This thesis traces the shift from liberal to neoliberal education from the nineteenth century to the present day, in order to provide a rich and previously underdeveloped narrative of value in higher education in England. Rather than attempting to justify the value of the humanities within the presiding economic frameworks, or writing a defence against market rationalism, this thesis offers an original contribution through an immersion in historical, financial, and critical debates concerning educational policy. Drawing upon close reading and discursive analysis, this thesis constructs a nuanced map of the intersections of value in the humanities. The discussion encompasses an exploration of policymaking practices, scientific discourse, mediated representations, and public cultural life. The structure of the thesis is as follows. The introductory chapter outlines the overarching methodology by defining the contemporary period of this project (2008-14), establishing relevant scholarship, and drawing out the correspondences between the nineteenth century and the present day. Chapter one establishes a history of the Payment by Results approach in policymaking, first established in the Revised Code of Education (1862) and recently re-introduced in the reforms of the Browne Report (2010). Understanding the predominance of such short-term and quantitative policy is essential for detailing how value is articulated. Chapter two reconsiders the two cultures debate. In contrast to the misrepresentative, yet pervasive, perception that the sciences and the humanities are fundamentally in opposition, I propose a more nuanced history of these disciplines. Chapter three addresses fictional representations of the humanities within literature in order to establish a vantage point from which to assess alternative routes for valuation beyond economic narratives. The final chapter scrutinises the rise of the impact criterion within research assessment and places it within a wider context of market-led cultural policy (1980-90s). This thesis argues that reflecting on Victorian legacies of economism and public accountability enables us to reconsider contemporary valuation culture in higher education. This analytical framework is of benefit to future academic studies interested in the marketisation and valuation of culture, alongside literary studies that focus on the relationship between higher education, the individual, and the state.

Indiana University-Purdue University Indianapolis (IUPUI) / The immune system initiates tissue repair following injury. In response to sterile tissue injury, neutrophils infiltrate the tissue to remove tissue debris and subsequently undergo apoptosis. Proper clearance of apoptotic neutrophils in the tissue by recruited macrophages, in a process termed efferocytosis, is critical to facilitate the resolution of inflammation and tissue repair. However, the events leading to suppression of sterile inflammation following efferocytosis, and the contribution of other innate cell types are not clearly defined in an in vivo setting. Using a sterile mouse peritonitis model, we identified IL-4 production from efferocytosing macrophages in the peritoneum that activate invariant NKT cells to produce cytokines including IL-4 and IL-13. Importantly, IL-4 from macrophages functions in autocrine and paracrine circuits to promote alternative activation of peritoneal exudate macrophages and augment type-2 cytokine production from NKT cells to suppress inflammation. The increased peritonitis in mice deficient in IL-4, NKT cells, or IL-4Ra expression on myeloid cells suggested that each is a key component for resolution of sterile inflammation. The phagocyte NADPH oxidase, a multi-subunit enzyme complex we demonstrated to require a physical interaction between the Rac GTPase and the oxidase subunit gp91phox for generation of reactive oxygen species (ROS), is required for production of ROS within macrophage phagosomes containing ingested apoptotic cells. In mice with X-linked chronic granulomatous disease (X-CGD) that lack gp91phox, efferocytosing macrophages were unable to produce ROS and were defective in activating iNKT during sterile peritonitis, resulting in enhanced and prolonged inflammation. Thus, efferocytosis-induced IL-4 production and activation of IL-4-producing iNKT cells by macrophages are immunomodulatory events in an innate immune circuit required to resolve sterile inflammation and promote tissue repair.

Indiana University-Purdue University Indianapolis (IUPUI) / Rates of chronic disease and physical inactivity are disproportionately high among African American women. Despite the known benefits of physical activity and an increasing number of programs designed to increase activity, attendance rates to many exercise programs remain low. There is much to learn about program types, such as healthy lifestyle programs (HLP); individual factors, such as self-efficacy; and mediating variables that may influence exercise program attendance. An observational study design was used to compare exercise self-efficacy and attendance in a community-based exercise program in African American women who were enrolled in a HLP (N = 53) to women who were not (N = 27). Exercise program attendance was gathered across six months; demographics, self-efficacy and physical activity behaviors were assessed through surveys; and physiological variables (resting heart rate and blood pressure, height, and weight) and physical fitness (muscular strength and endurance and cardiovascular endurance) were measured at baseline. Descriptive statistics were used to describe participants and groups were compared using T-tests, chi-square and non-parametric statistics. Finally, mediation analyses were conducted using multiple regression models to assess self-efficacy as a potential mediator to exercise program attendance. Women who enrolled in this study were of low income (61% having an annual income less than $20,000), obese with a mean (standard deviation) body mass index (BMI) of 37.7 (7.6), pre-hypertensive with a mean (standard deviation) systolic blood pressure of 125.9 (14.4), and scored poorly and marginally on two fitness tests. On average, women reported being Moderately Confident in their ability to exercise regularly, yet had low attendance in the exercise program with a median number .5 days over six months and there were no significant differences in exercise self-efficacy (p = .23) or attendance in the exercise program between groups (p = .79). Additionally, exercise self-efficacy was not a mediating variable to program attendance. Women in this study had little discretionary income and several chronic disease risk factors, yet exercise program attendance was low even in those enrolled in a HLP. Identifying factors that increase exercise self-efficacy and factors that influence attendance beyond self-efficacy may help future program design and attendance.

Indiana University-Purdue University Indianapolis (IUPUI) / Existing zakat research reports little information about the living conditions of Indonesian zakat recipients. This study examined the perceptions of zakat recipients at Rumah Zakat, a charitable institution, in Yogyakarta. Semi-structured interviews solicited seven economic empowerment and seven socio-health program respondents’ narratives. This data collection method incorporating multiple approaches to data analysis, including phenomenology, revealed that economic empowerment respondents with more education and spousal support could better subsist after utilizing Rumah Zakat’s interest-free loans. And, compared to individual efforts or group support, spousal support helped significantly with business growth. These respondents typically earned incomes above the national standard of poverty. As their businesses grew, four respondents planned to employ the jobless. In the socio-health program, respondents had minimal education and incomes that fell below the national standard of poverty. A Rumah Zakat clinic gave these respondents four to five years of free health care services; it also facilitated collaborative learning. Although the services lowered their expenses, three respondents requested food distribution in addition to health care. Respondents benefiting from both programs reported a significant positive impact on their home economies, health, and social lives. Thus, an integrative program offering assistance with micro-credits, health care, food security, and education would better serve the poor.

Indiana University-Purdue University Indianapolis (IUPUI) / Endothelial Colony Forming Cells (ECFCs) are highly proliferative endothelial progenitor cells with clonal proliferative potential and in vivo vessel forming ability. While endothelial cells have been derived from human induced pluripotent stem cells (hiPS) or human embryonic stem cells (hES), they are not highly proliferative and require ectopic expression of a TGFβ inhibitor to restrict plasticity. Neuropilin-1 (NRP-1) has been reported to identify the emergence of endothelial precursor cells from human and mouse ES cells undergoing endothelial differentiation. However, the protocol used in that study was not well defined, used uncharacterized neuronal induction reagents in the culture medium, and failed to fully characterize the endothelial cells derived. We hypothesize that NRP-1 expression is critical for the emergence of stable endothelial cells with ECFC properties from hES cells. We developed a novel serum and feeder free defined endothelial differentiation protocol to induce stable endothelial cells possessing cells with cord blood ECFC-like properties from hES cells. We have shown that Day 12 hES cell-derived endothelial cells express the endothelial markers CD31+ NRP-1+, exhibit high proliferative potential at a single cell level, and display robust in vivo vessel forming ability similar to that of cord blood-derived ECFCs. The efficient production of the ECFCs from hES cells is 6 logs higher with this protocol than any previously published method. These results demonstrate progress towards differentiating ECFC from hES and may provide patients with stable autologous cells capable of repairing injured, dysfunctional, or senescent vasculature if these findings can be repeated with hiPS.

Indiana University-Purdue University Indianapolis (IUPUI) / A constant-volume combustor is used to investigate the ignition initiated by a traversing jet of reactive hot gas, in support of combustion engine applications that include novel wave-rotor constant-volume combustion gas turbines and pre-chamber IC engines. The hot-jet ignition constant-volume combustor rig at the Combustion and Propulsion Research Laboratory at the Purdue School of Engineering and Technology at Indiana University-Purdue University Indianapolis (IUPUI) was used for this study. Lean premixed combustible mixture in a rectangular cuboid constant-volume combustor is ignited by a hot-jet traversing at different fixed speeds. The hot jet is issued via a converging nozzle from a cylindrical pre-chamber where partially combusted products of combustion are produced by spark- igniting a rich ethylene-air mixture. The main constant-volume combustor (CVC) chamber uses methane-air, hydrogen-methane-air and ethylene-air mixtures in the lean equivalence ratio range of 0.8 to 0.4. Ignition delay times and ignitability of these combustible mixtures as affected by jet traverse speed, equivalence ratio, and fuel type are investigated in this study.

Indiana University-Purdue University Indianapolis (IUPUI) / This study seeks to improve the understanding of inlet conditions of a large rotor-stator cavity in a turbofan engine, often referred to as the drive cone cavity (DCC). The inlet flow is better understood through a higher fidelity computational fluid dynamics (CFD) modeling of the inlet to the cavity, and a coupled finite element (FE) thermal to CFD fluid analysis of the cavity in order to accurately predict engine component temperatures. Accurately predicting temperature distribution in the cavity is important because temperatures directly affect the material properties including Young's modulus, yield strength, fatigue strength, creep properties. All of these properties directly affect the life of critical engine components. In addition, temperatures cause thermal expansion which changes clearances and in turn affects engine efficiency. The DCC is fed from the last stage of the high pressure compressor. One of its primary functions is to purge the air over the rotor wall to prevent it from overheating. Aero-thermal conditions within the DCC cavity are particularly challenging to predict due to the complex air flow and high heat transfer in the rotating component. Thus, in order to accurately predict metal temperatures a two-way coupled CFD-FE analysis is needed. Historically, when the cavity airflow is modeled for engine design purposes, the inlet condition has been over-simplified for the CFD analysis which impacts the results, particularly in the region around the compressor disc rim. The inlet is typically simplified by circumferentially averaging the velocity field at the inlet to the cavity which removes the effect of pressure wakes from the upstream rotor blades. The way in which these non-axisymmetric flow characteristics affect metal temperatures is not well understood. In addition, a constant air temperature scaled from a previous analysis is used as the simplified cavity inlet air temperature. Therefore, the objectives of this study are: (a) model the DCC cavity with a more physically representative inlet condition while coupling the solid thermal analysis and compressible air flow analysis that includes the fluid velocity, pressure, and temperature fields; (b) run a coupled analysis whose boundary conditions come from computational models, rather than thermocouple data; (c) validate the model using available experimental data; and (d) based on the validation, determine if the model can be used to predict air inlet and metal temperatures for new engine geometries. Verification with experimental results showed that the coupled analysis with the 3D no-bolt CFD model with predictive boundary conditions, over-predicted the HP6 offtake temperature by 16k. The maximum error was an over-prediction of 50k while the average error was 17k. The predictive model with 3D bolts also predicted cavity temperatures with an average error of 17k. For the two CFD models with predicted boundary conditions, the case without bolts performed better than the case with bolts. This is due to the flow errors caused by placing stationary bolts in a rotating reference frame. Therefore it is recommended that this type of analysis only be attempted for drive cone cavities with no bolts or shielded bolts.

Indiana University-Purdue University Indianapolis (IUPUI) / In mammalian cells DNA double strand breaks (DSBs) are highly variable with respect to sequence and structure all of which are recognized by the DNA- dependent protein kinase (DNA-PK), a critical component for the resolution of these breaks. Previously studies have shown that DNA-PK does not respond the same way to all DSBs but how DNA-PK senses differences in DNA substrate sequence and structure is unknown. Here we explore the enzymatic mechanism by which DNA-PK is activated by various DNA substrates. We provide evidence that recognition of DNA structural variations occur through distinct protein-protein interactions between the carboxy terminal (C-terminal) region of Ku80 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Discrimination of terminal DNA sequences, on the other hand, occurs independently of Ku 80 C-terminal interactions and results exclusively from DNA-PKcs interactions with the DNA. We also show that sequence differences in DNA termini can drastically influence DNA repair through altered DNA-PK activation. Our results indicate that even subtle differences in DNA substrates influence DNA-PK activation and ultimately Non-homologous End Joining (NHEJ) efficiency.

Indiana University-Purdue University Indianapolis (IUPUI) / Drug addiction is a behavioral disorder characterized by impulsive behavior and continued intake of drug in the face of adverse consequences. Millions of people suffer the financial and social consequences of addiction, and yet many of the current therapies for addiction treatment have limited efficacy. Therefore, there is a critical need to characterize the neurobiological substrates of addiction in order to formulate better treatment options. In the first chapter, the striatal dopamine system is interrogated with [11C]raclopride PET to assess differences between chronic cannabis users and healthy controls. The results of this chapter indicate that chronic cannabis use is not associated with a reduction in striatal D2/D3 receptor availability, unlike many other drugs of abuse. Additionally, recent cannabis consumption in chronic users was negatively correlated with D2/D3 receptor availability. Chapter 2 describes a retrospective analysis in which striatal D2/D3 receptor availability is compared between three groups of alcohol-drinking and tobacco-smoking subjects: nontreatment-seeking alcoholic smokers, social-drinking smokers, and social-drinking non-smokers. Results showed that smokers had reduced D2/D3 receptor availability throughout the striatum, independent of drinking status. The results of the first two chapters suggest that some combustion product of marijuana and tobacco smoke may have an effect on striatal dopamine concentration. Furthermore, they serve to highlight the effectiveness of using baseline PET imaging to characterize dopamine dysfunction in addictions. The final chapter explores the use of [18F]fallypride PET in a proof-of-concept study to determine whether changes in cortical dopamine can be detected during a response inhibition task. We were able to detect several cortical regions of significant dopamine changes in response to the task, and the amount of change in three regions was significantly associated with task performance. Overall, the results of Chapter 3 validate the use of [18F]fallypride PET to detect cortical dopamine changes during a impulse control task. In summary, the results reported in the current document demonstrate the effectiveness of PET imaging as a tool for probing resting and activated dopamine systems in addiction. Future studies will expand on these results, and incorporate additional methods to further elucidate the neurobiology of addiction.

Indiana University-Purdue University Indianapolis (IUPUI) / It has traditionally been posited that women show a "telescoped" development of alcohol use disorders (Kuhn, 2011). In particular, a number of clinical studies support striking sex differences in the progression from initial use of alcohol to dependence on the compound; with women showing a faster progression through landmark events associated with the development of alcohol addiction (Randall et al., 1999). However, recent studies have challenged this tenet (Keyes et al., 2010). The work presented herein was designed to determine whether females are indeed more vulnerable to the development of behavioral maladaptations following binge drinking and whether sex differences in GABA(A) receptor regulation might underlie this vulnerability. Using a mouse model of binge drinking this dissertation established that, compared to males, females escalate their binge drinking at a faster rate and maintain altered responsivity to the locomotor effects of alcohol after extended abstinence from binge drinking. Female mice also displayed significant increases in ethanol preference and intake in a continuous, two-bottle choice protocol following a shorter history of binge drinking than males. The final goal was to determine if binge drinking results in unique patterns of anxiety- or depressive-like symptoms in males and females and whether these behaviors would be associated with the dimorphic regulation of GABAA receptor subunits across the prefrontal cortex and hippocampus. Male binge drinkers displayed anxiety-like behavior during early withdrawal that dissipated after 2 weeks of abstinence. There were no significant changes in the expression of delta or gamma2 GABAA receptor subunit mRNA at this time point in the regions analyzed. Females also showed temporary anxiety-like behavior during early withdrawal from binge drinking. Additionally, females displayed significant depressive-like behavior after 2 weeks of abstinence from binge drinking. In particular, diestrus-phase females displayed significantly greater immobility in the forced-swim test after ethanol exposure and no longer maintained the reduced swim-time behavior associated with this phase of the cycle at baseline (when compared to the estrus-phase). qPCR analysis of hippocampal tissues from diestrus females supported a significant reduction in expression of gamma2 GABA(A) subunit mRNA after binge drinking. This effect was not noted for RNA isolated from hippocampal tissues taken during the estrus phase of bingers. These final data suggest possible interaction of estrous-cycle and binge drinking history that may result in the unique expression of deficits following binge drinking for females. Taken together, this work supports sex and estrous dependent effects of binge drinking on behavior and gene regulation.