2017 MU dissertations - Access restricted to UM
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Item Family support and prosocial behaviors in U. S. Mexican and European American young adults : the intervening roles of respect and sociocognitive/emotive traits(University of Missouri--Columbia, 2017) Streit, Cara; Carlo, Gustavo[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The primary aim of this study is to consider mothers, fathers, and siblings as socialization agents of young adult's prosocial behaviors and to consider the mediating roles of cultural values and sociocognitive/emotive traits. In order to build on previous work, these relations are examined in a sample of European American and U.S. Latino young adults. The final sample included 184 U.S. Latino (N = 143, 78.6 % female; M age = 20.68, SD =2.05) and 348 European American young adults (N = 275, 79.5 % female; M age = 19.52, SD =1.11). Results from path analyses demonstrate complex and differential predictors associated with prosocial behaviors, as distinguished by the target of helping. Cultural values and young adults' sociocognitive and emotive traits largely served as underlying mechanisms in the relations between family support and prosocial behaviors, although these relations were differentiated by the target of helping. There was also evidence for the moderating role of young adults' gender in the model assessing prosocial behaviors toward family members, such that for men, there were several indirect and direct effects of paternal support (but not maternal or sibling support) in fostering prosocial behaviors toward family members. Discussion will focus on the integration of socialization, cognitive developmental, and cultural theories in predicting prosocial behaviors towards different helping targets.Item Canine degenerative myelopathy : perspectives from aging, microglia and neurofilaments(University of Missouri--Columbia, 2017) Toedebusch, Christine Marie; Garcia, Michael L.; Coates, Joan R.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Canine degenerative myelopathy (DM) is a late-onset neurodegenerative disease similar to some forms of amyotrophic lateral sclerosis (ALS). Mutations in superoxide dismutase 1 (SOD1) are a risk factor for disease; however, disease penetrance is also age-related. Microglia, the immune effector cells of the CNS, undergo phenotypic changes with age that may predispose to neurodegeneration. Furthermore, they have been directly implicated in disease pathogenesis in ALS. We tested the hypotheses that 1) microglia in aged, neurologically normal dogs have increased activation toward a neurotoxic phenotype compared to adult dogs and 2) microglia in DM-affected dogs will transition from a neuroprotective (M2) to neurotoxic (M1) phenotype as disease progresses and 3) increased fractalkine, a chemotactic molecule for microglia, will correlate with increased M2 microglia in DM-affected dogs. We found that aged, neurologically normal dogs had increased numbers of M1 and M2-activated microglia; however, total M2 microglia per motor neuron was reduced from adult dogs. Furthermore, compared to adult dogs, aged canine spinal cord had increased expression of genes associated with phagocytosis and proteolysis, which also are elevated in ALS and Alzheimer's disease models. Within the context of DM, microglia in close proximity to motor neurons were increased at all disease stages. M2 microglia per motor neuron were increased in early stages of DM, whereas the number of M1 microglia per motor neuron were indistinguishable from aged controls at all stages of disease. Fractalkine levels did not change throughout disease progression. These findings collectively suggested that aged canine microglia are highly activated with reduced neuroprotective microglia near motor neurons. In the context of DM, concomitant loss of motor function and increased M2 microglia, without a change in M1 microglia, suggested that SOD1E40K M2 microglia could have contributed to neurodegeneration through a toxic gain of function. Currently, there is no definitive ante-mortem diagnostic test for DM. We tested the hypothesis that phosphorylated neurofilament heavy (pNF-H), an abundant structural protein of myelinated motor axons, is readily detectable in CSF and serum of DM-affected dogs, and can be used as a diagnostic biomarker for DM. We identified pNF-H as a sensitive and specific diagnostic test for SOD1E40K-associated canine DM. This work may provide the first ante-mortem diagnostic test for canine DM.Item Utilizing multi-commodity flow formulations to solve network protection problems(University of Missouri--Columbia, 2017) Karakose, Gokhan; McGarvey, Ronald G.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] The identification of critical network components is of interest to both interdictors wishing to degrade the network's performance, and to defenders aiming to preserve network performance in the face of disruption. This dissertation focuses on methods for identifying critical subsets of nodes and/or arcs to fortify and/or disable for the purpose of network protection. A common link connecting all studies in this dissertation is our incorporation of the multi-commodity flow formulations into larger multi-level (e.g., minimax) optimization models. ... The last study examines network fortification models that are able to differentiate between failures that are random (e.g., caused by nature) and strategic network failures (e.g., caused by terrorist activities) when performing the allocation of protective resources. This distinction cannot be achieved in the models presented previously in this dissertation. The desired properties of such differentiating formulations are derived by specifying a set of priori assumptions. The criticality indexes in these models, which are necessary to assess the impact of a disruption, are pre-computed through the resolution of the multi-commodity based User Equilibrium (UE) traffic assignment model and applied to urban transportation networks. Novel valid inequalities and linearization techniques are applied to the dual version of the nonlinear UE multi-commodity model to improve its computational efficiency. Computational results demonstrate that the reformulated linear dual model is effective to solve large size instances to near-optimality; and that the optimal allocation of resources as identified by a component-based formulation may potentially be suboptimal when a network is at risk of multiple simultaneous failures for both types of disruptions (i.e., nature- and terrorist-based). We also demonstrate that fortification models for component or scenario-based disruptions can provide different resource allocations for both types of disruptions.Item Discovery of novel hepatitis B virus (HBV) antivirals and analysis of mechanisms of action of HBV-targeting agents(University of Missouri--Columbia, 2017) Huber, Andrew Douglas; Sarafianos, Stefan G.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.Item Deep eutectic solvents : investigation of solvent structure and its applications(University of Missouri--Columbia, 2017) Wagle, Durgest Vinod; Baker, Gary A.[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Deep eutectic solvents (DESs) represent an alternative class of ionic fluids closely resembling room-temperature ionic liquids (RTILs), they are distinguished by the fact that they also contain an organic molecular component (typically, a hydrogen-bond donor like a urea, amide, acid, or polyol), frequently as the predominant constituent. DESs possess several advantages over RTILs while being less expensive, synthetically accessible, nontoxic, and biodegradable. In this work we have probed into liquid structure of DES using quantum chemical calculations and neutron scattering experiments to elucidate the molecular interactions, charge transfer interactions, thermodynamics and mass transport associated with these systems. The DESs studied comprise 1:2 choline chloride/urea (reline), 1:2 choline chloride/ethylene glycol (ethaline), 1:2 molar ratio of choline chloride to glycerol (glyceline) and 1:1 choline chloride/malonic acid (maloline). The DESs were found to be stabilized by both conventional hydrogen bonds and C-H...[pi] interactions with significant charge transfer from choline and chloride to the hydrogen-bond donors, further confirmed by density of states analysis. Consequently, it was found that the sum of the bond orders of various choline-C1[minus] interactions in the DESs correlates directly with the melting temperatures of the DESs. From macroscopic measurements of glyceline, it was observed that the long-range translational diffusion of the larger cation (choline) is slower compared to the smaller glycerol molecule. However, the diffusion dynamics analyzed on the subnanometer length scale revealed that the displacements associated with the localized diffusive motions are actually larger for choline. This is due to ability of glycerol to form stronger hydrogen bonds with chloride anions compared to choline cation. Quantum chemical simulations performed on ASCs paired reline and ethaline DES systems revealed that ASCs interacted with the choline and HBD components of DESs through multiple unconventional non-covalent interactions i.e., CH...[pi], C=O...[pie], O-H...[pi] and N-H...[pi] interactions. Oxidation of ASCs improved interaction with DES components due enhanced ability to form multiple hydrogen bonds. ASCs exhibited significant improvement in change free energy of solvation upon oxidation indicating that oxidation could aid in enhancing selective extraction of oxidized ASCs from liquid fuel using DES.