Sacred geographies: Religion, race, and the Holy Land in U.S. literature, 1819--1920

This dissertation explores how representations of the Holy Land shaped nineteenth-century Americans' conceptions of racial identity in the emerging United States. In the nineteenth century, Americans physically encountered Palestine for the first time, exploring, mapping, and essentially inventing the Holy Land during a century of U.S. nation-building, expansion, and imperialism. "Sacred Geographies" reveals how the Holy Land provided a durable and fertile resource for writers wrestling with the place of race in the burgeoning nation. Analyzing a variety of "national" writings, including frontier romances, Gothic tales, slave narratives, and domestic novels, I demonstrate U.S. writers' engagement with a rapidly growing Holy Land industry. Attention to this often overlooked fascination with the Holy Land highlights the interdependence of racial and religious histories in U.S. culture. By examining the Holy Land's fundamental impact on U.S. perceptions of racial and national belonging, "Sacred Geographies" exposes the flexibility of the racial categories used to constitute U.S. culture, and it demonstrates the vital role religious identity played in the development of U.S. racial ideologies

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

Towards the Promotion of Positive Development among Boys in Challenging Contexts: A Mixed-Methods Study of Engagement in the Scoutreach Initiative

Engagement in youth development programs reflects the quality of young people’s program-related experiences. However, more research is needed that explores cognitive, emotional, and behavioral dimensions of engagement in programs that serve underrepresented youth of color. The present cross-sectional and mixed-methods study assessed potential relations among dimensions of engagement in the Boston-area Scoutreach initiative, character attributes, self-perceived school competence, and intentional self-regulation. We analyzed data from 32 Scouts (Mage = 9.97 years, SD = 2.46, Range = 6 to 14), 32 parents/guardians, and five Scoutreach leaders. Scouts demonstrated that they were cognitively, emotionally, and behaviorally engaged in Scoutreach, and these dimensions were related differentially to indicators of healthy development. Qualitative data elucidated key aspects of Scoutreach (e.g., camping, peer relationships) that were linked to youth engagement. We discuss limitations of the present study and implications for future research and practice

A mathematical model of tumour & blood pHe regulation: The HCO-3/CO2 buffering system

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the View the MathML source buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe

Spatial Resolution of Gated X-Ray Pinhole Cameras

The new camera FXI was investigated. Spatial resolution, or its Fourier transform, the modulation transfer function (MTF), is critical for quantitative interpretation of recent hydrodynamic instability data taken on the Nova laser. We have taken data corresponding to backlit straight edges, pinholes, and grids, both on the bench and {ital in}{ital situ} on Nova. For both the pinhole and edge data, the MTF at all wavelengths of interest can be deduced from a single image. Grids are of more limited usefulness, giving the MTF value only at the spatial period of the grid. These different techniques for characterizing the MTF of gated x-ray pinhole cameras are discussed, with results specific to the FXI presented

E2F1 drives chemotherapeutic drug resistance via ABCG2

Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy