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Rapid prototyping of electrode materials for fuel cells.

Polymeric materials have realized a broad range of applications in the biomedical world due to their customizability, innocuity, and their ability to mimic biomacromolecules. Amphiphilic copolymers are especially useful because they can associate with hydrophobic motifs while remaining soluble in aqueous solution. Thus, they have been useful in applications including drug delivery, therapeutics, and biomimetic materials. Herein, we investigate the structure-property relationship of polymers in two applications: (i) Promoting the aqueous supersaturation of hydrophobic drug molecules to enhance their bioavailability, and (ii) stabilization of cell membranes to protect them from a variety of stresses. Amorphous solid dispersions (ASDs), consisting of a mixture of a polymer excipient and a hydrophobic drug, are an attractive means to enhance the concentration and bioavailability of hydrophobic drug molecules. In this work, the solution behavior of poly(N-isopropylacrylamide-co-N,N-dimethyl acrylamide) (PND) and poly(vinylpyrrolidone-co-vinylacetate) (PVPVA), as polymer excipients, and phenytoin (PHY), nilutamide (NLT) and itraconazole (ITN), as drug models, were monitored using an in-vitro dissolution assay, cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and polarized optical microscopy (POM). Amorphous nanoparticles were coincident with periods of drug supersaturation in each system. In this study, we propose that the kinetic stability of the nanoparticles is based on whether the polymer excipient interacts more strongly with water or the particle’s drug-rich phase. Achieving a better understanding of how polymer excipients interact with drug-rich phases in aqueous solution will help inform the design of future ASD systems. Poloxamers are a class of block copolymers composed of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) segments. They have been used pharmaceutically to restore cell membrane integrity and to treat conditions such as Duchenne’s muscular dystrophy and ischemia reperfusion injury. In this project, we investigated the mechanism with which poloxamers stabilize cell membranes by studying (a) the effect of polymer hydrophobicity on polymer/membrane binding and cell protection efficacy, and (b) the effect of poloxamers on the elasticity and toughness of model lipid membranes. In (a) we compared a series of poly(1,2-butylene oxide)-b-PEO (PBO-b-PEO) copolymers to PPO/PEO analogues using a combination of pulsed-field-gradient NMR experiments and a lactate dehydrogenase (LDH) cell assay. We found that PBO-b-PEO copolymers bound significantly more to model liposomes composed of 1-palmitoyl-2-oleoyl-glycero-3- phosphocholine (POPC) compared to PPO/PEO copolymers. However, both classes of polymers performed similarly when compared by an LDH assay. In (b) we used micropipette aspiration to measure the effect of poloxamer molar mass, hydrophobicity and concentration on the mechanical properties of POPC membranes. We found that at poloxamers increase the elasticity of POPC membranes through a decrease in their stretching modulus, while having minimal effect on their bending modulus. Additionally, poloxamers can slightly increase or decrease membrane toughness, based on their PPO/PEO composition. Studies (a) and (b) provide important insights into the protection mechanism of poloxamers by attempting to directly relate polymer-membrane binding to properties such as cellular resistance to osmotic stress and membrane elasticity.

This dissertation is about implicit prosody, the prosodic structure that readers assign during silent reading. The dissertation has several goals: determining which reading tasks are appropriate for studying implicit prosody, establishing how grammatical principles could guide incremental assignment of prosodic structure, and investigating how implicit prosody interacts with other properties such as focus in order to influence syntactic parsing and interpretation. On the methodological side, this dissertation demonstrates that the Maze task is suitable for studying implicit prosody by replicating several major findings on metrical and phrasal prosody in both the Maze task and in self-paced reading. In addition to showing that the Maze is sensitive to implicit prosody, the methodological comparison confirms previously reported advantages of the Maze over self-paced reading, such as more localized and larger effects. On the theoretical side, the dissertation lays the groundwork for developing an incremental model of prosodic parsing. I provide an overview of the major grammatical constraints that govern the syntax-prosody interface, drawing on work from the theoretical phonology literature. I discuss how and when these grammatical constraints, which are typically invoked to model the final phrasing for a complete sentence structure, could be deployed by an incremental parser that assigns a prosodic structure word-by-word. Using a toy model of an incremental parser, I also show how the parser’s first pass implicit prosody may differ from the final prosody, arguing that future work in this area should more closely consider these potential differences. The final set of experiments investigates both the timing of implicit prosodic assignment and how prosodic structure and information structure affect attachment decisions. Based on the results of these experiments, I propose the Visibility First Hypothesis, according to which attachment decisions are determined primarily by prosodic visibility, while other factors such as focus only exert an influence when two potential attachment sites are equally visible. I then outline several experiments to test the Visibility First Hypothesis in future work.

Semiconducting nanoparticles have received significant attention due to their uniqueoptoelectronic properties. Quantum dots (QDs), a class of spherical nanoparticles, possessa size-dependent bandgap and photoluminescence at visible wavelengths. QDs have manyapplications including biological labelling, solar cells, chemical impurity detection, andoptical glasses. Doping QDs into optical glasses is highly desirable. High-quality QDscan be synthesized via liquid solution methods. However, solution-synthesized QDs oftendegrade over time and they cannot survive incorporation into a glass melt without protection. In this work, the aqueous synthesis of ZnSe QDs and coating with nanometer silicaand alumina protective shells are investigated. The effects of synthesis conditions on thestructure and coating quality of ZnSe nanocrystals are systematically assessed via X-RayDiffraction, Electron Microscopy, and UV-Vis Spectroscopy. Results indicate the successful fabrication of ZnSe nanocrystals and deposition of both silica and alumina shells.

Licensed drivers arrested for driving under the influence (DUI) of alcohol have increased rates of vehicle crashes, moving violations, traffic tickets, and contribute to an estimated 120 million occurrences of impaired driving per year (Evans, 2004; Jewett et al., 2015). Survey research on DUI offenders indicates traits of impulsivity (e.g., sensation seeking). Together, these pieces of evidence suggest that DUI offenders display patterns of impulsive action and risk-taking while driving. However, to-date DUI offenders are rarely studied in a laboratory setting, and not much is known about how they respond to a dose of alcohol. The present study examined the degree to which DUI offenders display an increased sensitivity to the acute impairing effects of alcohol on mechanisms of behavioral impulsivity, skill and risk-based driving simulations, and subjective evaluations of driving fitness and perceived intoxication following alcohol consumption. A sample of 20 DUI offenders were compared to a demographically-matched sample of 20 control drivers. All participants attended two dose sessions in which they received either a 0.65 g/kg dose of alcohol or a placebo dose, counterbalanced, on separate days. Results indicated that alcohol affected all of the behavioral outcome measures. More specifically, alcohol increased impulsive choice responses and decreased response inhibition on the behavioral impulsivity tasks. Alcohol also increased risky driving behaviors and decreased driving-related skills. Furthermore, alcohol generally decreased participants’ self-reported willingness and ability to drive a motor vehicle, and increased levels of intoxication and BAC estimations relative to placebo. With regard to group differences, DUI offenders showed an increased sensitivity to the disrupting effects of alcohol on impulsive choices, such that DUI offenders showed a significantly greater preference for impulsive choices under alcohol relative to placebo than controls. Taken together, these findings provide some of the first pieces of evidence that compared to controls, DUI offenders display an increased tendency for impulsive decisions under alcohol, which likely contributes to risky decisions to drive after drinking, despite clear evidence for their behavioral impairment. These findings could have important implications for understanding the mechanisms underlying maladaptive behaviors in this high-risk population, and sheds light on possible targets for intervention to reduce DUI recidivism.

Visual short-term memory (VSTM) is commonly perceived as a temporary buffer into which information is moved for retention across relatively short intervals. Guided by work on the “standard model” of working memory, these buffers are assumed to reside in modality-specific areas of the prefrontal cortex (PFC). Recent converging evidence has begun to call these conventional views into question, with a growing consensus that working memory is the emergent result of attention-guided activity across many areas of the brain. This “emergent-property” view suggests that working memory is sustained in part by the very same sensory areas involved in encoding external input. If visual short-term memory is represented and maintained on the same neural populations involved in common perceptual tasks as evidence suggests, we might expect possible interactions. The current thesis describes a series of experiments designed to build a detailed profile of these interactions. In Chapter 2 we establish the utility of using visual aftereffects as investigative tools in two behavioral experiments. In the first experiment we measure the magnitude of static and dynamic motion aftereffects before and after perceptual learning on a motion discrimination task using identical stimuli. Our results indicate that learning does not affect the duration of the aftereffects, strongly suggesting that improvements in discrimination are not mediated by changes in the underlying perceptual representations of the stimuli. Rather, our evidence supports the view that practice changes the relative contributions of perceptual outputs to decision-making areas. A second experiment rules out a competing explanation in which the locus of learning does not share enough overlap with the neural populations responsible for the observed aftereffects. Next, in Chapter 3 we demonstrate the efficacy of analyzing multivariate response data over traditional reliance on accuracy or response time alone. We apply the diffusion model (DM) to accuracy and response time distributions on data from two perceptual learning experiments. Results reveal that practice-induced improvements in motion direction discrimination arise from the combination of stimulus-specific improvements in the quality of sensory information entering decision areas, and non-specific gains in the timing of decision-making processes. Following this, in Chapter 4 we leverage the methodological gains of the previous results to test the hypothesis that the contents of VSTM can influence the perception of stimuli during the memory retention interval. We use a dual-task design to test the effect of VSTM on perception. Results suggest that orientation information in memory has a repulsive effect on the perception of subsequently presented orientations, not unlike tilt aftereffects. Further DM analysis confirms that our results are perceptual in nature and do not arise from artifacts in response time shifts. Finally, in Chapter 5 we describe an experiment designed to test if the interactions observed in Chapter 4 share the same neural mechanism as memory masking, and what, if any, effect practice has on these two forms of interference. An asymmetrical effect due to memory-stimulus similarity, as well as contrasting effects due to training on the two sources of interference strongly indicate the involvement of two separate processes. Taken together, this collection of studies highlights the existence of another form of VSTM-perception entanglement that is complementary to memory masking, but behaves much differently, particularly under the influence of practice. The results indicate that VSTM and perception interact in systematic ways that are critical to understand, most notably in laboratory settings where the effects can disrupt the subtle differences upon which observers must make decisions. A novel model is proposed that parsimoniously reconciles observed patterns of perceptual learning, as well as the apparently disparate forms of interactions measured throughout. Collectively, the present work supports the emergent-property hypothesis of working memory, as well as a revised version of the standard model.

Licensed drivers arrested for driving under the influence (DUI) of alcohol have increased rates of vehicle crashes, moving violations, and traffic tickets (Evans, 2004). To date, no research has examined specific self-regulatory mechanisms of the DUI driver under a dose of alcohol that might underlie risky driving behavior. The present study examined the degree to which DUI drivers display an increased sensitivity to the acute impairing effects of alcohol on driving performance and overestimate their driving fitness following alcohol consumption. Adult drivers with a history of DUI and a demographically-matched group of control drivers without a DUI were tested following a 0.65 g/kg dose of alcohol and a placebo. Results indicated that while alcohol impaired several measures of simulated driving performance, there were no differences between DUI offenders and controls on any of these measures. Compared with controls, intoxicated DUI drivers self-reported greater ability and willingness to drive as BAC declined despite no differences in levels of self-reported intoxication or BAC estimation. These findings provide evidence that DUI drivers might perceive themselves as more fit to drive after drinking despite clear evidence for their behavioral impairment. These findings could have important implications in the decisions to drink and drive.

Abstract: Ectromelia virus (ECTV) is the causative agent of lethal mousepox, and is highly related to the human pathogen, variola virus, the causative agent of smallpox. Poxviruses contain large dsDNA genomes that encode numerous open reading frames that manipulate cellular signalling pathways. We used bioinformatics to identify a family of four genes encoded by ECTV that contain N-terminal ankyrin repeats in conjunction with a C-terminal F-box domain. The ECTV encoded ankyrin/F-box proteins: EVM002, EVM005, EVM154 and EVM165, all interact with the cellular SCF (Skp1/Cul-1/F-box) ubiquitin ligase complex through an interaction mediated by their C-terminal F-box domain. These four proteins bind to the SCF complex in a similar manner to cellular F-box-containing substrate adaptor proteins. We hypothesize that each of the ECTV encoded ankyrin/F-box proteins recruits a unique family of target proteins to the SCF complex for ubiquitylation. The NF-κB signalling cascade is an important mediator of innate immunity, and is tightly regulated by ubiquitylation. A critical step in the activation of NF-κB is the ubiquitylation and degradation of the inhibitor of kappaB (IκBα), by the cellular SCFβ-TRCP ubiquitin ligase. Upon stimulation with TNFα or IL-1β, orthopoxvirus-infected cells display an accumulation of phosphorylated IκBα, indicating that NF-κB activation is inhibited during poxvirus infection at the point of IκBα degradation. Since degradation of IκBα is catalyzed by the SCFβ-TRCP ubiquitin ligase complex we investigated the role of the ECTV encoded ankyrin/F-box proteins in the regulation of NF-κB activation. Expression of Flag-EVM005 inhibited both IκBα degradation and p65 nuclear translocation in response to TNFα or IL-1β. Regulation of the NF-κB pathway by EVM005 was dependent on the F-box domain, and interaction with the SCF complex. Additionally, we created ECTV knockout viruses devoid of each of the four ankyrin/F-box genes using a novel “Selectable and Excisable Marker” system. The EVM005 deletion virus was shown to inhibit NF-κB activation despite lacking the EVM005 open reading frame; however, this virus was attenuated in two mouse strains. The contribution of EVM005 to virulence is therefore independent from its ability to inhibit NF-κB activation, and is potentially linked to unique target proteins ubiquitylated through the SCF complex during infection.

One common method of representing images is to reduce an image to a collection of features. Many simple features have been proposed, such as pixel intensities and wavelet responses, but these choices are fundamentally unsuitable for capturing the configural relations of objects and object parts, as spatial information associated with each feature is lost. Another recent strategy, known as "feature-hierarchy" modeling, involves the use of overlapping, redundant features. These features are obtained by processing an image across a hierarchy of units tuned to progressively more complex properties. An open question is whether such approaches produce data structures rich enough for implicitly capturing configural relations. We implemented three experiments and severalcomputer simulations to address this issue. Our method involved the use of four classes of objects, each derived from the simple spatial relationships present in classic Vernier and bisection acuity tasks. All human observers achieved near perfect categorization performance after relatively few exposures to each stimulus class. This ability also transferred across several dimensions, including orientation and background context. By contrast, simulations on a feature-hierarchy model revealed poor performance for this class of models. Furthermore, themoderate categorization accuracy achieved did not transfer across even the simplest of dimensions. These results indicate that this approach to image representation lacks a fundamental property necessary for encoding the spatial configurations of object parts.

This thesis explores the relationship between refugee protest and the politics of asylum governance through the case of a 2005 protest in Egypt. It challenges prevalent views of refugees as victims, of the bodies that host and assist as benevolent, and of the relationships between them as apolitical. In a 2005 sit-in in Cairo, Sudanese demonstrators took collective political action as refugees – but found their action countered and undone by host states and humanitarian institutions. Drawing from this case, the thesis develops existing understandings of the politics of asylum governance, and political activism concerned with it, along three lines. First, it takes an inductive approach to understanding the politics at play, developing concepts that allow for comparison across contexts. Second, it integrates analysis of both protester and institutional accounts of a refugee protest. Third, it explores three hitherto understudied aspects of the politics of asylum governance: the political activity of asylees regarding the rules of asylum within host countries; the effects of political struggles within asylum governance on refugee political participation; and the interactions between refugees and asylum governance in an urban, southern context. This thesis argues that refugee protest and the politics of asylum governance are related in causal, discursive, and epistemological ways: that the politics of asylum governance play a causal role in refugee protest; that protest and governance concerned with asylum share a discursive repertoire, which may be mobilised agonistically; and that the study of refugee protest is a compelling approach through which to gain insight into the politics of asylum governance. Through this study, the thesis opens new dimensions within existing scholarship on the depoliticisation of refugees, and of humanitarianism as a dominating force.

This thesis explores the encounter between the Afghan-American community and the U.S. military-industrial complex in the production of cultural knowledge for counterinsurgency (COIN) operations in Afghanistan. It focuses on the narratives mobilized as 'expertise' by Afghan-American contractors from the major diaspora hubs in California and Virginia, who were employed as role-players, translators, and cultural advisors by the U.S. military and defense contractors. I discuss how such narratives gained currency and shaped the perceptions of Afghanistan in the U.S. foreign and security policy communities. The goal of the thesis is to demonstrate the extent to which COIN-centered cultural knowledge production both defined political strategies toward Afghanistan and also reconstituted the Afghan diaspora in America. The thesis contributes to emergent ethnographic studies on militarism by looking at its effect on American society in general and the Afghan diaspora in particular. The broader application of the thesis findings is to move beyond critiques of the troubled connection between anthropology and the military, and to analyze the relationship between citizens and the state in terms of national and biopolitical security.