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.

SAXOPHONE SONATAS 1980-2010

The purpose of this dissertation project identifies contemporary solo saxophone literature, specifically sonatas between the years 1980 and 2010. The overwhelming majority of repertoire written during these thirty years consisted primarily of either multi-movement or through-composed character pieces. By limiting the selected repertoire to sonatas one can still investigate the breadth of the literature that has helped validate the saxophone in the realm of classical music in a format that has seemingly fallen out of favor with composers. The saxophone had developed a unique voice by the middle of the twentieth century in both Europe and in the United States. European composers such as Claude Debussy, Florent Schmidt, Jacques Ibert, Darius Milhaud, Alexander Glazounov, Erwin Schulhoff and Bernard Heiden recognized the potential and beauty of the instrument, while the saxophone had found quite a different niche in vaudeville, jazz, and military bands in the United States. If not for the dynamic performances by concert saxophonist such as Marcel Mule, Sigurd Rascher, Jean-Marie Londeix, Daniel Deffayet, Cecil Lesson, Larry Teal, Eugene Rousseau, Fredrick Hemke and Donald Sinta, the timbral possibilities and technical virtuosity of the saxophone would not have been discovered. The awe inspiring performances by these soloists led to the commissioning of a multitude of works by composers looking to expand the sonic possibilities of this relatively new instrument. Through the 1970's American composers such as Leslie Bassett, Paul Creston, Henry Brant, Robert Muczynski, and Karel Husa were writing significant works for the saxophone, while European composers such as IngolfDahl, Edison Denisov, Alfred Desenclos, Henri Tomasi and Marius Constant were each making their own contributions, all leading to a significant quantity of repertoire that met the quality demands set by the performers. The compositions chosen for this dissertation project were selected after numerous performance, pragmatic, programming and pedagogical considerations were taken into account. The three recitals occurred on: March 7, 2010, December 10, 2010 and May 1, 2011 in either the Gildenhorn Recital Hall or Lecture Hall 2100.

Lukas Foss's The Prairie (1942): Building Community through Music

Lukas Foss's The Prairie, a seven-movement cantata for SATB soloists, mixed chorus, and orchestra, is a well-crafted and audience-friendly setting of the poem of the same name by Carl Sandburg. Acclaimed at its 1944 premiere, The Prairie has not enjoyed a robust performance history due in large part to numerous inconsistencies between the score and parts which render the work challenging to perform. Heretofore, each conductor has individually located these inconsistencies and made the necessary adjustments for performances. In this document, resources have been assembled which identify and correct many of the inconsistencies, thus facilitating more performances in the future. The Prairie is an ideal vehicle for a project-based chorus, which is itself an opportunity to create a new community. A correlation may exist between "community" and "vulnerability;" that is, when a choral singer feels comfortably connected to fellow singers, he or she may be more likely to open up to new ways of making sounds for the ultimate service of the music. Results are inconclusive, but the project points to a successful strategy for creating an affirming new community and to positive musical and nonmusical results of intentional community-building.

La polémica entre bonaventura cavalieri y Paul Guldin o jesuatos contra jesuitas sobre los indivisibles

Se analiza la polémica entre Cavalieri y Guldin sobre el concepto de lo indivisible.

[Recording review] Paul Hindemith, Die Harmonie der Welt, soloists, Rundfunkchor Berlin, Rundfunk-Sinfonieorchester Berlin, conductor Marek Janowski

Tony Mann provides a review of the recording: Paul Hindemith, Die Harmonie der Welt [opera], soloists, Rundfunkchor Berlin, Rundfunk-Sinfonieorchester Berlin, conductor Marek Janowski. Wergo 6652-2 (160 minutes, 3CDs priced as two)

Una revisión de la Cadena Datos-Información-Conocimiento desde el Pragmatismo de Peirce

La Cadena Datos-Información-Conocimiento (DIC), denominada “Jerarquía de la Información” o “Pirámide del Conocimiento”, es uno de los modelos más importantes en la Gestión de la Información y la Gestión del Conocimiento. Por lo general, la estructuración de la cadena se ha ido definiendo como una arquitectura en la que cada elemento se levanta sobre el elemento inmediatamente inferior; sin embargo no existe un consenso en la definición de los elementos, ni acerca de los procesos que transforman un elemento de un nivel a uno del siguiente nivel. En este artículo se realiza una revisión de la Cadena Datos-Información-Conocimiento examinando las definiciones más relevantes sobre sus elementos y sobre su articulación en la literatura, para sintetizar las acepciones más comunes. Se analizan los elementos de la Cadena DIC desde la semiótica de Peirce; enfoque que nos permite aclarar los significados e identificar las diferencias, las relaciones y los roles que desempeñan en la cadena desde el punto de vista del pragmatismo. Finalmente se propone una definición de la Cadena DIC apoyada en las categorías triádicas de signos y la semiosis ilimitada de Peirce, los niveles de sistemas de signos de Stamper y las metáforas de Zeleny.