Syntaxin 6 and Vti1b form a novel SNARE complex, which is up-regulated in activated macrophages to facilitate exocytosis of tumor necrosis factor-alpha

A key function of activated macrophages is to secrete proinflammatory cytokines such as TNF alpha; however, the intracellular pathway and machinery responsible for cytokine trafficking and secretion is largely undefined. Here we show that individual SNARE proteins involved in vesicle docking and fusion are regulated at both gene and protein expression upon stimulation with the bacterial cell wall component lipopolysaccharide. Focusing on two intracellular SNARE proteins, Vti1b and syntaxin 6 (Stx6), we show that they are up-regulated in conjunction with increasing cytokine secretion in activated macrophages and that their levels are selectively titrated to accommodate the volume and timing of post-Golgi cytokine trafficking. In macrophages, Vti1b and syntaxin 6 are localized on intracellular membranes and are present on isolated Golgi membranes and on Golgi-derived TNF alpha vesicles budded in vitro. By immunoprecipitation, we find that Vti1b and syntaxin 6 interact to form a novel intracellular Q-SNARE complex. Functional studies using overexpression of full-length and truncated proteins show that both Vti1b and syntaxin 6 function and have rate-limiting roles in TNF alpha trafficking and secretion. This study shows how macrophages have uniquely adapted a novel Golgi-associated SNARE complex to accommodate their requirement for increased cytokine secretion.

A study of business user based information systems development, and modelling success factors

This thesis describes research into business user involvement in the information systems application building process. The main interest of this research is in establishing and testing techniques to quantify the relationships between identified success factors and the outcome effectiveness of 'business user development' (BUD). The availability of a mechanism to measure the levels of the success factors, and quantifiably relate them to outcome effectiveness, is important in that it provides an organisation with the capability to predict and monitor effects on BUD outcome effectiveness. This is particularly important in an era where BUD levels have risen dramatically, user centred information systems development benefits are recognised as significant, and awareness of the risks of uncontrolled BUD activity is becoming more widespread. This research targets the measurement and prediction of BUD success factors and implementation effectiveness for particular business users. A questionnaire instrument and analysis technique has been tested and developed which constitutes a tool for predicting and monitoring BUD outcome effectiveness, and is based on the BUDES (Business User Development Effectiveness and Scope) research model - which is introduced and described in this thesis. The questionnaire instrument is designed for completion by 'business users' - the target community being more explicitly defined as 'people who primarily have a business role within an organisation'. The instrument, named BUD ESP (Business User Development Effectiveness and Scope Predictor), can readily be used with survey participants, and has been shown to give meaningful and representative results.

Elastic and inelastic scattering of fast neutrons in fusion reactor materials

In this work, the angular distributions for elastic and. inelastic scattering of fast neutrons in fusion .reactor materials have been studied. Lithium and lead material are likely to be common components of fusion reactor wall configuration design. The measurements were performed using an associated particle time-of- flight technique. The 14 and 14.44 Mev neutrons were produced by the T(d,n} 4He reaction with deuterons being accelerated in a 150kev SAMES type J accelerator at ASTON and in.the 3. Mev DYNAMITRON at the Joint Radiation Centre, Birmingham respectively. The associated alpha-particles and fast. neutrons were detected.by means of a plastic scintillator mounted on a fast focused photomultiplier tube. The samples used were extended flat plates of thicknesses up to 0.9 mean-free-path for Lithium and 1.562 mean-free-path for Lead. The differential elastic scattering cross-sections were measured for 14 Mev neutrons for various thicknesses of Lithium and Lead in the angular range from zero to; 90º. In addition, the angular distributions of elastically scattered 14,.44 Mev .neutrons from Lithium samples were studied in the same angular range. Inelastic scattering to the 4.63 Mev state in 7Li and the 2.6 Mev state, and 4.1 Mev state in 208Pb have:been :measured.The results are compared to ENDF/B-IV data files and to previous measurements. For the Lead samples the differential neutron scattering:cross-sections for discrete 3 Mev ranges and the angular distributions were measured. The increase in effective cross-section due to multiple scattering effects,as the sample thickness increased:was found to be predicted by the empirical .relation ....... A good fit to the exoerimental data was obtained using the universal constant............ The differential elastic scattering cross-section data for thin samples of Lithium and Lead were analyzed in terms of optical model calculations using the. computer code. RAROMP. Parameter search procedures produced good fits to the·cross-sections. For the case of thick samples of Lithium and Lead, the measured angular distributions of :the scattered neutrons were compared to the predictions of the continuous slowing down model.

The influence of political, economic and passenger market factors on international civil aviation

Civil aviation plays an essential role in maintaining international communications. Many extraneous factors influence the daily operations of the air transport industry. This thesis begins by investigating the major categories of so­ called "external interests" in civil aviation. These are shown to have played a significant part in ensuring the need for international agreement over the adoption of regulating principles. The combination and interaction of the various influences has produced a particular type of regulatory environment in which all commercial air services have to operate. The need for such regulation and the extreme difficulty experienced in trying to define universally acceptable methods of supervision is discussed. It is shown how opportunity for the development of on-scheduled air services was created by default on the part of the European Governments.The concept of so-called "scheduled" and "non-scheduled" sectors" is considered and it is suggested that growth of the inclusive tour industry resulted from inappropriate categorisation of the air services involved. The means by which development opportunities were created for inclusive tour operations is considered and the work then investigates the importance of British air transport policy in their exploitation. The politics of British civil aviation in the post-war years is the subject of detailed examination and the process by which Independent airlines were encouraged to develop inclusive tours, is identified. This theme is expanded to demonstrate the vital contribution of British air transport policy in the restructuring of the international industry. The subsequent involvement of the United States is shown to have been directed specifically towards the satisfaction of domestic issues. British objectives, however, are considered to have been more generally concerned with improving the tariff structure. The unique opportunities for British experimentation with international fares are seen to have major influence in forcing the pace of tariff rationalisation.

A study into the effectiveness of quality management training:a focus on tools and critical success factors

Purpose – The purpose of this paper is to investigate the effectiveness of quality management training by reviewing commonly used critical success factors and tools rather than the overall methodological approach. Design/methodology/approach – The methodology used a web-based questionnaire. It consisted of 238 questions covering 77 tools and 30 critical success factors selected from leading academic and practitioner sources. The survey had 79 usable responses and the data were analysed using relevant statistical quality management tools. The results were validated in a series of structured workshops with quality management experts. Findings – Findings show that in general most of the critical success factor statements for quality management are agreed with, although not all are implemented well. The findings also show that many quality tools are not known or understood well; and that training has an important role in raising their awareness and making sure they are used correctly. Research limitations/implications – Generalisations are limited by the UK-centric nature of the sample. Practical implications – The practical implications are discussed for organisations implementing quality management initiatives, training organisations revising their quality management syllabi and academic institutions teaching quality management. Originality/value – Most recent surveys have been aimed at methodological levels (i.e. “lean”, “Six Sigma”, “total quality management” etc.); this research proposes that this has limited value as many of the tools and critical success factors are common to most of the methodologies. Therefore, quite uniquely, this research focuses on the tools and critical success factors. Additionally, other recent comparable surveys have been less comprehensive and not focused on training issues.

Corporate governance and the central factors influencing the roles of public and private sector board directors in the United Kingdom

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