Chemokines and alcoholic liver disease

Alcoholic liver disease is characterised by infiltration of the liver with leucocytes; alcoholic hepatitis is characterised by a neutrophil infiltrate whilst both hepatitis and cirrhosis are characterised by monocytic and lymphocytic infiltration. Chemokines are chemoattractant molecules that regulate leueocyte adhesion and migration at sites of tissue damage. In this thesis I studied the hypothesis that chemokines regulate the leucocyte infiltration and tissue damage characteristic of alcoholic liver disease and thereby determine the nature of the liver damage. Immunohistochemical and in situ hybridisation demonstrated increased expression of several chemokines in alcoholic liver disease. The neutrophil chemokine IL-8 and the lymphoeyte and monocyte ehemokines MCP-1, MIP-1α and MIP-1β were present throughout the hepatic acinus in patterns corresponding to the severity of infiltration with these leucocytes. Chemokine mRNA was mainly localised to non-parenchymal eells including sinusoidal cells, fibroblasts and infiltrating leueocytes. In patients with alcoholic liver disease, circulating serum levels of the ehemokine MCP-1 were raised compared to healthy controls and in proportion to histological severity of liver disease. Peripheral mononuclear cell secretion of both MCP-1 and MIP-1α were raised in alcoholic hepatitis with evidence for both liver-derived and circulating monocyte-derived synthesis. In vitro studies with radiolabelled chemokine protein demonstrated uptake of chemokines into isolated hepatocytes from surrounding culture medium, with uptake increased by the addition of alcohol or the pro-inflammatory cytokine TNF-α. Uptake was predominantly by low-affinity receptors but immunohistochemical studies suggest that specific receptors may nevertheless be up-regulated in alcoholic liver disease. Secretion of the chemokine MCP-1 from peripheral mononuclear cells and hepatocytes in vitro was diminished by alcohol or acetaldehyde with a dose-dependent effect. However, an ex vivo study in healthy volunteers showed that mononuclear cell secretion of MCP-1 may be increased when alcohol is ingested together with a balanced meal. An uncontrolled pilot study of the xanthine-derivative pentoxifylline in subjects with severe alcoholic hepatitis, together with in vitro studies of its effect upon chemokine seeretion, showed that this agent may have a role in the treatment of the disease. In a controlled study examining genetic predisposition to symptomatic alcoholic liver disease, we examined two TNF-α promoter polymorphisms and HLA haplotypes DR3 and DQ2; however we failed to show any associations between these markers and the disease

Swelling and shrinking kinetics of a lamellar gel phase

We investigate the swelling and shrinking of L_beta lamellar gel phases composed of surfactant and fatty alcohol after contact with aqueous poly(ethylene-glycol) solutions. The height change $\Delta h(t)$ is diffusion-like with a swelling coefficient, S: $\Delta h = S \sqrt{t}$. On increasing polymer concentration we observe sequentially slower swelling, absence of swelling, and finally shrinking of the lamellar phase. This behavior is summarized in a non-equilibrium diagram and the composition dependence of S quantitatively described by a generic model. We find a diffusion coefficient, the only free parameter, consistent with previous measurements.Comment: 3 pages, 4 figures to appear in Applied Physics Letter

A water sensitive urban design framework for South Africa

South Africa (RSA) is a ‘developing country’ still facing the challenge of providing basic water services to a significant proportion of the population. Water security is increasingly a matter of major concern, with most of the surface water resources fully accounted for and poor water quality downstream of urban areas. Whereas service delivery and social upliftment are high on the political agenda, the challenge is to promote economic and social equity, whilst simultaneously ensuring environmental sustainability; this challenge is greatest in the rapidly growing urban areas. Alternative approaches to conventional urban water management, which account for these water-supply and -quality constraints as well as the impacts of extreme weather-related events, are thus required. It is postulated that, from a water-management perspective, this will require strategic planning for the wide-scale implementation of Water Sensitive Urban Design (WSUD) – a systems-based approach that focuses on the interactions between the built form and water-resources management. This article describes a way forward for an integrated management (infrastructure and planning) approach for urban water. It defines what ‘water sensitivity’ might mean in the RSA context, and outlines the process that was followed to develop a framework and guidelines for implementing WSUD in South Africa. The four complementary components of the framework – research, vision, narrative, and implementation – highlight what will be required in order to manage the challenges facing the country’s urban water sector and enable the transition towards water sensitivity

A benefit cost analysis of the proposal to eradicate Mediterranean fruit fly from Western Australia

It is estimated that it would cost between $205M and$250M to eradicated Mediterranean Fruit Fly (MFF) from Western Australia (WA). While eradication would be beneficial for fruit growers, it is unlikely that benefits would outweigh costs. The most important factor influencing the economic outcome is, how the eradication program affects the export volume and price of fruit

Exact location of dopants below the Si(001):H surface from scanning tunnelling microscopy and density functional theory

Control of dopants in silicon remains the most important approach to tailoring the properties of electronic materials for integrated circuits, with Group V impurities the most important n-type dopants. At the same time, silicon is finding new applications in coherent quantum devices, thanks to the magnetically quiet environment it provides for the impurity orbitals. The ionization energies and the shape of the dopant orbitals depend on the surfaces and interfaces with which they interact. The location of the dopant and local environment effects will therefore determine the functionality of both future quantum information processors and next-generation semiconductor devices. Here we match observed dopant wavefunctions from low-temperature scanning tunnelling microscopy (STM) to images simulated from first-principles density functional theory (DFT) calculations. By this combination of experiment and theory we precisely determine the substitutional sites of neutral As dopants between 5 and 15A below the Si(001):H surface. In the process we gain a full understanding of the interaction of the donor-electron state with the surface, and hence of the transition between the bulk dopant (with its delocalised hydrogenic orbital) and the previously studied dopants in the surface layer.Comment: 12 pages; accepted for publication in Phys. Rev.

Axial Load Capacity of Sheeted C and Z Members

An equation is developed for calculating the axial load capacity of C and Z shaped members used in roof or wall systems. The equations were determined to be valid for through fastened metal decking but not standing seam roof decking

Using local citation data to relate the use of journal articles by academic researchers to the coverage of full-text document access systems

The methodology and findings are presented of an empirical study comparing local citation patterns with the holdings lists of a number of sources of journal articles. These sources were the British Library Document Supply Centre (BLDSC and the BL inside service, library holdings, ProQuest Direct, SearchBank, EiText and a linking system including both the Geobase database and the BLDSC. The value of local citation figures is discussed, as is the concept of a 'core' of journal titles, from both theoretical and practical perspectives. Using these figures to represent the local use of journal articles, the coverage of the document sources was found to vary widely. Unsurprisingly, the BLDSC was found to offer the widest coverage. Newer, electronic systems generally fared less well, but may offer other advantages

Governing for ecosystem health and human wellbeing

Governance arrangements and processes influence access to and benefits from ecosystem services, and therefore the potential for ecosystem services to alleviate poverty. Governance also then influences the health of ecosystems. This chapter learns from decades of governance-related research to identify how to make ecosystem governance more effectively ‘pro-poor’. It is informed by a systematic mapping of literature related to governance of ecosystem services and renewable natural resources for improved wellbeing and poverty alleviation, expert interviews and a workshop with government and non-government actors across a range of sectors from both North and South. The chapter is organised around the concept of trade-offs, considering first ecosystem-focused approaches, then rights-based approaches and lastly, participatory approaches to governance. The chapter further addresses the relevance of scale and multiple administrative levels (multi-level governance) and the importance of informal, or socially embedded, institutions. The chapter concludes that there is no single governance approach that can definitively deliver on improved ecosystem health and human wellbeing, that trade-offs are inevitable and governance is therefore an inherently political process