Distributed processing, reconfigurable processes and active network

The fast spread of the Internet and the increasing demands of the service are leading to radical changes in the structure and management of underlying telecommunications systems. Active networks (ANs) offer the ability to program the network on a per-router, per-user, or even per-packet basis, thus promise greater flexibility than current networks. To make this new network paradigm of active network being widely accepted, a lot of issues need to be solved. Management of the active network is one of the challenges. This thesis investigates an adaptive management solution based on genetic algorithm (GA). The solution uses a distributed GA inspired by bacterium on the active nodes within an active network, to provide adaptive management for the network, especially the service provision problems associated with future network. The thesis also reviews the concepts, theories and technologies associated with the management solution. By exploring the implementation of these active nodes in hardware, this thesis demonstrates the possibility of implementing a GA based adaptive management in the real network that being used today. The concurrent programming language, Handel-C, is used for the description of the design system and a re-configurable computer platform based on a FPGA process element is used for the hardware implementation. The experiment results demonstrate both the availability of the hardware implementation and the efficiency of the proposed management solution.

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

Thermodynamics of binding of regulatory ligands to tissue transglutaminase

The transamidating activity of tissue transglutaminase is regulated by the ligands calcium and GTP, via conformational changes which facilitate or interfere with interaction with the peptidyl-glutamine substrate. We have analysed binding of these ligands by calorimetric and computational approaches. In the case of GTP we have detected a single high affinity site (K (D) approximately 1 muM), with moderate thermal effects suggestive that binding GTP involves replacement of GDP, normally bound to the protein. On line with this possibility no significant binding was observed during titration with GDP and computational studies support this view. Titration with calcium at a high cation molar excess yielded a complex binding isotherm with a number of "apparent binding sites" in large excess over those detectable by equilibrium dialysis (6 sites). This binding pattern is ascribed to occurrence of additional thermal contributions, beyond those of binding, due to the occurrence of conformational changes and to catalysis itself (with protein self-crosslinking). In contrast only one site for binding calcium with high affinity (K (D) approximately 0.15 muM) is observed with samples of enzyme inactivated by alkylation at the active site (to prevent enzyme crosslinkage and thermal effects of catalysis). These results indicate an intrinsic ability of tissue transglutaminase to bind calcium with high affinity and the necessity of careful reassessment of the enzyme regulatory pattern in relation to the concentrations of ligands in living cells, taking also in account effects of ligands on protein subcellular compartimentation.

Mechanisms contributing to the enhanced respiratory burst of neutrophils observed in periodontitis

The aim of this thesis is to investigate possible mechanisms that may contribute to neutrophil hyperactivity and hyper-reactivity. One possibility is the presence of a neutrophil priming factors within the peripheral circulation of periodontitis patients. To examine this possibility differentiated HL-60 cells and primary neutrophils were studied in the presence and absence of plasma from periodontitis patients. In independent experiments, plasma was depleted of IL-8, GM-CSF, interferon-a, immunoglobulins and albumin. This work demonstrated that plasma factors such as IL-8, GM-CSF, and interferon-a present during periodontitis may contribute towards the reported hyperactive neutrophil phenotype. Furthermore, this work demonstrated that products from Pg may regulate neutrophil accumulation at infected periodontal sites by promoting gingipain-dependent modification of IL-8-77 into a more biologically active chemokine. To elucidate whether the oxidatively stressed environment that neutrophils are exposed to in periodontitis could influence hyperactivity and hyper-reactivity, neutrophils were depleted of glutathione. This work showed that during oxidative stress, where cellular redox-levels have been altered, neutrophils exhibit an increased respiratory burst. In conclusion, this work highlights the multiple mechanisms that may contribute to neutrophil hyperactivity and hyperreactivity including gingipain-modulated activity of IL-8 variants, the effect of host factors such as IL-8, GM-CSF, interferon-a on neutrophils priming and activation, and the shift of neutrophil GSH:GSSG ratio in favour of a more oxidised environment as observed in periodontitis.

An evaluative analysis of the practice of teamwork in Health and Personal Social Services

This report describes the practice of teamwork as expressed in case conferences for care of the elderly and evaluates the effectiveness of case conferences in their contribution to care. The study involved the observation of more than two hundred case conferences in sixteen locations throughout the West Midlands, in which one thousand seven hundred and three participants were involved. Related investigation of service outcomes involved an additional ninety six patients who were interviewed in their homes. The pu`pose of the study was to determine whether the practice of teamwork and decision-making in case conferences is a productive and cost effective method of working. Preliminary exploration revealed the extent to which the team approach is part of the organisational culture and which, it is asserted, serves to perpetuate the mythical value of team working. The study has demonstrated an active subscription to the case conference approach, yet has revealed many weaknesses, not least of which is clear evidence that certain team members are inhibited in their contribution. Further, that the decisional process in case conferences has little consequence to care outcome. Where outcomes are examined there is evidence of service inadequacy. This work presents a challenge to professionals to confront their working practices with honesty and with vision, in the quest for the best and most cost effective service to patients.

Schoolgirls in a rural context

It is proposed that, for rural secondary schoolgirls, school is a site of contestation. Rural girls attempt to `use' school as a means of resisting traditional patriarchal definitions of a `woman's place'. In their efforts, the girls are thwarted by aspects of the school itself, the behaviour and attitudes of the boys in school, and also the `careers advice' which they receive. It is argued that the girls perceive school as being of greater importance to them than is the case for the boys, and that these gender differentiated perceptions are related to the `social' lives of the girls and boys, and also to their future employment prospects. Unlike the boys, the girls experience considerable restrictions concerning these two areas. This theory was grounded in an ethnographic study which was conducted in and around a village in a rural county in England. As well as developing the theory through ethnography, the thesis contains tests of certain hypotheses generated by the theory. These hypotheses relate to the gender differentiated perspectives of secondary school pupils with regard to the areas of school itself, life outside school, and expectations for the future. The quantitative methods used to test these hypotheses confirm that there is a tendency for girls to be more positively orientated to school than the boys; to feel less able to engage in preferred activities outside school time than the boys, and also to be more willing to move away from the area than the boys. For comparative purposes these hypotheses were tested in two other rural locations and the results indicate the need for further research of a quantitative kind into the context of girls' schooling in such locations. A critical review of literature is presented, as is a detailed discussion of the research process itself.

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

Coherence and understanding in informal conversations between native and non-native speakers of English

This study investigates informal conversations between native English speakers and international students living and studying in the UK. 10 NNS participants recorded themselves during conversations with native speakers. The audio-recordings were transcribed and a fine-grained, qualitative analysis was employed to examine how the participants jointly achieved both coherence and understanding in the conversations, and more specifically how the NNSs contributed to this achievement. The key areas of investigation focused on features of topic management, such as topic initiations, changes and transitions, and on the impact which any communicative difficulties may have on the topical continuity of the conversations. The data suggested that these conversations flowed freely and coherently, and were marked by a relative scarcity of the communicative difficulties often associated with NS-NNS interactions. Moreover, language difficulties were found to have minimal impact on the topic development of the conversations. Unlike most previous research in the field, the data further indicated that the NNSs were able to make active contributions to the initiation and change of topics, and to employ a range of strategies to manage these effectively and coherently. The study considers the implications which the findings may have for teaching and learning, for second language acquisition research, and for non-native speakers everywhere.

Embedded fibre Bragg grating array sensors in aluminium alloy matrix by ultrasonic consolidation

Fibre Bragg Grating (FBG) array sensors have been successfully embedded in aluminium alloy matrix by ultrasonic consolidation (UC) technique. The temperature and loading responses of the embedded FBG arrays have been systematically characterised. The embedded grating sensors exhibit an average temperature sensitivity of ~36pm/°C, which is three times higher than that of normal FBGs, and a loading responsivity of ~0.1nm/kg within the dynamic range from 0kg to 3kg. This initial experiment clearly demonstrates that FBG array sensors can be embedded in metal matrix together with other passive and active fibres to fabricate smart materials to monitor the operation and health of engineering structures.

Embedded fibre Bragg grating array sensors in aluminium alloy matrix by ultrasonic consolidation

Fibre Bragg Grating (FBG) array sensors have been successfully embedded in aluminium alloy matrix by ultrasonic consolidation (UC) technique. The temperature and loading responses of the embedded FBG arrays have been systematically characterised. The embedded grating sensors exhibit an average temperature sensitivity of ~36pm/°C, which is three times higher than that of normal FBGs, and a loading responsivity of ~0.1nm/kg within the dynamic range from 0kg to 3kg. This initial experiment clearly demonstrates that FBG array sensors can be embedded in metal matrix together with other passive and active fibres to fabricate smart materials to monitor the operation and health of engineering structures.

Excipients in medicines for children:scientific and regulatory paradigms

There is an ongoing debate over the use of pharmaceutical excipients in medicines for children, triggered by the increased number of formulations suitable for this target patient population. Pharmaceutical excipients can be regarded as essential / necessary enablers in formulation development. These are materials other than the 'active pharmaceutical ingredient' which are added to the formulation to achieve a specific function1. This may include aiding in the processing or manufacture of the drug delivery system such as lubricants or flow aids, controlling the release of the active ingredient to achieve modified release, enhance patient acceptability by improving taste of medicines or to develop easily swallowed dosage forms.