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Program synthesizers promise to save time for the programmer by writing parts of their code for them, provided the programmer knows exactly what they want. For it to suggest that code, the programmer must convey the nuances of their specification to the synthesizer. Is there a place for program synthesizers when those nuances are unclear, and a programmer must explore the design space of their problem? This dissertation argues that program synthesizers can facilitate exploring for code, and that techniques to validate explored code are needed to reduce cognitive effort.To use a traditional synthesizer successfully, the programmer needs a deep understanding of the problem. Firstly, a programmer must convert their intent into the specific language their tool understands, which may not match how they think about their intent. Secondly, a programmer needs to know all the edge cases of their problem and how each one should behave. If both of these cannot be met, then a traditional synthesizer will usually be more effort to use than simply writing the desired program.As modern, probabilistic synthesizers require less overall information to offer a suggestion, they can fill a new role in the programming workflow: code exploration. A programmer no longer needs complete understanding of their problem nor be able to communicate all nuances to the tool. This new exploration domain presents new challenges, particularly one of validating the code matches the often incomplete intent of the programmer. Validating code against intent must be quicker or easier to justify a tool’s use in exploration to be useful. In this dissertation, I show that both traditional and probabilistic program synthesizers can aid in this exploratory process of programming, and that techniques to validate that explored code reduce the cognitive effort.

Microfluidics-based sorting of cells after encapsulation in water-in-oil or water/oil/water droplet emulsions has great potential to significantly accelerate the designbuild-test cycle for production strain engineering. This is especially true for non-conventional hosts and products that are secreted, as screening can be performed with minimal prior biological knowledge (relative to rational engineering) and entrapment of secreted product with the responsible producer cell can enable high throughput screening directly for extracellular product concentration. Microfluidic technology for droplet sorting has advanced and become more available in recent years, but gaps remain, including the limited number of droplet-compatible methods for transducing extracellular product titers into sortable fluorescence signals, and a lack of direct, matched comparisons to more established techniques such as fluorescence activated cell sorting (FACS). This research used yeast-based systems (Saccharomyces cerevisiae and Yarrowia lipolytica) as test beds for focusing on and addressing three areas that are related to these limitations. In the first focus area, we develop RNA aptamers in droplets (RAPID) screening, a method that expands the generality of high throughput microfluidic droplet screening. Using RNA aptamers, we transduce extracellular titer into fluorescence, enabling the screening of millions of yeast variants and ultimately enhancing secretion of a recombinant protein (streptavidin) from yeast. For the second focus area, we undertook a comparative analysis of traditional single cell fluorescence activated cell sorting (single cell FACS) and microdropletenabled FACS (droplet FACS) using water/oil/water (w/o/w) emulsions. To do so, we engineered and evolved the non-conventional yeast Y. lipolytica for high extracellular production of riboflavin (vitamin B2), an innately fluorescent product. In a parity-matched comparison ofsingle cell FACS and droplet FACS, both techniques led to significant increases in total riboflavin. However, single cell FACS favored intracellular accumulation, while droplet FACS favored extracellular product accumulation and yielded higher total riboflavin production. In the third focus area, a droplet-based bacterial-fungal consortium/co-culture approach was applied, wherein Escherichia coli biosensors were used to screen for improved extracellular polyketide production from Y. lipolytica. This droplet sorting strategy was used to screen genome-wide piggyBac transposon libraries, leading to the identification of several alleles for enhancing triacetic acid lactone (TAL) production.

Nucleation and growth of crystalline substances from solution is ubiquitous in the production of active pharmaceutical ingredients. However, a basic understanding of nucleation is still lacking after many years of study. One major problem in studies is due to the stochastic nature of nucleation, causing direct observation to be challenging. One possible solution to this is to use optical tweezers to promote nucleation localised to the tweezer focus. Although temporospatial influence and control over nucleation is achievable, some secondary considerations not usually part of the design of crystallisation processes must be considered, with a focus on optical properties with the aim of limiting laser induced heating. A preliminary study was conducted to allow crystal nucleation and growth experiments performed using the optical tweezer setup to be fully understood within context, examining nucleation and growth kinetics up to a scale of 3 mL on high throughput platforms. This study examined the effect of deuterated solvent and doping with spherical microparticles. The use of deuterated solvents resulted in the reduction of primary nucleation rates. Its impact on secondary nucleation and growth depended on the crystallising material. Doping with spherical microparticles was particle material dependent, with silica promoting nucleation and polystyrene's effect being system and solvent isotopologue dependent. Optical tweezers allow direct control over localised growth of macroscopic crystals with the effect being dependent upon the solvent isotopologue, when using low laser power. Higher laser power allows the time and position of nucleation to be controlled within certain conditions of supersaturation, laser power and relative location of the tweezing focus within the solution. As well as allowing the growth rates of crystals nucleated from bulk undersaturated solutions to be measured, suggesting the enhancement of the local solute concentration in the region surrounding the optical tweezing focus.

Breadboarding is an essential part of Do-It-Yourself (DIY) electronic music. It is often used to investigate, test or refine a design prior to the construction of a finished instrument. It is part of a well-established design process that is often regarded as a stepping-stone or means to an end, and breadboard-based prototypes are generally not viewed as practical or complete instruments in their own right. Instead, they are viewed as fiddly and imprecise, with their intermittent connections and delicately mounted controls. Despite these, and other shortcomings, breadboard-based instruments have a number of features and affordances that make them worthy of exploration as legitimate musical instruments. Furthermore, the practice of breadboarding can be seen as an act of musical composition or performance. This thesis sets out to define and defend a domain that I will refer to as breadboard music. I will also present an appropriate framework or set of strategies, including the underpinning logic and philosophy behind them. The research undertaken is practice-related and uses empirical and iterative processes to derive new knowledge and understanding of breadboard music and DIY electronic music. I refer to the research as practice-related because it is both practice-based and practice-led; as well as presenting a framework developed through the practice of creative breadboarding, I will also present a series of original artefacts in the form of creative works. To conclude, I explore the limitations of black box devices and the importance of breadboarding and experimentation as a means to combat the shortcomings of such designs. I postulate that despite advancements in technology, breadboarding will continue to remain relevant as a creative musical practice.

In this work we investigate the conjectural ADE classification of exact Lagrangian fillings of Legendrian links. We begin by showing that two methods of constructing exact Lagrangian fillings -- Legendrian weaves and decomposable exact Lagrangian cobordisms without Reidemeister I or II moves -- yield Hamiltonian isotopic exact Lagrangian fillings. Using the method of Legendrian weaves, we construct and distinguish exact Lagrangian fillings in D_n-type. We then investigate Legendrian loops, Legendrian isotopies fixing a Legendrian link pointwise at time one. Legendrian loops act on the set of exact Lagrangian fillings by concatenating the trace of the Legendrian isotopy. We investigate this action first in type A_n, and then more generally, leveraging techniques from the theory of cluster algebras and connections to the theory of mapping class groups. In particular, we give a complete description of the orbital structure of the cluster modular group action on exact Lagrangian fillings of Legendrian (2, n) torus links. Beyond type A_n, we compile and extend known results interpreting Legendrian loops as generators of cluster modular groups for affine and extended affine type cluster algebras. We show that Legendrian loops virtually generate these cluster modular groups. By extending an analogy between cluster modular groups to mapping class groups, we provide new tests for detecting when a Legendrian loop produces infinitely many distinct exact Lagrangian fillings. Finally, we discuss possible avenues towards producing generating sets for cluster modular groups using Legendrian loops.

Direct-fired supercritical carbon dioxide (sCO2) power cycles offer emissions-free electricity production from the combustion of fossil fuels. Chemical kinetic mechanisms are validated for combustion at lower pressures and much lower CO2 concentrations. The work critically investigates the ability of existing chemical kinetic mechanisms to simulate combustion under these conditions. This is done by investigating ignition delay time (IDT) data recorded using the shock tube experimental technique. The first key chapter of this Thesis details the development of a new High-Pressure Kinetic Shock Tube (HPST) at the University of Sheffield's (UoS) Translational Energy Research Centre (TERC). The HPST will be utilised for the research of high-pressure chemical kinetics. The project was delivered in the summer of 2022, with commissioning taking until the end of the year. The HPST will be used in a variety of research projects at the TERC from the combustion of supercritical CO2, ammonia, and synthetic aviation fuels. Chapter 3 details the development of a new chemical kinetic mechanism for modelling combustion in CO2. The University of Sheffield sCO2 mechanism (UoS sCO2) was developed based on IDT datasets of methane, hydrogen, and syngas. The UoS sCO2 Mechanism was developed and shown through a detailed qualitative analysis to be on average a better fit to the datasets measured for each of the three fuels. Chapters 4 and 5 focus on the validation of the UoS sCO2 2.0, the second iteration of the mechanism in collaboration with King Abdullah University of Science and Technology (KAUST). Eight IDT datasets for both hydrogen and syngas and ten for methane and methane hydrogen blends were recorded using the KAUST HighPressure Shock Tube between 20 and 40 bar. This data and subsequent modelling analysis are essential to the detailed understanding of the fundamentals of combustion in CO2.

This mixed method arts-based study aims to answer the research question: How do undergraduates enrolled in an online course investigating visual culture at a large public Midwestern university relate to possibly manipulative and misleading online media imagery? Before educators can attempt to improve student media literacy, they must first understand how students experience visual media online. A holistic approach where students visualize their relationship with online media, respond to a survey of their attitudes and behaviors concerning online media, and demonstrate their abilities on anassessment of their critical media literacy, provides a rich snapshot of how members of Generation Z or Zoomers relate to online media.My findings reveal that students are extremely susceptible to manipulative or misleading media and that their unwarranted overconfidence may compound that vulnerability. Meanwhile, their art depicted feelings of anxiety, distrust, confusion, and helplessness regarding their relationships with media. With the increasing reliance on online media, exacerbated by the COVID-19 pandemic, it seems as though misinformation online will only continue to proliferate with increasingly dangerous consequences in the real world. As a result, educators, especially art educators, are urged to try to help students develop visual and critical media literacy skills. Recommendations and lesson ideas are provided.

Within institutions of higher education, shared governance is an essential component to a healthy functionality. Among the many stakeholders at these institutions, students are the largest in number and hold primacy. Participation in student governance establishes a sense of shared ownership over their communities while also providing a unique avenue for students to gain wisdom and develop critical skill sets. Senior administrators at these institutions have many inherent challenges due to an organization that is largely decentralized and autonomous (Duderstadt, 2007). Regarding agenda setting, the Garbage Can Model (Cohen et al., 1972) was utilized as a theoretical framework. The purpose for conducting this study was to analyze Student Government Associations (SGA) at 8 select land-grant institutions of higher education in order to establish the answers to 4 research questions. (1) How do student leaders at select land-grant intuitions of higher education describe their policy priorities? (2) How do the presidents at the same institutions describe their priorities in select institutional or media documents? (3) To what extent are the agendas of SGAs and institutional presidents aligned? (4) How did student body presidents describe their working relationship with their respective institutional leader and does that impact agenda alignment? The answers to these questions were found utilizing a qualitative methodology. Specifically, official documents from the SGAs were reviewed and coded. Additionally, the student body presidents of 6 of the 8 universities in question were subjects in a semi-structured interview. Finally, official university documents, public remarks, and media coverage were analyzed and coded to establish the policy agendas for each institution’s president. The study found that Student Government Associations conduct policy implementation in the form of organizational management as the most prominent agenda item. In addition to that, it was shown that SGAs prioritize campus infrastructure improvements, campus safety, and the overall wellness of the student body. Presidents at the same institutions discussed issues related to research and innovation most prominently. They also prominently discussed campus infrastructure. The semi-structured interviews and document analysis showed a minimal alignment between the agendas. However, student body presidents indicated that they did not necessarily anticipate alignment given the differences in their constituencies. They also mostly described having positive relationships built upon mutual trust despite the lacking alignment. Institutional presidents were also found to rarely prioritize issues related to campus safety and sexual assault in direct contrast with SGAs. These findings emphasize the importance of shared governance within these institutions. Positive relationships between SGAs and their presidents emphasize constructive communication and reciprocity between the subjects which leads to more buy-in by stakeholders and innovative ideas.

Informed by a critical realist perspective and using a multiple case study methodology, this PhD study recruited, interviewed and analysed 12 cases of white South African (wSAn) learners in the post-apartheid era who reached a high proficiency in an indigenous African language (AfL) as a second or additional language (L2). The phenomenon of study, L2 AfL learning (L2AfLL) by wSAns, was characterised as a form of L2 indigenous language learning (L2ILL) by settler-descendants occurring in other post-colonial contexts like New Zealand and Kenya, among others. As an overall framing device, an investment metaphor was reconceptualised for the purposes of this study as the 'L2 Investment' framework - inspired, but divergent, from Norton's (1995) construct of investment and later investment model (with Darvin, 2015). Six core cases were selected and analysed in depth; in the cross-case analysis, these were complemented by a further six peripheral cases, in order to achieve a measure of analytic generalisation from the inclusion of limit cases (Campbell & Yin, 2018). Viewed through an L2 Investment frame, it was found that successful investment in L2AfLL occurred in cases with nominal access to AfLs in high school; ideal neurophysiology and prior human capital; and intrinsic motivation. For those who lacked such ideal personal conditions, guardian investment by parents was sufficient to catalyse investment behaviour, or the introduction of circumstantial necessity through moving to an AfL-dominant, rural area. All successful cases were found to have committed to a 'transgressive modality' of L2AfLL, in which class and spatial boundaries were overcome. This was undertaken either in isolation, or in addition to an academic modality (high school or university). Beyond a narrow focus on the conditions for and development of linguistic capital, fluency in an AfL was typically found to be leverageable for further social and symbolic capital, limited occupational gain, as well as what was termed zookairotic capital - e.g. emergent senses of rootedness, legitimacy, physical and psychological security, and joy. This emerged primarily for investors themselves, but also for most AfL-speaking interlocutors. Evidence was thus found for the value of multiple instances of symmetrical multilingualism (Orman, 2007), with implications for broader social welfare and nation-building.

Nosocomial infections (those that are hospital-acquired) lead to patient morbidity and mortality, and are further complicated by the growing problem of antimicrobial resistance. Wastewater plumbing systems (WPS) are bacterial reservoirs and vehicles for bacterial transmission. Sink traps form a barrier between users and the WPS, but breaches can lead to contamination and have been implicated in outbreaks of infections. This project sought to address the need for a novel antimicrobial nanocoating to reduce bacterial colonisation and biofilm formation in sink traps. A nanocoating was developed by embedding silver nanoparticles in a matrix of commercially-available and low-cost pipe cement, applied to unplasticised polyvinyl chloride. Material characterisation and nanotopography imaging revealed that roughness was increased by surface grinding, with nanotopography images showing the troughs produced, and high silver stability was evident with very low dissolution under controlled dialysis experiment conditions. Culture-dependent and -independent techniques were used to characterise the bacteria present in hospital sink traps, revealing certain dominant genera such as Citrobacter, Pseudomonas and Serratia. Sequencing of 16S rDNA from sink traps has previously been an under-reported area. A bacterial isolate of interest, Cupriavidus pauculus MF1, was further investigated and found to be multidrug-resistant with biofilm formation comparable to Pseudomonas aeruginosa. Whole genome sequencing, producing a hybrid assembly of short- and long-reads, allowed annotation of a number of antibiotic and metal resistance and virulence factor genes of interest, supporting the suggestion that awareness should be increased for this and other opportunistic pathogens in hospital sink traps. Silver nanocoatings demonstrated potent antiplanktonic and antibiofilm activity against the nosocomial pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Enterococcus faecalis. Novel, more realistic experimental conditions were developed, first using a hospital sink trap community to colonise a benchtop model sink trap system. Antibiofilm activity was evident over long time periods, up to 11 days, but waned by day 25. Placement of silver nanocoated specimens in real-world sink traps in two university buildings provided little overall evidence of a consistent antibiofilm effect. Follow-up in vitro experiments using hospital and university building sink trap communities confirmed that the silver nanocoating was active against those same polymicrobial communities. It is possible that certain realistic environmental conditions mask the surface of nanocoatings and limit their activity, with relevance to antimicrobial nanocoating development in plumbing systems and other environments. The results indicate that there can be significant discord between in vitro and in situ experiments, emphasising the need for novel antimicrobial nanocoatings to be evaluated in real-world settings.

The defence of plants against pathogen infection is a topical issue critical for maintaining food security in the face of climate change. Plants have evolved complex mechanisms to regulate gene expression, enabling transcriptional reprogramming in the face of threats like herbivores and infectious pathogens. Plant hormones are crucial signalling components which contribute to transcriptional reprogramming, and for stresses like herbivores and necrotrophic pathogens the hormone jasmonic acid plays a central role. Jasmonic acid perception occurs via the F-box protein Coronatine Insensitive 1 (COI1), which enables the targeted degradation of Jasmonate Zim Domain (JAZ) proteins, the focus of this work.

The β-barrel assembly complex (BAM), functions to fold outer membrane proteins (OMPs) into the outer membrane of diderm bacteria. High resolution structures of BAM exist in a variety of conformations, and in complex with OMP substrates that could represent folding intermediates. Despite this, the mechanism by which BAM folds its array of OMP substrates remains unresolved.

This dissertation examines the relational philosophy of Quichua Indigenous people living along the Bobonaza river in the Ecuadorian Amazon. I argue that Bobonaza river Quichuas cultivate social relationships with nonhuman beings such as plants and animals to navigate the web of biosemiotic relations that constitute the Amazon forest. I examine Amazonian Quichua and anthropological notions of ‘self’ and kinship in more-than-human contexts. Bobonaza Quichuas understand nonhuman beings such as plants and animals to be selves imbued with intentionality, sociality, and subjectivity. They become yacharishka (familiar with or accustomed to) with nonhuman selves through specific practices such as songs, dreaming, and the ingestion of entheogens. By becoming yacharishka and come to intimately know and be aligned with nonhuman selves, Bobonaza Quichuas are able to cultivate intersubjective relationships of mutual care and utility with nonhuman selves to harness their attributes and powers. My principal intervention is to rethink the widespread Amazonian Indigenous practice of capturing and raising forest animals (huibana in Quichua). This practice has largely been theorized within the neostructuralist paradigm of predation, mastery, and ownership which frames the human-forest animal relationship as one of master/owner and pet. However, my ethnographic research shows how Bobonaza Quichua women raise huiba (forest) animals to act as sensors in locating dangers in the forest such as snakes, spiders, and ants. Bobonaza women become yacharishka with the huiba animals by being attentive to their particular calls, signals, and bodily movements. In this way, Bobonaza women are able to tap into the biosemiotic web of forest relations using the huiba animals as a sensory medium. I argue that rather than taming and ownership, the Quichua-huiba relationship is a semiotic intersubjective relationship of mutual care and utility. Furthermore, the centrality of women in navigating nonhuman relationships with huiba animals and other practices joins other scholarship in problematizing the neostructuralist theorization of women in dichotomous ways: consanguienty to men’s affinity, interiority to men’s exteriority, women’s domestic and domesticating, to men’s wild and predation. Finally, in contrast to scholars working in the vein of ontological politics and ontological turn that posit a pluriverse or multiple worlds, I argue that Bobonaza Quichua and nonhuman being relation-making is bound up in the overarching biosemiotic relational schema within all beings participate and co-become. Bobonaza Quichuas very much inhabit this relational and phenomenological world and are attuned to the political, social, and semiotic contours of the world they live in. The crucial difference is the ways that Bobonaza Quichuas are attentive to, become yacharishka with, and cultivate intersubjective relationships with the nonhuman plants and animals that constitute the world they share.

This dissertation addresses a number of questions which relate to a growing body of evidence for the rise of markups among large firms, and concentration in many industries, in the United States over time. Although existing evidence suggests that markups have been on the rise, there are a number of competing explanations for these trends which have differing policy implications. In this dissertation I argue that, in the retail food industry, the most likely cause of rising markups over time is the growing prevalence of “niche” goods which more closely match consumers’ idiosyncratic needs, and estimate a number of structural models of consumer demand in order to study the evidence for this hypothesis. The first chapter discusses the existing evidence that markups have been on the rise in the United States and introduces the theoretical framework and empirical evidence motivating the study of markups in the retail food industry. In this chapter I show that the number of goods carried by retail food stores in my data has grown significantly between 2006 and 2017, and that the characteristics of the offered goods have changed over time. Using a simple theoretical model, I argue that firms’ incentives to offer “niche” goods, which I define herein, grow as they become able to stock a larger portfolio of goods. I also introduce the data set which is used in all three chapters of this dissertation and briefly discuss the way in which I select the categories which are the focus of my empirical work in Chapters 2 and 3. The second chapter introduces three empirical models of consumer choice in nine retail food categories. The first is a traditional mixed logit model in the spirit of Berry, Levinsohn and Pakes (1995), which has been applied in many studies in industrial organization. The second is an approximation of this model, developed by Salanie and Wolak (2019), which allows consumer preferences to differ flexibly in every three-digit ZIP code in my data. The third model is a constant elasticity model of demand, which makes different assumptions than do mixed logit models and serves in part as a robustness check against their potentially strong assumptions. I estimate each of these models separately in nine large categories of products in 2006 and 2017 and demonstrate that each model implies that consumers have become significantly less price sensitive over time. A simple pricing rule demonstrates that the firms in my data may have been able to sustain larger markups over time solely due to the observed changes in the price sensitivity of consumers, absent any changes in firm pricing behavior. In the third and final chapter, I estimate two additional models of demand in order to determine the structural reasons that consumers have become less price sensitive. First, I demonstrate that an assumption restricting changes in unobserved product quality over time allows us to distinguish between the effects of rising horizontal differentiation and changes in the direct disutility of price due to, for example, changing consumer demographics and wealth. In a second model, I introduce a new scaling parameter which allows me to measure differences in consumers’ price sensitivity for newer and older goods (as measured by how long a good has been sold in a store in my sample) separately. Together, these models provide evidence that horizontal differentiation has increased significantly over time and that consumers are particularly insensitive to changes in the prices of newer goods. I take these findings as evidence that niche products do play a significant role in explaining the results of Chapter 2, as predicted by the model introduced in Chapter 1.

Graphics Processing Units (GPUs) and other throughput processing architectures have scaled performance through simultaneous improvements in compute capability and aggregate memory bandwidth. Satisfying the increasing bandwidth demands of future systems without a significant increase in the power budget for the DRAM is a key challenge going forward. A new DRAM architecture, Fine-Grained DRAM, significantly reduces the energy consumption by partitioning the DRAM die into many small independent units, called grains, each of which has a local I/O link to the processor. With this architecture, the on-DRAM data movement energy is greatly reduced due to the much shorter wiring distance between the cell array and the local I/O. At the same time, the energy on the link between the DRAM and GPU remains low by leveraging novel energy-efficient encoding techniques well-suited to the narrow buses. Furthermore, wasteful row overfetch energy due to sparse accesses to large DRAM rows is significantly reduced by reducing the effective DRAM row size in an area efficient manner. This Fine-Grained DRAM architecture enables future reliable, multi-TB/sec memory systems within a power budget comparable to current GPU memory systems.

Reversibly switchable fluorescent proteins (RSFPs) switch between a highly and weakly fluorescent state upon photoexcitation. This switching is known to be driven by reversible photoisomerisation and a change in protonation state of the chromophore. However, the exact sequence of events after optical excitation is unclear. In this thesis, time-resolved crystallography and vibrational spectroscopy are used to study the ultrafast dynamics of a new RSFP. Time-resolved serial femtosecond crystallography (TR-SFX) is used to probe the trans/cis reaction and reveals ultrafast sub-Angstrom motions of the chromophore and surrounding hydrogen bonding network. The addition of a stokes pulse (shown to dump the excited state population) increases these displacements and allows assignment of the light-induced signals to a vibrationally excited electronic ground state structure instead of an excited state structure. Temperature analysis of the steady-state switching rates resolves an intermediate ground-state structure using conventional crystallography which supports the TR-SFX assignments. Ultrafast pump-probe vibrational spectroscopy confirms that excited state photoisomerisation occurs (~70 ps), proceeded by rearrangement of a nearby arginine residue (~7 ps) with deprotonation (trans-neutral/cis-anion) occurring between 2 ns - 1 ms. An additional dump pulse is then shown to repress product formation and reforms the ground state, further supporting the structural observations of the pump-dump-probe crystallography measurements. These results improve our understanding of photoswitching in RSFPs and have important implications for structural assignments in future TR-SFX experiments. Time-resolved serial synchrotron crystallography (TR-SSX) is an accessible and emerging technique for studying protein dynamics on millisecond timescales. Here, the trans/cis isomerisation of an RSFP is probed at 10 ms with a range of pump intensities to demonstrate precise control of the cis-state formation yields. The population transfer is resolved crystallographically using quantitative analysis of the occupancy, showing excellent agreement with optical flash-photolysis measurements. The issue of X-ray induced heating, which leads to partial thermal recovery, is also addressed. A temperature increase of 82-112 K is extracted for the fixed-target sample delivery used, which should be accounted for in all future TR-SSX experiments. Finally, the effect of pH on the protonation step is investigated by studying a RSFP mutant with a destabilised ground state conformation. Structural and spectroscopic evidence is presented for a new class of reaction at low pH, involving a cis-neutral/trans-cation isomerisation, in contrasts to the typical cis-anion/trans-neutral reaction at neutral pH. These steady-state observations expand our understanding of acid/base equilibria in the photoreactions of RSFPs.

The present study sought to examine four key factors to mathematical anxiety research. First, examine if adult learner is less impacted by mathematical anxiety interventions than their younger peers. Second, the potential effect of incubation theory on mathematical anxiety treatment involving low math anxious individuals. Third, if older adults, low in mathematical anxiety are affected differently by mathematical anxiety interventions than younger individuals. Fourth, if a significant difference exists between the benefits of asynchronous based interventions and synchronous interventions when treating mathematical anxiety within adult learners. To achieve these four goals, undergraduate students from a large mid-western university that were enrolled in math-based courses were recruited for involvement in a systematic desensitization intervention for mathematical anxiety. This study found individuals who take part in systematic desensitization interventions, asynchronous and synchronous, for mathematical anxiety see a significant reduction in level of math anxiety when compared to individuals who do not take part in an intervention. It was also found that there is no significance in the effects of the intervention when traditional and adult learners were compared. The present study further found that there is not a significant increase in mathematical anxiety for low math anxious individuals who participated in the intervention. Implementation of these results and directions for future research are also included.

This dissertation examines the moral and political responsibilities that are generated because of climate change. What are our moral and political responsibilities vis-à-vis pollution levels caused by past generations? What are our moral and political responsibilities vis-à-vis the environment today? What are our obligations to future generations? To answer these questions, I employ content analysis from philosophical texts, academic works and international environmental agreements and law in global justice, intergenerational justice, environmental ethics, and cosmopolitanism. I argue that current domestic and international environmental policies ought to consider past pollution levels and the injustices as well as harms rendered to do justice to those today who are most affected by climate change and pollution. Next, I show that our current formulation of environmental protection in the form of domestic and international environmental law is falling short by way of protecting the environment today, and that more aggressive and stringent environmental policies in the form of climate adaptation and mitigation policies are needed. Third, I assert that we have a clear duty and responsibility to engage in environmental protection to ensure that future generations can enjoy a stable climate from which they can realize their interests and rights. To connect all these arguments together, I argue for a cosmopolitan vision of intergenerational justice to promote the rights and interests of present and future generations. This dissertation aims to contribute to environmental ethics and global justice, offering an account of intergenerational justice and cosmopolitanism, grounded in the problem of climate change. My goal for doing so is to hopefully shed some light on how we can better respond to the spatial and temporal dilemmas generated because of climate change, by having concrete, substantial and stronger moral and political responsibilities to other human beings both across and within generations.

The question of what makes a text 'literary' has been philosophically evergreen, stretching back to Aristotle's Poetics and weathering every critical approach through the modern era. Since the 1970s, researchers in the field of Empirical Studies in Literature (ESL) have tried to determine whether literary processing is principally text-directed (the formalist position) or reader-directed (the conventionalist position), based on observations of actual readers. Given the widespread characterisation of reading as intensely subjective, we might expect to see a huge diversity of response-yet major studies in ESL have reported results in favour of the formalist position. In expanding its sample beyond undergraduates, this survey-based study of Japanese poetry in English translation gives diversity of response a greater chance to emerge, and produces evidence suggesting that the case for the formalist position is not as strong as previously thought. Moreover, this thesis engages with recent work in Translation Studies to account for the translated-ness of its stimulus texts. Recognising translation as an important litmus test for understanding 'literariness,' this thesis operationalises a major contemporary theory of translation for the first time: Venuti's ([1995] 2008) theory of foreignisation. Against its proponent's objections, I make the case for the amenability of this theory to empirical testing, laying the groundwork for further study. Building on Eco (1990), I advance a useful new concept (intentio translatoris) to schematise the dynamics of reader response in Venuti's theory and explain the shifting criteria by which he describes translations as foreignising. Following an in-depth comparison between Russian Formalism and Venuti's foreignisation, I conclude that the latter theory does not totally escape the instrumental model it rejects. I do this to challenge unspoken assumptions about the translator as source of invariance, and to encourage a reassessment of the role of intentio lectoris in reading literature in translation.

An agitated tube reactor (ATR) has been converted from a commercially available flow chemistry reactor into a working solvent extraction contactor. It has been determined that the ATR has potential to be an industrial option for solvent extraction. Mass transfer coefficients have been calculated for a wide range of agitation frequencies and residence times using Cu(II) extraction by extractant Mextral® 84H. Mass transfer has then been compared to a Taylor-Couette Disc Contactor, and a novel design, presented in this work, called a D-cell contactor. Varying liquid volume by including an air phase has been shown to improve mass transfer within the ATR. The motion of liquid in the tube at each volume has also been monitored and compared against power per volume and droplet diameter calculations. In most operational parameters, liquid in the ATR is found to bypass agitation, therefore not achieving the expected extraction equilibrium. The volume of unmixed liquid is determined and a mass transfer coefficient for the mixed liquid is calculated. Based on the current design, optimum parameters are found when a tube is half filled and subject to an agitation frequency of 5 Hz. With these operational conditions, the ATR is shown to mix 95% of the fluid and reaches equilibrium within approximately 160 s. The viability of the ATR as a solvent extractor has been compared against a Taylor-Couette Disc Contactor and a Pulsed Column. It is seen that at 5 Hz, with 50% fill fraction, that the ATR produces a comparable mass transfer coefficient to a pulsed column correlation, as well as other mass transfer coefficients in literature.

Two separate lines of research in object recognition are studies of materials perception and studies of real-world object size perception. Recent object size investigations of texture indicate mid-level features may cue representations of object size in the absence of object identity. However, these findings are somewhat controversial, and beyond that what mid-level features cue object size is not clear. Mid-level features have always been the focus of materials perception studies of gloss and specular highlights, but to date no research has been conducted that attempts to link findings on the perception of materials to high-level object features like real-world object size. Three separate experiments were conducted to study the relationship between perceived surface glossiness and specular highlights, and perceived real-world object size. Previous research on the relationship between perceived object size and real-world object size were replicated. A significant two-way interaction between ratings of perceived glossiness, object size, and texture was found. Follow-up analyses indicated that perceptions of gloss were present across categorical differences in real-world object size in both the object image and texture image task groups. For the normal object images, small objects were perceived as being glossier than big objects. For the texture images, big objects were perceived as being glossier than small objects. Between the conditions, small normal and small texture object images were not significantly different in perceived glossiness. Between the conditions, glossiness ratings for big texture object images were significantly greater than those for the normal big object images.

Diseases like malaria claim the lives of millions of people every year. This deadly disease can result in considerable morbidity, which presently affects countries in Africa, Eurasia, and South America. Anopheline mosquitoes transmit this disease. Studies look at the identification first of the species to accurately determine their distribution. For identification, sequencing of the Internal Transcribed Spacer 2 region of the ribosomal DNA is analyzed. Although African Anophelines are very well studied species, there has been no recent significant research for Holarctic Anophelines. In particular, in North America and Eurasia, because of the eradication of malaria in the northern territories and the focus on other diseases transmitted by Aedes and Culex mosquitoes. In this study, we first look at the Holarctic species Anopheles punctipennis in North America from the Midwest to the eastern United States. Then we look at samples received from Eurasia, in particular Russia and Iran. We physically harvested 500 mosquitoes from ten breeding sites to analyze the identity and distribution of An. punctipennis. We received 110 samples from Russia and 180 samples from Iran to examine the identification and geographic distribution of An. daciae and An. persiensis. Mosquito ITS2 ribosomal DNA was extracted and amplified using polymerase chain reaction (PCR) methods. The PCR products were then sequenced and analyzed based on GenBank information obtained. An analysis by Restriction Fragment Length Polymorphism using ITS2 PCR products on An. punctipennis was conducted. Seven hundred ninety samples were processed to look at the identity and geographic distribution of Holarctic Anophlines. An. puntipennis has no current ITS2 records in GenBank. The distribution of An. daciae and An. persiensis was analyzed by ITS2 and location data. The identity and presence of a malaria vector in new areas or existing areas would prove to be vital if the disease were to re-emerge due to climate changes.

Spiking neural networks (SNNs) have recently gained a lot of attention for use in low-power neuromorphic and edge computing. On their own, SNNs are difficult to train, owing to their lack of a differentiable activation function and their inherent tendency towards chaotic behavior. This work takes a strictly neuroscience-inspired approach to designing and training SNNs. We demonstrate that the use of neuromodulated synaptic time dependent plasticity (STDP) can be used to create a variety of different learning paradigms including unsupervised learning, semi-supervised learning, and reinforcement learning. In order to tackle the highly dynamic and potentially chaotic spiking behavior of SNNs both during training and testing, we discuss a variety of neuroscience-inspired hoemeostatic mechanisms for keeping the network's activity in a healthy range. All of these concepts are brought together in the development of a SNN model that is trained and tested on the MNIST handwritten digits dataset. In order to achieve this, we introduce also introduce a custom Python package called Ganglion that can be used to rapidly design and test SNN architectures.

This study examines the presence of Zen Buddhism in Robert Bresson’s unique method of film construction. I argue that Bresson’s minimalist choices regarding film form and his emphasis on sensory experience at the expense of intellectual analysis overlap significantly with Zen. In addition, I explore Bresson’s unique theory of film acting and discuss the parallels between his idea of the actor-as-model and the process of transcending the self through Zen meditation. The aim of this thesis is to open the door to a new approach to film studies: a method that highlights direct experience and the achievement of a meditative state as opposed to the Western tradition of critical thinking and conceptual analysis.

Composite materials are an attractive material for use in the aerospace and automotive sectors, due to their high specific strength and specific stiffness. However, most composites fail suddenly in a brittle manner, which may result in catastrophic failure. This inherent lack of tailorability in the mechanical response of composites has made their widespread application limited. Aligned discontinuous composites (ADCs) are a new type of material that offers increased mechanical tailorability, as subtle changes to the ADC microstructure can change its stress-strain response from high-strength linear elastic behaviour, to a non-linear response with high levels of pseudo-ductility. This work aims to understand mechanisms for mechanical tailorability in ADCs, and determine the suitability of ADCs for applications in real-world structures. A Virtual Testing Framework (VTF) is used and developed throughout this thesis, to give an in-depth understanding of the behaviour of ADCs. The VTF consists of a multiscale framework to simulate complete ADC specimens with hybrid or non-hybrid reinforcement; final failure of ADCs is simulated in the VTF by a non-linear fracture mechanics failure criterion. The VTF is successfully validated throughout this thesis against a variety of experimental data with good agreement. The first study explores the use of different hybrid fibre-type arrangements, to explore their influence on the pseudo-ductile behaviour of hybrid ADCs. The addition of a fibre-migration algorithm (used to capture the effects of fibre movement in ADCs during their manufacture), and developments to the fracture-based failure criterion, enable the VTF to successfully capture the effects of various levels of fibre-type grouping. Hybrid ADCs with larger groups of low-elongation fibres demonstrate a more brittle response, whereas intimate intermingling of the fibre-types increases pseudo-ductility. The ultimate strength and pseudo-ductility are then maximised by employing a fibre-type arrangement where the low-elongation fibres are completely isolated from one-another. Having shown variability in the fibre-type arrangement has a significant influence on tailorability, the concept of variability is explored further. Several new sources of variability and defects are added to the VTF, and the non-linear fracture-based failure criterion is further improved to accurately predict the failure of any type of ADC microstructure. The VTF indicates that the most critical source of variability (i.e. the source of variability that most readily promotes premature failure) depends on the microstructural design of the composite: hybrid-fibre ADCs are most sensitive to the fibre-type arrangement, while short-fibre non-hybrid ADCs are most sensitive to variability in the fibre overlap lengths, and long-fibre non-hybrid ADCs are more sensitive to weaker fibres. The VTF is then coupled with an intelligent optimisation routine to maximise the mechanical performance of ADCs that feature inherent variability. The use of a surrogate model helps minimise the number of design iterations before optimal design(s) are converged upon; surrogate modelling is also demonstrated to be invaluable when assessing the optimality of materials which feature high levels of inherent variability (such as ADCs). The true tailorability of ADCs is showcased, with an initial stiffness of 505 GPa, an ultimate strength of 1.92 GPa, or an ultimate strain of 3.92 % all achievable in ADCs via single-objective optimisation. While significant trade-offs between competing mechanical performance characteristics are found, useful combinations of mechanical properties remain, with an optimal ultimate strength & ultimate strain combination of 982 MPa and 3.27 %, or an optimal combination of 720 MPa yield strength & 1.91 % pseudo-ductile strain all possible. ADCs are shown throughout this thesis to fail by translaminar fracture, yet the resistance of ADCs to translaminar cracks has never been measured; the translaminar fracture toughness is therefore a key material property that must be characterised, to enable accurate failure predictions using the VTF, and to enable the use of ADCs as part of a damage tolerant structure. Specially-designed compact tension tests are performed to measure the translaminar fracture toughness of hybrid and non-hybrid ADCs for the first time in literature. Results show that the translaminar fracture toughness of non-hybrid ADCs is significantly higher than hybrid ADCs, and that analytical predictions of the translaminar fracture toughness are sufficiently accurate to ensure realistic failure predictions using the VTF. The new understanding and optimisation of aligned discontinuous composites demonstrates the feasibility of ADCs as an alternative material for the aerospace and automotive sectors. The models developed as part of this study can be used to support the design of new materials, perform parametric studies, and perform intelligent optimisation campaigns.

Predicated upon the contention that higher education (HE) lecturers perform in their classrooms in ways which have similarities with the performances that theatrical performers give for their audiences; this research set out to observe, listen to, understand, interpret and then represent in text the meaning an aesthetic conception of performance has for a small number of teacher-performers in a single UK HE institution. Whilst classroom performances differ in content, presentation and delivery there is a fundamental commonality of purpose; each performance is given with the intention of establishing change in the student audience - broadly defined as learning. Learning may not be the declared intention of performance outside of the classroom; however, theatrical performers use language, movement and other expressive devices to engage and influence their audiences. Their performances therefore also change the audience; whilst the audience may not feel they have learned anything through a traditional understanding of learning, they often leave performances, in some respect, different. The aim of this research has been to seek out and examine similarities between the HE lecture - one of the “forbidden pedagogies” according to Burgan (2006, p. 31) - and a notion of performance developed for this research, and to explore whether an understanding of any such similarities might enrich the repertoire of the HE lecturer. There are significant volumes of literature available which refer, separately, to teaching and learning in HE and theatrical performance. However, a dearth of literature exists where those domains interact. This work identifies that gap in the literature and plays a part in addressing it. This two-phase research has been undertaken in a single UK HE institution, using a descriptive case study approach in the second phase of the work (Yin, 2014). The first phase of data collection involved twelve overt and non-participatory classroom observations each with a different participant. Fifteen overt and non-participatory observations were conducted in the first element of the second phase – three with each of five cases who are subsequently referred to as the players. The second element of data collection in the case study phase involved a single semi-structured interview with each of the players. A further single, semi-structured interview – outside of the case study – was conducted with Serena. Serena is a senior member of academic staff who also performs at Bright Club venues – where academic research is ‘performed’ in a comedy club environment to audiences made up of academics, students and the general public looking for a ‘good night out’. Data analysis has been undertaken using Template Analysis (TA); utilising NVivo software for the classroom observations in the first phase and a hand-coded approach for the analysis of the observations and the semi-structured interview transcripts in the case study phase. The research offers three conclusions; founded upon notions of similarity, collaboration and liaison. The research has concluded that there is evidence to demonstrate a significant number of points of similarity between classroom and theatrical performance. The presence of such similarity should therefore encourage collaborations between teacher-performers and colleagues experienced in performance practice from both within and without the HE academy. Such collaborations, in contributing to both initial teacher preparation and continuing professional development activities, have significant potential to enrich the performance repertoire of the HE lecturer. The final conclusion is that improved liaison of, to use the performance vernacular, an ensemblic nature - between teacher-performers and those in the HE institution who play key roles in designing, developing, allocating and resourcing spaces used for classroom performance - offers potential to improve the spaces in which the HE lecture is delivered and, through that, to enhance the classroom experience of HE students.

Regulatory B cells (Bregs) play a critical role in the control of autoimmunity and inflammation. IL-10 production is the hallmark for the identification of Bregs. However, the molecular determinants that regulate the transcription of IL-10 and control the Breg developmental program remain unknown. The aryl hydrocarbon receptor (AHR) is an environmental sensor that binds to a variety of ligands, including physiological compounds derived from the digestion of dietary components by commensal microbiota. Here, we demonstrate that AHR regulates the differentiation and function of IL-10-producing CD19+CD21hiCD24hi Bregs and limits their differentiation into B cells that contribute to inflammation. Chromatin profiling and transcriptome analyses show that loss of AHR in B cells reduces expression of IL-10 by skewing the differentiation of CD19+CD21hiCD24hi B cells into a pro-inflammatory program, under Breg-inducing conditions. B cell AHR-deficient mice develop exacerbated arthritis, show significant reductions in IL-10-producing Bregs and regulatory T cells (Tregs), and show an increase in T helper (Th) 1 and Th17 cells compared with B cell AHR-sufficient mice. The most abundant source of AHR ligands are derived from the diet and the metabolism of dietary tryptophan. We have previously established a link between microbiota-driven signals in the gut and the differentiation of Bregs. Of the gut microbiota-derived metabolites, the short-chain fatty acids (SCFAs) are the most well characterised. More recently, the SCFA butyrate has been demonstrated to act as an AHR ligand in an intestinal epithelial cell line. Given the association of butyrate with AHR activation and the supporting findings showing that butyrate promotes Treg function, these data led us to hypothesise that butyrate acts via AHR to enhance Breg suppression. Here, we demonstrate that mice supplemented with butyrate reduces arthritis severity by inhibiting the differentiation of GC B cells and plasma cells, whilst maintaining Breg numbers and promoting the suppressive function of Bregs. We show that supplementation of mice with butyrate, changes the composition of the microbiota to favour species which metabolise tryptophan; a major source of AHR ligands. Therefore, we hypothesised that butyrate controls the balance between pro-arthritogenic and regulatory B cell differentiation, through the generation of microbiota derived AHR ligands. To date, the AHR ligands which direct Breg function are unknown. We rule out that butyrate acts as a direct ligand of AHR and establish that supplementation with butyrate increases the availability of 5-Hydroxyindole-3-acetic acid (5-HIAA), a downstream metabolite of serotonin, which we identify as a novel ligand of AHR in B cells. Mice supplemented with 5-HIAA promote Breg function and suppress arthritis severity, only in mice with AHR-sufficient B cells. Thus, we identify AHR as a relevant contributor to the transcriptional regulation of Breg differentiation and show that microbiota in the gut influence Breg differentiation by increasing the availability of AHR ligands.

Feedback in higher education (HE) is an important determinant of student success despite its variable impacts. Assessment and feedback have also been highlighted as one of the least satisfactory aspects of the learning experience. However, more scholarship has focussed on what constitutes ‘good feedback’ than about the factors that influence how it is perceived, engaged with, and used by students. This study aims to redress this imbalance by investigating what measures can be taken by teachers to support feedback engagement processes. It explores how the existing literature on dialogism, technology, can be synthesised into a new model of feedback engagement. Principles from the resulting USM model were employed in the design of dialogic technology-mediated feedback practices used over a semester with 14 South Korean undergraduates on an academic writing course. Utilising a qualitative approach, data from reflections, questionnaires (N=14) and the main method, in-depth semi-structured interviews (N=13), were analysed to understand perceptions of the relationship between navigating the feedback activities and feedback engagement and use. The data was also used to consider how the model could be empirically enhanced. The findings were analysed inductively, and the practices reportedly contributed to feedback engagement in four ways. Dialogism supported understanding of peer/teacher feedback, facilitated group knowledge co-construction, and motivated feedback engagement. Open access to peers’ work helped participants to make comparisons and understand how their work could be improved. Screencast feedback was perceived to be more thorough, usable, and affectively supportive. After initial disappointment with feedback, participants reportedly engaged with the feedback by employing certain pre-introduced concepts related to learning from feedback. Overall, the practices were demonstrated to support the development of feedback receptivity. The data supported contributed to the refinement of the USM model; thus, contributions to both theory and practice were made.

New challenges in structural biology are driving the development of new technology, such as photon counting pixel array detectors, and new modes of data collection, such as serial synchrotron crystallography (SSX), in macromolecular crystallography at synchrotrons. This in turn is creating the need for better algorithms and software to extract the maximum amount of information from the diffraction data. The aim of this project is to develop statistically robust methods for the integration and analysis of X-ray diffraction data to address these challenges. A method for estimating the background under each reflection during integration that is robust in the presence of pixel outliers is presented. This uses a generalised linear model (GLM) approach that is more appropriate for use with Poisson distributed data than traditional approaches to pixel outlier handling in integration programs. The algorithm is most applicable to data with a very low background level where assumptions of a normal distribution are no longer valid as an approximation to the Poisson distribution. A second algorithm for modelling the background for each Bragg reflection in a series of X-ray diffraction images containing Debye-Scherrer diffraction from ice in the sample is also presented. This method involves the use of a global background model which is generated from the complete X-ray diffraction dataset. Fitting of this model to the background pixels is then done for each reflection independently. Finally, a model for the observed reflection profiles is described for the purpose of improving the refinement of the crystal unit cell and orientation for still image diffraction data collected at synchrotrons. This model consists of two components: a Normal distribution is used to describe the distribution of wavelengths and a Multivariate Normal distribution (MVN) is used to describe the distribution of reciprocal lattice vectors for each reflection; this allows non-isotropic spot shapes to be easily described. The parameters of the model are estimated from the data via a simple maximum likelihood algorithm. The algorithms are incorporated into the DIALS integration package.

This dissertation consists of two essays in experimental economics and one in applied microeconomics. The first chapter, Preferences over Exploration: Simple Bandits in the Lab, presents an experimental study about how people view the trade-off between exploration (trying a new option) and exploitation (taking a familiar option). This study documents a large and persistent tendency of people to under-explore, even in the simplest possible bandit setting. By simplifying the environment, the study can directly control for risk preferences, abstract from other issues such as ambiguity, Bayesian updating, or failures to reduce compound lotteries. The second chapter, Complexity and Procedural Choice: Evidence from Experimental Bandits, presents an experiment about how subjects select procedural rules to make decisions in a simple bandit task. The optimal strategy involves a relatively sophisticated 4-state decision rule. When complexity costs are low, subjects conform to the optimal behavior; when complexity costs are higher, holding other aspects of the problem constant, subjects systematically employ lower-complexity rules. This suggests that aversion to complexity causes subjects to play simpler strategies and earn lower payoffs. The final chapter, The Economics of the Montana Liquor License System, is an applied microeconomics paper about the the liquor license system in the state of Montana. The state has a complicated system of quotas for liquor licenses, involving multiple license types, which are tradable within quota area (and occasionally between quota areas). The study offers a simple model of the system, providing testable hypotheses. Empirical results support these hypotheses, indicating that gambling revenue, non-permanent population, and income all positively affect prices, while the emergence of small-scale producers (e.g., craft breweries) negatively affect license prices.

This thesis presents a joint computational and experimental approach to developing a novel diamond surface termination with aluminium that has a negative electron affinity (NEA). There is a need for a thermally stable NEA for thermionic applications, since hydrogen termination desorbs from the diamond surface at thermionic temperatures. The choice of aluminium is based on it being a light, electropositive element that bonds strongly to different diamond surfaces. Using density functional theory, the adsorption of Al onto bare, oxygenated and nitrogenated diamond surfaces was studied. The two key parameters considered were the adsorption energy and the electron affinity values, for different coverages and configurations of Al. NEA values of up to -1.47 eV and 1.88 eV were observed for Al addition to the (100) and (111) bare surfaces, respectively, at 1 monolayer (ML) coverage, and up to -1.36 eV and -2.17 eV for Al addition to the (100) and (111) oxygen-terminated surfaces, respectively, at 0.25 ML coverage. Al adsorbed more strongly on the ketone O-terminated surface than the ether surface. Adsorption energies for the AlO-terminations were up to -6.36 eV/atom and -8.19 eV/atom for the (100) and (111) surfaces, respectively, at 0.25 ML Al coverage, considerably larger than that of H termination (~-4 eV/atom). Three different oxidation procedures were investigated experimentally. It was determined that oxidation of diamond by UV/ozone treatment results in a large ketone component on the surface, whilst also having ~1 ML coverage. The surface structure and electronic behaviour were determined for both hydrogen and oxygen terminations. AlO-terminations were fabricated experimentally by depositing Al onto O terminated diamond. Three different methods were explored: (i) thick-film deposition of Al followed by an acid etch to remove excess metal, (ii) thin-film deposition of Al by atomic layer deposition, and (iii) thin-film deposition of Al by electron-beam evaporation. Low work function and NEA were observed for each method, but these values were spatially and temperature dependant. Annealing caused a change in surface structure, identified as the incorporation of O atoms into the Al layer. Tests of thermionic emission showed a small emission current density, but at a higher temperature than attainable for H termination. Thus, AlO-terminated diamond shows promise but further optimisation is required for use in devices.

Objective Organizations in fields from manufacturing to health care use process improvement teams, an important aspect of LEAN practice, to improve their work. The library faced challenges with interfaces for electronic resources, including a dated electronic journals interface, out-of-control LibGuides, and lack of control over our web presence. The library formed the Electronic Resources Task Force to foster a collaborative approach to solving these problems. This poster will show techniques used and what we accomplished. Methods The library experienced many changes in the last year including changes in leadership and staff. With our new director’s emphasis on improving electronic access, new staff members, and a staff member’s recent training in Lean, we had a great opportunity to incorporate new techniques in team development. Our goal was to provide attractive, modern, and seamless access to evidence-based, high quality information resources. To share information and improve accountability, the team developed a shared flowchart document that allows any team member to update progress on any task at any time. The team meets regularly, further improving accountability and providing opportunities to address electronic resources and collections issues as a group. Results To date, the Electronic Resources Task Force has reduced the number of active LibGuides from 71 to 33 updated guides. Our transition to EBSCO’s Full Text Finder is complete. Additionally, we developed a new search box for LibGuides, introduced a LibGuides-based Databases A-Z page, updated LibAnswers, and rolled out a new literature search form and database. The team continues to follow up on a list of future improvements. Conclusions Incorporating Lean into our work is ongoing, as is our staff member’s training in these techniques. However, we can conclude that the techniques originally developed in manufacturing and being used in healthcare can also be used to improve library work.

It is widely accepted that school leadership has both a direct and indirect impact on student achievement. Hitt and Tucker’s (2016) Unified Leadership Framework summarized a decade of work by numerous researchers identifying the five most effective leadership domains that influence student learning. Using that work as a conceptual framework, this qualitative case study analyzed one of the five interdependent leadership domains in an urban elementary school that succeeded in educating traditionally marginalized students and outperformed other schools with similar demographics in the district. This study focused on Hitt and Tucker’s (2016) leadership domain of connecting with external partners. Specifically, it examined whether leadership practices that supported family and community partnerships were present at the school. Family and community partnerships are important because they support two essential, yet frequently overlooked, contexts where student learning and development take place. In addition, this study examined whether school leadership practices promoted these partnerships in a culturally proficient manner. This analysis was informed by the culturally responsive school leadership (CRSL) framework, which describes principal behaviors that promote cultural responsiveness in urban settings. Several leadership practices that supported the criteria established by Hitt and Tucker (2016) under the domain of connecting with external partners were evident at the school, including: building productive relationships with families and the community; engaging families in collaborative processes to strengthen student learning; and anchoring the school in the community. However, leadership practices promoting family and community partnerships did not fully support a finding of being a culturally proficient school culture. This finding was primarily based on a “one size fits all” approach to working with students and families, which has been described in the literature as “cultural blindness”. Recommendations to practitioners as a result of this study include expanding informal opportunities for parent input and engagement, conducting an equity audit, and pursuing cultural proficiency professional development.

The purpose of this thesis is to examine the accuracy of the RAPID (Real-Time Analysis for Particle Transport and In-situ Detection) eigenvalue algorithm based on a few problems from the ICSBEP (International Criticality Safety Benchmark Evaluation Project) Handbook. RAPID is developed based on the MRT (Multi-Stage Response-Function Transport) methodology and it uses the fission matrix (FM) method for performing eigenvalue calculations. RAPID has already been benchmarked based on several real-world problems including spent fuel pools and casks, and reactor cores. This thesis examines the accuracy of the RAPID eigenvalue algorithm for modeling the physics of problems with unique geometric configurations. Four problems were selected from the ICSBEP Handbook; these problems differ by their unique configurations which can effectively examine the capability of the RAPID code system. For each problem, a reference Serpent Monte Carlo calculation has been performed. Using the same Serpent model in the pRAPID (pre- and post-processing for RAPID) utility code, a series of fixed-source Serpent calculations are performed to determine spatially-dependent FM coefficients. RAPID calculations are performed using these FM coefficients to obtain the axially-dependent, pin-wise fission density distribution and system eigenvalue for each problem. It is demonstrated that the eigenvalues calculated by RAPID and Serpent agree with the experimental data within the given experimental uncertainty. Further, the detailed 3-D pin-wise fission density distribution obtained by RAPID agrees with the reference prediction by Serpent which itself has converged to less than 1% weighted uncertainty. While achieving accurate results, RAPID calculations are significantly faster than the reference Serpent calculations, with a calculation time speed-up of between 4x and 34x demonstrated in this thesis. In addition to examining the accuracy of the RAPID algorithm, this thesis provides useful information on the use of the FM method for simulation of nuclear systems.

The prevalence of type 2 diabetes mellitus (T2DM) worldwide has increased dramatically in the last three decades. In 2014 there were 64.5 million individuals with diabetes in India alone. South Asians (SA) have a two to fourfold increased risk of T2DM at a significantly lower body mass index (BMI), occurring at a younger age and with a greater risk of diabetic related complications, when compared with white Europeans (EU). The rise in T2DM rates have coincided with increased levels of adiposity, 'westernised' diets and lower levels of physical activity, with more people living in urbanised environments. Even adjusting for these variables SA still have an increased risk of T2DM and the reason for this is unknown. Observational studies have demonstrated that SA phenotypically have higher levels of total fat (adipose tissue), less lean tissue (muscle), and lower cardiorespiratory fitness, as well as typically undertaking less physical activity compared with their EU counterparts. Whilst studies have indicated that these factors contribute to insulin resistance with varying degrees, the relationship between adipose tissue (AT) and insulin resistance has never been properly understood. Triacylglycerol is the main storage form of fat. Due to poor diet and lower levels of physical activity, excess calories are stored in adipocytes in several adipose tissue depots in the body. Location of depots appears important, and evidence indicates that visceral (VAT) and ectopic fat depots significantly correlate with insulin resistance. Subcutaneous adipose tissue (SAT), and specifically superficial subcutaneous adipose tissue (SSAT) depots, have been associated with lower levels of insulin resistance and metabolic inflammation. As well as fat depot location cellular response of adipocytes is relevant, adipocytes can either expand in size (hypertrophy), or increase in cell number (hyperplasia) to accommodate excess energy. Hyperplasia has been associated with lower levels of inflammation and insulin resistance whilst hypertrophy has been associated with increased risk of T2DM and pro-inflammatory metabolic state. Adipogenesis is the process by which new adipocytes are recruited and fully differentiate to mature adipocytes with the ability to safely store triacylglycerol. Impairment of this process and dysfunctional adipogenesis has been associated with insulin resistance, T2DM, increased number of hypertrophic adipocytes, small adipocytes and ratio of small to large adipocytes. South Asians have higher levels of total fat compared to EU, and it has been commonly presumed that more visceral and ectopic fat is present in SA causing insulin resistance. However, the limited number of studies analysing fat depots in SA have not all consistently demonstrated this. Cross-sectional studies of SA adipocyte morphology and function have found hypertrophic adipocytes associated with insulin resistance, but the causality and pathogenesis underlying these observations is not known. In 2007 the adipose tissue expandability hypothesis was proposed, implying that SA have limited ability to safely store fat in SSAT and therefore store excess fat in visceral and ectopic depots, causing insulin resistance and diabetes. To explore the relationship between adiposity and insulin resistance in South Asians the Glasgow Visceral and ectopic fat with weight gain in South Asians (Glasvegas) study was proposed in 2014. This thesis is based on initial findings as part of the Glasvegas study and includes meta-analysis conducted to investigate adiposity distribution in South Asians. Given limitations of cross-sectional research the best way to observe underlying mechanisms is via a prospective weight gain/overfeeding study. In this thesis a group of male SA and EU participants gained ~6.4% body weight via supplemental overfeeding diet. Measurements were taken at baseline and following weight gain. These included whole-body MRIs to analyse fat depots, metabolic rate assessments, fitness tests, mixed-meal tolerance tests, subcutaneous adipose tissue biopsies, physical activity and dietary measurements. The findings of this thesis demonstrated that whole-body insulin sensitivity decreased by 38% in young, lean South Asian men with ~6.4% weight gain, but not in white Europeans. Adiposity analysis indicated that South Asians at baseline had more total fat, subcutaneous, deep subcutaneous (DSAT) and liver fat, but not visceral fat. South Asians had twice as much DSAT compared to EU (0.17 litres vs. 0.08 litres, p=0.003) and more liver fat (4.11% vs. 2.05%, p=0.01). Meta-analysis of studies of SA adipose distribution supported the finding that male SA have more SAT but not necessarily VAT. The novel aspect of this study was prospective overfeeding. Unexpectedly the EU group gained more VAT than SA (0.56 litres vs. 0.23 litres, p=0.005) but there were no differences in liver or muscle fat gained between groups. White Europeans also gained significantly more lean tissue with overfeeding than SA (2.43 litres vs. 0.67 litres, p=0.02). There was no indication of a limited SSAT capacity in SA, which is contrary to expectations and the adipose tissue expandability hypothesis. Correlations were observed in SA with insulin resistance and the deep subcutaneous adipose tissue depot, which is larger in South Asians and metabolically akin to VAT. There were no contributions of fitness, physical activity or metabolic rate accounting for differences in insulin sensitivity. Adipocyte findings indicated that EU increased size of adipocytes by hypertrophy in response to weight gain, without any change in insulin sensitivity. South Asians conversely already had larger adipocytes but did not change mean size with weight gain. South Asians increased numbers of very small and large adipocytes, and this is associated with dysfunctional adipogenesis and T2DM. There was also a trend to adipocyte hyperplasia noted in SA. The combined findings of this thesis supported our hypothesis that SA would develop insulin resistance with weight gain, but adiposity findings were contrary to expectations. South Asians appear to have more subcutaneous and deep subcutaneous fat, but not visceral fat. This likely contributes to excess insulin resistance at lower BMI and there is evidence of dysfunctional adipogenesis with weight gain. Ongoing analysis of samples taken during this thesis, to investigate adipocyte gene expression and signalling pathways, is underway. Future studies are also required to help prevent adiposity in SA, reduce risk of dysfunctional adipogenesis and type 2 diabetes.

The ritual and incantation series Šurpu 'Burning' is one of the most important sources for understanding religious and magical practice in the ancient Near East. The purpose of the ritual was to rid a sufferer of a divine curse which had been inflicted due to personal misconduct. The series is composed chiefly of the text of the incantations recited during the ceremony. These are supplemented by brief ritual instructions as well as a ritual tablet which details the ceremony in full. This thesis offers a comprehensive and radical reconstruction of the entire text, demonstrating the existence of a large, and previously unsuspected, lacuna in the published version. In addition, a single tablet, tablet IX, from the ten which comprise the series is fully edited, with partitur transliteration, eclectic and normalised text, translation, and a detailed line by line commentary.

Sporadic Creutzfeldt-Jakob Disease (sCJD) is the most common form of human prion disease. It is a rapidly progressive dementia with other associated neurological abnormalities which is invariably fatal, usually within 4-6 months of first symptoms, and affects around 80-100 patients in the UK each year. It is caused by propagation around the central nervous system of PrPSc, an abnormal conformational form of the host PrPC protein, which causes the transformation of PrPC to PrPSc, essentially self-replicating. This process causes neuronal loss and other pathological abnormalities, explaining the clinical presentation. sCJD is believed to occur as a de novo convolutional change which seems to occur as an unfortunate chance event. The existence of other forms of CJD, including variant CJD (vCJD) and iatrogenic CJD (iCJD) highlight the fact that the abnormally folded forms of the prion protein are infective agents, which can be transmitted by diet (from bovine spongiform encephalopathy - BSE - in cattle to humans in vCJD), or by medical intervention (predominantly from contaminated dura mater grafts, and cadaveric pituitary derived growth hormone in iCJD). These two routes of transmission can be associated with long intervals (up to around 40 years has been described) between exposure to the infective agent and subsequent symptom onset. It is possible that some cases classified as sCJD may in fact be acquired through other means of transmission. As part of the UK National CJD Surveillance process, the NCJDRSU collect data on potential routes of CJD transmission. In this thesis, I describe and analyse the data concerning three potential such routes for the definite or probable cases of sCJD reviewed by the NCJDRSU between 2010 and 2015 inclusive: 1) Packed red cell blood transfusion has been associated with iatrogenic transmission of variant CJD. We found no evidence of such transmission in sporadic CJD. I also describe the first two reported cases of sCJD occurring in patients with clotting disorders who had received numerous transfusions and other blood products; there have been no further published cases since this report, and these two cases are considered likely both to represent the chance development of sCJD. 2) Tissue and organ transplantation is another recognised route, with iatrogenic transmission of CJD described in corneal transplantation. A small number of sCJD patients have undergone surgery involving transplantation of tissues or organs. Although a few cases of interest were identified as recipients of potentially infective materials, including three patients who are suspected to have received dura mater grafts and one patient who underwent definite corneal transplantation, it was not possible to confirm the exact nature and source of these materials, meaning it is not certain that these cases definitely represent iatrogenic transmission. Therefore, I found no evidence that tissue or organ transplantation is responsible for the development of cases of iCJD among this patient cohort. 3) Other surgical procedures may convey the risk of transmission of PrPSc through incomplete sterilisation of instruments. I assessed the potential for UK sCJD patients to have come into contact with instruments used on another CJD patient, looking at associations between surgical procedures occurring within the same year, at the same hospital, and within the same surgical domain. While some such associations were identified, interpreting these associations is extremely difficult, in large part due to the absence of a suitable control group, as well as incomplete data availability. Overall, this work has identified no definite transmission of iCJD masquerading among the sCJD 2010-2015 patient cohort. There are significant limitations to each aspect of this work, in large part pertaining to incomplete medical records; these limitations are addressed in the relevant chapters. Some of these limitations may be difficult to overcome if future these studies are repeated in the future with a new cohort.

The thesis examines shifting representations of trade unions in the work of six contemporary poets. The thesis considers how it is that poets have come to contend with, and contribute to, narratives surrounding trade unions and industrial disputes, and puts these representations into conversation with one another. Through these conversations, the thesis attempts to question the ways in which our union narratives and our legacies are constructed, and to investigate the power dynamics that underpin the presentations of our histories (and the way they are presented to us), through a specific focus on what it means to tell the stories of our labour histories. Trade unions have long been at the forefront of the struggle for working conditions, pay and labour polics more broadly in the UK. Taking unions as the 'subject' and using poetry as the 'medium' enables the thesis to investigate the ways in which union narratives have come to occupy the relatively marginalised position they currently inhabit in the UK's polical and social landscape, while also putting forward an argument for these poems to be seen as a form of alternative 'storytelling', where questions of dominant narratives and official histories can be rightly contested. The fact that trade unions are as much about the individual as they are the collective ties into the poem's ability to affirm and extend 'community by being true to what is individual and particular'. My attention to trade unions allows an exploration of questions regarding shifting ideas of the collective, the individual and notions of (post-industrial) place. The thesis focusses on two distinct poetic eras: from 1972 to the late 1980s through the work of Barry MacSweeney, Tony Harrison and Sean O'Brien, and the 2010s, through the writings of Helen Mort, Steve Ely and Paul Bentley. The poems discussed bring influences from other poems, from movies and from 'official' narratives on to the page, sometimes brazenly, sometimes obscured, but always with a sense that they are writing out of and into a trade union history. The thesis explores these influences and that engagement with trade union history. The poets that my research examines see our union legacies as artful constructions, foregrounding an awareness of working-class stories and histories as products, products that have been manufactured and arranged, in the same way that the poems themselves are artfully rendered and established on the page. These poems (and my work) are a continuation of, and comment on, the 'legacy' of these trade union stories and histories.

A statistically designed slow speed orthogonal machining experiment was conducted to compare the effects of various metal-working gases upon the cutting process. Several metals with different crystalline structures and materials conditions were utilized (face centered cubic aluminum alloy 6061 with three tempers (T0, T4 and T6), close packed hexagonal AZ31B at two tempers (H0 and H24), and body centered cubic steel alloy 4130 at three levels of hardness (22, 32, and 42 HRC). A single tool material of High-Speed Steel (HSS) was utilized with three different tool rake angles () of 25°, 30° and 35°. The cutting fluids utilized were air, argon, and nitrogen. Classic Merchant Force Diagram (MFD) data was collected using a Kistler force Dynamometer and processed using LabVIEW software. The tools were pushed through the 2” long x 0.125” thick piece of stock material at two different depths of 0.004 inches and 0.008 inches. After 10 inches of cut, each tool was studied under a Keyence 3-D microscope in order to quantify the tool wear. High speed, high magnification video was taken of each cut to study all the visible shear angles. The video analysis was completed using KINOVEA video analysis software. The force data was then used to explore different orthogonal metal working models to validate against literature. Statistical analysis was utilized to determine the relationships between visual shear angles and cutting environment. Analysis was made between tool wear and cutting atmosphere.

Offshore wind turbines present unique engineering challenges, many of which stemming from founding the superstructure in the shallow ocean floor rather than on dry land. Several foundation types are available for offshore wind turbines, one of which is relatively short, stiff monopiles. Current design standards for laterally loaded monopiles were developed in the early 1970s, based on tests conducted on long slender piles on Mustang Island, Texas. These lateral load tests serve as the basis for many design standards, which work well for piles subjected to large lateral deformations but are unverified for the small strain range. This thesis presents a laboratory testing methodology developed to find more relevant design standards for piles subjected to small strain lateral loading in sands. This methodology was developed using laboratory model tests of two different sand cell scales. Preliminary tests were conducted to determine the best method to measure small-strain in-situ properties of sands. Shear wave velocity was of greatest interest in these preliminary tests as it can be used to determine small-strain shear modulus, or G, of sand. Small soil cells were instrumented with 28Hz geophones, then seismic waves were propagated through the soil body to determine small-strain properties including small-strain shear modulus. Various receiver arrays and seismic sources were used in preliminary testing to find the most reliable test setup before final testing. In final testing, spherical penetrometers of various diameters, embedded at various depths, were used to subject a soil body to small strains under 1G monotonic and cyclic loading. Load-displacement curves were obtained from these final tests and compared to those found from numerical modeling conducted in a parallel study. This study concludes that the developed methodology for preparing a soil cell and subjecting a zone to small strains through the use of a spherical penetrometer can be reliably repeated. This study also concludes that the developed testing methodology is representative of those in-situ conditions felt by laterally loaded monopiles.

The exponential growth in medical pharmaceuticals and related clinical trials have created a need to better understand the decision-making factors in the processes for developing hospital medication formularies. The purpose of the study was to identify, rank, and compare major factors impacting hospital formulary decision-making among three prescriber groups serving on a hospital's pharmacy and therapeutics (P&T) committee. Prescribers were selected from the University of Texas, MD Anderson Cancer Center which is a large, multi-facility, academic oncology hospital. Specifically, the prescriber groups studied were comprised of physicians, midlevel providers, and pharmacists. A self-administered online survey was disseminated to participants. Seven major hospital formulary decision-making factors were identified in the scientific literature. Study participants were asked to respond to questions about each of the hospital formulary decision-making factors and to rank the various formulary decision-making factors from the factor deemed most important to the factor deemed least important. There are five major conclusions drawn from the study including three similarities and two significant differences among the prescriber groups and factors. Similarities include: (1) the factor "pharmacy staff's evaluation of medical evidence including formulary recommendations" was ranked highest for all three prescriber groups; (2) "evaluation of medications by expert physicians" was ranked second for physicians and midlevel providers while pharmacists ranked it third; and (3) the factor, "financial impact of the treatment to the patient" was fifth in terms of hospital formulary decision-making statement and ranking by all three prescriber groups. Two significant differences include: (1) for the hospital-formulary decision making statement, "I consider the number of patients affected by adding, removing, or modifying a drug on the formulary when making hospital medication formulary decisions," midlevel providers considered this factor of significantly greater importance than did physicians; and (2) for the ranked hospital formulary decision-making factor, "financial impact of treatment to the institution," pharmacists ranked this factor significantly higher than did physicians. This study contributes to a greater understanding of the three prescriber groups serving on a P&T committee. Also, the study contributes to the body of literature regarding decision-making processes in medicine and specifically factors impacting hospital formulary decision-making. Furthermore, this study has the potential to impact the operational guidelines for the P&T committee at the University of Texas, MD Anderson Cancer Center as well as other hospitals.

This thesis explores the social construction and performance of Technological Human Enhancement Advocacy through multi-sited ethnographically inspired participant observation across a range of sites. It argues that advocacy efforts surrounding the ideal of technological human enhancement share the ideational feature of Techno-centrism - an object-level belief embedded in the material present while simultaneously future-oriented and thus principally immaterial. This purposive neo-dualism blurs 'real' and 'imagined' futures to satiate the materialist ontological grounding associated with the scientific worldview, while granting extended licence to more indulgent, compelling visions for technology as an enabler of affirmative, forward-facing action - including revivifying pursuit of humanist ideals associated with the modernisation project. The thesis makes contributions to three areas. Firstly, in substantive terms, it contributes towards sociological knowledge by detailing the intersubjective values, semiotic framing mechanisms and narrative tropes evoked to both justify and promote the notion of Technological Human Enhancement Advocacy (THEA), an area which remains under-researched. Secondly, the thesis makes a theoretical contribution through its modelling of a non- spatially determined constant which recurs across sites associated with THEA: The Techno-centred Imagination (TCI). Finally, the thesis offers a methodological contribution through its novel and creative application of multi-sited research strategy for the study of non-spatially determined cultures of extreme support for science and technology. A 24-month programme of fieldwork was undertaken, comprising multi-locational participant-observation, interviews and surveys. The thesis concludes that far from being new, the emerging social forms associated with THEA capture ambivalences which have long cast a shadow over late-modern society and culture. Although TCI appears most pronounced in the practice of transhumanism - where it is acted out in extreme, almost hyperbolic ways - the phenomena mirrors broader concerns around the future of science, technology and human self-identity in the new millennium. As such, it is deserving of further study.

The coming century will bring numerous environmental challenges and understanding the strategic decisions involved in energy production and consumption will be central to addressing them effectively. In this dissertation, I use methods from applied econometrics, behavioral economics, and industrial organization to investigate various lines of inquiry around this broader motivation. In Chapter 1, I study how residential electricity consumers respond to increasingly complicated incentives that are meant to improve allocative efficiency and test whether their behavior is consistent with standard models. In Chapter 2, I estimate the impact of temperature on high school students' standardized test performance in order to understand how environmental factors affect educational outcomes. In Chapter 3, I evaluate a targeting strategy meant to improve the efficiency of an electricity pricing program and develop a theoretical framework to ground the findings. The first chapter studies whether consumers are attentive to time-varying incentives to reduce electricity consumption. Dynamic pricing models typically assume that consumers respond to marginal incentives. I use a field experiment to assess the impact of dynamic pricing on residential electricity consumption and find strong evidence of inattention. I propose a model to interpret the results which suggests that the benefits of dynamic pricing may be substantively undermined by inattention. I also explore the role of automation in dynamic pricing, which holds the promise of reducing the cognitive choice frictions that cause inattention and lowering the effort cost of responding to price changes. I report three primary findings. First, households---both with and without automation---significantly respond to a short term price increase by reducing consumption. Second, responses are very insensitive to the size of the price change. A price increase of 31 percent causes consumption to fall by 12 percent on average, whereas a price increase of 1,875 percent causes an average reduction of 14 percent. Third, automation causes responses that are more than three times larger than the average effect, but are still insensitive to the price level. The results suggest that households use simplifying heuristics when facing dynamic prices and that automation reduces effort costs, but does not resolve inattention. I apply the model to recover bounds on the price elasticity of demand and shed light on the potential attention costs of dynamic pricing. The second chapter, coauthored with Maximilian Auffhammer and Catherine Wolfram, studies the impacts of extreme temperature on over 5 million students standardized test performance. We exploit plausibly exogenous year-to-year within-school daily weather variation in order to measure the contemporaneous effect of maximum outdoor temperature on aggregate student performance. The exam studied is the California High School Exit Exam, a state-wide standardized test that evaluates high school students' mathematics and English-language arts aptitude and was a requirement for receiving a diploma from 2006-2015. We document a nonlinear relationship between temperature and performance. Temperatures above 27.5$^\circ$C show statistically significant negative impact on pass rates in both subjects and scores in the math assessment. We also document heterogeneity in the effect by income in the area surrounding the school and find more pronounced effects for schools in the lowest income quartile. The third chapter, coauthored with Maximilian Balandat and Datong Zhou, evaluates the effect of targeting based on heterogeneous treatment effects using an experiment. We provide a theoretical framework for how various factors undermining external validity affect targeting and the how experimental evaluation of targeting can be used to parse competing mechanisms. Our theoretical framework distinguishes between group-level heterogeneity as defined by covariates and subject-level effects we call individual treatment effects (ITEs). ITEs can only be gleaned through observing program participation using panel data, but capture additional effect heterogeneity within the group-level effects. We partnered with a energy technology company in order to examine the impact using ITEs to target in the field. We find our targeting strategy reduces the costs of the partner by 52 percent and the results are highly significant. The strategy also reduces revenue by 24 percent, indicating an overall increase in profit on the order of 28 percent. We also examine the persistence of the effects and find the cost savings begin to diminish only 60 days after deployment of the targeting strategy. These findings suggest significant potential for reducing the cost of the program, but only in the short-term. Importantly, the experimental evaluation allows us to understand its performance without having to rely on the common practice of conducting ex-post simulations.

Oligometastatic colorectal cancer represents an intermediate disease state potentially treatable with curative intent. Novel treatment strategies are expanding the opportunity to offer local treatment for limited metastatic disease. It is therefore increasingly important to define patients likely to benefit from these targeted treatments. Diagnostic imaging is central to patient management, to establish the burden and distribution of metastatic disease. This thesis explores the potential value of novel imaging biomarkers in patients with colorectal liver metastases (CRLM). In a prospective study, perfusion CT (pCT) and dynamic contrast-enhanced MRI (DCE-MRI) were performed prior to resection, and a retrospective series of patients with resected CRLM was collated. Resected metastases were analysed for relevant morphological features and IHC expression. Novel and conventional imaging variables were derived based on CT, MRI, pCT, DCE-MRI and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET), and their associations with histopathological features, immunohistochemical expression and patient outcomes analysed. A novel subregion analysis based on DCE-MRI data was developed to classify tumour subregions, using a histological reference standard. The results presented in this thesis confirm that the number and distribution of hepatic metastases are prognostic markers for patients with resected CRLM, and that higher SUVmean of liver metastases, and higher SUVmax of the background liver, are potential prognostic biomarkers. Histopathological assessment of resected CRLM highlighted that there is significant between and within patient variability of clinically relevant histopathological features and IHC expression, which would support the potential utility of imaging biomarkers to characterise multi- site disease. Analysis of functional imaging data demonstrated positive correlations between imaging variables and clinically relevant markers of tumour vascularity and metabolism, while subregion analysis of DCE-MRI data produced good spatial correlation with viable and non-viable tumour based on histopathology, with significant differences in derived phamacokinetic parameters between subregions.

Future pre-eclampsia research should ultimately improve patient care. For this to be possible, randomised trials must select, collect, and report outcomes that genuinely reflect the perspectives of key stakeholders, including healthcare professionals, researchers, and women with pre-eclampsia. The objective of this study was to develop a core outcome set for pre-eclampsia, along with standardised definitions, to ensure outcomes and outcome measures are consistently selected, collected, and reported across future primary research, secondary research, and clinical practice guidelines. A long list of 116 potential core outcomes was developed by undertaking a systematic review of 79 published pre-eclampsia trials and thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. The long list of potential core outcomes was entered into a modified Delphi method. Four hundred and thirty-two participants, including 281 healthcare professionals, 41 researchers, and 110 patients, representing 31 high-income countries and 25 low- and middle-income countries participated in a three-round Delphi survey. One hundred and fifty-nine participants (37%) withdrew. Forty-seven consensus outcomes were identified and entered into a modified nominal group technique. Eleven healthcare professionals, two researchers, and three women with lived experience of pre-eclampsia prioritised 14 maternal, four fetal, and four neonatal core outcomes. A long list of 86 potential definitions were identified by reviewing four formal definition development initiatives, eight international and national guidelines, 11 Cochrane systematic reviews, and 79 pre-eclampsia trials. During a consensus development conference involving ten healthcare professionals and three researchers, consensus definitions were successfully developed for all core outcomes. Embedding the core outcome set within future pre-eclampsia research could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes.

This thesis is a study of aboutness. It defends the claim that we have singular thoughts about ordinary objects and argues that an essential part of how we do so is by maintaining singular representations. This proposal allows us to avoid traditional, unsatisfying conceptions of the scope of singular thought while restoring the sense in which such thought is a distinctively epistemic achievement. Reconnecting the study of aboutness with epistemology promises to alleviate the sense of directionlessness in the contemporary literature, offering a firmer grip on the phenomenon along with new, systematic resources for its investigation. Chapters 1-2 explore the effects of contextualist machinery on orthodox views about singular thought. It is widely thought that if there is to be a plausible connection between the truth of a de re attitude report about a subject and that subject's possession of a singular thought, then there can be no acquaintance requirement(s) on singular thought. Chapter 1 shows that this view rests on a faulty picture of how we talk about attitudes. Indeed, the truth of a de re attitude report cannot be taken to track the singular/non-singular distinction without collapsing it. A new, contextualist picture is needed. That there must be a distinction between singular and non-singular intentionality is emphasized in Chapter 2, where a key explanatory role for singular thought - brought out by a thought experiment due to Strawson - is examined. I show that the role does not call for any distinctive kind of mental content. Once we abandon the two widespread views questioned in Chapters 1-2, our grip on the phenomenon of singular aboutness is loosened: it is not constitutively tied to the kinds of attitude-reporting data or mental content by which it is often assumed to be revealed. Where are we to look for insight? What makes something the object of a singular thought? According to Russell, it is a datum of intuition that singular thought involves a kind of knowledge; a theory of aboutness will precisify the intuitive notion of 'knowing which thing one is thinking about' in order to capture this demand in a philosophically revealing way. If Russell is right, teasing out this connection to knowledge will allow us to see what it takes for a particular thing to be the immediate subject matter of thought. Chapter 3 discusses Evans's theory of this kind. Chapter 4 examines recent work by Dickie. While serious concerns emerge in each case, insights recovered are used to precisify Russell's requirement, leading to a novel picture of singular representation and the epistemic character of this achievement. While the chapters follow a narrative, providing an extended rationale for the proposal in Chapter 4, each may be read in isolation by those familiar with the philosophical issues. For those who are not, the Introduction provides sufficient background.