PIANIST-COMPOSERS WHOSE WORKS INCLUDE PIANISTIC INNOVATIONS

Throughout the piano’s history, certain composers have created innovations in the areas of virtuosity and sonority. These innovations came not only from the composers’ imagination, but also from the development of instruments and changes in musical style from one period to another. To investigate what kinds of innovations these pianist composers made, I divided them into technique and sound from Mozart to Cowell. I chose two-piano music (Sonata in D major, K.448 by Mozart and Rachmaninoff’s Second Suite) to demonstrate their experiments with varieties of textures and sonorities, using different registers of the two pianos orchestrally. En Blanc et noir by Debussy shows this composer’s deep interest and originality in piano sonorities. For solo piano music, Beethoven’s Piano Sonata Op.53 shows extensive technical invention. His use of long pedal effects shows a pianistic possibility not explored by Mozart. Hummel’s Piano Sonata in D major represents orchestral devices as well as pianistic techniques showing recent developments in the instrument. Chopin’s Ballade No.3 and Scherzo No.3 show virtuosic moments and also the expanded range of the keyboard. His Nocturne Op.27, no.2, with its sonorities resulting from the combination of pedal, and widespread accompaniments derived from Alberti bass figures, is a perfect example of Chopin’s characteristic sound-world. “Vallée d’Obermann” by Liszt uses many virtuosic techniques as well as the extreme wide ranges of keyboard in both hands to create dramatic contrasts of texture. Debussy’s etude, “Pour les Sonorités opposés” is probably the first etude designed for sonority rather than for keyboard virtuosity. Albeniz’s “Evocación” and “Triana” show Spanish atmosphere. Prokofiev’s Sonata no.3 shows frequent motoric driving elements that demand percussive virtuosity. Cowell’s piano music is some of the earliest to explore the sonorities of tone clusters and playing on the strings. This performance dissertation consists of three recitals performed in the Orchestra Room, Leah Smith Hall, and Gildenhorn Recital Hall at the University of Maryland, College Park. These recitals are documented on compact disc recordings that are housed within the University of Maryland Library System.

Recombinant Adeno-Associated Virus-Mediated Gene Therapy for Treatment of Familial Hypercholesterolemia in Rabbits

Familial hypercholesterolemia (FH) is a genetic disorder characterized by abnormally high concentrations of low-density lipoprotein-cholesterol (LDLcholesterol) in the blood that can contribute to heart disease. FH can result from a defect in the gene for the LDL receptor (LDL-R). FH patients lacking functional LDL-R may benefit from viral-mediated transfer of a functional copy of the open reading frame (ORF) of the LDL-R. Since a recombinant adeno-associated virus (rAAV) is not immunogenic and can be mass-produced, it shows promise for gene therapy applications. AAV6 and AAV8 have been shown to specifically transduce hepatocytes in several species, which normally remove the majority of LDL-cholesterol from the blood via LDL-R-mediated endocytosis. Because of the potential of rAAV to treat FH by delivery of a correct LDL-R ORF to hepatocytes, the liver specificity of these two AAV serotypes was evaluated. Additionally, rabbits were chosen as the animal model for this study because a specific strain of rabbits, Watanabe heritable hyperlipidemic (WHHL), adequately mimics the pathology of FH in humans. Exposure of rabbit liver to rAAV with the marker LacZ and subsequent inspection of liver tissue showed that AAV8 transduced rabbit liver more efficiently than AAV6. To assess the feasibility of producing a rAAV capable of transferring the LDL-R ORF to rabbit hepatocytes in vivo, rAAV8-LDL-R was mass-produced by a baculovirus system in suspension grown insect cells.