Vitamin C supplementation in normal subjects reduces constitutive ICAM-1 expression

Regulation of monocyte adhesion molecule gene expression is via redox sensitive transcription factors. We have investigated whether dietary antioxidant supplementation with vitamin C (250mg/day) can modulate monocyte ICAM-1 expression in healthy male subjects with low plasma vitamin C at baseline. In a randomised, double-blind, crossover study, monocyte ICAM-1 mRNA was analysed using quantitative reverse transcriptase PCR. Protein was determined by flow cytometry (monocytes) and ELISA (plasma). Monocyte numbers were unaltered by supplementation. Subjects with low plasma vitamin C (<50μM) prior to supplementation expressed higher levels of monocyte ICAM-1mRNA, and showed a significant (50%) reduction in ICAM-1mRNA expression after 6 weeks of 250mg/day vitamin C supplementation (p<0.05). This was paralleled by a reduction in sICAM-1 (p<0.05). For the first time, these results show that dietary vitamin C can modulate monocyte ICAM-1 gene expression in vivo, where regulation of gene expression represents a novel mechanism for benefit from dietary antioxidants. © 2003 Elsevier Inc. All rights reserved.

Modelling Apoptotic cell clearance within the atherosclerotic plaque

The aged population have an increased susceptibility to infection, therefore function of the innate immune system may be impaired as we age. Macrophages, and their precursors monocytes, play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Classically-activated 'M1' macrophages are pro-inflammatory, which can be induced by encountering pathogenic material or pro-inflammatory mediators. Alternatively activated 'M2' macrophages have a largely reparative role, including clearance of apoptotic bodies and debris from tissues. Despite some innate immune receptors being implicated in the clearance of apoptotic cells, the process has been observed to have a dominant anti-inflammatory phenotype with cytokines such as IL-10 and TGF-ß being implicated. The atherosclerotic plaque contains recruited monocytes and macrophages, and is a highly inflammatory environment despite high levels of apoptosis. At these sites, monocytes differentiate into macrophages and gorge on lipoproteins, resulting in formation of 'foam cells' which then undergo apoptosis, recruiting further monocytes. This project seeks to understand why, given high levels of apoptosis, the plaque is a pro-inflammatory environment. This phenomenon may be the result of the aged environment or an inability of foam cells to elicit an anti-inflammatory effect in response to dying cells. Here we demonstrate that lipoprotein treatment of macrophages in culture results in reduced capacity to clear apoptotic cells. The effect of lipoprotein treatment on apoptotic cell-mediated immune modulation of macrophage function is currently under study.

Metabolic memory effect of the saturated fatty acid, palmitate, in monocytes

Hyperglycaemia has a deferred detrimental effect on glucose metabolism, termed "metabolic memory". Elevated saturated fatty acids promote insulin resistance, hyperglycaemia and associated atherosclerotic complications, but their effect on "metabolic memory" is unknown. Therefore we investigated whether basal and insulin-stimulated (10(-6)M for 12h) glucose (2-deoxy-D-[(3)H]-glucose) uptake was affected by palmitate pre-treatment human THP-1 monocytes. Palmitate-induced a time-dependent and concentration-dependent inhibition of insulin-stimulated glucose uptake, showing almost complete abolition of the insulin-stimulatory effect with 300 microM palmitate. Basal glucose uptake was unaffected by palmitate. When palmitate was washed out, the inhibitory effect on insulin-stimulated glucose uptake persisted for at least 60 h.

'The prime minister said...': voices in translated political texts

A variety of texts are translated to fulfil functions for political communication across languages, cultures, and ideologies. For example, newspapers regularly provide quotes of statements by foreign politicians, without explicitly indicating that these politicians were actually speaking in their own languages. Politicians react to statements by other politicians as they were presented to them in translation. Political scientists and other experts often debate the potential political consequences of (the translation of) a statement. This chapter addresses the (in)visibility of translation in political communication and the link between textual profiles of translations and the socio-political contexts in which they are produced. The analyses are conducted from the perspective of Translation Studies. The focus is on institutionalised forms of political discourse, i.e. texts that originate in political or media institutions. The link between translation profiles and the social, institutional, ideological conditions of text production is illustrated with reference to authentic political texts (interviews, speeches by politicians, press conferences), mainly involving English, French and German as source and target languages.

Downregulation of ubiquitin-dependent proteolysis by eicosapentaenoic acid in acute starvation

A number of acute wasting conditions are associated with an upregulation of the ubiquitin-proteasome system in skeletal muscle. Eicosapentaenoic acid (EPA) is effective in attenuating the increased protein catabolism in muscle in cancer cachexia, possibly due to inhibition of 15-hydroxyeicosatetraenoic acid (15-HETE) formation. To determine if a similar pathway is involved in other catabolic conditions, the effect of EPA on muscle protein degradation and activation of the ubiquitin-proteasome pathway has been determined during acute fasting in mice. When compared with a vehicle control group (olive oil) there was a significant decrease in proteolysis of the soleus muscles of mice treated with EPA after starvation for 24 h, together with an attenuation of the proteasome 'chymotryptic-like' enzyme activity and the induction of the expression of the 20S proteasome α-subunits, the 19S regulator and p42, an ATPase subunit of the 19S regulator in gastrocnemius muscle, and the ubiquitin-conjugating enzyme E214k. The effect was not shown with the related (n-3) fatty acid docosahexaenoic acid (DHA) or with linoleic acid. However, 2,3,5trimethyl-6-(3-pyridylmethyl)1,4-benzoquinone (CV-6504), an inhibitor of 5-, 12- and 15-lipoxygenases also attenuated muscle protein catabolism, proteasome 'chymotryptic-like' enzyme activity and expression of proteasome 20S α-subunits in soleus muscles from acute fasted mice. These results suggest that protein catabolism in starvation and cancer cachexia is mediated through a common pathway, which is inhibited by EPA and is likely to involve a lipoxygenase metabolite as a signal transducer. © 2001 Academic Press.

The semiology of changing brand image

This article considers the attempted change to the image of an established brand by studying the semiotics within the brand’s historical advertising campaigns. The use of semiotics to study the interpretation of messages is discussed, and the link between interpretation of messages and advertising effectiveness in changing brand image is explored. The authors deconstruct advertisements of a brand to provide a model containing opposing dialectics that may aid managers by highlighting alternative symbolic messages contained in advertisements. Oncwe identified, these alternative symbolic messages may be used to help change brand image and influence advertising effectiveness. Although the study focuses upon a major brand of beer, this is an industry in which there are numerous small firms, and many of those have constrained marketing budgets, and thus need to make sure that their advertising is effective. Equally, entrepreneurial marketing is not to found only in the small firm, and the case study discusses a radical and imaginative brand repositioning of a well established product.

40Gbit/s dispersion managed soliton transmission

This thesis contains the results of experimental and numerical simulations of optical transmission systems using dispersion managed transmission techniques. Theoretical background is given on the propagation of pulses in optical fibres before extending the arguments to optical solitons, their applications and uses in communications. Dispersion management for transmission systems is introduced and then a brief explanation of quasi-linear pulse propagation is given. Techniques for performing laboratory transmission experiments are divulged and focus on the construction and operation of a recirculating loop. Laser sources and modulators for 40Gbit/s transmission rates are discussed and techniques for acquiring information from the resultant eye are explained.The operation of optically time division demultiplexing with a nonlinear elecro-absorption modulator is considered and then is replaced by the used of a linear electro-optic modulator and Dispersion unbalanced loop mirror (DILM). The use of nonlinearity as a positive effect for the use of processing and regenerating optical data is approached with an insight into the operation interferometers. Successful experimental results are given for the characterisation of the DILM and 40Gbit/ to l0Gbit/s demultiplexing is demonstrated.Modelling of a terrestrial style system is performed and the methods for computer simulation are discussed. The simulations model single channel 40Gbit/s transmission, 16 x 40Gbit/s WDM transmission and WDM transmission with varying channel separation. Three modulation formats are examined over the single mode fibre span. It is found that the dispersion managed soliton is not suitable for terrestrial style systems and that return-to-zero was the optimum format for the considered system.

The design of robust protocols for distributed real-time systems

Modern distributed control systems comprise of a set of processors which are interconnected using a suitable communication network. For use in real-time control environments, such systems must be deterministic and generate specified responses within critical timing constraints. Also, they should be sufficiently robust to survive predictable events such as communication or processor faults. This thesis considers the problem of coordinating and synchronizing a distributed real-time control system under normal and abnormal conditions. Distributed control systems need to periodically coordinate the actions of several autonomous sites. Often the type of coordination required is the all or nothing property of an atomic action. Atomic commit protocols have been used to achieve this atomicity in distributed database systems which are not subject to deadlines. This thesis addresses the problem of applying time constraints to atomic commit protocols so that decisions can be made within a deadline. A modified protocol is proposed which is suitable for real-time applications. The thesis also addresses the problem of ensuring that atomicity is provided even if processor or communication failures occur. Previous work has considered the design of atomic commit protocols for use in non time critical distributed database systems. However, in a distributed real-time control system a fault must not allow stringent timing constraints to be violated. This thesis proposes commit protocols using synchronous communications which can be made resilient to a single processor or communication failure and still satisfy deadlines. Previous formal models used to design commit protocols have had adequate state coverability but have omitted timing properties. They also assumed that sites communicated asynchronously and omitted the communications from the model. Timed Petri nets are used in this thesis to specify and design the proposed protocols which are analysed for consistency and timeliness. Also the communication system is mcxielled within the Petri net specifications so that communication failures can be included in the analysis. Analysis of the Timed Petri net and the associated reachability tree is used to show the proposed protocols always terminate consistently and satisfy timing constraints. Finally the applications of this work are described. Two different types of applications are considered, real-time databases and real-time control systems. It is shown that it may be advantageous to use synchronous communications in distributed database systems, especially if predictable response times are required. Emphasis is given to the application of the developed commit protocols to real-time control systems. Using the same analysis techniques as those used for the design of the protocols it can be shown that the overall system performs as expected both functionally and temporally.

The fatigue ageing of vulcanised rubbers

The cause of the respective rough and smooth fatigue failure surfaces of Neoprene GS : Neoprene W and Neoprene GS : natural rubber vulcanisates is investigated. The contrasting morphology of the vulcanisates is found to be the major factor determining the fatigue behaviour of the blends. Neoprene GS and Neoprene W appear to form homogeneous blends which exhibit physical properties and fatigue failure surfaces intermediate between those of the two horropolymers. Neoprene GS and natural rubber exhibit heterogeneity when blended together. The morphology of these blends is found to influence both the fatigue resistance and failure surface of the vulcanisates. Exceptional uncut and cut initiated fatigue lives are observed for blends having an interconnecting network morphology. The network structure and cross-link density of the elastomers in the blends and the addition of carbon black and antioxidant are all found to influence the fatigue resistance but not the failure mechanism of the vulcanisate.

Simulation of robot manipulator control strategies

The high capital cost of robots prohibit their economic application. One method of making their application more economic is to increase their operating speed. This can be done in a number of ways e.g. redesign of robot geometry, improving actuators and improving control system design. In this thesis the control system design is considered. It is identified in the literature review that two aspects in relation to robot control system design have not been addressed in any great detail by previous researchers. These are: how significant are the coupling terms in the dynamic equations of the robot and what is the effect of the coupling terms on the performance of a number of typical independent axis control schemes?. The work in this thesis addresses these two questions in detail. A program was designed to automatically calculate the path and trajectory and to calculate the significance of the coupling terms in an example application of a robot manipulator tracking a part on a moving conveyor. The inertial and velocity coupling terms have been shown to be of significance when the manipulator was considered to be directly driven. A simulation of the robot manipulator following the planned trajectory has been established in order to assess the performance of the independent axis control strategies. The inertial coupling was shown to reinforce the control torque at the corner points of the trajectory, where there was an abrupt demand in acceleration in each axis but of opposite sign. This reduced the tracking error however, this effect was not controllable. A second effect was due to the velocity coupling terms. At high trajectory speeds it was shown, by means of a root locus analysis, that the velocity coupling terms caused the system to become unstable.

Statistical mechanics of distribution networks

This thesis presents an analysis of the stability of complex distribution networks. We present a stability analysis against cascading failures. We propose a spin [binary] model, based on concepts of statistical mechanics. We test macroscopic properties of distribution networks with respect to various topological structures and distributions of microparameters. The equilibrium properties of the systems are obtained in a statistical mechanics framework by application of the replica method. We demonstrate the validity of our approach by comparing it with Monte Carlo simulations. We analyse the network properties in terms of phase diagrams and found both qualitative and quantitative dependence of the network properties on the network structure and macroparameters. The structure of the phase diagrams points at the existence of phase transition and the presence of stable and metastable states in the system. We also present an analysis of robustness against overloading in the distribution networks. We propose a model that describes a distribution process in a network. The model incorporates the currents between any connected hubs in the network, local constraints in the form of Kirchoff's law and a global optimizational criterion. The flow of currents in the system is driven by the consumption. We study two principal types of model: infinite and finite link capacity. The key properties are the distributions of currents in the system. We again use a statistical mechanics framework to describe the currents in the system in terms of macroscopic parameters. In order to obtain observable properties we apply the replica method. We are able to assess the criticality of the level of demand with respect to the available resources and the architecture of the network. Furthermore, the parts of the system, where critical currents may emerge, can be identified. This, in turn, provides us with the characteristic description of the spread of the overloading in the systems.

Performance analysis of DSRC priority mechanism for road safety applications in vehicular networks

Dedicated short range communications (DSRC) has been regarded as one of the most promising technologies to provide robust communications for large scale vehicle networks. It is designed to support both road safety and commercial applications. Road safety applications will require reliable and timely wireless communications. However, as the medium access control (MAC) layer of DSRC is based on the IEEE 802.11 distributed coordination function (DCF), it is well known that the random channel access based MAC cannot provide guaranteed quality of services (QoS). It is very important to understand the quantitative performance of DSRC, in order to make better decisions on its adoption, control, adaptation, and improvement. In this paper, we propose an analytic model to evaluate the DSRC-based inter-vehicle communication. We investigate the impacts of the channel access parameters associated with the different services including arbitration inter-frame space (AIFS) and contention window (CW). Based on the proposed model, we analyze the successful message delivery ratio and channel service delay for broadcast messages. The proposed analytical model can provide a convenient tool to evaluate the inter-vehicle safety applications and analyze the suitability of DSRC for road safety applications.

Downregulation of muscle protein degradation in sepsis by eicosapentaenoic acid (EPA)

Eicosapentaenoic acid (EPA) has been shown to attenuate muscle atrophy in cancer, starvation and hyperthermia by downregulating the increased expression of the ubiquitin-proteasome proteolytic pathway leading to a reduction in protein degradation. In the current study EPA (0.5 g/kg) administered to septic mice completely attenuated the increased protein degradation in skeletal muscle by preventing the increase in both gene expression and protein concentration of the alpha- and beta-subunits of the 20S proteasome, as well as functional activity of the proteasome, as measured by the 'chymotrypsin-like' enzyme activity. These results suggest that muscle protein catabolism in sepsis is mediated by the same intracellular signalling pathways as found in other catabolic conditions.

Service differentiation for the bandwidth request scheme in fixed IEEE 802.16 networks

IEEE 802.16 standards have been developed as one of the technical solutions for broadband wireless access systems. It has high data rate, large network coverage, flexible QoS schemes and cheap network deployment. Various flexible mechanisms related to QoS provisioning have been specified for uplink traffic at the medium access control (MAC) layer in the standards. Among the mechanisms, contention based bandwidth request scheme can be used to indicate bandwidth demands to the base station for the non-real-time polling and besteffort services. These two services are used for most application with unknown traffic characteristics. Due to the diverse QoS requirements of those applications, service differentiation (SD) is anticipated over the contention based bandwidth request scheme. In this paper we investigate the SD with the bandwidth request scheme by means of assigning different channel access parameters and bandwidth allocation priorities. The effectiveness of the differentiation schemes are evaluated by simulations. It is observed that the initial backoff window can be efficient in SD, and if combined with the bandwidth allocation priority, the SD performances will be better. ©2008 IEEE.

Peer mentoring works!

This report draws on the findings of a three year study into peer mentoring conducted at 6 Higher Education Institutions (HEIs), 5 of which were in the UK, 1 of which was in Norway. Following a multiple case-study design, quantitative and qualitative research was conducted in collaboration with the project partners. The research findings provide empirical evidence that peer mentoring works! In particular the report provides: - An Executive Summary outlining the main project findings - A synopsis of the relevant literature – and a link to a much larger literature review undertaken at the beginning of the study - A working conceptual framework and set of research questions - An overview and rationale of the methodological approach and tools - Evidence of the value of peer mentoring in promoting a ‘smooth’ transition into university - Evidence that peer mentoring works by providing the means by which new students can access peer support in both social and academic spheres throughout their first year - Identification of the main challenges of peer mentoring - Evidence of the manner in which writing peer mentoring works by providing bespoke help for individual students - A discussion section in which a new approach to peer mentoring, Transition+, is proposed. The report concludes with recommendations for: Higher Education Institutions: Students: Policy Makers: and, Individuals within HEIs wishing to establish peer mentoring.