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- All Subjects: Biochemistry
- Genre: Doctoral Dissertation
- Creators: Holbrook, Amy
- Creators: Ghirlanda, Giovanna
Description
A new arrangement of the Concerto for Two Horns in E-flat Major, Hob. VIId/6, attributed by some to Franz Joseph Haydn, is presented here. The arrangement reduces the orchestral portion to ten wind instruments, specifically a double wind quintet, to facilitate performance of the work. A full score and a complete set of parts are included. In support of this new arrangement, a discussion of the early treatment of horns in pairs and the subsequent development of the double horn concerto in the eighteenth century provides historical context for the Concerto for Two Horns in E-flat major. A summary of the controversy concerning the identity of the composer of this concerto is followed by a description of the content and structure of each of its three movements. Some comments on the procedures of the arrangement complete the background information.
ContributorsYeh, Guan-Lin (Author) / Ericson, John (Thesis advisor) / Holbrook, Amy (Committee member) / Micklich, Albie (Committee member) / Pilafian, J. Samuel (Committee member) / Arizona State University (Publisher)
Created2011
Description
The purpose of this project was to commission, perform, and discuss a new work for an instrument pairing not often utilized, oboe and percussion. The composer, Alyssa Morris, was selected in June 2009. Her work, titled Forecast, was completed in October of 2009 and premiered in February of 2010, as part of a program showcasing music for oboe and percussion. Included in this document is a detailed biography of the composer, a description of the four movements of Forecast, performance notes for each movement, a diagram for stage set-up, the full score, the program from the premiere performance with biographies of all the performers involved, and both a live recording and MIDI sound file. The performance notes discuss issues that arose during preparation for the premiere and should help avoid potential pitfalls. TrevCo Music, publisher of the work, graciously allowed inclusion of the full score. This score is solely for use in this document; please visit the publisher's website for purchasing information. The commission and documentation of this composition are intended to add to the repertoire for oboe in an unusual instrument pairing and to encourage further exploration of such combinations.
ContributorsCreamer, Caryn (Author) / Schuring, Martin (Thesis advisor) / Hill, Gary (Committee member) / Holbrook, Amy (Committee member) / Micklich, Albie (Committee member) / Spring, Robert (Committee member) / Arizona State University (Publisher)
Created2011
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
Telomerase ribonucleoprotein is a unique reverse transcriptase that adds telomeric DNA repeats to chromosome ends. Telomerase RNA (TER) is extremely divergent in size, sequence and has to date only been identified in vertebrate, yeast, ciliate and plant species. Herein, the identification and characterization of TERs from an evolutionarily distinct group, filamentous fungi, is presented. Based on phylogenetic analysis of 69 TER sequences and mutagenesis analysis of in vitro reconstituted Neurospora telomerase, we discovered a conserved functional core in filamentous fungal TERs sharing homologous structural features with vertebrate TERs. This core contains the template-pseudoknot and P6/P6.1 domains, essential for enzymatic activity, which retain function in trans. The in vitro reconstituted Neurospora telomerase is highly processive, synthesizing canonical TTAGGG repeats. Similar to Schizosaccharomycetes pombe, filamentous fungal TERs utilize the spliceosomal splicing machinery for 3' processing. Neurospora telomerase, while associating with the Est1 protein in vivo, does not bind homologous Ku or Sm proteins found in both budding and fission yeast telomerase holoenzyme, suggesting a unique biogenesis pathway. The development of Neurospora as a model organism to study telomeres and telomerase may shed light upon the evolution of the canonical TTAGGG telomeric repeat and telomerase processivity within fungal species.
ContributorsQi, Xiaodong (Author) / Chen, Julian (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Chaput, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Telomerase is a specialized enzyme that adds telomeric DNA repeats to the chromosome ends to counterbalance the progressive telomere shortening over cell divisions. It has two essential core components, a catalytic telomerase reverse transcriptase protein (TERT), and a telomerase RNA (TR). TERT synthesizes telomeric DNA by reverse transcribing a short template sequence in TR. Unlike TERT, TR is extremely divergent in size, sequence and structure and has only been identified in three evolutionarily distant groups. The lack of knowledge on TR from important model organisms has been a roadblock for vigorous studies on telomerase regulation. To address this issue, a novel in vitro system combining deep-sequencing and bioinformatics search was developed to discover TR from new phylogenetic groups. The system has been validated by the successful identification of TR from echinoderm purple sea urchin Strongylocentrotus purpuratus. The sea urchin TR (spTR) is the first invertebrate TR that has been identified and can serve as a model for understanding how the vertebrate TR evolved with vertebrate-specific traits. By using phylogenetic comparative analysis, the secondary structure of spTR was determined. The spTR secondary structure reveals unique sea urchin specific structure elements as well as homologous structural features shared by TR from other organisms. This study enhanced the understanding of telomerase mechanism and the evolution of telomerase RNP. The system that was used to identity telomerase RNA can be employed for the discovery of other TR as well as the discovery of novel RNA from other RNP complex.
ContributorsLi, Yang (Author) / Chen, Julian Jl (Thesis advisor) / Yan, Hao (Committee member) / Ghirlanda, Giovanna (Committee member) / Arizona State University (Publisher)
Created2011
Description
Owen Middleton (b. 1941) enjoys an established and growing reputation as a composer of classical guitar music, but his works for piano are comparatively little known. The close investigation offered here of Middleton's works for piano reveals the same impressive craftsmanship, compelling character, and innovative spirit found in his works for guitar. Indeed, the only significant thing Middleton's piano music currently lacks is the well-deserved attention of professional players and a wider audience. Middleton's piano music needs to be heard, not just discussed, so one of this document's purposes is to provide a recorded sample of his piano works. While the overall repertoire for solo piano is vast, and new works become established in that repertoire with increasing difficulty, Middleton's piano works have a significant potential to find their way into the concert hall as well as the private teaching studio. His solo piano music is highly effective, well suited to the instrument, and, perhaps most importantly, fresh sounding and truly original. His pedagogical works are of equal value. Middleton's piano music offers something for everyone: there one finds daring virtuosity, effusions of passion, intellectual force, colorful imagery, poetry, humor, and even a degree of idiomatic innovation. This study aims to reveal key aspects of the composer's musical style, especially his style of piano writing, and to provide pianists with helpful analytical, technical, and interpretive insights. These descriptions of the music are supported with recorded examples, selected from the works for solo piano written between 1962 and 1993: Sonata for Piano, Childhood Scenes, Katie's Collection, and Toccata for Piano. The complete scores of the recorded works are included in the appendix. A chapter briefly describing the piano pieces since 1993 concludes the study and invites the reader to further investigations of this unique and important body of work.
ContributorsMoreau, Barton Andrew (Author) / Hamilton, Robert (Thesis advisor) / Holbrook, Amy (Committee member) / Campbell, Andrew (Committee member) / Spring, Robert (Committee member) / Gardner, Joshua (Committee member) / Arizona State University (Publisher)
Created2011
Description
A major goal of synthetic biology is to recapitulate emergent properties of life. Despite a significant body of work, a longstanding question that remains to be answered is how such a complex system arose? In this dissertation, synthetic nucleic acid molecules with alternative sugar-phosphate backbones were investigated as potential ancestors of DNA and RNA. Threose nucleic acid (TNA) is capable of forming stable helical structures with complementary strands of itself and RNA. This provides a plausible mechanism for genetic information transfer between TNA and RNA. Therefore TNA has been proposed as a potential RNA progenitor. Using molecular evolution, functional sequences were isolated from a pool of random TNA molecules. This implicates a possible chemical framework capable of crosstalk between TNA and RNA. Further, this shows that heredity and evolution are not limited to the natural genetic system based on ribofuranosyl nucleic acids. Another alternative genetic system, glycerol nucleic acid (GNA) undergoes intrasystem pairing with superior thermalstability compared to that of DNA. Inspired by this property, I demonstrated a minimal nanostructure composed of both left- and right-handed mirro image GNA. This work suggested that GNA could be useful as promising orthogonal material in structural DNA nanotechnology.
ContributorsZhang, Su (Author) / Chaut, John C (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Yan, Hao (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
Discovering Puerto Rican art song: a research project on four art song works by Héctor Campos Parsi
Description
Puerto Rico has produced many important composers who have contributed to the musical culture of the nation during the last 200 years. However, a considerable amount of their music has proven to be difficult to access and may contain numerous errors. This research project intends to contribute to the accessibility of such music and to encourage similar studies of Puerto Rican music. This study focuses on the music of Héctor Campos Parsi (1922-1998), one of the most prominent composers of the 20th century in Puerto Rico. After an overview of the historical background of music on the island and the biography of the composer, four works from his art song repertoire are given for detailed examination. A product of this study is the first corrected edition of his cycles Canciones de Cielo y Agua, Tres Poemas de Corretjer, Los Paréntesis, and the song Majestad Negra. These compositions date from 1947 to 1959, and reflect both the European and nationalistic writing styles of the composer during this time. Data for these corrections have been obtained from the composer's manuscripts, published and unpublished editions, and published recordings. The corrected scores are ready for publication and a compact disc of this repertoire, performed by soprano Melliangee Pérez and the author, has been recorded to bring to life these revisions. Despite the best intentions of the author, the various copyright issues have yet to be resolved. It is hoped that this document will provide the foundation for a resolution and that these important works will be available for public performance and study in the near future.
ContributorsRodríguez Morales, Luis F., 1980- (Author) / Campbell, Andrew (Thesis advisor) / Buck, Elizabeth (Committee member) / Holbrook, Amy (Committee member) / Kopta, Anne (Committee member) / Ryan, Russell (Committee member) / Arizona State University (Publisher)
Created2013
Description
In addition to his many other works, Russian-American composer Leo Ornstein (1893-2002) contributed a substantial body of literature for cello and piano, including Sonata No. 1 (1915-1916), Sonata No. 2 (circa 1920), Composition No. 1 (date unknown), Two Pieces (date unknown), and Six Preludes (1930-1931). His cello music is an eclectic mix of twentieth-century Neoromantic and atonal styles. This study includes a recording of the complete works for cello and piano by Leo Ornstein and a description of the music that details the formal procedures and how the cello and piano relate to one another. The discussion offers extensive musical examples in support of the descriptions. The recording was completed at the Banff Centre for the Arts in Alberta, Canada (October 2009), with R. Nicolas Alvarez, cello, in collaboration with pianist Keith Kirchoff. Andre Shrimski produced and edited the recording.
ContributorsAlvarez, Rodolfo Nicolas (Author) / Landschoot, Thomas (Thesis advisor) / Rotaru, Catalin (Committee member) / Jiang, Danwen (Committee member) / Holbrook, Amy (Committee member) / Arizona State University (Publisher)
Created2013