Physical Sciences and Mathematics Commons^™

Ambient Ionization - Mass Spectrometry: Advances Toward Intrasurgical Cancer Detection, Alan Keith Jarmusch

Open Access Dissertations

My dissertation research has focused on the development of ambient ionization – mass spectrometry (MS) for clinical measurements, specifically intrasurgical cancer detection. The molecular differences between normal and cancerous tissue were detected via direct tissue analysis in vitro by touch spray ionization (TS) or by analyzing sectioned or smeared tissue using desorption electrospray ionization (DESI). The physical form of the tissue, e.g. in vitro sampling, sectioned, or smeared, was inconsequential in differentiating normal from cancerous tissue; however, the spectra acquired by TS and DESI differed due to differences in ionization processes. We envision that TS-MS and DESI-MS could impact diagnostic …

Gonadal Intersex In Teleosts: Mechanisms, Molecular Biomarkers And Diagnostic Assays, Ahmed M.E. Abdel-Moneim Mohamed

Open Access Dissertations

Natural and synthetic estrogenic and androgenic compounds are continuously released into aquatic ecosystems. Exposure of teleost fishes to these contaminants can negatively impact sex differentiation and reproductive output. Specifically, development of gonadal intersex in gonochoristic (fixed sex) fish species has been studied extensively in relation to exposure to this class of compounds. The main objectives of this dissertation were to: 1) conduct field and laboratory studies to investigate the molecular signaling pathways behind the development of gonadal intersex; and 2) establish molecular biomarkers and assays for testing the ability of environmental pollutants to develop this condition using a battery of …

Modeling, Optimization, And Sensitivity Analysis Of A Continuous Multi-Segment Crystallizer For Production Of Active Pharmaceutical Ingredients, Bradley James Ridder

Open Access Dissertations

We have investigated the simulation-based, steady-state optimization of a new type of crystallizer for the production of pharmaceuticals. The multi-segment, multi-addition plug-flow crystallizer (MSMA-PFC) offers better control over supersaturation in one dimension compared to a batch or stirred-tank crystallizer. Through use of a population balance framework, we have written the governing model equations of population balance and mass balance on the crystallizer segments. The solution of these equations was accomplished through either the method of moments or the finite volume method. The goal was to optimize the performance of the crystallizer with respect to certain quantities, such as maximizing the …

Quantitative Modeling Of Spatiotemporal Systems: Simulation Of Biological Systems And Analysis Of Error Metric Effects On Model Fitting, James Hengenius

Open Access Dissertations

Understanding the biophysical processes underlying biological and biotechnological processes is a prerequisite for therapeutic treatments and technological innovation. With the exponential growth of computational processing speed, experimental findings in these fields have been complemented by dynamic simulations of developmental signaling and genetic interactions. Models provide means to evaluate "emergent" properties of systems sometimes inaccessible by reductionist approaches, making them test beds for biological inference and technological refinement.^ The complexity and interconnectedness of biological processes pose special challenges to modelers; biological models typically possess a large number of unknown parameters relative to their counterparts in other physical sciences. Estimating these parameter …

Evaluation Of Yttrium-90 Positron Emission Tomography Dosimetry, Katherine N. Tapp

Open Access Dissertations

Purpose: Radioembolization is a novel treatment which utilizes the liver's unique dual system blood supply to trap yttrium-90 (⁹⁰Y) microspheres in microvasculature near liver tumors. Radioembolization dose planning and dosimetry are based on crude, inaccurate assumptions due to the lack of knowledge of patient specific ⁹⁰Y microsphere distribution. In recent years, the very small 3.1867e-5 internal pair production decay branch of ⁹⁰Y has been shown to allow for positron emission tomography (PET) imaging following radioembolization. This work explores the accuracy and limitation of ⁹⁰Y PET imaging due to the extremely low signal to noise (SNR) …

Structured Deterministic Models Applied To Malaria And Other Endemic Diseases, Katia Patricia Vogt Geisse

Open Access Dissertations

This thesis includes modeling studies on three structured deterministic models. These models are used to study the disease dynamics of malaria or the joint disease dynamics of HIV and HSV-2. Each of the models includes multiple components containing individuals in various epidemiological classes for the purpose of addressing questions that are of interests to biologists and epidemiologists. Some of the compartments have a continuous age-structure, which is necessary for studying the specific biological questions under investigation.^ In Chapter 2 a chronological-age structured deterministic model for malaria is presented. The model includes the human and mosquito populations with the human population …

Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago

Open Access Dissertations

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 0.3% of the total U.S. population, and its prevalence increases with age. Two neuropathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain involved in initiating and sustaining movement, and the presence of cytosolic inclusions called Lewy bodies (LBs) in various brain regions. LBs are enriched with fibrillar forms of the presynaptic protein &agr;-synuclein (aSyn). Two autosomal recessive genes implicated in familial PD are PARK9, encoding the P-type ATPase ATP13A2, a lysosomal ATPase; and …

An Epidemic Model Structured By The Time Since Last Infection, Jorge Alturo Alfaro Murillo

Open Access Dissertations

Epidemiological models structured by time since infection have their origin in the seminal work of 1927 by Kermack and McKendrick. Compared to ordinary differential equations (ODE) models, they are able to capture differences in infectivity of the individuals in a more suitable manner. Their use declined in the second half of the 20th century, probably because the theory for ODE models is more robust, complete and has proved successful in providing insights and predictions for many epidemiological problems. Nevertheless, it is important to understand in what occasions the inclusion of time since infection may alter the outcomes in a significant …

Altered Cholesterol Metabolism In Human Cancers Unraveled By Label-Free Spectroscopic Imaging, Shuhua Yue

Open Access Dissertations

Despite tremendous scientific achievements, cancer remains the second leading cause of death in the United States. Metabolic reprogramming has been increasingly recognized as a core hallmark of cancer. My dissertation work identified novel diagnostic markers and therapeutic targets for human cancers through the study of cholesterol in cancer cells.

Enabled by label-free Raman spectromicroscopy, we performed the first quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases, but not in normal prostate, benign prostatic hyperplasia, or …