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 130
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
Photosynthesis, one of the most important processes in nature, has provided an energy basis for nearly all life on Earth, as well as the fossil fuels we use today to power modern society. This research aims to mimic the photosynthetic process of converting incident solar energy into chemical potential energy in the form of a fuel via systems capable of carrying out photo-induced electron transfer to drive the production of hydrogen from water. Herein is detailed progress in using photo-induced stepwise electron transfer to drive the oxidation of water and reduction of protons to hydrogen. In the design, use of more blue absorbing porphyrin dyes to generate high-potential intermediates for oxidizing water and more red absorbing phthalocyanine dyes for forming the low potential charge needed for the production of hydrogen have been utilized. For investigating water oxidation at the photoanode, high potential porphyrins such as, bis-pyridyl porphyrins and pentafluorophenyl porphyrins have been synthesized and experiments have aimed at the co-immobilization of this dye with an IrO2-nH2O catalyst on TiO2. To drive the cathodic reaction of the water splitting photoelectrochemical cell, utilization of silicon octabutoxy-phthalocyanines have been explored, as they offer good absorption in the red to near infrared, coupled with low potential photo-excited states. Axially and peripherally substituted phthalocyanines bearing carboxylic anchoring groups for the immobilization on semiconductors such as TiO2 has been investigated. Ultimately, this work should culminate in a photoelectrochemical cell capable of splitting water to oxygen and hydrogen with the only energy input from light. A series of perylene dyes bearing multiple semi-conducting metal oxide anchoring groups have been synthesized and studied. Results have shown interfacial electron transfer between these perylenes and TiO2 nanoparticles encapsulated within reverse micelles and naked nanoparticles. The binding process was followed by monitoring the hypsochromic shift of the dye absorption spectra over time. Photoinduced electron transfer from the singlet excited state of the perylenes to the TiO2 conduction band is indicated by emission quenching of the TiO2-bound form of the dyes and confirmed by transient absorption measurements of the radical cation of the dyes and free carriers (injected electrons) in the TiO2.
ContributorsBergkamp, Jesse J (Author) / Moore, Ana L (Thesis advisor) / Mariño-Ochoa, Ernesto (Thesis advisor) / Gust, Devens J (Committee member) / Gould, Ian (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
There is a lack of music therapy services for college students who have problems with depression and/or anxiety. Even among universities and colleges that offer music therapy degrees, there are no known programs offering music therapy to the institution's students. Female college students are particularly vulnerable to depression and anxiety symptoms compared to their male counterparts. Many students who experience mental health problems do not receive treatment, because of lack of knowledge, lack of services, or refusal of treatment. Music therapy is proposed as a reliable and valid complement or even an alternative to traditional counseling and pharmacotherapy because of the appeal of music to young women and the potential for a music therapy group to help isolated students form supportive networks. The present study recruited 14 female university students to participate in a randomized controlled trial of short-term group music therapy to address symptoms of depression and anxiety. The students were randomly divided into either the treatment group or the control group. Over 4 weeks, each group completed surveys related to depression and anxiety. Results indicate that the treatment group's depression and anxiety scores gradually decreased over the span of the treatment protocol. The control group showed either maintenance or slight worsening of depression and anxiety scores. Although none of the results were statistically significant, the general trend indicates that group music therapy was beneficial for the students. A qualitative analysis was also conducted for the treatment group. Common themes were financial concerns, relationship problems, loneliness, and time management/academic stress. All participants indicated that they benefited from the sessions. The group progressed in its cohesion and the participants bonded to the extent that they formed a supportive network which lasted beyond the end of the protocol. The results of this study are by no means conclusive, but do indicate that colleges with music therapy degree programs should consider adding music therapy services for their general student bodies.
ContributorsAshton, Barbara (Author) / Crowe, Barbara J. (Thesis advisor) / Rio, Robin (Committee member) / Davis, Mary (Committee member) / Arizona State University (Publisher)
Created2013
Description
When people look for things in their environment they use a target template - a mental representation of the object they are attempting to locate - to guide their attention around a scene and to assess incoming visual input to determine if they have found that for which they are searching. However, unlike laboratory experiments, searchers in the real-world rarely have perfect knowledge regarding the appearance of their target. In five experiments (with nearly 1,000 participants), we examined how the precision of the observer's template affects their ability to conduct visual search. Specifically, we simulated template imprecision in two ways: First, by contaminating our searchers' templates with inaccurate features, and second, by introducing extraneous features to the template that were unhelpful. In those experiments we recorded the eye movements of our searchers in order to make inferences regarding the extent to which attentional guidance and decision-making are hindered by template imprecision. We also examined a third way in which templates may become imprecise; namely, that they may deteriorate over time. Overall, our findings support a dual-function theory of the target template, and highlight the importance of examining template precision in future research.
ContributorsHout, Michael C (Author) / Goldinger, Stephen D (Thesis advisor) / Azuma, Tamiko (Committee member) / Homa, Donald (Committee member) / Reichle, Erik (Committee member) / Arizona State University (Publisher)
Created2013
Description
Two groups of cochlear implant (CI) listeners were tested for sound source localization and for speech recognition in complex listening environments. One group (n=11) wore bilateral CIs and, potentially, had access to interaural level difference (ILD) cues, but not interaural timing difference (ITD) cues. The second group (n=12) wore a single CI and had low-frequency, acoustic hearing in both the ear contralateral to the CI and in the implanted ear. These `hearing preservation' listeners, potentially, had access to ITD cues but not to ILD cues. At issue in this dissertation was the value of the two types of information about sound sources, ITDs and ILDs, for localization and for speech perception when speech and noise sources were separated in space. For Experiment 1, normal hearing (NH) listeners and the two groups of CI listeners were tested for sound source localization using a 13 loudspeaker array. For the NH listeners, the mean RMS error for localization was 7 degrees, for the bilateral CI listeners, 20 degrees, and for the hearing preservation listeners, 23 degrees. The scores for the two CI groups did not differ significantly. Thus, both CI groups showed equivalent, but poorer than normal, localization. This outcome using the filtered noise bands for the normal hearing listeners, suggests ILD and ITD cues can support equivalent levels of localization. For Experiment 2, the two groups of CI listeners were tested for speech recognition in noise when the noise sources and targets were spatially separated in a simulated `restaurant' environment and in two versions of a `cocktail party' environment. At issue was whether either CI group would show benefits from binaural hearing, i.e., better performance when the noise and targets were separated in space. Neither of the CI groups showed spatial release from masking. However, both groups showed a significant binaural advantage (a combination of squelch and summation), which also maintained separation of the target and noise, indicating the presence of some binaural processing or `unmasking' of speech in noise. Finally, localization ability in Experiment 1 was not correlated with binaural advantage in Experiment 2.
ContributorsLoiselle, Louise (Author) / Dorman, Michael F. (Thesis advisor) / Yost, William A. (Thesis advisor) / Azuma, Tamiko (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2013
Description
Concussion, a subset of mild traumatic brain injury (mTBI), has recently been brought to the forefront of the media due to a large lawsuit filed against the National Football League. Concussion resulting from injury varies in severity, duration, and type, based on many characteristics about the individual that research does not presently understand. Chronic fatigue, poor working memory, impaired self-awareness, and lack of attention to task are symptoms commonly present post-concussion. Currently, there is not a standard method of assessing concussion, nor is there a way to track an individual's recovery, resulting in misguided treatment for better prognosis. The aim of the following study was to determine patient specific higher-order cognitive processing deficits for clinical diagnosis and prognosis of concussion. Six individuals (N=6) were seen during the acute phase of concussion, two of whom were seen subsequently when their symptoms were deemed clinically resolved. Subjective information was collected from both the patient and from neurology testing. Each individual completed a task, in which they were presented with degraded speech, taxing their higher-order cognitive processing. Patient specific behavioral patterns are noted, creating a unique paradigm for mapping subjective and objective data for each patient's strategy to compensate for deficits and understand speech in a difficult listening situation. Keywords: concussion, cognitive processing
ContributorsBerg, Dena (Author) / Liss, Julie M (Committee member) / Azuma, Tamiko (Committee member) / Caviness, John (Committee member) / Arizona State University (Publisher)
Created2013
Description
As the genetic information storage vehicle, deoxyribonucleic acid (DNA) molecules are essential to all known living organisms and many viruses. It is amazing that such a large amount of information about how life develops can be stored in these tiny molecules. Countless scientists, especially some biologists, are trying to decipher the genetic information stored in these captivating molecules. Meanwhile, another group of researchers, nanotechnologists in particular, have discovered that the unique and concise structural features of DNA together with its information coding ability can be utilized for nano-construction efforts. This idea culminated in the birth of the field of DNA nanotechnology which is the main topic of this dissertation. The ability of rationally designed DNA strands to self-assemble into arbitrary nanostructures without external direction is the basis of this field. A series of novel design principles for DNA nanotechnology are presented here, from topological DNA nanostructures to complex and curved DNA nanostructures, from pure DNA nanostructures to hybrid RNA/DNA nanostructures. As one of the most important and pioneering fields in controlling the assembly of materials (both DNA and other materials) at the nanoscale, DNA nanotechnology is developing at a dramatic speed and as more and more construction approaches are invented, exciting advances will emerge in ways that we may or may not predict.
ContributorsHan, Dongran (Author) / Yan, Hao (Thesis advisor) / Liu, Yan (Thesis advisor) / Ros, Anexandra (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2012
Description
A clean and sustainable alternative to fossil fuels is solar energy. For efficient use of solar energy to be realized, artificial systems that can effectively capture and convert sunlight into a usable form of energy have to be developed. In natural photosynthesis, antenna chlorophylls and carotenoids capture sunlight and transfer the resulting excitation energy to the photosynthetic reaction center (PRC). Small reorganization energy, λ and well-balanced electronic coupling between donors and acceptors in the PRC favor formation of a highly efficient charge-separated (CS) state. By covalently linking electron/energy donors to acceptors, organic molecular dyads and triads that mimic natural photosynthesis were synthesized and studied. Peripherally linked free base phthalocyanine (Pc)-fullerene (C60) and a zinc (Zn) phthalocyanine-C60 dyads were synthesized. Photoexcitation of the Pc moiety resulted in singlet-singlet energy transfer to the attached C60, followed by electron transfer. The lifetime of the CS state was 94 ps. Linking C60 axially to silicon (Si) Pc, a lifetime of the CS state of 4.5 ns was realized. The exceptionally long-lived CS state of the SiPc-C60 dyad qualifies it for applications in solar energy conversion devices. A secondary electron donor was linked to the dyad to obtain a carotenoid (Car)-SiPc-C60 triad and ferrocene (Fc)-SiPc-C60 triad. Excitation of the SiPc moiety resulted in fast electron transfer from the Car or Fc secondary electron donors to the C60. The lifetime of the CS state was 17 ps and 1.2 ps in Car-SiPc-C60 and Fc-SiPc-C60, respectively. In Chapter 3, an efficient synthetic route that yielded regioselective oxidative porphyrin dimerization is presented. Using Cu2+ as the oxidant, meso-β doubly-connected fused porphyrin dimers were obtained in very high yields. Removal of the copper from the macrocycle affords a free base porphyrin dimer. This allows for exchange of metals and provides a route to a wider range of metallporphyrin dimers. In Chapter 4, the development of an efficient and an expedient route to bacteriopurpurin synthesis is discussed. Meso-10,20- diformylation of porphyrin was achieved and one-pot porphyrin diacrylate synthesis and cyclization to afford bacteriopurpurin was realized. The bacteriopurpurin had a reduction potential of - 0.85 V vs SCE and λmax, 845 nm.
ContributorsArero, Jaro (Author) / Gust, Devens (Thesis advisor) / Moore, Ana (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2014
Description
Solar energy is a promising alternative for addressing the world's current and future energy requirements in a sustainable way. Because solar irradiation is intermittent, it is necessary to store this energy in the form of a fuel so it can be used when required. The light-driven splitting of water into oxygen and hydrogen (a useful chemical fuel) is a fascinating theoretical and experimental challenge that is worth pursuing because the advance of the knowledge that it implies and the availability of water and sunlight. Inspired by natural photosynthesis and building on previous work from our laboratory, this dissertation focuses on the development of water-splitting dye-sensitized photoelectrochemical tandem cells (WSDSPETCs). The design, synthesis, and characterization of high-potential porphyrins and metal-free phthalocyanines with phosphonic anchoring groups are reported. Photocurrents measured for WSDSPETCs made with some of these dyes co-adsorbed with molecular or colloidal catalysts on TiO2 electrodes are reported as well. To guide in the design of new molecules we have used computational quantum chemistry extensively. Linear correlations between calculated frontier molecular orbital energies and redox potentials were built and tested at multiple levels of theory (from semi-empirical methods to density functional theory). Strong correlations (with r2 values > 0.99) with very good predictive abilities (rmsd < 50 mV) were found when using density functional theory (DFT) combined with a continuum solvent model. DFT was also used to aid in the elucidation of the mechanism of the thermal relaxation observed for the charge-separated state of a molecular triad that mimics the photo-induced proton coupled electron transfer of the tyrosine-histidine redox relay in the reaction center of Photosystem II. It was found that the inclusion of explicit solvent molecules, hydrogen bonded to specific sites within the molecular triad, was essential to explain the observed thermal relaxation. These results are relevant for both advancing the knowledge about natural photosynthesis and for the future design of new molecules for WSDSPETCs.
ContributorsMéndez-Hernández, Dalvin D (Author) / Moore, Ana L (Thesis advisor) / Mujica, Vladimiro (Thesis advisor) / Gust, Devens J. (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2014