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- Genre: Doctoral Dissertation
- Creators: Rockmaker, Jody
Description
In the 1970s James Watson recognized the inability of conventional DNA replication machinery to replicate the extreme termini of chromosomes known as telomeres. This inability is due to the requirement of a building block primer and was termed the end replication problem. Telomerase is nature's answer to the end replication problem. Telomerase is a ribonucleoprotein which extends telomeres through reverse transcriptase activity by reiteratively copying a short intrinsic RNA sequence to generate 3' telomeric extensions. Telomeres protect chromosomes from erosion of coding genes during replication, as well as differentiate native chromosome ends from double stranded breaks. However, controlled erosion of telomeres functions as a naturally occurring molecular clock limiting the replicative capacity of cells. Telomerase is over activated in many cancers, while inactivation leads to multiple lifespan limiting human diseases. In order to further study the interaction between telomerase RNA (TR) and telomerase reverse transcriptase protein (TERT), vertebrate TERT fragments were screened for solubility and purity following bacterial expression. Soluble fragments of medaka TERT including the RNA binding domain (TRBD) were identified. Recombinant medaka TRBD binds specifically to telomerase RNA CR4/CR5 region. Ribonucleotide and amino acid pairs in close proximity within the medaka telomerase RNA-protein complex were identified using photo-activated cross-linking in conjunction with mass spectrometry. The identified cross-linking amino acids were mapped on known crystal structures of TERTs to reveal the RNA interaction interface of TRBD. The identification of this RNA TERT interaction interface furthers the understanding of the telomerase complex at a molecular level and could be used for the targeted interruption of the telomerase complex as a potential cancer treatment.
ContributorsBley, Christopher James (Author) / Chen, Julian (Thesis advisor) / Allen, James (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
A systematic approach to composition has been used by a variety of composers to control an assortment of musical elements in their pieces. This paper begins with a brief survey of some of the important systematic approaches that composers have employed in their compositions, devoting particular attention to Pierre Boulez's Structures Ia . The purpose of this survey is to examine several systematic approaches to composition by prominent composers and their philosophy in adopting this type of approach. The next section of the paper introduces my own systematic approach to composition: the Take-Away System. The third provides several musical applications of the system, citing my work, Octulus for two pianos, as an example. The appendix details theorems and observations within the system for further study.
ContributorsHarbin, Doug (Author) / Hackbarth, Glenn (Thesis advisor) / DeMars, James (Committee member) / Etezady, Roshanne, 1973- (Committee member) / Rockmaker, Jody (Committee member) / Rogers, Rodney (Committee member) / Arizona State University (Publisher)
Created2011
Description
ABSTRACT études; written for violin ensemble, which include violin duets, trios, and quartets, are less numerous than solo études.; These works rarely go by the title "étude;," and have not been the focus of much scholarly research. Ensemble études; have much to offer students, teachers and composers, however, because they add an extra dimension to the learning, teaching, and composing processes. This document establishes the value of ensemble études; in pedagogy and explores applications of the repertoire currently available. Rather than focus on violin duets, the most common form of ensemble étude;, it mainly considers works for three and four violins without accompaniment. Concentrating on the pedagogical possibilities of studying études; in a group, this document introduces creative ways that works for violin ensemble can be used as both études; and performance pieces. The first two chapters explore the history and philosophy of the violin étude; and multiple-violin works, the practice of arranging of solo études; for multiple instruments, and the benefits of group learning and cooperative learning that distinguish ensemble étude; study from solo étude; study. The third chapter is an annotated survey of works for three and four violins without accompaniment, and serves as a pedagogical guide to some of the available repertoire. Representing a wide variety of styles, techniques and levels, it illuminates an historical association between violin ensemble works and pedagogy. The fourth chapter presents an original composition by the author, titled Variations on a Scottish Folk Song: étude; for Four Violins, with an explanation of the process and techniques used to create this ensemble étude.; This work is an example of the musical and technical integration essential to étude; study, and demonstrates various compositional traits that promote cooperative learning. Ensemble études; are valuable pedagogical tools that deserve wider exposure. It is my hope that the information and ideas about ensemble études; in this paper and the individual descriptions of the works presented will increase interest in and application of violin trios and quartets at the university level.
ContributorsLundell, Eva Rachel (Contributor) / Swartz, Jonathan (Thesis advisor) / Rockmaker, Jody (Committee member) / Buck, Nancy (Committee member) / Koonce, Frank (Committee member) / Norton, Kay (Committee member) / Arizona State University (Publisher)
Created2011
Description
Despite a quickly growing repertoire list for the brass quintet, the music of the early Argentine tango has remained relatively neglected by brass quintet arrangers and performers. With the goal of bringing a neglected art form to the brass quintet repertoire, three arrangements based on early twentieth century Argentine tango songs are presented here: "Elegante Papirusa" by Tito Roccatagliata, "A La Gran Muñeca" by Jesús Ventura, and "La Cotorrita" by Samuel Castriota. The arrangements follow the style of three early recordings produced by The Victor Talking Machine in 1920 and 1922, as performed by two authentic Argentine orquesta típicas: Orquesta Típica Select and Orquesta Típica Fresedo. A brief history of the style and instrumental evolution of tango music from its influences and origins up until 1920 is discussed, followed by a detailed account of the musicians and circumstances involved in the three early recordings. An explanation of the issues encountered by the author in adapting the early tango style to the brass quintet setting is discussed, along with the solutions realized in order to make the project successful and practical for a moderately advanced brass quintet. The full brass quintet scores are provided as part of the Appendix.
ContributorsCamacho, Gustavo (Musician) (Author) / Ericson, John Q (Thesis advisor) / Pilafian, Samuel (Committee member) / Schuring, Martin (Committee member) / Campbell, Andrew (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2011
Description
Cyanovirin-N (CV-N) is a naturally occurring lectin originally isolated from the cyanobacteria Nostoc ellipsosporum. This 11 kDa lectin is 101 amino acids long with two binding sites, one at each end of the protein. CV-N specifically binds to terminal Manα1-2Manα motifs on the branched, high mannose Man9 and Man8 glycosylations found on enveloped viruses including Ebola, Influenza, and HIV. wt-CVN has micromolar binding to soluble Manα1-2Manα and also inhibits HIV entry at low nanomolar concentrations. CV-N's high affinity and specificity for Manα1-2Manα makes it an excellent lectin to study for its glycan-specific properties. The long-term aim of this project is to make a variety of mutant CV-Ns to specifically bind other glycan targets. Such a set of lectins may be used as screening reagents to identify biomarkers and other glycan motifs of interest. As proof of concept, a T7 phage display library was constructed using P51G-m4-CVN genes mutated at positions 41, 44, 52, 53, 56, 74, and 76 in binding Domain B. Five CV-N mutants were selected from the library and expressed in BL21(DE3) E. coli. Two of the mutants, SSDGLQQ-P51Gm4-CVN and AAGRLSK-P51Gm4-CVN, were sufficiently stable for characterization and were examined by CD, Tm, ELISA, and glycan array. Both proteins have CD minima at approximately 213 nm, indicating largely β-sheet structure, and have Tm values greater than 40°C. ELISA against gp120 and RNase B demonstrate both proteins' ability to bind high mannose glycans. To more specifically determine the binding specificity of each protein, AAGRLSK-P51Gm4-CVN, SSDGLQQ-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN were sent to the Consortium for Functional Glycomics (CFG) for glycan array analysis. AAGRLSK-P51Gm4-CVN, wt-CVN, and P51G-m4-CVN, have identical specificities for high mannose glycans containing terminal Manα1-2Manα. SSDGLQQ-P51Gm4-CVN binds to terminal GlcNAcα1-4Gal motifs and a subgroup of high mannose glycans bound by P51G-m4-CVN. SSDGLQQ-wt-CVN was produced to restore anti-HIV activity and has a high nanomolar EC50 value compared to wt-CVN's low nanomolar activity. Overall, these experiments show that CV-N Domain B can be mutated and retain specificity identical to wt-CVN or acquire new glycan specificities. This first generation information can be used to produce glycan-specific lectins for a variety of applications.
ContributorsRuben, Melissa (Author) / Ghirlanda, Giovanna (Thesis advisor) / Allen, James (Committee member) / Wachter, Rebekka (Committee member) / Arizona State University (Publisher)
Created2013
Description
This thesis presents a new arrangement of Richard Peaslee's trombone solo "Arrows of Time" for brass band. This arrangement adapts Peaslee's orchestration - and subsequent arrangement by Dr. Joshua Hauser for wind ensemble - for the modern brass band instrumentation and includes a full score. A brief biography of Richard Peaslee and his work accompanies this new arrangement, along with commentary on the orchestration of "Arrows of Time", and discussion of the evolution and adaptation of the work for wind ensemble by Dr. Hauser. The methodology used to adapt these versions for the brass band completes the background information.
ContributorsMalloy, Jason Patrick (Author) / Ericson, John (Thesis advisor) / Oldani, Robert (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2013
Description
Bright Summer, a one-movement piece for orchestra, was composed in Arizona, and completed in February 2013. The piece is approximately twelve minutes long. The motivation for writing this piece was the death of my mother the year before, in 2012. The prevailing mood of this work is bright and pleasant, expressing my mother's cheerful personality when she was alive. It also portrays bright summer days which resemble my mother's spirit. Thus, soundscape plays an important role in this work. It depicts summer breeze, rustling sounds of leaves, and, to translate a Korean saying, "high blue skies." This soundscape opens the piece as well as closes it. In the middle section, the fast upbeat themes represent my mother's witty and optimistic personality. The piece also contains the presence of a hymn tune, The Love of God is Greater Far, which informs the motivic content and also functions as the climax of the piece. It was my mother's favorite hymn and we used to sing it together following her conversion to Christianity. The piece contains three main sections, which are held together by transitional material based on the soundscape and metric modulations. Unlike my earlier works, Bright Summer is tonal, with upper tertian harmonies prevailing throughout the piece. However, the opening and closing soundscapes do not have functional harmonies. For example, tertian chords appear and vanish silently, leaving behind some resonant sounds without any harmonic progression. Overall, the whole piece is reminiscent of my mother who lived a beautiful life.
ContributorsKim, JeeYeon (Composer) / DeMars, James (Thesis advisor) / Hackbarth, Glenn (Committee member) / Rogers, Rodney (Committee member) / Levy, Benjamin (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2013
Description
DNA nanotechnology has been a rapidly growing research field in the recent decades, and there have been extensive efforts to construct various types of highly programmable and robust DNA nanostructures. Due to the advantage that DNA nanostructure can be used to organize biochemical molecules with precisely controlled spatial resolution, herein we used DNA nanostructure as a scaffold for biological applications. Targeted cell-cell interaction was reconstituted through a DNA scaffolded multivalent bispecific aptamer, which may lead to promising potentials in tumor therapeutics. In addition a synthetic vaccine was constructed using DNA nanostructure as a platform to assemble both model antigen and immunoadjuvant together, and strong antibody response was demonstrated in vivo, highlighting the potential of DNA nanostructures to serve as a new platform for vaccine construction, and therefore a DNA scaffolded hapten vaccine is further constructed and tested for its antibody response. Taken together, my research demonstrated the potential of DNA nanostructure to serve as a general platform for immunological applications.
ContributorsLiu, Xiaowei (Author) / Liu, Yan (Thesis advisor) / Chang, Yung (Thesis advisor) / Yan, Hao (Committee member) / Allen, James (Committee member) / Zhang, Peiming (Committee member) / Arizona State University (Publisher)
Created2012
Description
The German pianist and composer Johannes Brahms (1883-1897) wrote more than 122 works for a wide variety of ensembles and genres. Despite this remarkable productivity, and his widely heralded talent for innovation and technique as a composer, few of his works have been arranged for solo guitar, and these have focused primarily on his simpler, more melodic works. Conventional wisdom is that his music is "too dense" to be played on the guitar. As a result, there are no arrangements of orchestral works by Brahms in the standard repertoire for the guitar. In arranging Brahms's Serenade in D Major, movt. 1 for the guitar, I provide a counter argument that not all of Brahms's orchestral music is too dense all of the time. In Part I, I provide a brief overview of the history of, and sources for, the Serenade. Part II describes a step-by-step guide through the process of arranging orchestral repertoire for the solo guitar. Part III is an examination of the editing process that utilizes examples from the guitar arrangement of the Serenade in order to illustrate the various techniques and considerations that are part of the editing process. Part IV is a performance edition of the arrangement. In summary, the present arrangement of Brahms's Serenade, op.11 is the beginning of a conversation about why the "guitar world" should be incorporating the music of Brahms into the standard repertoire. The lessons learned, and the technical challenges discovered, should help inform future arrangers and guitar performers for additional compositions by Brahms.
ContributorsLanier, William Hudson (Author) / Koonce, Frank (Thesis advisor) / Micklich, Albie (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2013
Description
The organ is in a continued state of evolution, tonally and mechanically, designed by the builder to meet certain expectations related to the musical aesthetics of the time. Organ building in the United States has been influenced by both European organ building traditions and American innovations. During the early twentieth century, Ernest M. Skinner emerged as one of the greatest organ builders in America. Throughout his life, Skinner's quest was to create an "ideal organ," capable of playing a variety of music. Skinner's vision was rooted in the Romantic Movement and influenced by the dynamic gradations and rich, colorful sonorities of orchestral and operatic music of the era. A number of technological developments were applied to the design of the organ which made the romantic organ possible. The prominent European organ builders of the nineteenth century created organs that defined the romantic-style instrument in their respective countries. By the end of the century, American organ builders were creating their own versions. Skinner traveled to Europe to learn what he could from the foreign builders. Skinner built organs that synthesized European and American elements, along with his own innovations, as continuation of nineteenth-century trends that brought the romantic-symphonic organ to its fullest realization. Additionally, Skinner developed many new organ timbres, including a number of stops that imitate various orchestral instruments. The result of Skinner's creative work is the the American symphonic organ. This paper attempts to illustrate how the tonal designs of organs built by Walcker, Cavaillé-Coll, and Willis influenced the work of Skinner and the American symphonic organ. The work of each builder is discussed with descriptions of their designs. The designs and innovations of Skinner are examined as related to these European builders. A number of organ specifications are provided to supplement the information presented here. Today, American symphonic organs, particularly those built by Skinner, are revered for their warmth and charm and are inspiring the work of present day organ builders who are incorporating elements of this style into their own designs.
ContributorsGerber, James Theodore (Author) / Marshall, Kimberly (Thesis advisor) / Pagano, Caio (Committee member) / Ryan, Russell (Committee member) / Rogers, Rodney (Committee member) / Rockmaker, Jody (Committee member) / Arizona State University (Publisher)
Created2012