Williams syndrome (WS) is a rare, neurodevelopmental disorder caused by the deletion of 26 genes on chromosome 7q11.23. WS has a well-defined auditory phenotype, characterized by a strong attraction and emotional reactivity to music, abnormal sensitivity to sounds (hyperacusis) and an aversion to or avoidance of sounds (phonophobia). Auditory abnormalities reported in WS also affect a wide range of neurodevelopmental, neuropsychiatric and neurological disorders. Little is known about sensory modulation, or the demonstration of maladaptive emotional and behavioral responses to sensory stimuli in WS. This study aims to describe a neural basis for impaired sensory modulation in atypical auditory processing characteristic of the WS phenotype. </p> To define functional and structural connectivity between brain regions involved in auditory processing, we recruited 18 individuals with WS and 18 controls, ages 16-50, for neuroimaging. In the absence of external stimuli, resting state fMRI (rs-fMRI) measures blood oxygenation level dependent (BOLD) signal that reflects baseline neuronal activation in functionally connected networks of brain regions, including the auditory processing network. We used rs-fMRI to identify a network of functional brain regions involved in auditory processing in WS. White matter (WM) integrity was assessed by DTI parameters providing a quantitative measure of water diffusion through axonal membranes. We used DTI to identify structural integrity differences in WM fiber tracts underlying auditory processing in WS. To provide a basis for understanding sensory modulation impairments in WS, 56 caregivers of individuals with WS, ages 5-49, were recruited to quantitatively describe sensory processing patterns, independent of clinical diagnoses. Atypical auditory response patterns, based on a self-report of sensory processing, were correlated with group differences in functional and structural connectivity in WS. This study constitutes the most comprehensive investigation of patterns of sensory processing in WS, spanning a wide age range, and provides a uniquely developmentally-informed basis for understanding behavioral difficulties and the clinical interventions that could address them. Investigating the relationship between patterns of auditory sensory responses and functional and structural connectivity measures elucidates a brain-behavior relationship related to atypical auditory processing.

The 2013 Report Card for the Nations Infrastructure, published by the American Society of Civil Engineers, estimates that more than 10% of the over 607,000 bridges in the United States are structurally deficient. Engendering a further sense of urgency for addressing bridge integrity is the impact of projected climate change and associated weather events. The most recent assessment report published by the IPCC concludes that the frequency of heavy precipitation events is increasing along with a concomitant increase in severe flooding. Several software applications are available that perform flood modeling and, in some instances, damage analysis resulting from the flood. Of the software identified, FEMAs HAZUS-MH, or Hazus, offers a balance between affordability, simplicity and accuracy. Hazus does demonstrate limitations when modeling floods in sub-county areas but at the county-level scale, predicted floods approximate observed floods. Using the US DOTs HEC-18 guide for bridge scour, a methodology was developed for estimating the monetary damage of bridge scour from a future flood event using flood parameters supplied by Hazus and other readily available resources. Results of the methodology indicated predicted and observed damage values did not exhibit a statistically significant difference (p=0.22, tá=0.05). Additionally, a Pearsons correlation coefficient of approximately 0.94 was observed. A demonstration of the methodology application was performed in which several bridges in Little Rock, Arkansas were assessed for adaptation planning prioritization.

Type 2 diabetes affects 10% of the United States population, and patients with diabetes have an increased risk for diseases such as atherosclerosis and hypertension. Since all these diseases are associated with insulin resistance, finding therapies to improve insulin sensitivity could be beneficial for many patients. Studies have shown CYP450 metabolites called epoxyeicosatrienoic acids (EETs) positively regulate insulin action. The purpose of this study is to provide further evidence to support endogenous EETs regulation of insulin action in vivo and to determine how EETs regulate insulin action. To study this in mice, endogenous production of EETs was disrupted by deleting a major EET-producing epoxygenase, Cyp2c44.Glucose tolerance tests (GTTs) were performed with global and liver-specific deletions [Cyp2c44(-/-) and hepCyp2c44(-/-)] to assess glucose homeostasis. Cyp2c44(-/-) mice had impaired glucose tolerance, while hepCyp2c44(-/- ) mice had no alteration. This suggests that EETs increase insulin action but shows disruption of liver-produced EETs, where Cyp2c44 is highly expressed, is not sufficient to alter glucose homeostasis. Therefore, production of EETs within other tissues (e.g., skeletal muscle, vascular endothelium, or adipocytes) must be contributing to decreased glucose tolerance in Cyp2c44(-/-) mice. Insulin signaling in skeletal muscle has previously been shown to be impaired in Cyp2c44(-/-) mice. Therefore, we investigated the effect of endogenous EETs on a critical protein in the insulin signaling cascade, AKT, and a downstream effector, FoxO1. In the present studies, insulin-stimulated AKT and FoxO1 phosphorylation were unaltered in Cyp2c44(-/-) mice. Therefore the effect of EETs on insulin signaling in skeletal muscle could either occur at a different downstream AKT effector or within other insulin-stimulated pathways, like the MAP kinase pathway. Complementary studies will help determine the roles of gender, age, dietary modifications and other experimental conditions on these differences in insulin sensitivity.

The norepinephrine transporter (NET) clears norepinephrine (NE) from the synapse after vesicular release. NET is a target of the psychostimulant amphetamine (AMPH). We have recently shown that AMPH alters trafficking of the transporter, causing a net decrease in surface NET in the monoaminergic CAD cell line. In this study we demonstrate, by confocal imaging of immunostained superior cervical ganglion (SCG) neurons, that AMPH causes an increase in NET levels inside terminal boutons. Further, the intracellular compartment in which NET accumulates upon AMPH exposure is not known; such information would inform investigation of the mechanism by which the drug affects NETs cellular distribution. We show that after AMPH treatment, NET co-fractionates with both Rab4 and Rab11, and that AMPH increases co-localization of NET with these endosomal markers as indicated by the intensity correlation quotient (ICQ). Finally, we show that the functions of both GTPases are involved in AMPH-regulated NET trafficking by transfection of dominant negative (DN) constructs followed by cell-surface biotinylation. Our results support the conclusion that AMPH-regulated NET trafficking occurs through endosomes.

Infrastructure systems, comprised of various assets, are central to the economic, environmental, and cultural functioning of our society. Understanding the potential impacts to these assets from various threats is fundamental to prudent strategic, operational and financial decision-making. This paper describes a methodology developed to identify the severity of impacts to various types of infrastructure located within the Tennessee State Park system when exposed to extreme weather events. It consists of the following steps: (1) defining and identifying critical park infrastructure; (2) identifying extreme weather event types experienced in Tennessee; (3) assessing damage to various types of park system infrastructure caused by these events; and (4) deriving an overall impact score associated with critical and specific types of park system infrastructure when exposed to certain types of extreme weather scenarios. It was found that hydrologic events, strong thunderstorm winds, winter storms, and in select cases, droughts, are the extreme weather events that pose the greatest risk to critical infrastructure within Tennessee State Parks. Locations that were shown to have critical infrastructure particularly vulnerable to extreme weather events include Shelby, Davidson, Wilson, Dickson, Van Buren, Lawrence, Lake, Franklin, Pickett, Carter, Putnam, Hamilton, Sullivan, and Union counties. The approach described in this article is applicable to other park systems as well as public sector assets in general and can be modified to assess other types of risk.

My overarching modeling goal for my dissertation is to maximize generalization â some function of data and knowledge â from one sample, with its observations drawn independently from the distribution D, to another sample drawn from D, while also obtaining interpretable insights from the models. The processes of collecting relevant data and generating features from the raw data impart substantive knowledge into predictive models (and the model representation and optimization algorithms applied to those features contain methodological knowledge). I combine this knowledge with the data to train predictive models to deliver generalizability, and then investigate the implications of those models with simulations systematically exploring parameter spaces. The exploration of parameter space provides insights about the relationships between key variables. Chapter 2 describes a method to generate descriptive models of strategic decision-making. I use an efficient representation of repeated game strategies with state matrices and a genetic algorithm-based estimation process to learn these models from data. This combination of representation and optimization is effective for modeling decision-making with experimental game data and observational international relations data. Chapter 3 demonstrates that models can deliver high levels of generalizability with accurate out-of-sample predictions and interpretable scores of variable importance that can guide future behavioral research. I combine behavioral-game-theory-inspired feature design with data to train predictive models to deliver generalizability, and then investigate interactive implications of those models with optimization and sensitivity analyses. Chapter 4 presents a computational model as a test-bed for designing climate prediction markets. I simulate two alternative climate futures, in which global temperatures are primarily driven either by carbon dioxide or by solar irradiance. These represent, respectively, the scientific consensus and the most plausible hypothesis advanced by prominent skeptics. Then I conduct sensitivity analyses to determine how a variety of factors describing both the market and the physical climate may affect tradersâ beliefs about the cause of global climate change. Market participation causes most traders to converge quickly toward believing the âtrueâ climate model.

Educational institutions have remained remarkably unchanged throughout the last century, even when the political, cultural and social environments have undergone very significant transformation (cf. Duderstadt, 2005; Fullan, 2007; Rowan & Miskel, 1999). Because of the noted similarity among educational institutions and the institutions perceived inability to change, I wanted to identify a significant change at an educational institution, and examine the context and policy process that promoted this change. The focus of this study was the process of policy development within one type of educational institution, the university.<p> In this case study, I examined the policy process involved in establishing a joint, interdisciplinary school, the School of Policy and Research. Data were gathered from three sources: interviews, documents, and policies. I conducted semi-structured interviews with thirteen participants who had some connection to the School, and analyzed the data by coding emergent themes. These were not discrete themes, but rather were interconnected and reflected the complexity of the policy development process. From the findings, the concept of policy windows, as suggested by Kingdon (2003), was evident in the policy origin stage. The policy stream, the political stream, and the problem stream came together at a critical juncture as a confluence of forces that allowed the initiative of the joint interdisciplinary policy School to move forward into adoption and implementation. Due to this presence of a policy window, the initiative moved through the adoption stage relatively smoothly, at least initially. The policy actors were essentially the same at both universities; there was a core group of grassroots level faculty members who were involved in policy work and believed in the potential of the interdisciplinary policy School. They were supported by senior administrative personnel who saw this initiative as one way to address perceived problems confronting the institutions. However, the implementation stage at both universities was messy and difficult as the proponents of the School encountered many tensions, including issues around securing resources, program development, the proposal approval process, and several sources of resistance to change. The discipline-driven culture of the universities appeared to be an impediment to innovative practices that bridge disciplinary boundaries. Although the timing of this study obviated full consideration of the evaluation stage, the participants did speculate upon several intended impacts of the School, and they proposed possible collateral impacts. Implications of this investigation for practice included a need for individual organizations to conduct a thorough examination of situation-specific organizational practices that promote or inhibit innovation, including reviews of current practice for determining what programs need to be discontinued, for articulating how to monitor progress in achieving outcomes, and for identifying how to promote a more collaborative culture. In terms of implications for research, further exploration of the implementation stage of successful policy development was seen to have some potential. In change theory, further research could address the stark absence of the voice of resistors to change. Two elements of neoinstitutional theory that merit further research are the roles of agents in initiating change, and the role of isomorphic processes (coercive, normative, and mimetic) in inhibiting change in organizations. One theoretical implication of this study was the relevance of certain lenses (political, temporal, organizational, and cultural) in examining change. Additionally, the theoretical dichotomy of incremental and transformative change merits further examination in relation to the dynamics of the policy process.

Educational institutions have remained remarkably unchanged throughout the last century, even when the political, cultural and social environments have undergone very significant transformation (cf. Duderstadt, 2005; Fullan, 2007; Rowan & Miskel, 1999). Because of the noted similarity among educational institutions and the institutions perceived inability to change, I wanted to identify a significant change at an educational institution, and examine the context and policy process that promoted this change. The focus of this study was the process of policy development within one type of educational institution, the university.<p> In this case study, I examined the policy process involved in establishing a joint, interdisciplinary school, the School of Policy and Research. Data were gathered from three sources: interviews, documents, and policies. I conducted semi-structured interviews with thirteen participants who had some connection to the School, and analyzed the data by coding emergent themes. These were not discrete themes, but rather were interconnected and reflected the complexity of the policy development process. From the findings, the concept of policy windows, as suggested by Kingdon (2003), was evident in the policy origin stage. The policy stream, the political stream, and the problem stream came together at a critical juncture as a confluence of forces that allowed the initiative of the joint interdisciplinary policy School to move forward into adoption and implementation. Due to this presence of a policy window, the initiative moved through the adoption stage relatively smoothly, at least initially. The policy actors were essentially the same at both universities; there was a core group of grassroots level faculty members who were involved in policy work and believed in the potential of the interdisciplinary policy School. They were supported by senior administrative personnel who saw this initiative as one way to address perceived problems confronting the institutions. However, the implementation stage at both universities was messy and difficult as the proponents of the School encountered many tensions, including issues around securing resources, program development, the proposal approval process, and several sources of resistance to change. The discipline-driven culture of the universities appeared to be an impediment to innovative practices that bridge disciplinary boundaries. Although the timing of this study obviated full consideration of the evaluation stage, the participants did speculate upon several intended impacts of the School, and they proposed possible collateral impacts. Implications of this investigation for practice included a need for individual organizations to conduct a thorough examination of situation-specific organizational practices that promote or inhibit innovation, including reviews of current practice for determining what programs need to be discontinued, for articulating how to monitor progress in achieving outcomes, and for identifying how to promote a more collaborative culture. In terms of implications for research, further exploration of the implementation stage of successful policy development was seen to have some potential. In change theory, further research could address the stark absence of the voice of resistors to change. Two elements of neoinstitutional theory that merit further research are the roles of agents in initiating change, and the role of isomorphic processes (coercive, normative, and mimetic) in inhibiting change in organizations. One theoretical implication of this study was the relevance of certain lenses (political, temporal, organizational, and cultural) in examining change. Additionally, the theoretical dichotomy of incremental and transformative change merits further examination in relation to the dynamics of the policy process.

Children with Down syndrome (DS) display language deficits in expressive and receptive skills beyond what is predicted by nonlingusitic cognitive skills. Clinically, a ubiquitous presumption is that vocabulary taught in one modality will generalize incidentally to the other, untreated modality. Five children with DS (four male, one female, ages 3;6-5;1) were each taught three orthogonal sets of receptive and expressive vocabulary within a multiple probe single subject design. During each probe condition, vocabulary knowledge for trained and untrained modalities was probed. Cross modal generalization probes for all five children indicated moderate transfer from expressive modality to receptive and relatively low receptive generalization to the expressive modality. These results support expressive vocabulary interventions for children with DS provided that clinicians systematically test for generalization to receptive knowledge. Conversely, receptive vocabulary training is much less likely to generalize across modality

<p>Konsumtion kan vara allt från ditt köp av tuggummi, ett par nya skor, en gammal päls från 70-talet, en resa till Indien, till en kebabrulle nere på hörnet. Samtidigt innebär detta att du betalar för smaker, utseende, åsikter, upplevelser, känslor och kulturer. Detta är att leva i ett konsumtionssamhälle. Det du konsumerar speglar vem du är och hur du vill att andra ska uppfatta dig – alltså din identitet. Konsumtion och identitet är det vår antologi handlar om.Den här antologin består av fyra olika delar som alla belyser några olika typer av konsumtion. Det första bidraget belyser hur några unga kvinnor har klädkonsumtion som ett sätt att umgås. Den andra delen handlar om hur en grupp killar och tjejer uppfattar reklam och trender vad gäller mode och kläder. I del tre kan du läsa om hur några unga kvinnor tänker kring sitt val att handla kläder i second-handaffärer. Till sist kan du läsa om några människor som handlar i butiker som säljer utländska varor och hur dessa människor på detta sätt väljer att konsumera det som de upplever som annorlunda. Gemensamt för delarna är att fokus ligger på identitetsskapande genom konsumtion i dagens postmoderna samhälle.</p>