The entirety of the investigation discussed in this paper was confined to a study of the spin resonance properties of unpaired electrons of an organic free radical. In the remainder of the paper the theory of electron spin resonance, the apparatus used in the investigation, and the experimental results obtained are discussed in that order.

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The primary goal of this research is to engineer solutions facilitating the utilization of bacteriophages as naturally occurring bactericidal agents for combatting multidrug-resistant (MDR) bacterial infections. Bacteriophages, which are bacterial viruses, represent self-replicating antibacterial agents known for their remarkable specificity in targeting bacterial cells. This specificity stands in sharp contrast to the indiscriminate and broad-spectrum actions of many currently employed antimicrobials across various sectors. Specificity of bacteriophages is a double-sided sword, often requiring large-scale phage hunting and phage biobank screening. This, combined with the lack of a global phage biobank can significantly limit access to phage therapeutics. I have developed a rapid, high-throughput platform focused on the detection of phage-mediated adenosine triphosphate (ATP) release via enzymatic ATP bioluminescence assay to identify highly lytic phages targeting MDR bacterial pathogens. I also used pullulan-trehalose sugar mixture to stabilize the ATP bioluminescence assay components at physiological temperatures. The sugar mixture also enhanced the desiccation tolerance of the ATP assay components along with phage, enabling the creation of all-inclusive shelf-stable tablets. The resulting tablets proved effectiveness and reliability in tracking phage-mediated bacterial cell lysis, and the pullulan-trehalose encapsulation significantly enhanced both the signal and desiccation tolerance of the phage and assay components. Next, I developed a bi-functional phage delivering nanoclay-based injectable hydrogel that can serve as both antibacterial and osteoinductive therapeutic hydrogel for treating bone and implant associated infections. The in vitro results for phage-loaded injectable hydrogels confirmed strong antimicrobial action against bacterial biofilms, in both biofilm prevention and biofilm dispersion challenges. Continuing the phage biomaterials research, I also co-developed a combination of phage-collagen conjugated liquid infused coating on titanium implant that enhanced osteointegration and was remarkably effective against implant-associated infections as a prophylactic measure in vivo. Lastly, and as a proof of the utility of phage biocontrol beyond biomedical applications, I demonstrated biofilm removal and full signal regeneration for dissolved oxygen (DO) sensors using a phage cocktail. / Thesis / Doctor of Philosophy (PhD) / Antibiotic resistance is rapidly spreading worldwide, leading to a substantial loss of lives each year and imposing a significant economic burden. Bacteriophages, natural bactericidal viruses, are emerging as a promising solution due to their unique properties. This thesis focuses on the practical implementation of bacteriophages to address real-world challenges linked to antibiotic resistance. I worked on facilitating the process of selecting phages for personalized phage therapy through detecting phage-mediated release of bacteria encoded biomolecules. I also developed phage-loaded injectable hydrogels and phage-conjugated liquid infused coatings to combat bone and implant-related infections. Moreover, I have shown the promise of phage biocontrol beyond biomedical application by demonstrating its effectiveness in restoring a heavily biofouled sensor used for measuring dissolved oxygen, a critical water quality indicator.

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Escalating product recalls as a consequence of Salmonella-contaminated poultry products have resulted in detrimental economic impacts. One long-term alternative to Salmonella prevention, receiving increased attention, is selection to improve genetic resistance. This study evaluated the effects of an oral Salmonella Heidelberg (SH) challenge on bacterial colonization, and the ex vivo effects of SH on phagocytic and bactericidal leukocyte function in turkeys from six pedigree lines (A-F). Data were analyzed using JMP Pro (SAS) and differences were determined using Student’s t-test following ANOVA with significance reported at P ≤ 0.05. Interaction effects of treatment X gender X genetic line were significant on bacterial colonization in the ceca. Cumulatively, females exhibited higher phagocytosis potential than males. The main effect of genetic line was significant bactericidal activity of PBMCs. Microbial profiling of cecal DNA was performed to examine differences in colonization of Salmonella, E. coli, and Enterococcus species among the genetic lines. Results indicated line E having the highest Enterococcus but lowest Salmonella colonization than all other lines, while line A birds displayed the highest Salmonella colonization. These results suggest that gender and genetic line have a marked effect on susceptibility to Salmonella colonization, while genetic line X gender has a more eminent effect on Enterococcus cecal colonization. If able to determine genetic markers associated with these immune responses to Salmonella, genetic selection for increased resistance could be feasible in turkeys. / Master of Science

<p>Magnetic resonance imaging is a research and clinical tool that has been applied in a wide variety of sciences. One area of magnetic resonance imaging that has exhibited terrific promise and growth in the past decade is magnetic susceptibility imaging. Imaging tissue susceptibility provides insight into the microstructural organization and chemical properties of biological tissues, but this image contrast is not well understood. The purpose of this work is to develop effective approaches to image, assess, and model the mechanisms that generate both isotropic and anisotropic magnetic susceptibility contrast in biological tissues, including myocardium and central nervous system white matter. </p><p>This document contains the first report of MRI-measured susceptibility anisotropy in myocardium. Intact mouse heart specimens were scanned using MRI at 9.4 T to ascertain both the magnetic susceptibility and myofiber orientation of the tissue. The susceptibility anisotropy of myocardium was observed and measured by relating the apparent tissue susceptibility as a function of the myofiber angle with respect to the applied magnetic field. A multi-filament model of myocardial tissue revealed that the diamagnetically anisotropy α-helix peptide bonds in myofilament proteins are capable of producing bulk susceptibility anisotropy on a scale measurable by MRI, and are potentially the chief sources of the experimentally observed anisotropy.</p><p>The growing use of paramagnetic contrast agents in magnetic susceptibility imaging motivated a series of investigations regarding the effect of these exogenous agents on susceptibility imaging in the brain, heart, and kidney. In each of these organs, gadolinium increases susceptibility contrast and anisotropy, though the enhancements depend on the tissue type, compartmentalization of contrast agent, and complex multi-pool relaxation. In the brain, the introduction of paramagnetic contrast agents actually makes white matter tissue regions appear more diamagnetic relative to the reference susceptibility. Gadolinium-enhanced MRI yields tensor-valued susceptibility images with eigenvectors that more accurately reflect the underlying tissue orientation.</p><p>Despite the boost gadolinium provides, tensor-valued susceptibility image reconstruction is prone to image artifacts. A novel algorithm was developed to mitigate these artifacts by incorporating orientation-dependent tissue relaxation information into susceptibility tensor estimation. The technique was verified using a numerical phantom simulation, and improves susceptibility-based tractography in the brain, kidney, and heart. This work represents the first successful application of susceptibility-based tractography to a whole, intact heart.</p><p>The knowledge and tools developed throughout the course of this research were then applied to studying mouse models of Alzheimer’s disease in vivo, and studying hypertrophic human myocardium specimens ex vivo. Though a preliminary study using contrast-enhanced quantitative susceptibility mapping has revealed diamagnetic amyloid plaques associated with Alzheimer’s disease in the mouse brain ex vivo, non-contrast susceptibility imaging was unable to precisely identify these plaques in vivo. Susceptibility tensor imaging of human myocardium specimens at 9.4 T shows that susceptibility anisotropy is larger and mean susceptibility is more diamagnetic in hypertrophic tissue than in normal tissue. These findings support the hypothesis that myofilament proteins are a source of susceptibility contrast and anisotropy in myocardium. This collection of preclinical studies provides new tools and context for analyzing tissue structure, chemistry, and health in a variety of organs throughout the body.</p> / Dissertation

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Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / David G. Renter / Salmonella and Campylobacter are two leading causes of human foodborne disease. Cattle can asymptomatically shed these organisms in their feces. Fluoroquinolones are antimicrobials used to treat both humans and animals. With concerns over antimicrobial resistance, antimicrobial use in livestock has become scrutinized. Data on prevalence and susceptibility of Salmonella and Campylobacter in feedlot cattle, particularly those exposed to fluoroquinolones, are sparse. The purpose of the research described in this dissertation was to determine the prevalence and quinolone susceptibility of Salmonella and Campylobacter isolated from feedlot cattle and to determine whether these outcomes were associated with fluoroquinolone use. First, an observational study was performed at five commercial feedlots that used enrofloxacin (a fluoroquinolone) as first-line treatment for bovine respiratory disease (BRD). Fecal samples were collected from cattle pens with various levels of BRD and exposure to enrofloxacin. Salmonella and Campylobacter prevalence and susceptibility to quinolones, nalidixic acid and ciprofloxacin, were evaluated. Prevalence of Salmonella and Campylobacter was highly variable among and within feedlots. All but one Salmonella isolate was susceptible to nalidixic acid and ciprofloxacin, whereas 49% (126/256) of the Campylobacter isolates were resistant to both antimicrobials. However, the number of enrofloxacin treatments was not associated with the prevalence or susceptibilities of either organism. A second, experimental study assessed prevalence and quinolone susceptibilities of Salmonella and Campylobacter in feces of feedlot cattle administered enrofloxacin for the control of BRD (metaphylaxis). Cattle with no history of fluoroquinolone exposure were randomly assigned to either an enrofloxacin treated pen or a non-treated, control pen. Cattle feces were repeatedly collected and cultured for Salmonella and Campylobacter, with isolates tested for susceptibilities to nalidixic acid and ciprofloxacin. Overall, Salmonella and Campylobacter prevalence estimates were relatively low and decreased over time. Resistance prevalence was negligible for Salmonella, but was high for Campylobacter. However, there was no evidence that enrofloxacin metaphylaxis impacted the prevalence of Salmonella or Campylobacter, nor did it significantly affect their susceptibility to human quinolones. In conclusion, enrofloxacin use in feedlot cattle does not appear to have a significant impact on the prevalence or resistance of Salmonella and Campylobacter.

Silty soils are a common occurrence and can exhibit low strengths, and minimal bearing capacity, causing widespread construction and performance problems. These soils are highly moisture-sensitive and their stability is greatly influenced by the degree of densification achieved during compaction. The strength and stiffness of silty-subgrade soils is also greatly reduced when moisture infiltrates the compacted soil during post construction period. This investigation concentrated on further developing the description of the pumping problem for soils with high silt content and the development of guidelines for stabilization of problematic silts. Using documented field experiences of the DOTD districts, the study presents a testing program to investigate the nature of the problem, the character of the silt materials, and their performance with modifying/stabilizing agents. Seven representative silt soil samples were used in the laboratory program. The unique characteristics that identify a soil with a high potential to pump were determined with standard laboratory tests. The response and stability of the silts under compaction and loading with various moisture levels and compaction efforts was also tested. The susceptibility to pumping of the different samples was reviewed in terms of their physical characteristics. In addition to the silt content percentage, the plasticity character was noted as being significant. The potential for the modification/stabilization of the problem silt soils was also studied. The laboratory tests were selected with respect to construction needs and possible post construction conditions. A limited number of specific additives were proposed with consideration for their ability to dry the subgrade silts sufficiently to be compacted and with the strength to provide a "working table" for the construction of the base and pavement. The additives selected included hydrated lime, portland cement, and class c fly ash. A unitary set of guidelines for stabilizing problematic silts is proposed.