SELECTED VARIATIONS BY COMPOSERS IN GERMANY AND FRANCE

The Haward of Dictionary of Music (1983), defines variation as "a technique modifying a given musical idea." From the Baroque period on, the form and the techniques of variation were developed and enriched in Germany and France. Therefore, I presented the works of composers from these two nations. Even though there was a vast number of possibilities, I wanted to be scholastically fair and interesting in making my selections by choosing well-known pieces along with lesser-known ones. Haydn's well-known Variations in F minor consist of two sets of double variations which break into an improvisation fantasy. The first movement of Beethoven Sonata in A flat major, Op. 26, is a set of five variations on the composer's original theme. The variations are positioned in the first movement instead of Sonata-Allegro form. In 1861 Brahrns composed the Variations and Fugue, Op. 24, on the theme of Handel. Brahms displays a wealth of rhythmic, harmonic and textural contrasts in the variations. Chopin's E Major Variations without opus number are written on a Swiss influenced German folksong. Faure's Theme and Variations in C sharp minor, Op. 73, includes eleven variations. The work displays the composer's subtlety, grace and reticence. 12 Variationen iiber ein eigenes Thema were written by Alban Berg as a composition study with Schonberg. The Finale of Dutilleux's Piano Sonata, titled "Chorale with Variations", is written in an impressionistic style. A rich expressiveness is well blended in a classical form. In 1742, the remarkable Aria and thirty variations known as the Goldberg Variations were composed by J. S. Bach. The thirty Variations are unified by the bass line, which forms the foundation of the Aria. The pieces discussed above were presented in three recitals. Compact disc recordings of these recitals are available in the Michelle Smith Performing Arts Library of the Clarice Smith Performing Arts Center at the University of Maryland.

ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY

Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein found on the surface of vascular endothelial cells (ECs). Its expression is upregulated at inflammatory sites, allowing for targeted delivery of therapeutics using ICAM-1-binding drug carriers. Engagement of multiple copies of ICAM-1 by these drug carriers induces cell adhesion molecule (CAM)-mediated endocytosis, which results in trafficking of carriers to lysosomes and across ECs. Knowledge about the regulation behind CAM-mediated endocytosis can help improve drug delivery, but questions remain about these regulatory mechanisms. Furthermore, little is known about the natural function of this endocytic pathway. To address these gaps in knowledge, we focused on two natural binding partners of ICAM-1 that potentially elicit CAM-mediated endocytosis: leukocytes (which bind ICAM-1 via β₂ integrins) and fibrin polymers (a main component of blood clots which binds ICAM-1 via the γ3 sequence). First, inspired by properties of these natural binding partners, we varied the size and targeting moiety of model drug carriers to determine how these parameters affect CAM-mediated endocytosis. Increasing ICAM-1-targeted carrier size slowed carrier uptake kinetics, reduced carrier trafficking to lysosomes, and increased carrier transport across ECs. Changing targeting moieties from antibodies to peptides decreased particle binding and uptake, lowered trafficking to lysosomes, and increased transport across ECs. Second, using cell culture models of leukocyte/EC interactions, inhibiting regulatory elements of the CAM-mediated pathway disrupted leukocyte sampling, a process crucial to leukocyte crossing of endothelial layers (transmigration). This inhibition also decreased leukocyte transmigration across ECs, specifically through the transcellular route, which occurs through a single EC without disassembly of cell-cell junctions. Third, fibrin meshes, which mimic blood clot fragments/remnants, bound to ECs at ICAM-1-enriched sites and were internalized by the endothelium. Inhibiting the CAM-mediated pathway disrupted this uptake. Following endocytosis, fibrin meshes trafficked to lysosomes where they were degraded. In mouse models, CAM-mediated endocytosis of fibrin meshes appeared to remove fibrin remnants at the endothelial surface, preventing re-initiation of the coagulation cascade. Overall, these results support a link between CAM-mediated endocytosis and leukocyte transmigration as well as uptake of fibrin materials by ECs. Furthermore, these results will guide the future design of ICAM-1-targeted carrier-assisted therapies.