Browse by

The UA Dissertations Collection provides open access to dissertations produced at the University of Arizona, including dissertations submitted online from 2005-present, and dissertations from 1924-2006 that were digitized from paper and microfilm holdings.

We have digitized the entire backfile of master's theses and doctoral dissertations that have been submitted to the University of Arizona Libraries - since 1895! If you can't find the item you want in the repository and would like to check its digitization status, please contact us.

QUESTIONS?

Please refer to the Theses & Dissertations - frequently asked questions guide for more details about UA Theses and Dissertations, and to find materials that are not available online. Email repository@u.library.arizona.edu with your questions about UA Theses and Dissertations.

Recent Submissions

• The Phase-Space Distribution of Galaxy Clusters

We provide the modeling framework to enable a proposed new measurement of the Hubble constant, using the radial extent of galaxy clusters as a standard ruler. Observationally, we plan to measure the angular extent of the cluster and the velocity of galaxies around the cluster. More massive clusters have galaxies that orbit faster, so we can use the velocity of galaxies within clusters to estimate an effective cluster mass. To enable this, we have calibrated the relation between line-of-sight galaxy velocity and cluster mass using cosmological simulations. With an estimate of halo mass now in hand, we can infer the radius of the dark matter halo containing it. To enable this, we have also calibrated the relationship between halo mass and radius with simulations. We find that a halo whose mass is $1\times10^{14}$ $M_\odot/h$ has a physical radius of $596\pm3$ kPc/h, better than $1\%$ precision. Comparing the halo radius inferred from galaxies' velocities to their angular extent allows us to estimate the distance to the cluster, which in turn can be used to assemble a Hubble diagram for galaxy clusters. The high level of precision in the halo radius needed to establish this measurement is founded on a recent insight in halo modeling: galaxies in halos can be split into two populations: those orbiting their host dark matter halo, and those falling into the host for the first time. Here, we present an algorithm that uses the galaxies' accretion history to distinguish between them. We use our split catalog to generate fits for the orbiting and infalling galaxy phase space densities. Importantly, each can be described as depending on a single fundamental scale, the halo radius $r_h$. Both the orbiting and density profiles can be described with 5$\%$ accuracy using $r_h$ as the length scale. In velocity space, we show that the infalling velocity distribution has a bimodal appearance due to the impact of the Hubble flow on galaxy velocities. Our model of the distribution of galaxy line-of-sight velocities is also 5\% accurate. Finally, to prepare the calibration for application to galaxy clusters, we characterize the impact of cluster selection effects the phase space distribution of galaxies. To do so, we select clusters based on the galaxy counts in cylinders of height $\pm$20 h$^{-1}$~Mpc and $\pm$60 h$^{-1}$~Mpc along the line of sight. The distributions of line-of-sight velocities for both orbiting and infalling galaxies are robust to cluster selection; so is the projected orbiting surface density. The projected surface density of the infalling population, however, exhibits a strong scale-dependent bias, where the scale is set by the aperture used in the process of cluster selection. Finally, we suggest the next steps needed to characterize the dependence of the halo radius on the assumed cosmology, as well as the possible influence of baryonic processes on it. As a coda, we also include work on the broadband emission of galaxy clusters, and examine the possible detection of extra-solar neutrinos (via the ICECUBE and Auger experiments) from the Coma cluster of galaxies, as well as for $\gamma$-ray-bright clusters.
• Ultrafast Carrier Dynamics in Two-Dimensional Materials

The discovery of graphene led to an eruption of research into the expansive collection of two-dimensional materials. The ability to fabricate stacked heterostructures with van der Waals materials layer-by-layer has allowed the production of unique devices and has rapidly advanced research in electronics and optics. Understanding the dynamics of carrier and phonon interactions within these systems is crucial for the development of optoelectronic devices. This thesis explores the dynamics of photo-excited carriers in two-dimensional systems: the effects of substrate choice on carrier relaxation in graphene and phonon induced bandgap renormalization in monolayer tungsten disulfide at high carrier densities. Graphene-hBN (hexagonal boron nitride) heterostructures show promising use in electronics applications due to high carrier mobility. We first explore the effect of the hBN substrate on the relaxation rates of photo-excited carriers in these heterostructures using femtosecond pump-probe spectroscopy. Time dynamics of photo-excited carriers in graphene-hBN heterostructures show a cooling rate approximately four times faster on hBN substrates compared to silicon oxide substrates. We next study the effect of variation in isotopic concentration in hBN substrates on the relaxation rates of photo-excited carriers. We measure and compare the time dynamics of photo-excited carriers in graphene-hBN heterostructures using naturally occurring hBN (containing 20% 10B and 80% 11B) and isotopically pure hBN (containing 100% 10B or 100% 11B). We observed a carrier relaxation rate ~1.7 times faster for isotopically pure hBN substrate. Isotopically pure hBN substrates samples allow more efficient decay of optical phonons from graphene into acoustic phonons in the substrate, while the isotopic disorder in naturally occurring hBN causes isotope-phonon scattering. Monolayer transition metal dichalcogenides are another van der Waals material which have garnered a lot of interest due to their direct optical band gap and strongly bound excitonic states in the visible light range. We utilize non-degenerate femtosecond pump-probe spectroscopy to measure the differential reflectivity in monolayer WS2 to investigate the interactions between carriers, defects, and phonons in the high carrier density regime. We find photo-excited carriers are trapped by defect states, which act as non-radiative recombination sites and emit phonons, which cause a phonon-induced band gap renormalization up to 23 meV.
• The “Bel Canto” Viola: The Role of Alessandro Rolla in the Viola Catalog

The music of Italian composer Alessandro Rolla (1757–1841) serves a vital role in the catalog of important viola repertoire. Nonetheless, his vast contributions are woefully neglected by the majority of modern viola players. Familiarity with Rolla’s music can help dispel the misconception that only a small pool of viola repertoire existed prior to the 20th century. As a violist and composer, Rolla championed the viola as a viable solo instrument on equal footing with the violin. Even more significant is the critical role he played as a musical leader in Milan during the pinnacle of the Bel Canto period. It is evident that his close connection to the world of Italian opera shaped his compositional style. It is because of this that Rolla’s music holds a special position in the viola catalog.Rolla’s mature style is best understood in the context with the Italian operatic idiom known as Bel Canto. Bel Canto translates simply to “beautiful singing,” but its true definition is more elusive and remains a topic of contention. The term Bel Canto has become heavily associated with vocal technique; however, it can be understood to have much broader implications as it relates to composition, performance practice, and overall aesthetics. When examining the origins and meaning of Bel Canto, it is crucial to recognize how the development of vocal and instrumental technique evolved simultaneously. The study of Rolla’s life and work grants an invaluable opportunity to illuminate this nebulous subject. The core of this research document will focus on several of Rolla’s compositions that incorporate versions of opera arias. Also, several of his original compositions will be analyzed through the lens of the Bel Canto tradition. Comparisons will be made between Rolla’s compositional elements and those of Rossini, Donizetti, and Bellini.
• The Preservation and Development of Black American Folk Music and of the Exodus Emblem in R. Nathaniel Dett’s the Ordering of Moses

Black American composer R. Nathaniel Dett (1882–1943) is a pioneering figure of American classical music composed by Black musicians. During his career—as a composer, performer, and educator—Dett advocated for the preservation of Black American folk music and its development via its use in “serious” classical music. While initially not interested in doing so, after hearing the masterful use of Black American folk music in Dvořák’s American Quartet during his student years at Oberlin College, Dett’s perspective changed; Dvořák’s composition provided a conceptual foundation for this fusion. In light of this, Dett’s career is defined by his mission to preserve and develop Black American folk music, of which his oratorio, The Ordering of Moses (1937), represents this fulfillment. This dissertation asserts that R. Nathaniel Dett’s The Ordering of Moses embodies his distinct views on preserving and developing Black American folk music, as demonstrated through his utilization of Negro Spirituals as thematic material within this work. Similarly, this dissertation holds that Dett’s symphonic work preserves and develops broader Black American idioms on account of its use of the Exodus emblem as its narrative focus, consistent with its use in the cultural expressions of Black arts, letters, and religion (Christianity).

• The Mexico City Metro: Appropriation and Assimilation of Foreign Technology To Stay on Track With Other Modern Capital Cities and To Produce a Technological and Cultural Marvel

This paper provides a review of the construction of the metro in Mexico City and evaluates themetro as a production of culture. The incorporation and Mexicanization of foreign technology allowed Mexico to build and service a metro while making it uniquely Mexican. The naming of the stations and the use of icons to identify them project Mexican culture and power. The art within the stations and the activities travelers see and participate in are also examples of how Mexico’s metro is unique to its culture. The use of newspaper articles from major cities from around the world demonstrated that the metro was accepted as a successful technological marvel. Newspaper articles, songs, and local art show that Mexicans accepted the metro as their own. We conclude that the metro was a cultural production that propelled Mexico City to the same level as other modern capital cities.

• The Association Between Oral Glucose-Control Agents and Incident Dementia in Type 2 Diabetes Within the Veteran’s Affairs Healthcare Enrollees

INTRODUCTION: Dementia is a major contributor to disability and death. A risk factor of dementia is type 2 diabetes (T2D). Current evidence suggests shared causes of the two diseases and a potential to repurpose specific glucose-control agents (GCAs) for dementia prevention or treatment. However, clinical trials and population studies focusing on this topic are insufficient to conclude GCAs anti-dementia effects and compare effectiveness of different GCAs. This dissertation intended to compare the effects of monotherapy and concomitant use of GCAs on dementia. The results should be able to provide suggestions on GCAs selection in T2D, in terms of dementia risk management. METHODS: In this dissertation, study 1 and study 2 used medical records from the Veteran’s Affairs Healthcare (VAH) database. Glucose-control treatment histories were extracted from prescription records and were aggregated at drug class level. Disease conditions were extracted from outpatient diagnosis records, coded by ICD-9 or ICD-10. Four antidiabetic drug classes were assessed based on a literature review and VAH data richness. Among T2D, study 1 compared the associations of first-generation antidiabetic drug classes (metformin [MET], sulfonylureas [SU], and thiazolidinedione [TZD]) with the risk of dementia. And study 2 compared the associations of adding dipeptidyl peptidase-4 inhibitors (DPP-4is) to MET and/or SU (MET/SU) treatment with risks of dementia and other vascular events. To capture the trends of clinical evidence in relevant fields, study 3 reviewed phase II, III, and IV clinical trials repurposing GCAs for Alzheimer's disease (AD). RESULTS: In T2D without prior dementia, study 1 found that after at least one year of treatment, compared with MET monotherapy users, the risk of all-cause dementia was 22% lower in TZD monotherapy users (HR: 0.78, 95% CI 0·75-0·81), and 11% lower in MET and TZD dual therapy users (HR 0.89, 95% CI 0·86-0·93), whereas the risk was 12% higher in sulfonylurea monotherapy users (HR 1.12 95% CI 1·09-1·15). In study 2, compared with participants staying on MET/SU treatment, participants who added DPP-4is to MET/SU regiments had lower risks for the cerebrovascular outcome (HR, 0.68, 95% CI, 0.62-0.74), and the microvascular outcome (HR, 0.91; 95% CI, 0.88-0.94), but not associated with the risk for the renal outcome (HR, 1.03, 95% CI, 0.97-1.10). In study 3, 26 clinical trials were reviewed and summarized in a narrative way. Elders with mild cognitive impairment, AD, and other types of dementia were the main trial participants. Among studied GCAs, insulin, MET, and pioglitazone showed protective effects on subsets of cognitive function but findings on global cognition and AD biomarkers were neutral. But evidence of other GCAs was either insufficient to make conclusions or unavailable. CONCLUSION: These studies suggest that different GCAs had varied effects on dementia risk within elder T2D, although GCAs may be unable to modify AD progression after AD onset. Without disturbing diabetes management, clinicians may consider lowering patients’ dementia risk through GCAs selection. Additional research is warranted to exam whether our findings apply to younger populations and minority groups.
• "I Don't Get Drunk. I Get Awesome!" Employing a Vulnerability-Stress-Adaptation Framework to Examine Alcohol Use in Emerging Adulthood

Building on emerging adulthood theory and the Vulnerability-Stress-Adaptation (VSA) framework, this dissertation research examined emerging-adult newlywed couples’ alcohol drinking behaviors. Four-annual-wave, dyadic data from 963 couples were analyzed with an Actor-Partner Interdependence Model (APIM) to investigate 1) personality traits and stressful life events (SLEs) as predictors of emerging adults’ alcohol use, and 2) personality traits and alcohol use as predictors of emerging adults’ experiences with SLEs. Results revealed great predictive power of personality traits, especially for emerging-adult men; trait kindness and trait sociability were influential in alcohol involvement while trait anxiety and trait depression were closely associated with SLEs. Emerging-adult women’s perceived stressfulness of SLEs displayed both actor and partner effects, positively predicting alcohol involvement for themselves as well as for their emerging-adult husbands. The potential vicious circle of SLEs and alcohol drinking behaviors suggested by the VSA model was not supported. The findings inspire researchers to further explore whether men are more affected by internal characteristics whereas women are more susceptible to the external circumstances, which may enlighten couple therapy on coping strategies.

• Interpretable Natural Language Processing with Applications to Information Extraction

Interpretability is very important for many NLP applications. Many such applications (e.g., information extraction, sentiment analysis) are applied to important decision-making areas like government policy, financial, law, and others. In these scenarios, machines must explain the information produced, if they are to be deployed in the real world. In this dissertation, we present some approaches for information extraction that mitigates the tension between generalization and explainability by jointly training for the two goals. First we investigate an approach uses an encoder-decoder architecture, which jointly trains a classifier for information extraction, and a rule decoder that generates syntactico-semantic rules that explain the decisions of the classifier. We evaluate the proposed approach on two different information extraction tasks and show that the decoder generates interpretable rules that serve as accurate explanations for the classifier's decisions, and, importantly, that the joint training generally improves the performance of the classifier. We show that our approach can be used for semi-supervised learning, and that its performance improves when trained on automatically-labeled data generated by a rule-based system. Second, we investigate another approach uses a multi-task learning architecture, which jointly trains a classifier for relation extraction, and a sequence model that labels words in the context of the relation that explain the decisions of the relation classifier. We also convert the model outputs to rules to bring global explanations to this approach. This sequence model is trained using a hybrid strategy: supervised, when supervision from pre-existing patterns is available, and semi-supervised otherwise. In the latter situation, we treat the sequence model's labels as latent variables, and learn the best assignment that maximizes the performance of the relation classifier. We evaluate the proposed approach on the two relation extraction datasets and show that the sequence model provides labels that serve as accurate explanations for the relation classifier's decisions, and, importantly, that the joint training generally improves the performance of the relation classifier. We also evaluate the performance of the generated rules and show that the new rules are great add-on to the manual rules and bring the rule-based system much closer to the neural models. Third, we also explore the usages of the model outputs in two ways: 1. Convert them to rules to bring global explanations to this approach; and 2. Use them for bootstrapping when we do not have enough data. Our globally-explainable models approach the performance of neural ones within a reasonable gap.
• Water Distribution Burst Detection and Localization Using Advanced Metering Infrastructure Data Collection Systems

Pipe bursts are one of the most common failures in water distribution networks (WDNs). To minimize their impact, numerous burst detection and localization methods have been developed that identify failures using hydraulic measurements (e.g., pipe flow and pressure) collected from supervisory control and data acquisition (SCADA) data collection systems (DCSs). However, since their monitoring networks are sparse, SCADA systems are often insufficient to identify realistic sized bursts. A clear next step is to develop detection and localization methods for smart systems that collect advanced metering infrastructure (AMI) data (i.e., AMI systems). However, no previous work has proposed tools for the AMI DCSs.The goal of this dissertation is to develop a series of burst detection and localization methods that employ AMI data. Depending on the data being measured (whether AMI flow and/or pressure), appropriate detection/localization approaches are proposed and tested under a range of realistic burst sizes. In addition, these methods are compared for different levels of AMI DCSs to identify which method works best for a given WDN. This dissertation is composed of six journal manuscripts that propose several burst detection and localization approaches for AMI DCSs. First, a new burst detection algorithm employing AMI demands is developed for AMI system where individual end-user demands and system inflow rates are measured. With that approach as a basis, the impact of missing AMI data is assessed. Then, convolutional neural network deep learning models and linear programming based burst detection and localization methods are developed for AMI DCSs where both AMI demand and pressure are measured. Finally, the proposed methods are tested for alternative WDNs and are evaluated using metrics of detection probability, false alarm rate, time to detect, and localization pipe distance.

• Multisensory Soft Robotic Explorer With a Biologically Inspired, Shape-Memory Alloy-Driven, Dual-Action Propulsion System for Extreme Aqueous Environments

The final frontier of extraterrestrial planetary exploration is the exploration of subsurface environments, such as caves and oceans. Inparticular, the existence of subsurface oceans on celestial bodies – e.g., Europa and Enceladus – known as ocean worlds has been backed by varying levels of evidence since the 1980s, but there has been no direct confirmation as of yet. Such environments are largely shielded from radiation, and in combination with the hypothesized presence of water, are prime candidate environments for finding extant or extinct life. However, the in-situ exploration of these subsurface oceans at hypothesized depths ranging anywhere from 1km to 100km (including terrestrial oceans up to 11km) necessitates disruptive advances in the design of robotic subsurface explorers capable of operating in such extreme aqueous environments, i.e., at such depths/pressures and temperatures. The field of underwater exploration systems is currently dominated by rigidly framed robots whose designs convey a philosophy of having widearenas in which to move about without interruption. However, such a design ideology is less suitable for confined environments, which might limit a rigid explorer’s ability to navigate, and for extreme environments characterized by high pressures and low temperatures, i.e., extreme aqueous environments, such as Titan’s hydrocarbon lakes. Limited efforts have gone towards designing underwater exploration systems with a soft robotics philosophy, which overcomes the limitations of stiff robotic systems and permits more flexibility in underwater exploration. It is in this soft robotics underwater exploration context that the research of this Ph.D.-Thesis takes root: The design of a multisensory soft robotic explorer with a biologically inspired propulsion system for extreme aqueous environments using silicone rubber, thereby reframing its flexibility in a space which physically hinders the use of commonly employed pneumatic or hydraulic drivers. Taking inspiration from various biological sources including jellyfish, squid, octopus, and even the chambers of the human heart, this work presentsthe prototype for an autonomous underwater soft robotic exploration system featuring a novel propulsion system for navigation that is devoid of any (electric) motors or actuators and thus well-suited for extreme aqueous environments. The soft robotic explorer features onboard sensors for depth/pressure and temperature, and an onboard computer in charge of data recording, navigation, and propulsion control. Silicone rubber, widely used in other soft robotics applications due to its flexibility, forms the overall shell of the soft robot and its thrusters, and encases the onboard electronics. In addition, its electric inertness to permit direct electronics enclosure, resistance to saltwater degradation, maintained flexibility in low temperatures, and suitability for an additive manufacturing process were reconfirmed. The resulting soft robotic explorer system is fully sealed for all electrical components and fully open in its propulsion design.
• Uncovering the Role Select Residues Play in Mediating RasC Activation and Interaction With mTORC2

Cellular migration toward a chemical gradient is chemotaxis and is a crucial biological function of embryonic development, immune response, and wound healing. On a cellular level, chemotaxis begins when a cell surface receptor binds a chemical messenger and transmits the signal across the plasma membrane. This signal transduction initiates the chemotaxis signaling network that culminates with cell polarization toward the chemical gradient and cellular protrusions in that direction. In Dictyostelium, two key players in this signaling network are thought to directly interact, RasC and mechanistic target of rapamycin complex 2 (mTORC2), and the work of this dissertation is to understand which residues of RasC play a role in this interaction. To this end, we designed mutations to RasC, expressed the mutant RasC proteins in Dictyostelium cells lacking rasC (rasC-), and analyzed the downstream effects. We found that mutation of A31 to aspartic acid prevents RasC activation by its guanosine exchange factor (GEF). We also found that disruption of membrane anchoring residues in the hypervariable region (HVR) prevents RasC from localizing to the membrane and participating in downstream signaling. Some residue changes in both the effector domain and allosteric domain of RasC disrupt chemotactic signaling and prevent Dictyostelium from developing and activating mTORC2 in the same way as RasCWT. We also began working on purification methods of RasC using both bacterial and Dictyostelium expression, and labeling RasC with a tetra-cysteine tag suitable for fluorescent labeling. This work on understanding the in vivo activity of RasC, purifying RasC from multiple expression vectors, and developing fluorescently tagged RasC has helped us understand the RasC-GEF interaction and has given insight into the RasC-mTORC2 signaling pathway. We found that RasC does not express as a soluble product in bacteria, and that purification from Dictyostelium is difficult to scale. The work on fluorescently tagging RasC is ongoing.
• A Descending Pain Modulation Pathway in Green Light-Induced Antinociception

In light of the opioid epidemic in the United States, the need for non-opioid treatments of pain is ever-growing. Over the past two decades, phototherapy has been increasingly shown to be efficacious for the treatment of chronic pain. Notably, recent reports have demonstrated green light therapy to be efficacious in the treatment of chronic pain in both pre-clinical and clinical studies. Previous studies in our laboratory have shown that green light therapy requires the visual pathway as well as pain modulating centers in the central nervous system to elicit its antinociceptive effects. However, the specific neural mechanisms engaged within the central nervous system have not yet been fully elucidated. The work in this dissertation sheds light on the involvement of the endogenous opioid system and the descending pain modulatory rostral ventromedial medulla (RVM) in the antinociception induced by green light (GLED) exposure. Chapter 1 elaborates on the various applications and mechanisms of pain phototherapy by way of a literature review, whereas Chapter 2 provides an overview of central pain modulation pathways, particularly that of the descending pain modulatory system. Chapter 3 presents data characterizing the requirement of μ- and d- opioid receptor agonist stimulation by their endogenous agonists, b-endorphin and enkephalin, respectively, in GLED-induced antinociception. Chapter 4 establishes the role of the pain- modulating RVM in GLED-induced antinociception. The results in Chapter 3 prompted an investigation into the role of endogenous opioids in RVM on GLED-induced antinociception, in which it was revealed that opioid-receptor antagonism in the RVM reversed GLED-induced mechanical antinociception, but not thermal antinociception. Selective CRISPR knockout experiments ultimately demonstrated that μ- and d- opioid receptor agonist stimulation in RVM GABAergic neurons is required for GLED-induced mechanical antinociception. To further the translatability of our findings on GLED-induced antinociception to human patients, we conducted a clinical investigation on healthy human subjects to determine the involvement of the ascending and descending pain pathways in GLED-induced antinociception, described in Chapter 4. By using thermal and mechanical assessments of temporal summation and conditioned pain modulation, we determined that GLED-induced antinociception does indeed involve the descending pain pathway. These findings corroborate the results from the animal studies, confirming the contribution of the descending pain pathway in GLED-induced antinociception in both rodents and humans. Finally, in Chapter 5 we report a case study on a colorblind patient in whom GLED exposure therapy was efficacious in decreasing migraine headache pain intensity and improving quality of life and sleep quality measures. The fact that GLED exposure is similarly efficacious in this colorblind patient as is in normal vision patients suggests that the visual pathway through which GLED exposure acts to eventually modulate central pain modulating processes involves a cone-independent, non-image forming mechanism. These findings provide substrate to support the hypothesis that intrinsically photosensitive retinal ganglion cells may be responsible for the route of entry for GLED exposure that eventually results in pain neuromodulation
• Improving Communication with Patients Expressing Vaccine Hesitancy in Primary Care

Purpose: This quality improvement project aimed to determine whether providers and patient care staff at a primary care clinic in Tucson, Arizona would report increased knowledge, self-efficacy, and intent to change practice after receiving an educational presentation on evidence-based communication with patients expressing vaccine hesitancy.Background: Data show that vaccine hesitancy is increasing among patients in the United States, and the World Health Organization has named vaccine hesitancy a top threat to global health. The literature supports high quality vaccine recommendations from primary care providers to improve patient acceptance of vaccines. There is evidence to support presumptive language and motivational interviewing along with clinician confidence as keys to high quality vaccine recommendations. However, most primary care providers have little or no training in the use of evidence-based and therapeutic communication techniques. Methods: An original educational presentation based on findings from the literature was created by the project director and hosted by YouTube. Recruited participants were asked to complete identical surveys in the online platform Qualtrics before and after viewing the presentation. A four-week period was allowed for asynchronous completion of the surveys and education. Survey items used a five-point Likert scale and survey content was designed to assess knowledge, self-efficacy, and intent to change practice. Data were analyzed for changes from pre- to post-intervention using descriptive statistics for variability and central tendency. Results: Twelve participants completed the pre-survey and intervention, with eleven also completing the post-survey. After receiving the intervention, participants reported increases in both knowledge of the evidence-based methods and intent to change practice. More modest 10 increases were seen in self-efficacy, and self-efficacy scores remained lower at both baseline and follow-up compared to the other two outcomes of interest. Conclusions: The results of this project suggest that at this clinic, an online presentation may be a feasible and effective method for improving knowledge and incorporation of evidence-based communication with vaccine hesitant patients. The small sample size did not allow for evaluation of statistical significance, and further studies are needed to determine the effect of therapeutic communication on vaccination rates.
• Investigations of Small Molecules for Their Use in Alzheimer’s Disease, Colorectal Cancer, and Fluorescent Studies

The research discussed in this dissertation is concentrated on the knowledge-based investigation into structure-activity relationships between small molecules and the resultant effects on kinase inhibition and pharmacokinetics. The medicinal chemistry approaches that optimize these relationships for their use in targeted kinase inhibitors including DYRK and CLK, and Wnt signaling inhibition for a variety of therapeutic uses such as Alzheimer’s disease and colorectal cancer. Lastly, the systematic study and tuning of efficiently synthesized fluorogenic probes through multicomponent reactions. To this end, this thesis combines work done to improve the pharmacological profiles of small-molecule CMGC kinase inhibitors and the investigations of economical fluorophores.
• Reductive Transformation of Insensitive Munitions Compounds by Reactive Iron-Based Minerals

Insensitive munitions compounds (IMCs) are emerging contaminants widely applied by the U.S. Armed Forces to prevent unintended detonations from legacy munitions due to their insensitivity to mechanical and thermal shock. The toxicity of IMCs towards aquatic organisms and mammals has recently been reported, raising concerns about potential adverse impacts of IMC emissions from contaminated sites at military training sites or storage areas, and from IMC manufacturing wastewaters. Therefore, the objective of this research is to develop effective remediation technologies for IMCs using reactive minerals. The IMCs 3-nitro-1,2,4-traizol-5-one (NTO), 2,4-dinitroanisole (DNAN), and nitroguanidine (NQ) contain nitro groups which are susceptible to reductive transformation. Therefore, the effectiveness of iron-based reactive materials, including zero-valent iron (ZVI), iron sulfide (FeS) minerals (synthesized mackinawite (FeS), and commercial FeS identified as pyrrhotite and troilite) and sulfidated ZVI (SZVI), as strong reductants to remove IMCs from contaminated water was investigated in batch and column experiments. The applied iron-based materials effectively reduced NTO, DNAN, and NQ and their transformation pathways were elucidated. NTO was reduced to its daughter product 3-amino-1,2,4-triazl-5-one (ATO). The selective reduction of the para- and ortho-nitro groups of DNAN led to the aromatic amine intermediates, 4-methoxy-3-nitroaniline (iMENA) and 2-methoxy-5-nitroaniline (MENA), which were further reduced to 2,4-diaminoanisole (DAAN), respectively. On the other hand, the initial product of the reactive transformation of NQ by ZVI and FeS was nitrosoguanidine (NsoQ). The nitroso intermediate was further reduced by ZVI to aminoguanidine (AQ), guanidine and cyanamide, whereas reduction of NsoQ by FeS resulted in the formation of guanidine, NH4+, and small amounts of urea. Sulfidation of nano-sized ZVI effectively reduced the anoxic corrosion of water, a reaction that is expected to compete with the reductive degradation of NTO. However, the suppressed anoxic corrosion did not lead to improved NTO reduction by SZVI than ZVI in pH ranging from 3.0 to 6.0. Mackinawite reacted with NTO and DNAN was oxidized to goethite (α-FeO(OH)) and elemental sulfur (S0). On the other hand, reduction of NTO by ZVI led to the concomitant formation of oxidized iron minerals, including magnetite (Fe3O4), lepidocrocite (γ-FeO(OH)), and goethite (α-FeO(OH)). Precipitation of oxidized iron minerals on the ZVI surface can hamper electron transfer, decreasing the performance of ZVI as confirmed in experiments with two ZVI materials with differing in the thickness of their surface iron oxide layer (~ 880 vs. 300 nm). This study demonstrated that NTO removal by ZVI could be greatly enhanced by removing the passivating layer using different pretreatments (in order of increasing effectiveness): washing with 1 M HCl > 60 mM NaHCO3 > 1 M acetic acid. Acid treatment using 1 M HCl was also shown to be an effective approach to fully reactive and extend the service life of ZVI in a continuous-flow packed-bed column treating NTO-contaminated water. Similarly, acidic conditions (pH 3.0) were beneficial to achieve faster NTO and NQ reduction by ZVI compared to circumneutral to moderately alkaline conditions (NTO transformation: pH 6.0 − 8.0; NQ transformation: pH 5.5 – 7.0) by preventing the precipitation of iron oxides. As an example, when the pH was kept constant at 3.0 during the reaction, the rate of NTO degradation by ZVI was 316-fold faster than at pH 6.0. In contrast, FeS (i.e., mackinawite and commercial FeS) was insensitive to changes in pH values in the range of pH tested for NQ (5.5 – 10.0) and DNAN (6.5 – 7.6). Additionally, sulfidated ZVI (SZVI) with a molar S/Fe ratio of 0.03 in alkaline conditions (pH 8.0) had 3-fold higher NTO reduction rate compared to acidic conditions (pH 3.0). Therefore, ZVI application in NTO and NQ remediation technologies is recommended when the influent is acidic, whereas FeS and SZVI are more applicable to treat water with circumneutral to alkaline pH values. Sulfidation increased the selectivity of ZVI towards the contaminants by suppressing the production of hydrogen gas resulting from ZVI corrosion by anoxic water. However, the enhanced selectivity did not improve the NTO reduction, presenting up to11-fold lower pseudo first-rate order constants for NTO reduction compared to those of ZVI at initial pH values ranging from 3.0 to 6.0. Only under mildly alkaline conditions (pH 8.0), the rate of NTO reduction by SZVI (S/Fe= 0.03) was higher (3-fold) compared to that of ZVI since SZVI (S/Fe= 0.03) was more negatively charged than ZVI above pH 7.6. This study demonstrated the feasibility of treating NTO and NQ in flow-through columns packed with ZVI or FeS. The service life of the ZVI-packed bed was strongly dependent on the influent pH. When treating an acidic NTO influent (pH 3.0) the service life until the breakthrough point (i.e., < 85% NTO removal) was 11-fold higher (2,930 pore volumes, PVs) compared to the treatment of a pH 6.0 influent (250 PVs). In spite of the long period of operation, the hydraulic behavior of the ZVI bed was good during most of the experiment and a moderate decrease in flow rate was only observed at the end of the experiment (7,200-10,912 PVs). ZVI is a more effective packing material for the remediation of NQ compared to FeS. Full removal of NQ was attained in a flow-through column packed with ZVI/quartz sand (1:1, v/v) until the end of the experiment (390 PVs). In contrast, NQ breakthrough was observed in the reactor packed with FeS/corundum (1:1, v/v) after only 100 PVs. The hydraulic conductivity of the two columns did not deteriorate during the experiment, suggesting that supplementation of quartz sand or corundum (Al2O3) in the column bed could diminish some of the hydraulic problems observed in ZVI-packed column treating acidic NTO influent. Taken together these results indicate that ZVI and FeS are promising materials for the reductive remediation of IMC-contaminated water with potential application in packed bed reactor systems and permeable reactive barriers (PRBs). Our findings can facilitate the selection of the most effective Fe-based reductant for implementation in full-scale remediation systems by providing detailed analysis of the impact of aqueous chemistry conditions (pH, presence of co-contaminants) on the reactivity of the different iron-based materials.