Reduced metal transferrin binding in neurological diseases

By employing G75 gel-filtration chromotography, it has been demonstrated that human plasma gallium speciation (and by implication, Al speciation) is bimodal. Normally, gallium was predominantly bound to a high molecular weight fraction which was presumably transferrin. Literature reviews and experimental work throughout this thesis provided evidence to support this idea. An aluminium-transferrin species was assumed to be relatively non-toxic and a protective function for this complex has been suggested. A second, low molecular weight species of gallium was observed and its identity has been suggested to be citrate. The results of this thesis support the concept citrate was a gallium binding ligand present in the plasma, but there was another species (tentatively identified as phosphate) which bound gallium to a much greater degree than did citrate in the majority of samples studied. The consequence of a low molecular weight species of aluminium is the possibility that this leads to a more rapid, uncontrolled deposition of the metal in the brain compared to a transferrin mediated mechanism. Plasma speciation studies in Alzheimer's disease, Parkinson's disease, Down's syndrome, and neonates has revealed an altered ratio of the two gallium species found in control subjects. In all groups there was an increase in the potentially more neurotoxic low molecular weight species. These observations have led to a suggested mechanism of accumulation of metals in the brain, which is known to occur in the first three groups. Possible pathogenic mechanisms are described. The results can also offer an explanation to the reported increased sensitivity to the toxic effects of aluminium in the neonate. Speciation studies on normal plasma has shown the balance between high and low molecular weight species of gallium to be influenced by many physiological factors. There appears to be a fine equilibrium between both species which can be altered without any great difficulty. Therefore, in the diseased groups studied, it is possible that there are subtle biochemical changes within the circulatory system to affect the equilibrium which results in an increased low molecular weight species of aluminium. Furthermore, it has been demonstrated that there is a group of normal controls with no clinical signs of Alzheimer's or Parkinson's disease which have reduced transferrin binding. This indicates there is a population of healthy people who are at risk to the development of either disease.

Predicting and diagnosing faults in wastewater treatment process by Bayesian Belief Networks

Diagnosing faults in wastewater treatment, like diagnosis of most problems, requires bi-directional plausible reasoning. This means that both predictive (from causes to symptoms) and diagnostic (from symptoms to causes) inferences have to be made, depending on the evidence available, in reasoning for the final diagnosis. The use of computer technology for the purpose of diagnosing faults in the wastewater process has been explored, and a rule-based expert system was initiated. It was found that such an approach has serious limitations in its ability to reason bi-directionally, which makes it unsuitable for diagnosing tasks under the conditions of uncertainty. The probabilistic approach known as Bayesian Belief Networks (BBNS) was then critically reviewed, and was found to be well-suited for diagnosis under uncertainty. The theory and application of BBNs are outlined. A full-scale BBN for the diagnosis of faults in a wastewater treatment plant based on the activated sludge system has been developed in this research. Results from the BBN show good agreement with the predictions of wastewater experts. It can be concluded that the BBNs are far superior to rule-based systems based on certainty factors in their ability to diagnose faults and predict systems in complex operating systems having inherently uncertain behaviour.

Corrosion and passivation of steel in concrete

A study of several chemical and electrochemical factors which affect the behaviour of embedded steel in cement pastes and concrete has been made. The effects of internal and external sources of chloride ions on the pore solution chemistry of Portland cement pastes, with and without additions of anodic corrosion inhibitors, have been studied using a pore solution expression device which has enabled samples of pore solution to be expressed from hardened cement pastes and analysed for various ionic species. Samples of pure alite and tricalcium aluminate have been prepared and characterised with respect to morphology, free lime content and fineness. Kinetics of diffusion of chloride ions in hardened pastes of alite and alite blended with tricalcium aluminate have been investigated and an activation energy obtained for the diffusion process in alite. The pore structures of the hardened pastes and the chloride ion binding capacity of alite have also been determined. Concrete cylinders containing embedded steel with four different surface conditions were exposed to various environments. The electrochemical behaviour of the steel was monitored during the period of exposure by means of rest potential measurements and the steel corrosion products analysed before and after being embedded. An examination was made of the nature of the interfacial zones produced between the embedded steel and cement. Rest potential measurements were monitored for steel embedded in alite paste in the presence of chloride ions and cement paste containing various levels of inhibitors in combination with chloride ions. In the latter case the results were supported by polarisation resistance determinations.

Insulin release from cultured B-cells

Established RlNm5F and lN111 R1 and newly available HlT-T15 and UMR 407/3 B-cell lines have been successfully maintained in vitro. With the exclusion of UMR 407/3 cells, all lines were continuously propagable. Doubling times and plating efficiencies for HlT-T15, RlNm5F, lN111 R1 and UMR 407/3 cells were 20 hours and 85%, 31 hours and 76%, 24 hours and 80% and 38 hours and 94% respectively. All the cell lines were anchorage dependent, but only UMR 407/3 cells grew to confluence. Only HlT-T15 and UMR 407/3 cells produced a true insulin response to glucose but glucose markedly increased the rate of D-[U14C]glucose oxidation by all the cell lines. Glucose induced insulin release from HlT-T15 cells was biphasic with an exaggerated first phase. Insulin release from HlT-T15, RlNm5F and IN111 R1 cells was stimulated by amino acids and sulphonylureas. Glucagon stimulated insulin release from HlT-T15 and RlNm5F cells while somatostatin and pancreatic polypeptide inhibited release. These observations suggest that net insulin release from the whole islet may be the result of significant paracrine interaction. HlT-T15 and RlNm5F cell insulin release was stimulated by forskolin and inhibited by imidazole. Ca2+ channel blockade and calmodulin inhibition suppressed insulin release from HlT-T15, RlNm5F and IN111 R1 cells. In addition phorbol esters stimulated insulin release from RlNm5F cells. These data implicate cAMP, Ca2+ and protein kinase-C in the regulation of insulin release from cultured B-cells. Acetylcholine increased insulin release from HlT-T15 and RlNm5F cells. Inhibition of the response by atropine confirmed the involvement of muscarinic receptors. HlT-T15 cell insulin release was also inhibited by adrenaline. These observations suggest a possible role for the autonomic nervous system in the modulation of insulin release. Preliminary studies with a human insulinoma maintained in monolayer culture have demonstrated a limited life span of some seven weeks, a continuous low level of insulin release but no insulin response to glucose challenge.

Adolescents and the experience of parental divorce:including reference to the expectations of teacher trainees

The aims of this study were to investigate the impact of parental divorce on adolescents, and the expectations of teacher trainees with regard to children of divorce. The literature related to children of divorce is reviewed and the results of interviews with a sample of recently divorced custodial parents and their adolescent children, using a structured interview schedule, are described. The semantic differential technique was used to obtain ratings of a sample of teacher trainees' expectations of children of divorce as compared with their ratings of several other categories of children. The results of the interviews with parents and their adolescent children suggested that parental divorce does not necessarily interfere with adolescent development and that for some adolescents the reduction of conflict in the home might enhance normal development. They also suggest that adolescents would prefer to live in a one parent home rather than a two parent home which is fraught with conflict, and that it is preferable for parents who are unable to resolve such conflict in any other way to separate rather than allow it to persist. The ratings of children of divorce by teacher trainees suggest that they hold more negative expectations of such children than of other groups • such as adopted children. The contrast between this finding and the results of the interviews with adolescents and their parents lends some support to the existence of the divorce myth; that is, the cultural belief that divorce has the inherent power to make people unhappy. The implications for policy, practice and further research are discussed.

On a distinction between casual and formative variable models:theoretical issues and practical implications for organizational researchers

Formative measurement has seen increasing acceptance in organizational research since the turn of the 21st Century. However, in more recent times, a number of criticisms of the formative approach have appeared. Such work argues that formatively-measured constructs are empirically ambiguous and thus flawed in a theory-testing context. The aim of the present paper is to examine the underpinnings of formative measurement theory in light of theories of causality and ontology in measurement in general. In doing so, a thesis is advanced which draws a distinction between reflective, formative, and causal theories of latent variables. This distinction is shown to be advantageous in that it clarifies the ontological status of each type of latent variable, and thus provides advice on appropriate conceptualization and application. The distinction also reconciles in part both recent supportive and critical perspectives on formative measurement. In light of this, advice is given on how most appropriately to model formative composites in theory-testing applications, placing the onus on the researcher to make clear their conceptualization and operationalisation.

Patients' perceptions and experiences of transitions in diabetes care: a longitudinal qualitative study

Objective To examine patients' perceptions and experiences over time of the devolvement of diabetes care/reviews from secondary to primary health-care settings. Design Repeat in-depth interviews with 20 patients over 4 years. Participants and setting Twenty type 2 diabetes patients recruited from primary- and secondary-care settings across Lothian, Scotland. Results Patients' views about their current diabetes care were informed by their previous service contact. The devolvement of diabetes care/reviews to general practice was presented as a 'mixed blessing'. Patients gained reassurance from their perception that receiving practice-based care/reviews signified that their diabetes was well-controlled. However, they also expressed resentment that, by achieving good control, they received what they saw as inferior care and/or less-frequent reviews to others with poorer control. While patients tended to regard GPs as having adequate expertise to conduct their practice-based reviews, they were more ambivalent about nurses taking on this role. Opportunities to receive holistic care in general practice were not always realized due to patients seeing health-care professionals for diabetes management to whom they would not normally present for other health issues. Conclusions It is important to educate patients about their care pathways, and to reassure them that frequency of reviews depends more on clinical need than location of care and that similar care guidelines are followed in hospital clinics and general practice. A patients' history of service contact may need to be taken into account in future studies of service satisfaction.

China and European economic security:study on medium to long term impact of technology transfer to China

Extended Summary.

Capabilities and competitiveness of Chinese state owned manufacturing enterprises:what has been learned over 20 years and what remains to be learned

Technological capabilities in Chinese manufacturing have been transformed in the last three decades. However, the extent to which and how domestic market oriented state owned enterprises (SOEs) have developed their capabilities remain important questions. The East Asian latecomer model has been adapted to study six Chinese SOEs in the automotive, steel and machine tools sectors to assess capability levels attained and the role of external sources and internal efforts in developing them. All six enterprises demonstrate high competence in operating established technology, managing investment and making product and process improvements but differ in innovative capability. While the East Asian latecomer model in which linking, leveraging and learning explain technological capability development is relevant for the companies studied, it needs to be adapted for Chinese SOEs to take account of types of external links and leverage of enterprises, the role of government, enterprise level management motives and means of financing development.

Technology and business integration

Editorial

Modularity and industrial complexes:perspectives for green operations in the automotive industry

This paper discusses the possible contributions from modularity and industrial condominiums towards enhancing environmental performance in the automotive industry. The research described in this study is underpinned by a review of journal articles and books on the topics of: modularity of production systems; green operations practices, and the automotive industry and sustainability. The methodology is based on theoretical analysis of the contribution of the modular production system characteristics used in the automotive industry for Green Operations Practices (GOP). The following GOPs were considered: green buildings, eco design, green supply chains, greener manufacturing, and reverse logistics. The results are theoretical in nature; however, due to the small number of studies that investigate the relationship between modularity and sustainability, this work is relevant to increase knowledge in academic circles and among practitioners in order to understand the possible environmental benefits from modular production systems.

Technology transfer and competitive operations:the valuation and collaboration questions

To improve competitiveness and find new markets companies are extending their operations through collaborations involving technology transfer. However, such collaborations have often been based on ad hoc agreements resulting from negotiations in which each side has been inadequately equipped with information about the other’s motivations and expectations. As a result there has been a gap in the ‘value’ attached to the technology, leading to delays or even failure in reaching an agreement. To address this problem a technology valuation and collaboration model has been developed using empirical data gathered from various points along the UK-China value chain for machine tool technology.