Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
Displaying 1 - 10 of 140
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
Distributed estimation uses many inexpensive sensors to compose an accurate estimate of a given parameter. It is frequently implemented using wireless sensor networks. There have been several studies on optimizing power allocation in wireless sensor networks used for distributed estimation, the vast majority of which assume linear radio-frequency amplifiers. Linear amplifiers are inherently inefficient, so in this dissertation nonlinear amplifiers are examined to gain efficiency while operating distributed sensor networks. This research presents a method to boost efficiency by operating the amplifiers in the nonlinear region of operation. Operating amplifiers nonlinearly presents new challenges. First, nonlinear amplifier characteristics change across manufacturing process variation, temperature, operating voltage, and aging. Secondly, the equations conventionally used for estimators and performance expectations in linear amplify-and-forward systems fail. To compensate for the first challenge, predistortion is utilized not to linearize amplifiers but rather to force them to fit a common nonlinear limiting amplifier model close to the inherent amplifier performance. This minimizes the power impact and the training requirements for predistortion. Second, new estimators are required that account for transmitter nonlinearity. This research derives analytically and confirms via simulation new estimators and performance expectation equations for use in nonlinear distributed estimation. An additional complication when operating nonlinear amplifiers in a wireless environment is the influence of varied and potentially unknown channel gains. The impact of these varied gains and both measurement and channel noise sources on estimation performance are analyzed in this paper. Techniques for minimizing the estimate variance are developed. It is shown that optimizing transmitter power allocation to minimize estimate variance for the most-compressed parameter measurement is equivalent to the problem for linear sensors. Finally, a method for operating distributed estimation in a multipath environment is presented that is capable of developing robust estimates for a wide range of Rician K-factors. This dissertation demonstrates that implementing distributed estimation using nonlinear sensors can boost system efficiency and is compatible with existing techniques from the literature for boosting efficiency at the system level via sensor power allocation. Nonlinear transmitters work best when channel gains are known and channel noise and receiver noise levels are low.
ContributorsSantucci, Robert (Author) / Spanias, Andreas (Thesis advisor) / Tepedelenlioðlu, Cihan (Committee member) / Bakkaloglu, Bertan (Committee member) / Tsakalis, Kostas (Committee member) / Arizona State University (Publisher)
Created2013
Description
Radio frequency (RF) transceivers require a disproportionately high effort in terms of test development time, test equipment cost, and test time. The relatively high test cost stems from two contributing factors. First, RF transceivers require the measurement of a diverse set of specifications, requiring multiple test set-ups and long test times, which complicates load-board design, debug, and diagnosis. Second, high frequency operation necessitates the use of expensive equipment, resulting in higher per second test time cost compared with mixed-signal or digital circuits. Moreover, in terms of the non-recurring engineering cost, the need to measure complex specfications complicates the test development process and necessitates a long learning process for test engineers. Test time is dominated by changing and settling time for each test set-up. Thus, single set-up test solutions are desirable. Loop-back configuration where the transmitter output is connected to the receiver input are used as the desirable test set- up for RF transceivers, since it eliminates the reliance on expensive instrumentation for RF signal analysis and enables measuring multiple parameters at once. In-phase and Quadrature (IQ) imbalance, non-linearity, DC offset and IQ time skews are some of the most detrimental imperfections in transceiver performance. Measurement of these parameters in the loop-back mode is challenging due to the coupling between the receiver (RX) and transmitter (TX) parameters. Loop-back based solutions are proposed in this work to resolve this issue. A calibration algorithm for a subset of the above mentioned impairments is also presented. Error Vector Magnitude (EVM) is a system-level parameter that is specified for most advanced communication standards. EVM measurement often takes extensive test development efforts, tester resources, and long test times. EVM is analytically related to system impairments, which are typically measured in a production test i environment. Thus, EVM test can be eliminated from the test list if the relations between EVM and system impairments are derived independent of the circuit implementation and manufacturing process. In this work, the focus is on the WLAN standard, and deriving the relations between EVM and three of the most detrimental impairments for QAM/OFDM based systems (IQ imbalance, non-linearity, and noise). Having low cost test techniques for measuring the RF transceivers imperfections and being able to analytically compute EVM from the measured parameters is a complete test solution for RF transceivers. These techniques along with the proposed calibration method can be used in improving the yield by widening the pass/fail boundaries for transceivers imperfections. For all of the proposed methods, simulation and hardware measurements prove that the proposed techniques provide accurate characterization of RF transceivers.
ContributorsNassery, Afsaneh (Author) / Ozev, Sule (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Kiaei, Sayfe (Committee member) / Kitchen, Jennifer (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
Low Power, High Speed Analog to Digital Converters continues to remain one of the major building blocks for modern communication systems. Due to continuing trend of the aggressive scaling of the MOS devices, the susceptibility of most of the deep-sub micron CMOS technologies to the ionizing radiation has decreased over the period of time. When electronic circuits fabricated in these CMOS technologies are exposed to ionizing radiations, considerable change in the performance of circuits can be seen over a period of time. The change in the performance can be quantified in terms of decreasing linearity of the circuit which directly relates to the resolution of the circuit. Analog to Digital Converter is one of the most critical blocks of any electronic circuitry sent to space. The degradation in the performance of an Analog to Digital Converter due to radiation effects can jeopardize many research programs related to space. These radiation effects can completely hamper the working of a circuit. This thesis discusses the effects of Ionizing radiation on an 11 bit 325 MSPS pipeline ADC. The ADC is exposed to different doses of radiation and performance is compared.
ContributorsVashisth, Siddharth (Author) / Barnaby, Hugh J (Thesis advisor) / Bakkaloglu, Bertan (Committee member) / Mikkola, Esko (Committee member) / Arizona State University (Publisher)
Created2013
Description
Micro Electro Mechanical Systems (MEMS) is one of the fastest growing field in silicon industry. Low cost production is key for any company to improve their market share. MEMS testing is challenging since input to test a MEMS device require physical stimulus like acceleration, pressure etc. Also, MEMS device vary with process and requires calibration to make them reliable. This increases test cost and testing time. This challenge can be overcome by combining electrical stimulus based testing along with statistical analysis on MEMS response for electrical stimulus and also limited physical stimulus response data. This thesis proposes electrical stimulus based built in self test(BIST) which can be used to get MEMS data and later this data can be used for statistical analysis. A capacitive MEMS accelerometer is considered to test this BIST approach. This BIST circuit overhead is less and utilizes most of the standard readout circuit. This thesis discusses accelerometer response for electrical stimulus and BIST architecture. As a part of this BIST circuit, a second order sigma delta modulator has been designed. This modulator has a sampling frequency of 1MHz and bandwidth of 6KHz. SNDR of 60dB is achieved with 1Vpp differential input signal and 3.3V supply
ContributorsKundur, Vinay (Author) / Bakkaloglu, Bertan (Committee member) / Ozev, Sule (Committee member) / Kiaei, Sayfe (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