm gold nanorods attached to the γ–subunit that provide an unprecedented 5 μs resolution of rotational position as a function of time. The product of velocity and drag, which were both measured directly, resulted in an average torque of 63±8 pN nm for the Escherichia coli F1-ATPase that was determined to be independent of the load. The rotational velocity had an initial (I) acceleration phase 15° from the end of the catalytic dwell, a slow (S) acceleration phase during ATP binding/ADP release (15°–60°), and a fast (F) acceleration phase (60°–90°) containing an interim deceleration (ID) phase (75°–82°). High ADP concentrations decreased the velocity of the S phase proportional to 'ADP-release' dwells, and the F phase proportional to the free energy derived from the [ADP][Pi]/[ATP] chemical equilibrium. The decreased affinity for ITP increased ITP-binding dwells by 10%, but decreased velocity by 40% during the S phase. This is the first direct evidence that nucleotide binding contributes to F1–ATPase torque. Mutations that affect specific phases of rotation were identified, some in regions of F1 previously considered not to contribute to rotation. Mutations βD372V and γK9I increased the F phase velocity, and γK9I increased the depth of the ID phase. The conversion between S and F phases was specifically affected by γQ269L. While βT273D, βD305E, and αR283Q decreased the velocity of all phases, decreases in velocity due to βD302T, γR268L and γT82A were confined to the I and S phases. The correlations between the structural locations of these mutations and the phases of rotation they affect provide new insight into the molecular basis for F1–ATPase γ-subunit rotation.
ContributorsMartin, James (Author) / Frasch, Wayne D (Thesis advisor) / Chandler, Douglas (Committee member) / Gaxiola, Roberto (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2012
Description
Insulation aging monitoring is widely used to evaluate the operating condition of power equipment. One important monitoring method is detecting partial discharges (PD). PD is a localized breakdown of dielectric and its characteristics can give information about the insulation aging. Most existing test methods cannot identify different kinds of defects. Also, the practical application of PD detection in most existing test methods is restricted by weak PD signals and strong electric field disturbance from surroundings. In order to monitor aging situation in detail, types of PDs are important features to take into account. To classify different types of PDs, pulse sequence analysis (PSA) method is advocated to analyze PDs in the rod-plane model. This method can reflect cumulative effects of PDs, which are always ignored when only measuring PD value. It also shows uniform characteristics when different kinds of detecting system are utilized. Moreover, it does not need calibration. Analysis results from PSA show highly consistent distribution patterns for the same type of PDs and significant differences in the distribution patterns among types of PDs. Furthermore, a new method to detect PD signals using fiber bragg grating (FBG) based PD sensor is studied in this research. By using a piezoelectric ceramic transducer (PZT), small PD signals can be converted to pressure signal and then converted to an optical wavelength signal with FBG. The optical signal is isolated from the electric field; therefore its attenuation and anti-jamming performance will be better than traditional methods. Two sensors, one with resonant frequency of 42.7 kHz and the other 300 kHz, were used to explore the performance of this testing system. However, there were issues with the sensitivity of the sensors of these devices and the results have been communicated with the company. These devices could not give the results at the same level of accuracy as the conventional methods.
ContributorsCui, Longfei (Author) / Gorur, Ravi (Thesis advisor) / Vittal, Vijay (Committee member) / Ayyanar, Raja (Committee member) / Arizona State University (Publisher)
Created2013
Description
In modern electric power systems, energy management systems (EMSs) are responsi-ble for monitoring and controlling the generation system and transmission networks. State estimation (SE) is a critical `must run successful' component within the EMS software. This is dictated by the high reliability requirements and need to represent the closest real time model for market operations and other critical analysis functions in the EMS. Tradi-tionally, SE is run with data obtained only from supervisory control and data acquisition (SCADA) devices and systems. However, more emphasis on improving the performance of SE drives the inclusion of phasor measurement units (PMUs) into SE input data. PMU measurements are claimed to be more accurate than conventional measurements and PMUs `time stamp' measurements accurately. These widely distributed devices meas-ure the voltage phasors directly. That is, phase information for measured voltages and currents are available. PMUs provide data time stamps to synchronize measurements. Con-sidering the relatively small number of PMUs installed in contemporary power systems in North America, performing SE with only phasor measurements is not feasible. Thus a hy-brid SE, including both SCADA and PMU measurements, is the reality for contemporary power system SE. The hybrid approach is the focus of a number of research papers. There are many practical challenges in incorporating PMUs into SE input data. The higher reporting rates of PMUs as compared with SCADA measurements is one of the salient problems. The disparity of reporting rates raises a question whether buffering the phasor measurements helps to give better estimates of the states. The research presented in this thesis addresses the design of data buffers for PMU data as used in SE applications in electric power systems. The system theoretic analysis is illustrated using an operating electric power system in the southwest part of the USA. Var-ious instances of state estimation data have been used for analysis purposes. The details of the research, results obtained and conclusions drawn are presented in this document.
ContributorsMurugesan, Veerakumar (Author) / Vittal, Vijay (Committee member) / Heydt, Gerald (Committee member) / Ayyanar, Raja (Committee member) / Arizona State University (Publisher)
Created2013