Zeolite-Loaded Alginate-Chitosan Hydrogel Beads as a Topical Hemostat

Hemorrhage is the leading cause of preventable death after a traumatic injury. Commercial hemostatic agents exist, but have various disadvantages including high cost, short shelf-lives, or secondary tissue damage. Polymer hydrogels provide a promising platform for the use of both biological and mechanical mechanisms to accelerate natural hemostasis and control hemorrhage. The goal of this work was to develop hydrogel particles composed of chitosan and alginate and loaded with zeolite in order to stop blood loss by targeting multiple hemostatic mechanisms. Several ii particle compositions were synthesized and then characterized through swelling studies, particle sizing, Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR). The in vitro interactions of the particles were evaluated through coagulation, degradation, platelet aggregation, and cytotoxicity studies. The results indicate that 4% alginate, 1% chitosan, 4% zeolite-loaded hydrogel beads can significantly reduce time to coagulation and increase platelet aggregation in vitro. Future research can look into the efficacy of these particles in vivo.

THE MUSIC PERFORMED FOR THE SACRIFICIAL RITE AT THE ROYAL ANCESTRAL SHRINE OF THE CHOSŎN DYNASTY (1392–1910): INDIVIDUAL AGENCY AND DISCOURSE ON MUSIC EXPRESSED IN THE EIGHTEENTH-CENTURY KOREAN ENCYCLOPEDIA _TONGGUK MUNHŎN PIGO_ (1770)

In 1964, the South Korean government designated the music for the sacrificial rite at the Royal Ancestral Shrine (Chongmyo) as Intangible Cultural Property No. 1, and in 2001 UNESCO awarded the rite and music a place in the Intangible Cultural Heritage of Humanity. The Royal Ancestral Shine sacrificial rite and music together have long been an admired symbol of Korean cultural history, and they are currently performed annually and publicly in an abridged form. While the significance of the modern version of the music mainly rests on the claimed authenticity and continuity of the tradition since the fifteenth century, scholarly inquiry sheds further light on contextual issues such as nationalism, identity, and modernity in the post-colonial era (after 1945), as well as providing additional insights into the music. This dissertation focuses on the Royal Ancestral Shrine’s musical past as reflected in documentary sources, especially those compiled in the eighteenth century during the Chosŏn dynasty (1392–1910). In particular, the substantial music section of an encyclopedic work, Tongguk Munhŏn pigo (Encyclopedia of Documents and Institutions of the East Kingdom, 1770), mainly compiled by a government official, Sŏ Myŏngŭng (1716–1787), provides a considerable amount of information on not only the music and sacrificial rite program, but also on eighteenth-century and earlier concerns about them, as discussed by the kings and ministers at the Chosŏn royal court. After detailed examination of various relevant documentary sources on the historical, social and political contexts, I investigate the various discourses on music and ritual practices. I then focus on Sŏ Myŏngŭng’s familial background, his writings on music prior to the compilation of the encyclopedia, and the corresponding content in the encyclopedia. I argue that Sŏ successfully converted the music section of the encyclopedia from a straightforward scholarly reference work to a space for publishing his own research on and interpretation of the musical past, illustrating what he considered to be the inappropriateness of the existing music for the sacrificial rite at the Royal Ancestral Shrine in the later eighteenth century.

Coarse Graining to Invesitigate Peptide-Lipid Interactions

Experimental characterization of molecular details is challenging, and although single molecule experiments have gained prominence, oligomer characterization remains largely unexplored. The ability to monitor the time evolution of individual molecules while they self assemble is essential in providing mechanistic insights about biological events. Molecular dynamics (MD) simulations can fill the gap in knowledge between single molecule experiments and ensemble studies like NMR, and are increasingly used to gain a better understanding of microscopic properties. Coarse-grained (CG) models aid in both exploring longer length and time scale molecular phenomena, and narrowing down the key interactions responsible for significant system characteristics. Over the past decade, CG techniques have made a significant impact in understanding physicochemical processes. However, the realm of peptide-lipid interfacial interactions, primarily binding, partitioning and folding of amphipathic peptides, remains largely unexplored compared to peptide folding in solution. The main drawback of existing CG models is the inability to capture environmentally sensitive changes in dipolar interactions, which are indigenous to protein folding, and lipid dynamics. We have used the Drude oscillator approach to incorporate structural polarization and dipolar interactions in CG beads to develop a minimalistic peptide model, WEPPROM (Water Explicit Polarizable PROtein Model), and a lipid model WEPMEM (Water Explicit Polarizable MEmbrane Model). The addition of backbone dipolar interactions in a CG model for peptides enabled us to achieve alpha-beta secondary structure content de novo, without any added bias. As a prelude to studying amphipathic peptide-lipid membrane interactions, the balance between hydrophobicity and backbone dipolar interactions in driving ordered peptide aggregation in water and at a hydrophobic-hydrophilic interface, was explored. We found that backbone dipole interactions play a crucial role in driving ordered peptide aggregation, both in water and at hydrophobic-hydrophilic interfaces; while hydrophobicity is more relevant for aggregation in water. A zwitterionic (POPC: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and an anionic lipid (POPS: 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine) are used as model lipids for WEPMEM. The addition of head group dipolar interactions in lipids significantly improved structural, dynamic and dielectric properties of the model bilayer. Using WEPMEM and WEPPROM, we studied membrane-induced peptide folding of a cationic antimicrobial peptide with anticancer activity, SVS-1. We found that membrane-induced peptide folding is driven by both (a) cooperativity in peptide self interaction and (b) cooperativity in membrane-peptide interactions. The dipolar interactions between the peptide and the lipid head-groups contribute to stabilizing folded conformations. The role of monovalent ion size and peptide concentration in driving lipid domain formation in anionic/zwitterionic lipid mixtures was also investigated. Our study suggest monovalent ion size to be a crucial determinant of interaction with lipid head groups, and hence domain formation in lipid mixtures. This study reinforces the role of dipole interactions in protein folding, lipid membrane properties, membrane induced peptide folding and lipid domain formation. Therefore, the models developed in this thesis can be used to explore a multitude of biomolecular processes, both at longer time-scales and larger system sizes.