My dissertation consists of two parts: a music composition, a Concerto for So- Ajaeng and Orchestra entitled “Breakthrough,” and an essay presenting analysis of two concertos – Tan Dun’s “Concerto for String Orchestra and Pipa” (1999) and Unsuk Chin’s “Šu for Sheng and Orchestra” (2009). For a long time I have worked to make connections between traditional Korean and Western classical influences in my music. My dissertation piece continues this effort. A concerto for a Korean instrument solo with Western orchestra seemed an ideal genre in which to move forward in this direction. Korean So-Ajaeng is chosen for solo instrument because of its penetrating and strong sounds that can compete with full orchestra.

Both Tan Dun and Unsuk Chin composed for a Chinese solo instrument with Western orchestra, but the composers’ musical and philosophical approaches to Asian traditions in their pieces are quite different. On the one hand, Tan Dun quotes from both Western and Chinese traditions strongly and directly. Melodies and styles from both traditions freely cross over the cultural borders and are often overlaid. On the other hand, Unsuk Chin resists any explicit reference to either Asian or Western tradition. Rather, she focuses on the technical characteristics of the sheng – particularly its ability to build and sustain multi-voice chords almost indefinitely. She takes this technical capability as a model for her writing for the orchestra. Tan Dun’s embrace of cultural references and Unsuk Chin’s avoidance of them could be said to represent extremes of a continuum of composers’ approaches and philosophies toward multicultural composition.

Regulated changes in the affinity of integrin adhesion receptors ("activation") play an important role in numerous biological functions including hemostasis, the immune response, and cell migration. Physiological integrin activation is the result of conformational changes in the extracellular domain initiated by the binding of cytoplasmic proteins to integrin cytoplasmic domains. The conformational changes in the extracellular domain are likely caused by disruption of intersubunit interactions between the alpha and beta transmembrane (TM) and cytoplasmic domains. Here, we reasoned that mutation of residues contributing to alpha/beta interactions that stabilize the low affinity state should lead to integrin activation. Thus, we subjected the entire intracellular domain of the beta3 integrin subunit to unbiased random mutagenesis and selected it for activated mutants. 25 unique activating mutations were identified in the TM and membrane-proximal cytoplasmic domain. In contrast, no activating mutations were identified in the more distal cytoplasmic tail, suggesting that this region is dispensable for the maintenance of the inactive state. Among the 13 novel TM domain mutations that lead to integrin activation were several informative point mutations that, in combination with computational modeling, suggested the existence of a specific TM helix-helix packing interface that maintains the low affinity state. The interactions predicted by the model were used to identify additional activating mutations in both the alpha and beta TM domains. Therefore, we propose that helical packing of the alpha and beta TM domains forms a clasp that regulates integrin activation.

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