Other Chemistry Commons^™

The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow

Arts & Sciences Electronic Theses and Dissertations

This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …

Production Of Medical Radioisotopes Using Titanium Accelerator Targets, Christopher Shaun Loveless

Arts & Sciences Electronic Theses and Dissertations

Theranostic radiopharmaceuticals enable diagnostic imaging and radionuclide therapy in patients using a single molecular agent labeled with a diagnostic-therapeutic pair (e.g., 68Ga/177Lu) or a theranostic radionuclide (e.g., 131I). This theranostic approach can help inform patient-specific treatment plans and improve clinical outcomes. Radionuclide pairs used in theranostic agents fall into two categories: pseudo matched-pairs (e.g., 68Ga/177Lu) and matched-pairs (e.g., 124I/131I). Pseudo matched-pair radionuclides have similar chemistries and pharmacokinetics when bound to the same bioconjugate molecule. In contrast, identical chemistries and pharmacokinetics can be obtained by using the matched-pair radionuclides.

The isotopes of Sc include two diagnostic radioisotopes, 43Sc & 44Sc, and …

Fast-Forward Protein Folding And Design: Development, Analysis, And Applications Of The Fast Sampling Algorithm, Maxwell Isaac Zimmerman

Arts & Sciences Electronic Theses and Dissertations

Molecular dynamics simulations are a powerful tool to explore conformational landscapes, though limitations in computational hardware commonly thwart observation of biologically relevant events. Since highly specialized or massively parallelized distributed supercomputers are not available to most scientists, there is a strong need for methods that can access long timescale phenomena using commodity hardware. In this thesis, I present the goal-oriented sampling method, Fluctuation Amplification of Specific Traits (FAST), that takes advantage of Markov state models (MSMs) to adaptively explore conformational space using equilibrium-based simulations. This method follows gradients in conformational space to quickly explore relevant conformational transitions with orders of …

A Physics-Based Intermolecular Potential For Biomolecular Simulation, Joshua Andrew Rackers

Arts & Sciences Electronic Theses and Dissertations

The grand challenge of biophysics is to use the fundamental laws of physics to predict how biological molecules will move and interact. The atomistic HIPPO (Hydrogen-like Intermolecular Polarizable Potential) force field is meant to address this challenge. It does so by breaking down the intermolecular potential energy function of biomolecular interactions into physically meaningful components (electrostatics, polarization, dispersion, and exchangerepulsion) and using this function to drive molecular dynamics simulations. This force field is able to achieve accuracy within 1 kcal/mol for each component when compared with ab initio Symmetry Adapted Perturbation Theory calculations. HIPPO is capable of this accuracy because …

Isotopically-Resolved Neutron Cross Sections As Probe Of The Nuclear Optical Potential, Cole Davis Pruitt

Arts & Sciences Electronic Theses and Dissertations

Neutron scattering experiments provide direct access to the forces experienced by nucleons in the nuclear environment. Due to the experimental difficulty of cross section measurements with neutrons, isotopically-resolved neutron scattering cross sections are sorely needed as inputs for many nuclear models. This dissertation presents the results from a campaign of isotope-specific neutron total cross section measurements on 16,18O, 58,64Ni, 112,124Sn, and 103Rh from 3-450 MeV and elastic scattering differential cross section measurements on 112,nat,124Sn at 11 and 17 MeV. Equipped with these new data and with computational improvements to the Dispersive Optical Model (DOM), we present DOM treatments of 16,18O, …

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

McKelvey School of Engineering Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on …

Modeling The Bioactivation And Subsequent Reactivity Of Drugs, Tyler Brian Hughes

Arts & Sciences Electronic Theses and Dissertations

Metabolism can convert drugs to harmful reactive metabolites that conjugate to DNA and off-target proteins. Reactive metabolites are a significant driver of both drug candidate attrition and withdrawal from the market of already approved drugs. Unfortunately, reactive metabolites are difficult to study in vivo, because they are transitory and generally do not circulate. Instead, this work computationally models both metabolism and reactivity. Using deep learning, predictive models were developed for the metabolic formation of quinones and epoxides, which together account for about half of known reactive metabolites. Additionally, an accurate model of DNA and protein reactivity was constructed, which predicts …

Radiolabeled Nanohydroxyapatite As A Platform For The Development Of New Pet Imaging Agents, Stacy Lee Queern

Arts & Sciences Electronic Theses and Dissertations

Positron emission tomography (PET) imaging utilizes drugs labeled with positron emitters to target and evaluate different biological processes occurring in the body. Tailoring medicine to the individual allows for higher quality of care with better diagnosis and treatment and is a key purpose for advancing research into developing new platforms for PET imaging agents. A PET nuclide of high interest for the development of these agents is 89Zr. This can be attributed to the long half-life of 3.27 days and low positron energy of 89Zr.

In this work, we developed a production method for 89Zr using Y sputtered coins that …

Spin Alignment Generated In Inelastic Nuclear Reactions, Daniel Hoff

Arts & Sciences Electronic Theses and Dissertations

The spin alignment of inelastically excited 7Li projectiles, when the target remains in its ground state, was determined through angular-correlation measurements between the breakup fragments of 7Li_ (_ + t). It was found that 7Li_ is largely aligned along the beam axis (longitudinal) in this type of inelastic reaction, regardless of the target. This longitudinal alignment is well described by DWBA calculations, which can be explained by an angular-momentum-excitation-energy mismatch condition. These calculations also explain the longitudinal spin alignment of excited nuclei in several other systems, showing the phenomenon is more general. The experiment involving 7Li was performed at the …

Cyclotron Production And Biomedical Imaging Applications Of The Pet Isotope Manganese-52, Andrew Lake Wooten

McKelvey School of Engineering Theses & Dissertations

Manganese is an important element for biomedical research because of its roles as an essential micronutrient and as a neurotoxin from chronic elevated exposure, as well as the role of manganese(II) as a paramagnetic core for contrast agents in T1-weighted magnetic resonance imaging (MRI). Using a radiotracer of manganese provides excellent sensitivity for studying these phenomena, but only 52Mn met the criteria for our experiments: (1) a half-life (t1/2=5.6 days) that was long enough to examine timepoints over several days, (2) a half-life that was short enough to emit sufficient counts for a realistic scan time, and (3) emitted radiation …