University of arkansas and dissertations

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University of arkansas and dissertations

Recent Dissertations We are pleased to showcase several examples of the research accomplishments of our doctoral students. Analysis of protein-protein interactions using chemical cross-linking mass spectrometry CXMS: Novel computational approaches by Mihir Jaiswal Chemical cross-linking mass spectrometry CXMS is a useful method for studying protein-protein interactions.

Short length non-specific cross-linkers are able to capture many interactions between and within proteins. However, due to the complexity of mass spectra of the non-specific cross-linked peptides coupled with unavailability efficient data analysis tool non-specific cross-linkers are not widely used.

The XLPM algorithm has a novel b-y ion filter. The XLPM is validated on non-specific cross-linker data successfully. Furthermore, I have developed a new probabilistic scoring system for the protein mass spectrometry data analysis using database searching.

The scoring system can be applied to large scale CXMS data analysis.

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In nutshell, the higher charges, abundance of non-cross-linked peptide over cross-linked peptides and different chemistries of cross-linking reagents make the CXMS data analysis difficult.

The XLPM algorithm and the new scoring system open new frontiers for the CXMS data analysis for the overall application of the short length non-specific cross-linkers. Construction of class I HLA-binding peptidome by Heng Luo The human leukocyte antigens HLAs can capture endogenous or exogenous peptides and set up a cascade which results in immune activation to fight a pathogen or sometimes to trigger autoimmune diseases or adverse drug reactions.

Understanding HLA-peptide binding is essential for the development of vaccines and protein therapies, the identification of methods to prevent autoimmune diseases and the prediction of adverse drug reactions.

Using an in silico approach we generated a 9-mer peptidome for Class I HLAs from the human proteome and harvested experimental HLA-peptide binding data from a variety of databases. Unfortunately, many peptides in the peptidome do not have experimental HLA binding data in the databases.

To construct a complete HLA-binding peptidome, these will need to be predicted. After a literature review, we found the current prediction models for HLA-peptide binding have limitations and are not reliable for all the peptides in the absence of experimental data. Therefore, we developed a network-based algorithm to overcome the limitations and to provide HLA binding predictions for the peptides without experimental data.

We found network analysis is an effective approach for analysis of sparse big datasets such as the HLA-binding of peptides.

We developed sNebula, a similar neighbor-edges based and unbiased leverage algorithm and this outperformed the existing methods. Since the HLAs and peptides are two core components to trigger immunologic responses, the complete Class I HLA-binding peptidome accomplished in this study provides the scientific community a rich source for understanding the interactions between Class I HLAs and peptides, potentially assisting in the development of vaccines and protein therapeutics, facilitating studies of autoimmune diseases and improving the prediction of drug adverse reactions.

Applications of structure based drug design to generate high affinity anti-methamphetamine immunotherapy and to identify novel inhibitors of Lox-1 to treat atherosclerosis by Shraddha Thakkar Computer-aided rational drug design is one of the most promising approaches for the development of effective drug therapies.

This dissertation describes applications of rational structure-based techniques in two cases. In the first study, we enhanced the potency of a therapeutic antibody against methamphetamine. In the second study we identified potentially therapeutic molecules to treat atherosclerosis.

Methamphetamine abuse is a serious health hazard and a single chain variable fragment scFv of a therapeutic anti-METH antibody has been developed at this University.

In this research we introduced rationally designed point mutations in the binding pocket to enhance the affinity towards METH and its active metabolite amphetamine AMP. One mutant, scFv-S93T, showed a 3. Structural analysis of the scFv-S93T: METH complex revealed that the mutation caused the expulsion of a water molecule from the cavity, creating a more hydrophobic environment in the binding pocket.

We also applied computer-aided rational drug design techniques to identify anti-atherosclerotic drugs using the lectin-like oxidized low-density lipoprotein receptor 1 LOX-1 as a target.

Atherosclerotic related diseases are a major cause of death in the United States. This key event causes endothelial dysfunction and plaque formation and leads to the development of atherosclerosis. In this research, we used the high-resolution crystal structure of LOX-1 to perform rational virtual screening and docking studies to identify novel inhibitors of LOX-1 with the goal to inhibit LOX-1 and ox-LDL interaction.

In addition, the cell-based assays Dr. A multifaceted analysis of triple negative breast cancer with high-throughput technologies by Aleksandra Markovets As a subtype of breast cancer, Triple Negative Breast Cancer TNBC is characterized by a unique molecular profile, distinct patterns of metastasis and a very aggressive phenotype.

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Without viable, confirmed therapeutic targets, treatment of TNBC remains one of the most pressing clinical challenges. Hypothesis-driven research on TNBC has focused on a handful of molecules suspected of playing a role in the disease etiology and has yielded limited success.

The mechanisms underlying the origin and development of this disease still remain unknown.

University of arkansas and dissertations

This gap in understanding the molecular mechanisms in TNBC was critical for undertaking the following analysis of this disease. In this study, we applied a systems biology approach and analyzed TNBC cells on multiple molecular levels to explore the different aspects of tumor cells and to obtain maximum insights into the biology of this disease.

High-throughput transcriptomic RNA-Seq and proteomic tandem mass-spectrometry sequencing technologies were particularly valuable for this type of exploratory research. Briefly, mRNAs and proteins from cancer and cancer-free surrounding tissue were extracted from clinical surgical breast specimens.

Transcriptome analysis of TNBC revealed molecular differences in global gene expression profiles between cancer and cancer-free control samples.preparing your master’s thesis or doctoral dissertation for final submission to the world-wide-web as part of the University of Arkansas Electronic Thesis and Dissertation Collection.

The Graduate School wishes you every success in preparing your document, and we . I received my Ed.D. from the University of Phoenix in My Chair and Committee Members were very helpful and supportive.

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The University of Phoenix School of Academic Studies offered demanding classes that fit perfectly with my busy schedule and travels.

Thesis: “A Guide to Selected Manuscript Collections in the University of Arkansas Library” Advisor: Walter Brown Dianna Susan Kirk Thayer. World Languages, Literatures & Cultures. Message from the Chair Welcome from Dr.

Steve Bell. Welcome to the Department of World Languages at the University of Arkansas. Whether you are a prospective student, a current student, an alumnus or a visitor from elsewhere, we hope you will find reflected here some of the energy, diversity, and. The University of Southern Mississippi was founded on March 30, , as Mississippi Normal College, a teacher-training Normal College was created to standardize the process of training upcoming teachers.

part of the University of Arkansas Electronic Thesis and Dissertation Collection. The Graduate School wishes you every success in preparing your document, and we are pleased to serve as a resource.

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