Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    Impact of lipopolysaccharide administration on novel RNA biomarkers for systemic inflammation in swine
    (2020) Swain, Trevon Brandon; Dayie, Theodore K; Myers, Michael J; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    In veterinary medicine, inflammation in swine is evaluated solely by clinical signs. This method is often unreliable when assessing large animal populations because of inconsistent interpretations of clinical observations between different clinicians. The lack of a validated swine animal model prevents an accurate measurement of inflammation and inhibits the development of new veterinary effective drugs for swine. This study examined whether changes in miRNA expression can predict the severity of the inflammatory response in swine after administration of lipopolysaccharide (LPS) from Escherichia coli (E.coli). Identification of a reliable biomarker from a systemic inflammatory response needs to be easily obtained, safe, and provide the lowest risk of discomfort to the subject. The correlation of the clinical signs with individual miRNA levels may establish a plasma biomarker that can determine the severity of inflammation in swine. The long-term goal is to determine the most powerful tool for analysis and biomarker discovery. Exploring the different methodologies and monitoring different miRNAs increases the likelihood for potential advancements in disease detection applications
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    FOOD PROTEIN-BASED NANOPARTICLES AS BIOAVAILABILITY ENHANCING ENCAPSULANTS
    (2015) Teng, Zi; Wang, Qin; Food Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Proteins are attractive bioavailability enhancers for poorly absorbed nutraceuticals or drugs, owing to their natural abundance, amphiphilic nature, and desirable biocompatibility. This study systematically investigated the preparation, characterization, and application of protein-based nanoparticles as effective nutraceutical/drug carriers. Soy protein, one of the most widely utilized proteins, was firstly employed for preparing nanoparticles. The particle formation involved partial unfolding of protein molecules, limited aggregation in the presence of the antisolvent, crosslinking via chemical bonds, and refolding of the constituent monomers. Satisfactory encapsulation efficiency (EE) and time-dependent release of curcumin, a chemopreventive compound, were observed. The nanoparticles were further subjected to conjugation with folic acid, a cancer cell-targeting ligand. A pronounced increase in the accumulation in tumor cells such as Caco-2 was achieved upon folic acid conjugation, which demonstrated the potential of this technique for the targeted delivery of anti-cancer drugs. To overcome the rapid digestion of soy protein nanoparticles in the gastrointestinal tract, carboxymethyl chitosan was employed as a second coating layer by a simple ionic gelation method. The formed particles exhibited satisfactory EE for vitamin D3 and controlled releasing profile in vitro. Beta lactoglobulin (BLG) as another protein of interest is a major component of whey protein, serving as a natural carrier for lipophilic nutrients. Our study suggested that the interaction between BLG and curcumin could be promoted by tuning the antisolvent content. A loading capacity (LC) and EE of up to 11% and 98% respectively could be achieved under the optimal conditions. Moreover, nanoparticles prepared with cationic beta-lactoglobulin (CBLG) were able to transport most of the encapsulated drug intact through the gastrointestinal (GI) tract owing to its desirable particle integrity. Other advantages of CBLG-based systems included superior mucoadhesion, permeation across the small intestine epithelia, and cellular uptake. Finally, as CBLG molecules/nanoparticles absorbed the negatively charged serum proteins in the cell culturing medium, their surface properties, cytotoxicity, and cellular uptake were significantly altered. This series of studies not only demonstrated the efficiency and versatility of protein-based nanoparticles as bioavailability enhancers but also shed some light on the mechanisms for the encapsulation, transport, and delivery of nutraceuticals or drugs.
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    A Proteomics Approach to the Examination of Proteins in Marine Systems
    (2014) Faux, Jessica Felicia; Harvey, Henry R; Marine-Estuarine-Environmental Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The response of global carbon and nitrogen cycles to future climate change is uncertain. In order to understand the impacts that future changes to climate will have on these cycles, a more detailed understanding of them is essential. This dissertation utilizes a combined approach of molecular biomarkers and proteomic investigations to elucidate historic source material contributions and microbial protein production to contribute to a more thorough understanding of the marine carbon and nitrogen cycles. The examination of molecular organic biomarkers throughout an Arctic sediment core showed the dominant input in the area was from marine sources with lower but steady contributions from terrestrial sources during the Holocene. Attempts to recover proteins from deeper sediments to correlate with lipid biomarkers were unsuccessful but led to the optimization of an extraction protocol for an added protein standard, bovine serum albumin, from sediments. An investigation into the expressed proteome of the heterotrophic marine bacterium, Ruegeria pomeroyi, under environmentally realistic carbon supply conditions during exponential and stationary growth phases identified over 2000 proteins. The most abundant proteins identified were responsible for porins, transport, binding, translation, and protein refolding and could represent potential biomarkers of bacterial processes and/or activity. A parallel study of R. pomeroyi, in which 13C-labeled leucine was added to the culture during exponential growth phase, showed labeled incorporation ranging from 16 to 21% of the total proteins produced depending on growth phase. The widespread distribution of the label among the growth phases indicates active recycling by the bacteria. This study demonstrates a method through which bacterial protein synthesis can be tracked. A study of the marine diatom Thalassiosira pseudonana acclimated to iron replete or iron-limited conditions showed iron-limited organisms increased proteins involved in pathways associated with intracellular protein recycling, the pentose phosphate pathway, lower photosynthetic energy production, enhancement of photorespiration, and increased polysaccharide production. This application of proteomics to the examination of proteins in marine sediments, a marine diatom, and a heterotrophic marine bacterium shows the potential for these techniques to help elucidate the fate of proteins in marine environments and could be used in conjunction with well-established molecular organic marker studies.
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    Photolytic Studies of Aryl and Heteroaryl Nitrenium Ions: Laser Flash Photolysis Studies
    (2006-05-07) Thomas, Selina Ivan; Falvey, Daniel E; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    The objective of the thesis was to understand the chemical and kinetic behavior of arylnitrenium ions and a heteroaromatic nitrenium ion through photolytic studies. N-(4,4'-dichlorodiphenyl) nitrenium ion and N-(4,4'-dibromodiphenyl) nitrenium ion are the halogenated counterparts of diphenylnitrenium ions and are generated photochemically from their respective N-(4,4'-dihalogenated diphenylamino)-2,4,6-trimethylpyridinium tetrafluoroborate salts. The halogenated diarylnitrenium ions are ground state singlets that live for more than 1 x 105 ns in acetonitrile. In the absence of nucleophiles, these ions decay to form a dimerized hydrazine. These ions react with nucleophiles such as water and alcohol at a rate constant of 104 - 105M-1s-1 and at diffusion limit with chlorides. With arenes, these ions react via electron transfer mechanism and nucleophilic addition process. The rate constants for the electron transfer mechanisms are between 105 - 109 M-1 s-1 and depend on the Eox of the arenes. Arenes with Eox above 1.78 V showed no reactivity towards the ion. Unlike other diarylnitrenium ions, the halogenated diarylnitrenium ions react with hydrogen atom donors via a hydrogen atom transfer mechanism. The triplet behavior of these ions is attributed to singlet-triplet intersystem crossing facilitated by the lower singlet-triplet energy gap. Therefore, it has been concluded that substituting halogens in diphenylnitrenium ion lowers the singlet-triplet energy gap and increases the lifetime of these ions. (N-Methyl-N-4-biphenylyl) nitrenium ion generated by photolysis was reacted with amino acids and proteins to determine their reactivity with these ions. Eight amino acids were observed to react with the ion at a rate constant of 107 - 109 M-1 s-1. The rate constants depend on the nucleophilicity of the side chains of the amino acids. In addition, this ion also reacts rapidly with proteins with a rate constant of 108 M-1 s-1, comparable to their reactions with ss-DNA. Investigations on generating the quinoline N-oxide nitrenium ions showed that the transient species from the photolysis of 4-azidoquinoline N-oxide (4-AzQO) shows more characteristics of a nitrenium ion. The formation of 4-aminoquinoline N-oxide upon photolysis of 4-AzQO in acetonitrile with 10% sulphuric acid and the electron transfer reactions observed with arenes, indicate that the transient species generated could be a heteroaromatic nitrenium ion. However, more experiments are needed to confirm the assignment.