Physical Sciences and Mathematics Commons^™

A Framework For The Statistical Analysis Of Mass Spectrometry Imaging Experiments, Kyle Bemis

Open Access Dissertations

Mass spectrometry (MS) imaging is a powerful investigation technique for a wide range of biological applications such as molecular histology of tissue, whole body sections, and bacterial films , and biomedical applications such as cancer diagnosis. MS imaging visualizes the spatial distribution of molecular ions in a sample by repeatedly collecting mass spectra across its surface, resulting in complex, high-dimensional imaging datasets. Two of the primary goals of statistical analysis of MS imaging experiments are classification (for supervised experiments), i.e. assigning pixels to pre-defined classes based on their spectral profiles, and segmentation (for unsupervised experiments), i.e. assigning pixels to newly …

Synthesis And Performance Of Novel Supramolecular Tools For Single-Particle Cryogenic Electron Microscopy And Drug And Gene Delivery, Kyle J. Wright

Open Access Dissertations

High-resolution biomacromolecular structure elucidation is fundamentally important to structure-based drug design and basic research into complex biochemical processes. Cryo-EM is an emerging alternative to XRD and NMR that is complementary in many ways relative to XRD and NMR. Materials approaches to cryo-EM are anticipated to greatly facilitate the cryo-EM process, allowing progress toward a more high-throughput application of cryo-EM to address challenges in structural biology. ^ Various affinity-based approaches inspired by approaches previously introduced for 2D crystallization were developed for facilitation of cryo-EM. A library of affinity lipopolymer constructs were synthesized consisting of lipopolymers of various PEG molecular weights conjugated …

Bioorthogonal Reactions: Synthesis And Evaluation Of Different Ligands In Copper Catalyzed Azide-Alkyne1,3-Dipolar Cycloaddition (Cuaac), Zainab Abdullah Almansaf

Graduate Theses and Dissertations

The Copper CatalyzedAzide-Alkyne1,3-Dipolar Cycloaddition (CuAAC) reaction has unique features that qualify it to be one of the best click reactions. Its applications have been shown in different aspects and for multiple purposes. The oxidative degradation of biological systems (labile proteins and live cells) is, however, generally recognized as the major problem when using this reaction in living systems. Reactive oxidation species can be easily produced in the presence of copper(II), ascorbate and air, and this is the main cause of toxicity. However, the uses of ligands have shown a major impact on reducing copper toxicity, protecting Cu(I) from the redox …

Intestinal Adaptation To Repeated Exposure Of Flavonoid-Rich Foods: In Vitro And Clinical Data, Bejamin W. Redan

Open Access Dissertations

Interest in application of flavonoids for chronic disease prevention has grown significantly, but the low oral bioavailability of these compounds from acute doses is commonly highlighted as a limitation when considering their biological significance. Still, the impact of broad dietary patterns such as repeated exposure on flavonoid’s absorption, metabolism, and eventual efficacy is critical to consider since evidence suggests that their bioavailability may be enhanced with repeated exposure. To fill this gap in knowledge, this dissertation will focus on three major areas including characterization of flavonoid metabolites, in addition to use of in vitro models and clinical work to test …

Investigation Of Cellular Microenvironments And Heterogeneity With Biodynamic Imaging, Daniel Alexander Merrill

Open Access Dissertations

Imaging of biological tissue in a relevant environment is critical to accurately assessing the effectiveness of chemotherapeutic agents in combatting cancer. Though many three-dimensional (3D) culture models exist, conventional in vitro assays continue to use two-dimensional (2D) cultures because of the difficulty in imaging through deep tissue. 3D tomographic imaging techniques exist and are being used in the development of 3D efficacy assays. However, most of these assays look at therapy endpoint (dead or living cancer cell count) and do not capture the dynamics of tissue response.

Biodynamic imaging (BDI) is a 3D tomographic imaging and assay technique that uses …

Enhancing Silymarin Fractionation Via Molecular Modeling Using The Conductor-Like Screening Model For Real Solvents, Emma C. Brace

Open Access Theses

The market for bio-based products from plant sources is on the rise. There is a global challenge to implement environmentally clean practices for the production of fuels and pharmaceuticals from sustainable resources. A significant hurdle for discovery of comparable plant-derived products is the extensive volume of trial-and-error experimentation required. To alleviate the experimental burden, a quantum mechanics based molecular modeling approach known as the COnductor-like Screening Model for Real Solvents (COSMO-RS) was used to predict the best biphasic solvent system to purify silymarins from an aqueous mixture. Silymarins are a class of flavonolignans present in milk thistle ( Silybum marianum …

Investigation Of The Interaction Of Dimeric Ruthenium Complexes With Cytochrome B5, Christopher Dain Rupar

Graduate Theses and Dissertations

Photoreactive complexes to study the kinetics of electron transfer of proteins have been in use for a long time. It has always been speculated that complexes bind near the heme or the electron transfer reaction would not occur. But it is unkown exactly how the complex interacts with the protein. The structural, thermodynamic, and kinetic properties of rat liver microsomal cytochrome b5 were investigated when bound to ruthenium dimer complexes. Heteronuclear Single Quantum Coherence studies support a dynamic binding model of a dimer Ru complex bound near the protein’s heme involving residues H39, E44, G42, V61, G62, and H63. The …

Mechanism Of Rapid Electron Transfer Reactions Involving Cytochrome Bc1, Cytochrome C And Cytochrome Oxidase, Jeremy Erik Durchman

Graduate Theses and Dissertations

Electron transfer between mitochondrial proteins complexes represents the primary means by which living things acquire the requisite energy for survival. The coupling of electron transfer to proton translocation creates an electrochemical gradient that drives the synthesis of highly energetic compounds such as ATP. The purpose of these studies is to measure rates of electron transfer and elucidate the important governing factors in the redox events involving cytochrome bc1, cytochrome c and cytochrome oxidase. Using rapid initiation of redox events triggered by laser flash excitation of ruthenium compounds, and strategically monitoring unique spectral properties of these proteins in the visible region …

Spread Trading In Corn Futures Market, Ryan D. Napier

Graduate Theses and Dissertations

The non-linear relationship between old crop – new crop year spreads in corn futures market and stock-to-use (S-U) ratios published by the United States Department of Agriculture is analyzed. Using a non-linear logarithmic smooth transition regression (LSTR) model, we capture asymmetric market behaviors in high and low S-U regimes. Capturing this relationship and understanding the non-linear aspects of the relationship is of interest of grain merchandizers and speculators in the market. A spread trading strategy is simulated for the sample period, January 1985 through April 2015, to determine if the non-linear relationship is a profitable arbitrage opportunity in the market.

Identification Of Biomarkers For The Overall Survival Of Ovarian Cancer Patients, Kristi Mai

Graduate Theses and Dissertations

Rapid advance in sequencing technology has led to genome-wide analysis of genetic and epigenetic features simultaneously, making it possible to understand the biological mechanisms underlying cancer initiation and progression. However, how to identify important prognostic features poses a great challenge for both statistical modeling and computing. In this thesis, a network-based approach is applied to the Cancer Genome Atlas (TCGA) ovarian cancer data to identify important genes related to the overall survival of ovarian cancer patients. In the first step, a stepwise correlation-based selector is used to reduce the dimensionality of TCGA data, by filtering out a large number of …

Experimental And Computational Studies Of Cortical Neural Network Properties Through Signal Processing, Wesley Patrick Clawson

Graduate Theses and Dissertations

Previous studies, both theoretical and experimental, of network level dynamics in the cerebral cortex show evidence for a statistical phenomenon called criticality; a phenomenon originally studied in the context of phase transitions in physical systems and that is associated with favorable information processing in the context of the brain. The focus of this thesis is to expand upon past results with new experimentation and modeling to show a relationship between criticality and the ability to detect and discriminate sensory input. A line of theoretical work predicts maximal sensory discrimination as a functional benefit of criticality, which can then be characterized …

Advances In Solid Phase Microextraction For The Analysis Of Volatile Compounds In Explosives, Tire Treatments, And Entomological Specimens, William D. Kranz

Open Access Dissertations

Solid phase microextraction is a powerful and versatile technique, well-suited to the analysis of numerous samples of forensic interest. The exceptional sensitivity of the SPME platform, combined with its adaptability to traditional GC-MS systems and its ability to extract samples with minimal work-up, make it appropriate to applications in forensic laboratories.

In a series of research projects, solid phase microextraction was employed for the analysis of explosives, commercial tire treatments, and entomological specimens. In the first project, the volatile organic compounds emanating from two brands of pseudo-explosive training aids for use in detector dog imprinting were determined by SPME-GC-MS, and …

Mutlifunctional Platforms For Gene And Drug Delivery For Cancer Therapy, Jeffery J. Ambrose Jr.

Doctoral Dissertations

The National Cancer Institute and the American Cancer Society estimate that 1.6 million new cancer incidences and over half a million cancer related deaths occur annually [1][2]. Cancer the second most common cause of death in the United States [1], [2]. Although the causes of cancer can vary depending on cell type, all or almost all instances of cancer arise from a mutation or from an abnormal activation of the cellular genes that control cell growth and mitosis [3].

Treatment of a given cancer type depends on the subtype, stage and progression of the cancer. Varieties of cancer therapy include …