Search

Many types of cancer exhibit high heterogeneity between individual cells, a key factor that promotes the overall ability of the tumor to both proliferate and resist treatment. By identifying what drives this heterogeneity, these cancers can be better understood, modeled, and treated. Single-cell RNA sequencing elucidates transcriptomic features that define subpopulations within heterogeneous samples that are not easily detected through conventional means. The transcriptome is distinct between different forms of cancer and changes in response to treatment as subpopulations die off and survivors exhibit changed dynamics. By looking at only data sequenced from untreated cells, but across several distinct types of cancer, and in each case identifying the features that most distinctly separate the subpopulations, certain commonalities are found. These commonly differentially expressed features, including both overarching gene sets such as ribosomal proteins and individual oncogenes such as PTTG1, are implicated as key elements of heterogeneity in cancer in a general sense.

Pitchers with higher spin rates generally see higher swing and miss rates when pitching. The goal of this study was to find out how to improve spin rates without cheating (using foreign substances like pine tar). The hypothesis was that an increase in grip strength would show a positive correlation to spin rate. The study split 37 athletes into two groups. Both groups went through preliminary testing. The test group received extra grip strength exercises while the control group did the normal lifting routine for a three-month period. At the end of the study, post-testing data was collected for both groups. The data proved to be inconclusive, as there were no significant differences in grip strength between the test group and the control group.

This thesis provides a thorough evaluation of current state-of-the-art robotic grasping methods and contributes to a subset of data-driven grasp estimation approaches, termed generative models. These models aim to directly generate grasp region proposals from a given image without the need for a separate analysis and ranking step, which can be computationally expensive. This approach allows for fully end-to-end training of a model and quick closed-loop operation of a robot arm. A number of limitations are identified within these generative models, which are identified and addressed. Contributions are proposed that directly target each stage of the training pipeline that help to form accurate grasp proposals and generalise better to unseen objects. Firstly, inspired by theories of object manipulation within the mammalian visual system, the use of multi-task learning in existing generative architectures is evaluated. This aims to improve the performance of grasping algorithms when presented with impoverished colour (RGB) data by training models to perform simultaneous tasks such as object categorisation, saliency detection, and depth reconstruction. Secondly, a novel loss function is introduced which improves overall performance by rewarding the network to focus only on learning grasps at suitable positions. This reduces overall training times and results in better performance on fewer training examples. The last contribution analyses the problems with the most common metric used for evaluating and comparing offline performance between different grasping models and algorithms. To this end, a Gaussian method of representing ground-truth labelled grasps is put forward, which optimal grasp locations tested in a simulated grasping environment. The combination of these novel additions to generative models results in improved grasp success, accuracy, and performance on common benchmark datasets compared to previous approaches. Furthermore, the efficacy of these contributions is also tested when transferred to a physical robotic arm, demonstrating the ability to effectively grasp previously unseen 3D printed objects of varying complexity and difficulty without the need for domain adaptation. Finally, the future directions are discussed for generative convolutional models within the overall field of robotic grasping.

The hippocampal formation plays an important role in spatial navigation and episodic memory. At the core of the neuroscience community's understanding of this role, are classes of functional cell types, such as place cells and grid cells. Despite being the subject of intense study for over half a century, how the complex recurrent circuitry of the hippocampal formation generates these functional classes, and how they interact with each other to support the critical cognitive processes the hippocampal formation underlies, is an area of open research. In this thesis, we present experimental and computational work aimed at addressing some aspects of these questions. First, we develop a novel technique to optically access the transverse plane of the hippocampus in vivo, allowing - for the first time - the neural activity of multiple subregions of the hippocampus to be simultaneously recorded. We utilize this tool to characterize functional and structural properties across the hippocampal circuit, finding stable and unstable populations of dendritic spines on the apical dendrites of CA1 pyramidal neurons and heterogeneity in the amount of spatial information encoded by place cells along the CA1-CA3 axis. Second, we test a long held assumption on properties of grid cells in medial entorhinal cortex, analyzing recent cutting-edge experimental data. We find evidence for the distribution of grid spacings and orientations in individual modules to be non-uniform, having small, but significant variation. Computational modeling leads us to conjecture that a grid code with such heterogeneity in its properties enables robust encoding of local spatial information. And third, we study the emergence of localized responses in artificial neural network models. We find that, as these local features form, the statistics of the internal representations of the network become increasingly non-Gaussian, in-line with theoretical work that has suggested this to be a general mechanism for driving localized responses. Sparsifying the network, via pruning or regularization, amplifies the non-Gaussian statistics, emphasizing the role of sparsification on internal representations. Each of these experimental and computational approaches motivates exciting avenues of future direction to shed light on the computations performed by the hippocampal formation.

Patients differ in their response to clinical interventions. Both genetics and the environment contribute to the phenotype of a patient after a chemical intervention such as a drug. Well-validated interventions have large population effect sizes, meaning they are valuable for an individual on average. However, for complex conditions such as autoimmune disease and cancer, the precise outcomes of chemical interventions remain difficult to predict for an individual patient. Here we present methods for predicting chemical response and apply these methods to understand biological mechanisms. We discover a new biomarker associated with psoriasis patient response to the drug ustekinumab and use this biomarker to stratify patient populations at various clinical endpoints. Moving beyond association analyses, we develop a machine learning model that integrates chemical structures and gene expression information to predict cellular responses to hundreds of chemicals, and apply methods to investigate how this model works. Finally, we improve model generalizability by pretraining a new model on massive amounts of gene expression data and then applying it to downstream prediction tasks. This work contributes models that predict biological responses to chemicals and methods to interpret how these models work. We anticipate this work will advance precision medicine by improving the ability to predict how patients respond to drugs. Simultaneously, this work provides an in silico platform for screening new biological models against a diverse set of chemical probes. Lastly, our pretrained model may find broad applications in phenotype prediction tasks ranging from disease risk modeling to drug response prediction.

This dissertation is published in the format a white paper series which tells the story about Butler Tech's Fifth Day Experience across six issues. FDE is a student-centered initiative that was launched in the spring of 2020, and aims to operationalize deeper learning by exploring student voice, teacher agency, equity, personalized learning and innovation. FDE also aims to serve as a catalyst to redesign schools. A mixed methods approach was used to capture the action research process. Each white paper issue ranges between 12-15 pages and focuses on different themes within the research. Each issue include narratives, trends, and patterns from the data and highlights the evolution of FDE as it moves in real-time from a 1.0 model, to the 2.0, and eventual 3.0 versions. Issue one focuses on the origin of FDE. Issue two unpacks student voice in the design process. Issue three centers on the student experiences during the implementation process. Issue four focuses on an unexpected Covid-19 influenced model. Issue five captures the structural changes and highlights the rich programming. Issue six offers an executive summary, compares the three design models and provides a vision for the future of FDE. My hope is that school leaders, policymakers, and change agents use this white paper series as a vehicle to influence their own efforts to transform the educational world. Each publication is practical, applicable and offer critical insights into the FDE journey.

Out-of-school suspension is a growing concern in the United States education system and affects students at the three Title I schools in the Central School System at a particularly high frequency. The purpose of this applied study was to solve the problem of high-frequency out-of-school suspension for three Title I middle schools in the Central School system and to formulate a solution to address the problem. A multi-method design was used, consisting of both qualitative and quantitative approaches. The first approach was structured interviews with two administrators from each school. The second approach was the analysis of archival data using the discipline data from the school system. The third approach was a teacher survey using a Likert scale to determine teacher perspectives on out-of-school suspension. These tools were used to develop a focused program that will allow the schools to meet student needs while also maintaining safety, order, and a positive school climate. The results of the data showed that administrators and teachers were aware of the negative implications of out-of-school suspension but were experiencing tension between the need to maintain discipline within the school and teacher support while also desiring to reduce out-of-school suspension. The data showed that administrators identified significant differences in most of the student body and students who have frequent behavioral concerns and multiple suspensions. An alternative to suspension program was developed and proposed as a solution to reduce out-of-school suspension.

Enterococcus faecalis is a Gram-positive bacterium that normally exists as an intestinal commensal in humans. Additionally, it can survive in the environment for extended periods and cause infections in immunocompromised hosts, making E. faecalis a leading cause of nosocomial infections. Previous work noted that specific fatty acids found in serum contribute to tolerance of membrane damaging agents, including the drug daptomycin. However, not all fatty acids found in serum were able to induce such protection. Herein, we measured a wide array of physiological responses after supplementation with combinations of protective (i.e., induced daptomycin tolerance) and non-protective fatty acids. When supplementing cells with either non-protective fatty acid, palmitic acid or stearic acid, there was a significant increase in generation time and severely distorted morphology. Both physiological defects were rescued when these cultures were supplemented with one of the protective fatty acids identified in serum, oleic acid or linoleic acid. Similarly, membrane fluidity decreased with growth in either palmitic or stearic acid alone but returned to basal levels when supplemented in combination with a protective fatty acid. While cell envelope charge has been associated with tolerance to daptomycin in other Gram-positive bacteria, we concluded that it does not correlate with the fatty acid induced protection we observed. Further, daptomycin tolerance could be induced when cultures were supplemented with non-protective fatty acids in combination with a protective fatty acid. Beyond physiology, we measured changes in transcription after protective fatty acid supplementation, noting upregulation in a gene encoding for a glycoside hydrolase as well as the known daptomycin genetic resistance gene gdpD. Combined, we conclude that a single protective fatty acid is able to alleviate negative growth defects and protect cells from daptomycin.

The work presented in this thesis comprised two major projects. The first, a spectroscopic study of water clusters in the Terahertz vibrational region revealed a dramatic enhancement of tunneling motions involved in breaking and reforming hydrogen bonds. The second project involved constructing a second harmonic scattering (SHS) experiment which was used to probe buried interfaces. The study of water clusters provides a useful route towards unraveling the many body terms of the water potential. High-resolution vibrational-rotational-tunneling (VRT) spectroscopy is a particular sensitive measure of the repulsive walls of the water potential. While this method is extremely powerful, the major challenge is assigning the complex spectra that is output from the experiment. To that end, the major contribution of this thesis is an automated pattern matching algorithm based on the symmetric-top, rigid rotor model. Using this algorithm, transitions of the water dimer, pentamer, hexamer, and octamer were identified and assigned from a back log of experimental data. These assignments revealed a dramatic enhancement of tunneling motions in the librational (300 – 600 cm-1) region. These enhancements were most dramatic for motions involved in breaking and reforming the hydrogen bond in the clusters, adding to the evidence that understanding this region is essential to understanding hydrogen bond breaking dynamics. The use of 2nd order, nonlinear spectroscopy to probe surfaces is a well-established technique. Employing second harmonic generation in a scattering geometry enables probing buried interfaces in colloidal samples; these samples provide an appealing path forward towards studying real world polymers such as water purification membranes. We show that SHS can be used to probe resonant and non-resonant molecules at a polymer interface, and we extract free energies of adsorption from a variety of organic molecules. In the future, we plan to extend this technique to ionic species to supplement our existing studies of ion adsorption via sum frequency generation in reflection geometry.

This thesis introduces a web of concepts to analyse Brahmsian metre and move toward a more nuanced understanding of metrical expression and narrative in his music. Recent analytical studies of metre in common-practice Western classical music have utilised a powerful analogy of consonance and dissonance between tonal and metrical dimensions. More theoretical studies, particularly of Brahms's music, have investigated how metrical states can be systematised, both abstractly and by Brahms, to create a sense of tonicity. This thesis synthesises and extends these approaches. Metrical dissonance is suggested to offer only an insufficient purchase on Brahms's metrical style, and the concept of accentual counterpoint is suggested as an alternative that gives fuller power to the explication of Brahms's metrical complexity, but without reducing that complexity. The complexity of metrical states that Brahms employs, in turn, is explored. Brahms's path to the composition of extraordinary metrical complexity in his Op. 78 violin sonata shows both his increasing systematisation of metrical states and his increasing ability to separate and manipulate metrical accent-types, the latter supporting the concept of accentual counterpoint. That metre has expressive power invites the concept of metrical narrative. An attempt is made to unite a recent theory of musical narrative with metrical analysis, inviting readings of different narrative archetypes within Brahms's metrical trajectories, with a focus on non-romantic narratives as a complement to traditional readings of unity. The pitch-metre analogy, and particularly the typicality of tonicity in metrical organisation, is problematised by those works by Brahms that begin and end in different notated metres. These instances, apparent manifestations of directional metre, are analysed, principally using the theories of hypermetre, metrical dissonance, metrical states and accentual counterpoint, with the hypothetical concepts of organisation (directional metre, metrical narrative and metrical tonicity) as interactive heuristics. Moving from organisation back to expression, the thesis closes by exploring a problem within current theories of form and phrase structure: the difference between musical expansion and extension. It highlights a metrical manifestation of this created as an effect of accentual counterpoint, dubbed metrical expansiveness, and examines the interaction of this effect with form and narrative.

Environmental and natural resource issues are often framed in multiple ways by multiple stakeholders. This is especially the case in relation to Arctic natural resource development: a complex issue bearing the hallmarks of modern sustainability challenges. With the increasing attention placed towards the Arctic’s natural resources comes a growing number of diverse voices, producing a discursive environment fertile for frame-conflicts and susceptible to misunderstanding, confusion and conflation. For many, the central challenge in tackling socio-ecological problems deriving from these complex issues centres on conflicting frames: from how problems are initially defined to what are appropriate solutions, these issues are social and political constructs and arenas for deep disagreement. As such, if policy efforts to meet the sustainability challenges associated with Arctic natural resources are to be successful, an understanding of frames proves essential. This thesis contributes towards this important research area by undertaking a frame-analysis of contemporary Arctic natural resource development. This thesis consists of three empirical strands. The first examines media-frames in international news media coverage surrounding natural resources in an Arctic context. Using Greenland as a case-study, it illustrates a media portrayal of a close-knit relationship between a warming climate and natural resource development. The second strand uses Q-Methodology to explore frame-conflicts within a group of Arctic stakeholders around the issue of Arctic offshore petroleum, finding significant divergence across framings, with some bridges of consensus evident that could potentially facilitate collaborative policymaking. The third strand examines the role of scale-frames within the discussion around Arctic offshore petroleum, identifying several scale-challenges often related to the Arctic’s nebulous relationship with scale. Themes emerging across these three strands point to a need for alternative conceptual approaches to space that capture the inter-relational complexity behind Arctic natural resource development. Relational geographies and assemblage-thinking are presented as useful conceptual lens in which to engage with this complexity. This thesis argues that despite its inherent complexity, an understanding of the various ways Arctic natural resources are framed can offer guidance for policymakers such as highlighting the risks of dominant tropes, the existence of potential bridges and the need for more refined terminology when necessary. In doing so, this thesis highlights the utility of mixed-methods frame analysis as a heuristic tool to better understand complex socio-ecological issues.

Diabetes mellitus is a growing public health concern, presently affecting 25.8 million or 8.3% of the American population. While the availability of novel drugs, techniques, and surgical intervention has improved the survival rate of individuals with diabetes, the prevalence of diabetes is still rising. Type 2 diabetes (T2D) is a result of chronic insulin resistance and loss of -cell mass and function, and it is is always associated with the impairment in energy metabolism, causing increased intracellular fat content in skeletal muscle (SkM), liver, fat, as well as pancreatic islets. As such, the search for novel agents that simultaneously promotes insulin sensitivity and -cell survival may provide a more effective strategy to prevent the onset and progression of this disease. Kaempferol is a flavonol that has been identified in many plants and used in traditional medicine. It has been shown to elicit various pharmacological activities in epidemiological and preclinical studies. However, to date, the studies regarding its effect on the pathogenesis of diabetes are very limited. In this dissertation, I explored the anti-diabetic potential of the dietary intake of kaempferol in diet-induced obese mice and insulin-deficient diabetic mice. For the first animal study, kaempferol was supplemented in the diet to determine whether it can prevent insulin resistance and hyperglycemia in high fat (HF) diet-induced obese mice or STZ-induced obese diabetic mice. For the second animal study, kaempferol was administrated once daily via oral gavage to diet-induced obese and insulin-resistant mice or lean STZ-induced diabetic mice to evaluate its efficacy for treating diabetes and further determining the underlying mechanism. The results demonstrated that dietary intake of kaempferol for 5 months (mo) improved insulin sensitivity and glucose tolerances, which were associated with increased Glut4 and AMPKα expression in muscle and adipose tissues in middle-aged mice fed a high-fat (HF) diet. In vitro, kaempferol increased lipolysis and restored chronic high fatty acid-impaired glucose uptake and glycogen synthesis in SkM cells, which were associated with improved AMPKα activity and Glut4 expression. In addition, dietary kaempferol treatment preserved functional pancreatic -cell mass and prevented hyperglycemia and glucose intolerance in STZ-induced diabetic mice. Data from the second study show that oral administration of kaempferol significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole body insulin sensitivity without altering body weight gain, food consumption, or the adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase and glucose-6 phosphatase activity in the liver homogenate without altering their protein expression. Consistently, kaempferol decreased pyruvate carboxylase activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Kaempferol directly blunted the activity of purified pyruvate carboxylase. In the last study, we found that kaempferol stimulates basal glucose uptake in primary human SkM. In C2C12 mouse myotubes, kaempferol also increased insulin stimulated glycogen synthesis and preserved insulin dependent glycogen synthesis and glucose uptake in the presence of fatty acids. Kaempferol stimulated Akt phosphorylation in a similar time-dependent manner as insulin in human SkM cells. Consistent with this, kaempferol increased Akt and AMPK phosphorylation in isolated murine red SkM tissue. The effect of kaempferol on glucose uptake was blunted in the presence of chemical inhibitors of glucose transporter 4 (Glut4), phosphoinositide 3-kinase (PI3K), glucose transporter 1 (Glut1), and AMPK. The AMPK inhibitor also prevented kaempferol-stimulated Akt phosphorylation. Further, kaempferol improved the stability of insulin receptor substrate-1. Taken together, these studies suggest that the kaempferol is a naturally occurring compound that may be of use in the regulation of glucose homeostasis and diabetes by improving insulin sensitivity and glucose metabolism, as well as by preserving functional -cell mass.

Data from 158 loblolly pine (Pinus taeda L.) trees located in industrial plantations in the Ouachita Mountains of southeastern Oklahoma, USA were collected and used to develop taper, merchantable volume and merchantable green weight equations. These plantations are located near the north-west extreme but outside of the natural range of loblolly pine. Oklahoma loblolly pine was compared to predictions from previously published equations for loblolly pine’s native range in order to evaluate whether differences for taper, volume and green weight characteristics existed between these populations. This study indicates that Oklahoma loblolly pine has less merchantable green weight and volume for a given dbh, total height and merchantability limit than predicted by some well-known models. Diameter for a given height was also different. Since differences were observed the exponential merchantable diameter ratio equation, a new merchantable height based model and a new taper equation, which was derived from the merchantable height based model, were selected from among several well-known models for prediction of merchantable green weights and volumes. This work provides equations that have good predictive ability for trees across a wide range of conditions present in this region of Oklahoma, and which should work well in neighboring areas in the Ouachita Mountain region.

Metabolomic Insights into the Pharmacological and Genetic Inhibition of Cyclooxygenase-2 William T. E. Briggs The cyclooxygenase (COX)-2 inhibitors, or “coxibs,” are excellent anti-inflammatory agents, but their reputation has been tarnished by the adverse cardiovascular (CV) events, including heart failure (HF), with which they are associated. Whilst the risk of HF represents the greatest adverse CV event signal seen with these compounds, it is also perhaps the least well understood and has often been explained away as a consequence of the thrombotic risk with which the coxibs are also associated. One recent hypothesis, put forward by Ahmetaj-Shala et al., suggests that asymmetric dimethylarginine (ADMA) may serve as a mechanistic bridge between COX-2 inhibition and HF. However, the ADMA-COX-2 hypothesis was developed based on findings in a constitutive mouse model of COX-2 knock-out (KO), which is compromised by severe developmental cardio-renal pathology, and pharmacological studies which may not accurately reflect coxib use in clinical practice. Various studies have explored the metabolic changes induced by coxib treatment. However, these studies have been limited in scope and have tended to focus on specific pathways or certain tissues/bio-fluids. This has left large regions of the metabolome, in the context of coxib-treatment, unexplored. Given that metabolic remodelling is a key feature of HF, changes in these metabolites may hold the key to understanding the pathogenesis of coxib-induced HF. L-Carnitine shuttles activated long-chain fatty acids (FAs) across the inner mitochondrial membrane to the mitochondrial matrix, where they are oxidised by β-oxidation. This is especially important in the heart, which derives the majority of its energy from the metabolism of FAs. Changes in carnitine metabolism are also seen in HF. It is therefore biologically plausible that derangements in carnitine metabolism may contribute to the pathogenesis of coxib-induced HF. This thesis employs a combination of targeted and untargeted metabolomic techniques, stable isotope labelling and quantitative reverse transcription polymerase chain reaction (RT-qPCR) to i) profile the metabolic changes induced by celecoxib and rofecoxib, in the mouse; ii) specifically interrogate the effect of celecoxib, rofecoxib and global COX-2 gene deletion on carnitine synthesis, metabolism and shuttling, and iii) explore the advantages and disadvantages of the inducible post-natal global (IPNG) COX-2 KO (COX-2-/-) mouse, an alternative to the constitutive COX-2-/- mouse used by Ahmetaj-Shala et al. The results of this thesis demonstrate that i) celecoxib and rofecoxib have similar metabolomic consequences in the mouse; ii) carnitine metabolism may be affected by celecoxib, rofecoxib and dietary composition, via a peroxisome proliferator-activated receptor-alpha (PPAR-α) mediated effect on hepatic carnitine synthesis and iii) the IPNG COX-2-/- mouse neither exhibits the severe developmental cardio-renal pathology nor the altered ADMA metabolism observed in the constitutive COX-2-/- mouse. These findings contradict those of Ahmetaj-Shala et al., oppose the ADMA-COX-2 hypothesis and highlight a potential role for carnitine metabolism and diet in coxib induced HF.

How people create and use information scraps, the small informal messages that people write to themselves to help them complete a task or remember something, has changed rapidly in the age of mobile computing. As recently as 2008, information scraps had continued to resist technological support. Since then, however, people have adopted mobile connected devices at a rate unimagined in the pre-smartphone era. Developers have, in turn, created a varied and growing body of smartphone software that supports many common information scrap use-cases. In this thesis, we describe our research into how and why people have adopted smartphone technology to serve their information scrap needs. The results of our survey show broad adoption of smartphones for many common information scrap tasks, particularly ones involving prospective memory. In addition, the results of our diary studies show that mobile contexts or locations are highly correlated with people's choosing to use smartphones to record information scraps. Our analysis of our diary study data also provides fresh understanding of the information scrap lifecycle and how mobile digital technology affects it. We find people's smartphone information scraps tend toward automatic archival, and we find their information scraps in general tend toward substantial role overlap regardless of medium. We use these findings to formulate a new information scrap lifecycle that is inclusive of mobile technology. These insights will help mobile technology creators to better support information scraps, which, in turn will allow users to enjoy the huge benefits of digital technology in their information scrap tasks.

Some people become so deeply bonded to various causes that their beliefs define who they are. This deep bond with causes can be understood within a framework of identity fusion. When individuals view a cause as a self-defining aspect of their identity, they feel a sense of underlying similarity—or shared essence—with other cause supporters based on their common beliefs. Because strongly fused individuals feel essentially similar to fellow cause supporters, they may likewise essentialize opponents of the cause by categorizing them into distinct “natural kinds” based on their ideological stance toward the cause. This tendency for essentialist thinking leads strongly fused individuals to discriminate against people who hold opposing beliefs about the cause. To test these ideas, I conducted 6 studies. Two studies showed that fusion with a cause predicted the tendency to essentialize others based on their sentiments toward the cause with which participants were fused (Study 1), but not other causes (Study 2). Three follow-up studies (Studies 3-5) demonstrated that fusion with a cause predicted discrimination against cause opponents, and that this effect was mediated by essentialist beliefs. Study 5 also showed that strongly fused individuals demonstrated intentions to attend events where they could antagonize cause opponents. Study 6 showed that fusion with a cause predicted political voting behaviors, but not as strongly as fusion with political party. Collectively, these studies identified a class of individuals who were prone to discrimination on the basis of ideology and the cognitive underpinnings of this predisposition.

Influenza viruses are a major cause of morbidity and mortality worldwide, with seasonal epidemics of influenza resulting in around three to five million cases of severe illness globally each year. The evolution of influenza A viruses is characterised by rapid antigenic drift, which allows mutant viruses to evade host immunity acquired to previously circulating viruses. Antigenic variation is observed across a wide range of infectious organisms and can circumvent long-lasting immunity in hosts leading to repeated infection or non-clearance. Influenza A viruses can often be effectively combatted by the immune system and vaccines also exist to protect at-risk individuals, limiting the burden of disease. However, the effectiveness of the vaccine depends on constituents being antigenically similar to circulating viruses. Antigenic drift of influenza viruses therefore requires a global surveillance system responsible for the antigenic characterisation of circulating viruses. The identification of emerging antigenic variants is critical to the vaccine virus selection process and in addition experts must anticipate which viruses are likely to predominate in forthcoming epidemic seasons. Mutations to B-cell epitopes on the surface of haemagglutinin (HA) that facilitate escape from neutralising antibodies play a key role in influenza antigenic drift. Consequently the haemagglutination inhibition (HI) assay, which measures HA cross-reactivity, is commonly used to approximate antigenic phenotype. In this thesis, I investigate the genetic basis of antigenic variation among human influenza A viruses through analysis of HI data collected in recent decades and associated HA gene sequence data. In Chapter 2, I use phylogenetic methods and antigenic cartography to characterise the genetic and antigenic variation among the viruses studied and evaluate the usefulness of these methods for epitope identification. In Chapter 3, I extend a model developed to investigate antigenic differences among foot-and-mouth disease (FMD) viruses to former seasonal A(H1N1) viruses. By attributing variation in HI titre to amino acid differences between viruses, while accounting for phylogenetic relationships, I identify substitutions that have driven the antigenic evolution of the virus. Reverse genetics was then used to validate model predictions experimentally. In Chapter 4, I further extend the model and investigate the genetic drivers of antigenic drift among A(H3N2) viruses, comparing model results with published HI data generated using mutant recombinant viruses. In Chapter 5, I explore the power of the identified genetic determinants for predicting antigenic relationships among A(H1N1) and A(H3N2) viruses. Specifically I show that sequence-based models can be used to estimate the antigenicity of emerging viruses directly from their sequence and that by including substitutions of smaller antigenic impact, in addition to the high-impact substitutions that are often focused on, predictions were improved. I also demonstrate the versatility of these methods by extending this sequence-based approach to predict antigenic relationships among viruses of three serotypes of FMD virus. Determining phenotype from genotype is a fundamental challenge for virus research. It is of particular interest in the case of the antigenic evolution of influenza viruses, given the need to continually track changes in the virus population, anticipate which viruses will predominate in future seasons, and select vaccine viruses. Collectively, the results I present demonstrate an enhanced quantitative understanding of the molecular genetic basis of the adaptive phenotype of influenza viruses. The ability to quantify the phenotypic impact of specific amino acid substitutions should help to refine methods that predict, from genotype, the fitness and evolutionary success of influenza viruses from one season to the next, strengthening the theoretical foundations for vaccine virus selection. The techniques presented also have great potential to be extended to other antigenically variable pathogens and to elucidate the genetic basis of their antigenic variation.

The phenomenon of directed cell migration is one of many fundamental biological processes required for the existence of almost all living organisms. Efficient cell migration relies on a highly coordinated spatio-temporal system of sub-cellular processes, many of which are governed by transportation carriers known as vesicles. This thesis focuses on methods for analysing the dynamics of vesicles during directed cell migration via imaging and image analysis. Vesicle dynamics can be visualised in live cells by fluorescence microscopy. Different fluorescence microscopy techniques are better suited for studying different aspects of vesicle dynamics. First, the concept of multi-modality microscopy is explored, which combines the benefits of multiple methods into the same analyses. Thorough characterisation of vesicle dynamics requires accurately estimating thousands of trajectories from microscopy image sequences often consisting of hundreds or thousands of images. A highly efficient probabilistic multiple particle tracking frameworks is presented, which outperforms many of the state-of-the-art methods, but with a drastically reduced processing time. Finally, live cell studies show that there is a high degree of polarity of vesicle traffic of vesicles associated with the clathrin mediated endocytosis and early endosome pathways during cell migration.

This paper describes my interest in the artist’s multiple and the thesis body of work created in the exploration of them. I was especially interested in the relationship of individual components I could combine to form a singular object and how the resulting object had the ability to change through various methods of production and presentation. Also, in contrast to the idea that multiples are exact copies of each other I was interested in exploring the idea of the multiple being seen as an individual object. My interest in history and collecting unique objects from the past have heavily influenced the development of this work. Often, those objects at one time had a utilitarian function, but now because a certain amount of time has passed the objects have taken on the role of artifact. They have become a precious object that can no longer be used for the purpose they were created. This is a quality that I find fascinating. As an artist I find myself collecting these objects at an astounding level. This obsession with collecting has a direct connection with my current interest in multiples. The inspiration for this work came from many areas which include, but are not limited to the work of other artists, architects, graphic designers and specific periods of time when a certain visual aesthetic was highly valued, such as art nouveau, art deco, the arts and crafts movement, futurism, fluxus and modernism.

There is emerging, in the discipline of rhetoric and composition, a rhetoric of food. In this dissertation, I map the various approaches to food rhetorics, and I look at three different foods: burritos, kale, and kombucha. Using these foods as commonplaces, I explore the social and rhetorical discourse around them. I use “a cultural biography of things” methodology to describe the history of the burrito and use that history to contextualize Chipotle Mexican Grill’s new media strategies. Throughout the cultural biography of the burrito and the analysis of Chipotle’s marketing, I highlight a theatrical mimesis that blurs the lines between imitation and reality. I suggest that kale can be associated the books of Michael Pollan, whose work, I argue, constitutes a genre that establishes a set of conventions for how we think and communicate about food. I begin by looking at how Chipotle builds its corporate ethos by citing Michael Pollan’s books on its website. Then I approach Pollan’s body of work as a genre, showing how it establishes certain conventions in food discourse. We see transmissions of these conventions throughout food networks. I look at how fermented foods, like kombucha, travel through alternative food networks, like groups of “fermentos” led by Sandor Katz, until they have proliferated to the point of becoming mainstream. I show how Michael Pollan engages with the world of countercultural food movements like fermentos and argue that Pollan’s engagement with fermentos signals a move into posthuman rhetorics. Building on the idea of micropolitics, I posit a compostmodern micro(be)politics that re-articulates the human not as an agentive individual governed by autonomy, but as an ecology itself, situated within other ecologies. I conclude by reading “nobody cares what you ate for lunch” memes as a response to and provocation to an abundance of online food talk. We can read these memes as evidence of the significance of online food discourse. Instead of taking the memes at face value, we can ask, “who does care about food in online networks?”

Parkinson's Disease (PD) is the second most common neurodegenerative condition in humans, after Alzheimer's disease. It can be observed in all races and both genders, in the United States and worldwide. However, disparities in disease progression and manifestation exist between races and sexes. In addition, treatment options and overall health, impacted by insurance type, may affect a PD patient's disease state. The purpose of this study is to contribute to the background demographic information of PD patients, particularly as pertaining to insurance classification, which has not yet been addressed in the literature. The Hoehn and Yahr (H&Y) scores of patients both ON and OFF medication, a method of ranking and analyzing disease severity in Parkinson's patients, were analyzed in this study. The hypothesis is that the H&Y scores are impacted by race, gender, and insurance status. A univariate analysis of each variable was performed, the Student's t-test was used for gender and insurance status and a One-way ANOVA for race. A multivariate regression model analysis was then run for the primary outcomes and included all the variables and known confounders. A secondary analysis of disease complications utilizing Chi-square tests and logistic regression was also performed. Gender and insurance status did not differ significantly in H&Y scores. Black or African patients had a significantly increased PD progression as compared to Caucasian patients. Males and females differed significantly with regard to several disease complications. Subjects with public insurance also exhibited greater odds of some disease complications as compared to subjects with private insurance. In agreement with the literature, black PD patients exhibited a greater disease progression as compared to white PD patients. However, the reason for this has not yet been adequately addressed. In addition, more studies are needed to analyze other racial groups that were too small to appropriately address in this study. Despite a lack of difference in H&Y scores, PD is observed to be manifested differently between genders (disease complications), also in agreement with the literature. More studies are required to discover the reason for this disparity. Insurance classification does not impact H&Y scores. However, more studies are required to address whether this is maintained with a more sensitive outcome measure, such as the UPDRS. In addition, some complications differ between insurance categories, implying a disparity in treatment options and therapies.

According to Malcom Gladwell's Outliers, it takes 10,000 hours of practice to achieve mastery in any field. Two-thirds of my 10,000 hours have been spent deep within the fluorescent corridors here at UCSD, but I don't need to count hours to know I feel like a master. The obstacle course I have navigated these past three years has forged me in the process. The demands of the work dared me to fathom, face, and explore the facets of my own being. Along the way, my mentors have molded me, preparing me to meet any and all obstacles. It started in Louisiana, I tore my guts out in Italy, I sold myself in Florida, lost my family out west, caused some bloody mischief, ended lonely in Chicago, survived the Gringo Exodus, and rang a really big bell. Through encouragement, advice, and corrections, the faculty here gave me the tools that made success possible in all these places.My last show here, Mr. Burns: A Post-Electric Play, presented so many challenges, in table-work, rehearsal, tech and performance, but because of my training, I always knew we could overcome them. The tools I've been given have imbued me with such a confidence in my craft that no challenge is insurmountable. My voice, my awareness, my process, is stronger.The metaphor of my skillsets being tools is inaccurate. They are better described as organs, in me always, regulated without effort by my unconscious. Because they are with me, I am prepared for the unknown.

James Evans, AdvisorThe Devonian Berea Sandstone is an internally complex, heterogeneous unit that appears prominently both in outcrop and subsurface in Ohio. While the unit is clearly deltaic in outcrops in northeastern Ohio, its depositional setting is more problematic in southeastern Ohio where it is only found in the subsurface. The goal of this project was to search for evidence of a barrier island/inlet channel depositional environment for the Berea Sandstone to assess whether the Berea Sandstone was deposited under conditions in southeastern Ohio unique from northeastern Ohio. This project involved looking at cores from 5 wells: 3426 (Athens Co.), 3425 (Meigs Co.), 3253 (Athens Co.), 3252 (Athens Co.), and 3251 (Athens Co.) In cores, the Berea Sandstone ranges from 2 to 10 m (8-32 ft) thick, with an average thickness of 6.3 m (20.7 ft). Core descriptions involved hand specimens, thin section descriptions, and core photography. In addition to these 5 wells, the gamma ray logs from 13 wells were used to interpret the architecture and lithologies of the Berea Sandstone in Athens Co. and Meigs Co. as well as surrounding Vinton, Washington, and Morgan counties. Analysis from this study shows evidence of deltaic lobe progradation, abandonment, and re-working. Evidence of interdistributary bays with shallow sub-tidal environments, as well as large sand bodies, is also present. A prominent sequence of climbing ripples = 6 cm give evidence for distributary mouth bars. Frequently appearing massive bedding, sparse bioturbation, and a sequence of massive bedding to planar lamination overlying convoluted bedding provides evidence that high sedimentation rates were common during the deposition of the Berea Sandstone. Turbulent debris flows are interpreted based on the presence of a 10 cm incomplete turbidite lithofacies assemblage. Tidal processes can be inferred from tidal rhythmite sequences approximately 5 m thick, and clear storm activity is apparent from the presence of a 16 cm tempestite lithofacies assemblage. Geophysical log analysis allowed for the interpretation of the subsurface architecture of the formation. Combined, these features provide strong evidence for the interpretation that, in southeastern Ohio, the Berea Sandstone was deposited in a tidally-influenced, deltaic environment.

The impacts of global change on ecosystems from climate change and invasive species are likely to be complex. Rising atmospheric CO2 concentrations, the associated climate forcing and greater frequency of extreme weather are serious challenges to natural ecosystems. In tandem with climate change, globalisation has led to the spread of invasive alien species around the globe that threaten to interrupt food web dynamics. Advancing understanding of the effects of global change on trophic interactions therefore requires study of interspecific and multi-trophic interactions. The aim of this thesis was to examine how host-plant heterogeneity, native–invasive species interactions and climate change effects (elevated atmospheric CO2 (eCO2) or drought) influence trophic interactions. An experimental approach was used which centred on a study system comprising the European raspberry (Rubus idaeus), the herbivorous large raspberry aphid (Amphorophora idaei) and coccinellid beetle predators (native species: Adalia bipunctata, Coccinella septempunctata; invasive alien species Harmonia axyridis). Under eCO2, R. idaeus resistance to A. idaei was unchanged for two cultivars (Glen Clova, Glen Ample) partially susceptible to A. idaei, but significantly reduced for another (Octavia) with complete resistance in ambient climatic conditions. The inclusion of a coccinellid predator, however, mitigated the reduction in the resistance of Octavia by reducing aphid abundance. Behavioural responses to predation by A. idaei were also impaired under eCO2 after feeding on Glen Ample. The role of natural enemies in controlling herbivore abundance in future climates is therefore crucial. Native coccinellid species are currently declining in much of Europe, attributed to the occurrence of the invasive species, H. axyridis. Despite the declines in native coccinellid species, it was found that behavioural modification to feeding by both native and invasive coccinellid species can, theoretically, result in coexistence. Plant resistance in a future climate is likely to be modified significantly. Reduced resistance to aphid herbivory demonstrated here mirrors previous studies, highlighting the future importance of natural enemies to control aphid abundance. Changes to the abundance and behaviour of aphid prey and intraguild predators will modify the effectiveness of native and invasive natural enemies. Further mechanistic research is required to understand multi-trophic interactions in dynamic environments.

Language processing is a complex task requiring the integration of many different streams of information. Theorists have considered that working memory plays an important role in language processing and that a reduction in available working memory resources will reduce the efficacy of the system. In debate, however, is whether or not there exists a single pool of resources from which all language processes draw, or if the resource pool is functionally fractionated into modular subsections (e.g. syntactic processing, lexical processing etc.). This thesis seeks to investigate the role that working memory capacity plays in the utilisation of context to facilitate language processing. We experimentally manipulated the resources available to each participant using a titrated extrinsic memory load (a string of digits the length of which was tailored to each participant). Participants had to maintain the digits in memory while reading target sentences. Using this methodology we conducted six eyetracking experiments to investigate how a reduction of working memory resources influences the use of context in different language processes. Two experiments examined the resolution of syntactic ambiguities (reduced relative clauses); three examined the resolution of lexical ambiguities (balanced homonyms such as appendix); and one explored semantic predictability (It was a windy day so the boy went to the park to fly his… kite). General conclusions are hard to draw in the face of variable findings. All three experiment areas (syntactic, lexical, and semantic) show that memory loads interact with context, but there is little consistency as to where and how this occurs. In the syntactic experiments we see hints towards a general degradation in context use (supporting Single Resource Theories) whereas in the Lexical and Semantic experiments we see mixed support leaning in the direction of Multiple Resource Theories. Additionally, while individual experiments suggest that limiting working memory resources reduces the role that context plays in guiding both syntactic and lexical ambiguity resolution, more sophisticated statistical investigation indicates that these findings are not reliable. Taken together, the findings of all the experiments lead us to tentatively conclude that imposing limitations on working memory resources can influence the use of context in some language processes, but also that that influence is variant, subtle, and hard to statistically detect.

This study looks at two iron-rich phyllosilicates, which may be present on Mars. The minerals, greenalite and hisingerite, are rich in iron-II and iron-III, respectively. Small samples (~0.40 grams) of each mineral were crushed and heated in a Lindberg Tube Oven for approximately twenty-four hours at temperatures selected to mimic lava flows and impact events. Following heating, each sample was placed in a Fourier Transform Infrared (FT-IR) spectrometer to collect the near- and mid-infrared spectra. The spectra allowed for these terrestrial analogs to be analyzed with regards to how their structure breaks down with increasing temperature. The samples' colors were also recorded and show varying degrees of oxidation following heating, which is expected in the oxygen-rich ambient atmosphere they were heated under. It is apparent from the spectra that for greenalite, heating at 765°C and higher breaks the mineral down into hematite and a high-temperature silica, such as cristobalite. Hisingerite exhibits the same behavior, but its basic spectra structure is retained in the 710°C sample. The near-infrared spectra were compared with spectra from different locations on Mars, collected by both Mars Express and the Mars Reconnaissance Orbiter. The spectra were also compared with each other to allow for analysis of how the iron-III polymorph of a mineral reacts differently from its iron-II counterpart. The multiple facets of the study aim to help understand the current state, history, and evolution of Mars, specifically if clay formation occurred deep in Mars' past or as the result of impact-induced hydrothermal activity more recently in its history.

The conditionality agreements of the International Monetary Fund have received a significant amount of criticism from the 1980s and 1990s and into the 2000s.  Critics have found little reassurance from the IMF\'s attempts to reform conditionality after 2000.  The 1980s marked a time where conditionality on IMF loans required structural adjustment and the imposition of austere fiscal measures.  The streamlining initiative in 2000 possessed only slight quantitative modification to lending conditionality.  However, recent changes in the Fund\'s lending policy occuring between 2007 and 2012 may finally display the institution\'s ability to listen, learn, and adapt policy toward a conditionality regime utilizing policy outside of the neoliberal framework.  This thesis examines these new policies and their implications for neoliberalism where the term represents an approach to economic growth that demands privatization, deregulation, and  weakening the role of the public sector.  It provides a history of conditionality reforms and positions the most recent reforms in lending policy in the evolving neoliberal context.

This collection of short fiction is composed of six separate stories that are unified by place and time. Each story is set in the fictional town of Camelot, Ohio. This space is a fruitful place to investigate themes of normativity, judgment, deviance, freedom, greed, loneliness, fear, nostalgia and rebellion that structure and sometimes dictate the quotidian decisions of the characters. The stories are told from a third person perspective in order to experiment with the possible distances between two human psyches or subjectivities despite very close spatial proximity. Ultimately, my goal for the collection was to explore the tension between the uniquely American concept of individual determinism and the larger forces of history that have shaped the Midwestern landscape, and also, therefore, Midwesterners.

At any given time there are on the order of one hundred million cells undergoing mitosis in the human body. To accurately segregate chromosomes, the cell forms the bipolar mitotic spindle, a molecular machine that distributes chromosomes equally to the daughter cells. To this end, microtubules of the mitotic spindle must appropriately attach the kinetochores: protein structures that form on each chromatid of each mitotic chromosome. The majority of the time correct kinetochore microtubule attachments are formed. However, mis-attachments can and do form. Mis-attachments that are not corrected before chromosome segregation can give rise to aneuploidy, an incorrect number of chromosomes. Aneuploidy occurring in the germ line can cause both miscarriage and genetic diseases. Furthermore, aneuploidy is a major characteristic of cancer cells, and aneuploid cancer cells frequently mis-segregate chromosomes at high rates, a phenotype termed chromosomal instability (CIN). CIN has been correlated with both advanced tumorigenesis and poor patient prognosis and over the years there have been many hypotheses for what causes CIN. In this study, we identified two distinct mechanisms that are responsible for CIN. Both of these mechanisms cause a transient, abnormal geometric arrangement of the mitotic spindle. Specifically, cancer cells possess supernumerary centrosomes, which lead to the assembly of multipolar spindles during early mitosis when attachments between kinetochores and microtubules are forming. Supernumerary centrosomes facilitate the formation of merotelic attachments, in which a single kinetochore binds microtubules from more than one centrosome. As mitosis progresses the supernumerary centrosomes cluster, giving rise to a bipolar spindle by the time of chromosome segregation. However, the high rates of merotelic attachments formed during the transient multipolar stage result in high rates of chromosome mis-segregation. The second geometric defect characterized is caused by failure of centrosomes to separate before kinetochore-microtubule attachments begin to form. This mechanism, too, leads to high rates of kinetochore mis-attachment formation and high rates of chromosome mis-segregation. Finally, this study shows that the mechanisms characterized here are prevalent in human cancer cells from multiple organ sites, thus revealing that both mechanisms are a common cause of CIN.

Since the 1960s, the United States has experienced steady declines in news consumption and commensurate attrition in civic engagement and political participation. Americans read newspapers at less than one fourth the rate of 60 years ago; voter turnout has fallen to the point where the U.S. ranks 23 out of 24 established democracies; signing petitions, volunteering for a civic organization like the PTA and political party affiliation are all at contemporary lows. But these indicators only tell half the story…the younger half. Because among Americans over age 50, attrition in all these areas is much milder; among those under age 30 they are much steeper. So do young adults get news? If so, how do they get news? If not, how do they find out about things? A 21-year old journalism student reported that: “I usually just hear it from friends, when I talk to friends.” The present study employed four methods: Secondary analysis of longitudinal Pew data; interviews and focus groups about news consumption and media use habits, including social media and wireless devices; a survey on social media use and its relationship to news and news knowledge; and an experiment testing a novel game as a way to convey news and civics knowledge, all involving students at three large state universities. Findings include the following: students often rank social media use, like Facebook, as their most important and most-used media; social media are negatively related with traditional news use and with news knowledge; students draw clear and important distinctions between news and information; one method of teaching (direct instruction) works well while another (a news game) works, but not as well. Of particular interest is the role of opinion leaders in the two-step flow of news, and the role of relevance and need for orientation in agenda setting. Novel contributions include a clearer definition of students’ distinction between news and important information as they define it, a framework by which to experiment with creating an interactive game using news to promote news seeking, and some provocative recommendations for future research.

Since the 1960s, the United States has experienced steady declines in news consumption and commensurate attrition in civic engagement and political participation. Americans read newspapers at less than one fourth the rate of 60 years ago; voter turnout has fallen to the point where the U.S. ranks 23 out of 24 established democracies; signing petitions, volunteering for a civic organization like the PTA and political party affiliation are all at contemporary lows. But these indicators only tell half the story…the younger half. Because among Americans over age 50, attrition in all these areas is much milder; among those under age 30 they are much steeper. So do young adults get news? If so, how do they get news? If not, how do they find out about things? A 21-year old journalism student reported that: “I usually just hear it from friends, when I talk to friends.” The present study employed four methods: Secondary analysis of longitudinal Pew data; interviews and focus groups about news consumption and media use habits, including social media and wireless devices; a survey on social media use and its relationship to news and news knowledge; and an experiment testing a novel game as a way to convey news and civics knowledge, all involving students at three large state universities. Findings include the following: students often rank social media use, like Facebook, as their most important and most-used media; social media are negatively related with traditional news use and with news knowledge; students draw clear and important distinctions between news and information; one method of teaching (direct instruction) works well while another (a news game) works, but not as well. Of particular interest is the role of opinion leaders in the two-step flow of news, and the role of relevance and need for orientation in agenda setting. Novel contributions include a clearer definition of students’ distinction between news and important information as they define it, a framework by which to experiment with creating an interactive game using news to promote news seeking, and some provocative recommendations for future research.

The Supyire people of Mali practise levirate: when a woman is married, she permanently joins her husband’s family, and the marriage is not terminated by his death. Rather, it continues, with one of the husband’s younger brothers or cousins inheriting her and acting as a substitute levirate husband. The thesis describes how levirate is an integral part of the Supyire institution of marriage, how it gives marriage permanence, supporting the social structure, linking descent groups, determining access to land and providing a milieu for socializing children. The thesis highlights the experiences, positive and negative, that Supyire men and women have had of levirate, as related in interviews. It then begins to construct a practical theology of Supyire marriage by reflecting on it through four metaphors applied to Christ and his mission (redeemer, bridegroom, head of the church and the image of God) and the qualities particularly associated with these four metaphors (mercy, joyful love, permanent unity and respect for human dignity respectively). Despite its imperfections, the Supyire system of levirate gives security to widows and the fatherless, allows them continued access to farmland and thus to a livelihood, and can be a channel for Christ to mediate and teach about his faithful love. On these bases it is argued that levirate should be recognized by the church as a valid stage of marriage rather than treated as adultery or fornication. The thesis also reflects on the negative impact of sin on Supyire levirate and how marriage and levirate could be redeemed, with God at its centre rather than on the periphery. There are concluding reflections on lessons that might be learnt or relearnt that could be fed into a theology of marriage for the global church. An appendix outlines a possible Christian service of blessing for a Supyire levirate union.

Complex materials are emerging for use in heterogeneous catalysis and electrocatalysis with order on the atomic scale. One of the central issues for continued growth in this area is the ability to precisely control the size and shape of the nanoparticles, especially for sub 10 nm particles. Understanding the structure of these materials is of key importance in understanding their activity and developing this precise control, with which the exploitation of the key properties of nanoparticles becomes possible. The body of the work conducted in this thesis aimed to provide more accurate characterisation of the size and shape of carbon supported nanoparticle catalysts. Both monometallic (Pt or Au) and bimetallic (PtPd) catalysts were studied. In the first results chapter the strengths and weaknesses of various structural characterisation methods, TEM, XRD and EXAFS were explored. Subsequent chapters focussed on improving the EXAFS analysis by (i) using molecular dynamics simulations as the inputs for structural fitting and (ii) by using a Cu UPD layer to cap the surface of the nanoparticles, thereby reducing the effects of termination of the metallic structure on the EXAFS. The latter study also enabled the Cu UPD structure on nanoparticles to be compared to that obtained on single crystal surfaces

Atmospheric aerosols are the major component in the shorter-term variability governing the radiative balance of the climate system, particularly on regional scales. However, knowledge of the myriad of properties and processes associated with aerosols is often limited, which results in major uncertainties when assessing their climate effects. One such aspect is the chemical make-up of the atmospheric aerosol burden.Airborne measurements of aerosol properties across Northern Europe are presented here in order to facilitate constraint of the properties, processes and effects of aerosols in this highly populated and industrialised region. An Aerodyne Aerosol Mass Spectrometer (AMS) delivered highly time-resolved measurements of aerosol chemical components, which included organic matter, sulphate, nitrate and ammonium.The chemical composition of the aerosol burden was strongly determined by the dominant meteorological conditions in Northern Europe. Pollution loadings in North- Western Europe were strongly enhanced when air masses originated from Continental Europe. Conversely, much cleaner conditions were associated with air masses from the Atlantic Ocean.Organic matter was found to be ubiquitous across Northern Europe and predominantly secondary in nature, which is consistent with other analyses in polluted regions of the Northern Hemisphere. Furthermore, its concentration was generally comparable to, or exceeded that of, sulphate. Significant chemical processing of the organic aerosol component was observed. Highly oxidised secondary organic aerosol dominated, as the distance from source and photochemical processing increased.Ammonium nitrate was found to be a major component of the aerosol burden in Northern Europe, with peak contributions occurring in North-Western Europe, due to the co-location of its emission precursors (NH3 and NOx) in the region. Ammonium nitrate was found to be the dominant sub-micron chemical constituent during periods associated with enhanced pollution episodes. Its concentration was shown to be modulated by the thermodynamic structure of the lower troposphere, with enhanced concentrations prevalent at the top of the boundary layer. This phenomenon greatly enhanced the radiative impact of the aerosol burden; the increased mass and water uptake by the aerosol significantly amplified the aerosol optical depth in the region.The results presented in this thesis highlight a highly dynamic region, where major changes in emissions have played a significant role in determining the chemical composition of the aerosol burden. As substantial reductions in sulphur dioxide emissions have occurred over the past two decades in Northern Europe, the relative contribution of sulphate aerosols to the regional aerosol burden has decreased. Consequently, it is more pertinent to consider the roles of organic matter and ammonium nitrate, as their influence becomes more pronounced than sulphate on regional and global climate.

At the St Kilda archipelago, Outer Hebrides, declines have been recorded in the Leach's Storm-petrel breeding population, the largest in Britain and Ireland, and rapid increases in the population of Great Skuas. Leach's Storm-petrels have frequently been found in the diet of Great Skuas at St Kilda, where storm-petrels are active on land only at night and, unusually, skuas often hunt after dark. Apparent severe skua predation of Leach's Storm-petrels has raised conservation concerns regarding the sustainability of the St Kilda Leach's Storm-petrel population. However, it was recognised that this particular predator-prey relationship is a globally rare phenomenon, had not previously been studied for long at St Kilda (and never elsewhere), and warranted further research before conservation management interventions could be considered. Additionally, research on Leach's Storm-petrels was desirable in its own right, because the species had rarely been studied in the UK, due to its highly pelagic lifestyle and very remote breeding locations. The aim of this study was to increase our understanding of the ecology, behaviour and predator-prey interactions of Great Skuas and Leach's Storm-petrels at St Kilda. Results showed that Great Skua predation of Leach's Storm-petrels was considerable and sustained. Estimated numbers of Leach's Storm-petrels consumed annually by skuas were variable but averaged approximately 21,000 individuals per year. There was strong evidence from storm-petrel ringing and behavioural observations conducted at night that skuas fed predominantly on non-breeding Leach's Storm-petrels, which likely visit the archipelago in very large numbers each year, from huge colonies elsewhere, and probably play and important role in reducing impacts on the breeding population at St Kilda. It was found that Leach's Storm-petrels did not exhibit any specialised counter-predator adaptations to Great Skuas, and were very easily captured at night on the surface of the breeding colonies by skuas on foot. However, prey specialisation by skuas on nocturnally active seabirds (predominantly storm-petrels) did not create fitness advantages over prey specialisation on diurnally active seabirds or fish. Leach's Storm-petrel specialist skua pairs were very few and all pairs exhibited a tendency to feed on a diversity of prey and to switch prey-types between years. Adult and juvenile Leach's Storm-petrels were highly sensitive to light, and artificial light reduction measures in autumn helped prevent storm-petrel attractions and mortality in the village on Hirta. The St Kilda Great Skua population was found to be declining slightly, in contrast to the exponential growth recorded between 1990 and 2000, and Leach's Storm-petrel conservation issues now appear less severe than had been expected.

This research is a comprehensive investigation encompassing land use changes in an agricultural watershed and corresponding changes to the rainfall-runoff relationship and stream channel morphology. The Lac qui Parle (LqP) watershed is one of eleven major watersheds within the Minnesota River Basin (MRB). Agriculture is the dominant land use within the MRB occurring on more than 90-percent of the landscape. This research investigates the spatial and temporal changes in channel morphology and land use between 1965/66 and 2002/03. Historical data were obtained from the US Army Corps of Engineers for the South Fork Lac qui Parle (SF LqP) River. Sixty-five cross-section sites were re-surveyed and evaluated. Current channel morphology was assessed through a second year of data collection. Additional data were collected and analyzed for crop history, riparian vegetation, agricultural drainage, annual discharge, annual peak discharge, and monthly and annual precipitation. Results indicate crop diversity within the SF LqP River has diminished and is currently dominated by corn and soybean. Surface and subsurface drainage of agricultural lands was documented on 37-percent of the sub-watershed area evaluated. Analysis of the discharge and precipitation records indicates an increase in the Q/P ratio and average annual runoff volume post-1960. The analysis indicates land use changes within the SF LqP watershed have impacted the channel morphology of the SF LqP River post-1965/66. Significant changes in channel cross-sectional area were noted in the Middle and Upper watersheds. Results corresponds to a channel enlargement ratio (CER) of 1.02 - 1.30. Changes in cultivation practices and drainage activities correspond with higher CER of 2.32 - 2.6. Similar increases were noted for peak discharge (1.30 - 1.35). CERs match values developed for storm sewered streets in urbanized areas. All changes were significant at the 95-% confidence level. A separate investigation evaluated the use of natural channel design for agricultural ditches. Results indicate natural channel design provides more efficient sediment transport, increased channel diversity/complexity, and may reduce channel maintenance costs.

This thesis presents a generic passive non-contact based acoustic health monitoring approach using ultrasonic acoustic emissions (UAE) to facilitate classification of bearing health via neural networks. This generic approach is applied to classifying the operating condition of conventional ball bearings. The acoustic emission signals used in this study are in the ultrasonic range (20-120 kHz), which is significantly higher than the majority of the research in this area thus far. A direct benefit of working in this frequency range is the inherent directionality of the microphones capable of measurement in this range, which becomes particularly useful when operating in environments with low signal-to-noise ratios. Using the UAE power spectrum signature, it is possible to pose the health monitoring problem as a multi-class classification problem, and make use of a multi-layer artificial neural network (ANN) to classify the UAE signature. One major problem limiting the usefulness of ANN's for failure classification is the need for large quantities of training data. Artificial training data, based on statistical properties of a significantly smaller experimental data set is created using the combination of a normal distribution and a coordinate transformation. The artificial training data provides a sufficient sized data set to train the neural network, as well as overcome the curse of dimensionality. The combination of the artificial training methods and ultrasonic frequency range being used results in an approach generic enough to suggest that this particular method is applicable to a variety of systems and components where persistent UAE exist.

Molecular dynamics simulations are limited to very short time scales due to a need to resolve the thermal vibrations of atoms. This is a problem when attempting to model slow processes such as diffusion. A new method, called diffusive molecular dynamics (DMD), is presented for computer simulations of vacancy diffusion at the atomic scale. A variational free energy similar to that in the variational Gaussian method, with EAM potentials, of LeSar, et al. is derived in the grand canonical ensemble. A kinetic law based on the master equation is used to track vacancy diffusion over a site lattice. Static minimization of the variational free energy allows the site lattice to adjust to changes in the occupation probabilities of the sites.Some results from applications of the DMD method are also presented. Basic verification of the model is provided by reproducing basic material properties such as the lattice constant, bulk modulus, and vacancy formation energy, as well as matching the behavior of the kinetic law to a continuum random walker model. Void formation is observed for high vacancy concentrations. Creep under nanoindentation can also be seen.While the above verifications give confidence in the model, several issues are yet to be resolved. These are mostly related to the mean field approximation used in deriving the variational free energy. There is a disagreement in between the concentrations used in the free energy and the expectations of the kinetic law. The mean field approximation also loses information about individual vacancies leading to self-interactions. It is uncertain if the conditions of the approximation used to incorporate the embedding term of EAM potentials are always met. There is also currently no mechanism to add vacant sites to the system preventing, for example, dislocation climb by vacancy emission. In addition, the current implementation does not account for different diffusivities through the bulk and along defects.

This is a survey study of four Ohio pre-service teacher preparation programs to determine how they are meeting higher education (NCATE) and content area (TESOL) standards. This descriptive study uses online surveys and interviews, focus group members, and online program examinations and evaluations as data collection instruments with a purposeful sampling design. Findings show the critical need for improving pre- and in-service teacher preparation programs by including field practice with English Language Learners (ELL) and development of knowledge in second language issues. The implications are that pre-service teachers can be trained to meet the educational needs of ELL students. The implications are simple: Curriculum is the key. An infusion of courses and field experiences will make this happen.

Investigations into two different fields of plasma research are presented here. These include the study of ion engine performance and the use of plasma discharges for flow control. In the area of ion engine performance, optimizing electron confinement is the primary goal of this work. The work of prior researchers was expanded through the study of the cathode emission location and the energy of the primary electrons. Cathode position was shown to have minimal effect on confinement length. For electron energy values greater than 20eV the effect on confinement length was also found to be very small. The strength of the magnetic field was also tested and compared with results from prior researchers. The results showed that for a magnet circuit that is already optimized, increasing the magnetic field strength through adding more magnets or using stronger magnets only decreases the confinement. In the area of plasma actuators for flow control, the objective is to garner a qualitative understanding of both heating and the addition of forces to subsonic and hypersonic flows. This was done through the use of a commercially available CFD package. Results showed that for plasma discharges the dominant effect on surface pressure in the hypersonic regime is that of heating. Representative force sources showed some effect but were smaller. Subsonic computational studies showed that heating had no significant effect on the pressure distribution. Results for the force sources show that it is possible to get some small changes in the surface pressure through the use of a sufficiently large force. Experimental results conducted in a subsonic wind tunnel confirmed the minimal influence of the heating effect. Long range Lorentz forces were obtained by placing magnets within the plate. The resulting forces on the plate match well with the Lorentz force law, but due to limitations in power, the plasma discharge did not reach the desired length.

The basis of this research is the augmentation of turbulent boundary layer stability. Here stability is referred to as ,the boundary layer's ability to withstand adverse pressure gradient and therefore separation. A practical example of an' issue involving a requirement for greater stability, where separation is a typical and detrimental feature, would be a deployed flap during a critical regime of the flight envelope such as landing. A sub-boundary layer vortex generator (SBVG) is a static flow control device which does not carry the drag penalty of its traditional larger counterparts. It is however less effective. An excited SBVG may be more effective than a static model, in terms of enhancement of stability, with the added benefit of not requiring sophisticated feedback systems to prevent the device from generating detrimental effects during periods other than the flight regime for which it is intended to operate, since the SBVG is embedded within the boundary layer. Here an SBVG was oscillated (or swept) between three inclination ranges at a number of frequencies. The swept inclination ranges were 16° to 24°, 20° to 28° and 24° to 32°. These motions were executed at reduced frequencies of 0.1,0.6, 1.6,3.1,4.7, and 6.3. The data show that dynamic actuation of a sub-boundary layer vortex generator results in a weaker vortex with accelerated decay than is generated by a static vortex generator at equivalent incidence. The strength and persistence of the dynamically generated vortex is closely linked with the reduced frequency, in that increase in frequency results in an increasingly weak vortex with an increasing rate of decay.

This thesis argues for an unorthodox interpretation of John Rawls's egalitarianism as a hybrid of 'actual contractualism' and 'modal contractualism'. It also offers a defence of the theory so understood. According to actual contractualism, a system of political institutions and norms is just only if each person over whom it claims authority actually accepts it in some sense. Actual contractualists stand in contrast with modal contractualists, who take jusuce to require that no one could reasonably reject the institutions and norms in question. Rawls is standardly read as a modal contractualist, but I argue that his view includes an significant element of actual contractualism. The thesis is divided into three parts. The first part describes actual contractualism and contrasts it with modal contractualism. It goes on to consider the possibility of a hybrid theory, which appeals to modal contractualist reasons to justify an actual contractualist test for justice. I suggest that this is an attractive view. In trie second part I go on to argue that a careful understanding of Rawls's theory view reveals it to be hybrid contractualist. I elaborate Rawls's strategy of 'political constructivism' in the light of this interpretation, and attempt to show that it is very much in the Lockean actual contractualist tradition. The final part of the thesis concerns the justification of specifically Rawls's egalitananism. I contend that Rawls's argument for justice as fairness can be seen as a detailed effort to explain why his egalitarianism is, in the relevant sense, actually accepted by each person, and I argue that as such it succeeds. I then contrast the Rawlsian view with left-libertariamsm, another attempt to marry actual contractualism and egalitananism. I argue that Rawls's is the more thoroughgoing, unified view, and should be preferred on that basis.

The Jurassic Curtis, Summerville and Stump formations of Utah and Colorado consist of marine and marginal-marine strata deposited along the southern margin of the Western Interior Seaway. Although previous investigations have documented the distribution, lithologic characteristics, and environments of these units, they have been difficult to correlate regionally due to internal lithofacies variations and the lack of age-diagnostic fossils. In this study I present new data consisting of 34 biostratigraphic samples and 25 measured stratigraphic sections demonstrating the stratigraphic equivalency of the Curtis and Summerville formations with the Stump Formation and demonstrate that deposition occurred between early and late Oxfordian time (~161-155 Ma). Detailed sedimentological field data allows formulation of a sequence-stratigraphic model that indicates these formations were deposited during a single transgressive-regressive sequence. The new sequence stratigraphic model helps clarify the stratigraphic architecture of the Middle-Upper Jurassic rocks of the region and may serve as a guide for interpretations of other tidally-influenced depositional systems.

This topic will involve an analysis of architecture of the past to reveal how sustainable design techniques were dependent on the natural environment of a specific climate region. This analysis of ancient building strategies will examine similar climate areas to the Southeast United States and combined the information with modern 'green' technologies. The final result being a building whose expression reflects a new regional vernacular. Before the age of electric heating and cooling systems and thermal insulation, buildings were designed to take advantage of their natural surroundings. In fact, these structures depended on its natural surroundings and this dependence informed the architectural expression. Designers of the past had to create buildings that addressed their climate zone or else survival through a harsh winter or an extremely hot summer might not be possible. In addition, commercial industries of the past were dependent on specific climate conditions which in turn began to define the region's character. Today, due to mechanically conditioned spaces and other social factors, buildings designs have become independent from their natural environment and forgotten many of the important 'green' building techniques of the past. New environmental problems exist today which have increased the demand for sustainable building and lead to the invention of 'green' technologies such as green roofs, solar panels, and water collection and storage systems. Modern architects should use these technologies in their design schemes to demonstrate a return to a dependency on the natural environment.