Mechanisms of glucocorticoid-mediated inhibition of angiogenesis

Angiogenesis, the formation of new blood vessels from pre-existing vascular beds, is a requirement of embryonic development but only occurs in a limited number of discrete processes in the healthy adult. In contrast, abnormal angiogenesis is central to many pathological processes including: tumour growth, diabetic retinopathy and arthritis. Consequently, pharmacological manipulation of angiogenesis has great clinical potential.Angiogenesis is inhibited by glucocorticoids and this is exploited clinically for the treatment of proliferating capillary haemangiomas in children. Despite this, the exact mechanism(s) through which glucocorticoids inhibit angiogenesis is (are) unknown. Whilst glucocorticoids can act directly on the vessel wall their effects on individual cell types and on molecular signalling remain unclear. The work in this thesis explores the hypothesis that glucocorticoid-mediated inhibition of angiogenesis is the result of direct modulation of growth factor signalling within the vascular endothelial cells.A well-characterised 2-dimensional in vitro model of human endothelial tube formation was introduced. Glucocorticoids were shown to inhibit tube formation in this model via stimulation of glucocorticoid receptors and this process was not influenced by intra-cellular glucocorticoid metabolism by ll(3-hydroxysteroid dehydrogenases. This demonstration that glucocorticoids inhibit angiogenesis by acting directly on the endothelium is consistent with, and extends, observations of glucocorticoid-mediated angiostasis in rodent aortic rings and during cutaneous wound healing. Molecular and biochemical assays suggested that glucocorticoids inhibit tube formation by altering the balance of pro- and anti-angiogenic factor activity. Time-lapse imaging of tube formation, combined with assays of endothelial cell migration and proliferation, indicated that glucocorticoids reduce tube formation, rather than accelerating degradation of existing tubes, by preventing morphological changes in the cells but do not inhibit cell division or migration.In conclusion, these studies demonstrate that glucocorticoids can inhibit angiogenesis by directly inhibiting morphological changes required for tube formation by endothelial cells but without altering migration or proliferation

Ray Tracing Displacement Mapped Surface

Displacement mapping is a technique in computer graphics which allows a simple base surface to be deformed into a more complex surface by applying a texture to change the geometry. This is achieved by applying to each point on the surface a displacement, specified by a displacement function, with a magnitude specified by a height field. This technique makes it possible to transform the simple primitives used in computer graphics today into visually rich and geometrically complex surfaces. Displacement mapping is a texture mapping technique in which the texture is the height field defining the displacement magnitudes. But, unlike any other form of texture mapping, displacement mapping alters the surface geometry. This has many implications for the rendering of displacement mapped surfaces. It must be considered early in the rendering process during the visibility calculations (since it defines the actual geometry of the surface). This is in contrast to other forms of texture mapping which are applied after the visibility of the surface is known. This fact accounts for much of the power and complexity involved in rendering displacement mapped surfaces This thesis provides an investigation into ways to render such surfaces by the use of ray tracing. It is commonly believed that displacement mapped surfaces are too complex to be ray-traced due to the complex nature of the geometry they define. This myth is disproved by the algorithms contained herein. Three algorithms are presented which tackle the ray-surface intersection problem for displacement mapped surfaces (this being the core calculation in a ray tracer). The first algorithm tackles the problem geometrically by analysing the geometry of the intersection calculation. This approach provides a fast algorithm but with limited applicability. It is only suitable for simple base surfaces where the underlying geometry can be easily analysed. The second algorithm reduced the intersection calculation to a system of non-linear equations and applies existing numerical techniques to solve these. This approach, although very general, proves to unsuccessful due to the enormous amount of computation involved. The third approach polygonalises the displacement-mapped surface as it is rendered and calculates the intersections with the generated polygons. This, combined with a system to allow the efficient generation, storage and processing of the generated polygons, provides the first practical system for ray tracing displacement mapped surfaces

Exploring entrepreneurship and organizational culture in a higher education context

The United Kingdom Higher Education sector is undergoing a prolonged period of turbulence in its external environments. This is causing universities to seek to develop entrepreneurial activities to support the diversification of their traditional income streams, whilst also widening their societal and economic contribution at the Government’s request. The researcher has worked within this field for twenty years and has witnessed perceived tensions and barriers that have emerged as university organizational cultures have been required to adapt to meet these new challenges. The purpose of this research is to explore perceptions of entrepreneurship and organizational culture within this context.The research has been undertaken using a social constructionist ontology and interpretivist epistemology, utilizing two complementary qualitative research methods to draw out an understanding of the key issues perceived by twelve participants within a single study organization. Thematic analysis has been utilized to explore the research data drawn from the semi-structured interviews and participant diagrams.The research has identified five key themes that are perceived by participants to be antecedents for entrepreneurship: time; resources; support; leadership & management; and a supportive culture. Analysis has further suggested that some antecedents to entrepreneurship are themselves precursors for others, with a matrix developed herein to outline these interactions. Participants have highlighted that all of the perceived antecedents to entrepreneurship may be considered to be elements of organizational culture, with a belief expressed that these may be amended over time to become more supportive of entrepreneurship. It has further been reported that a university has many, not a single, organizational culture with local cultures being perceived to be generally more supportive than those associated with larger organizational units. In light of this research and its findings, contributions are made to knowledge and practice, with specific recommendations also made to the study organization around these issues

Lifting lockdown policies: A critical moment for COVID-19 stigma

COVID-19 'lockdown' policies may have unintended consequences for individuals, households and country economies. Hence lockdown may be unsustainable despite the risk of a resurgence of new COVID-19 infections. The repeal and alteration of lockdown policies mark a symbolic transfer of responsibility for epidemic control from state to individual. This has the potential to catalyse fear, blame and judgement within and between populations. We draw on experience from the HIV pandemic to show that this will worsen during later phases of the pandemic if COVID-19 stigma increases, as we fear it could. We suggest policy recommendations for 'lockdown lifting' to limit COVID-19 stigma. We suggest three policy priorities to minimise potential increases in COVID-19 stigma: limit fear by strengthening risk communication, engage communities to reduce the emergence of blaming, and emphasise social justice to reduce judgement. 'Lockdown' policies cannot continue uninterrupted. However, lifting lockdown without unintended consequences may prove harder than establishing it. This period has the potential to see the emergence of fear, blame and judgement, intersecting with existing inequalities, as governments seek to share responsibility for preventing further Sars-Cov-2 transmission. As we have learned from HIV, it is critical that a wave of COVID-19 stigma is prevented from flourishing

Changes in the capacity of visual working memory in 5- to 10-year-olds

Using the Luck and Vogel change detection paradigm, we sought to investigate the capacity of visual working memory in 5-, 7-, and 10-year-olds. We found that performance on the task improved significantly with age and also obtained evidence that the capacity of visual working memory approximately doubles between 5 and 10 years of age, where it reaches adult levels of approximately three to four items

‘Comons stories’ workshops:a toolkit for researching the history of Common Land in England Wales

Research guidance for volunteers researching the history of common land in England and Wales across 20th century, prepared for AHRC-funded 'Building Commons Knowledge' project, 2012-13

Contested Common Land Project:Ingleton (North Yorkshire) Historical Briefing Paper

Summary of historical evidence for property rights and governance of common land in Ingleton area, North Yorkshire, (including Ingleborough and Scales Moor commons) prepared fur AHRC-funded 'Contested Common Land' project 2007-10

Contested Common Land Project:Eskdale (Cumbria) Historical Briefing Paper

Summary of historical evidence for property rights and governance of common land in Eskdale, Cumbria, prepared fur AHRC-funded 'Contested Common Land' project 2007-10

Contested Common Land Project:Ingleton Commons

Abstract of historical data for each of the areas of registered common land in the Ingleton (North Yorkshire) area, prepared fur AHRC-funded 'Contested Common Land' project 2007-10