Investigative Techniques Commons^™

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam

Theses and Dissertations

Lack of standard guidelines for optimal needle insertion during high-dose-rate (HDR) intracavitary-interstitial (IC-IS) brachytherapy of the cervix means a sophisticated and technical skillset of inserting needles next to IC applicators must be developed to enhance plan quality. This study sought to evaluate the performance of two separate direction modulated brachytherapy (DMBT) tandem applicators used in conjunction with one set of novel DMBT ovoids, to effectively obviate the need for IS needles.

A cohort of 32 retrospective clinical HDR brachytherapy plans was re-planned with Varian’s BrachyVision^® treatment planning system, using VEGO^® inverse optimization algorithm, with dose heterogeneity accounted for …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Mass Spectrometry Based Lipidomic Investigation Of Staphylococcus Aureus Lipid Metabolism And Characterization Of Lipase A, Naren Gajenthra Kumar

Theses and Dissertations

Staphylococcus aureus produces an arsenal of virulence factors and is adept at colonizing multiple hosts by employing specific processes to persist at different sites of infection. Infections caused by this pathogen range from self-limiting infections of the skin like folliculitis to life threatening and chronic conditions like infective endocarditis, non-healing diabetic foot ulcers and atopic dermatitis. As the field continues to expand its understanding of the mechanisms by which this pathogen rapidly develops resistance to new antibiotics, the underlying mechanisms that facilitates niche adaptation and host colonization among healthy individuals remain elusive.

Bacterial and host lipid metabolism presents and area …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati

Theses and Dissertations

In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is …

Illumination Of The Golgi Apparatus Of Pathogenic And Nonpathogenic Naegleria Species, Tyler M. Poe

Theses and Dissertations

In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and …

Motion-Induced Artifact Mitigation And Image Enhancement Strategies For Four-Dimensional Fan-Beam And Cone-Beam Computed Tomography, Matthew J. Riblett

Theses and Dissertations

Four dimensional imaging has become part of the standard of care for diagnosing and treating non-small cell lung cancer. In radiotherapy applications 4D fan-beam computed tomography (4D-CT) and 4D cone-beam computed tomography (4D-CBCT) are two advanced imaging modalities that afford clinical practitioners knowledge of the underlying kinematics and structural dynamics of diseased tissues and provide insight into the effects of regular organ motion and the nature of tissue deformation over time. While these imaging techniques can facilitate the use of more targeted radiotherapies, issues surrounding image quality and accuracy currently limit the utility of these images clinically.

The purpose of …

Advanced Imaging Analysis For Predicting Tumor Response And Improving Contour Delineation Uncertainty, Rebecca N. Mahon

Theses and Dissertations

ADVANCED IMAGING ANALYSIS FOR PREDICTING TUMOR RESPONSE AND IMPROVING CONTOUR DELINEATION UNCERTAINTY

By Rebecca Nichole Mahon, MS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2018

Major Director: Dr. Elisabeth Weiss,

Professor,

Department of Radiation Oncology

Radiomics, an advanced form of imaging analysis, is a growing field of interest in medicine. Radiomics seeks to extract quantitative information from images through use of computer vision techniques to assist in improving treatment. Early prediction of treatment response is one way of improving overall patient care. This work …

An Association Study Between Adult Blood Pressure And Time To First Cardiovascular Disease, Yongjia Pu

Theses and Dissertations

BACKGROUND: Several studies have demonstrated the association between the time to hypertension event and multiple baseline measurements for adults, yet other survival cardiovascular disease (CVD) outcomes such as high cholesterol and heart attack have been somewhat less considered. The Fels Longitudinal Study (FLS) provides us an opportunity to connect adult blood pressure (BP) at certain ages to the time to first CVD outcomes. The availability of long-term serial BP measurements from FLS also potentially allows us to evaluate if the trend of the measured BP biomarkers over time predicts survival outcomes in adulthood through statistical modeling.

METHODS: When the reference …