The political shaping of energy technology:combined heat and power in Britain

There has been negligible adoption of combined heat and power (CHP) for district heating (DH) in Britain, despite continued advocacy. This thesis constructs an account of the treatment of the option, and devises a framework for explanation. Analysis of technological development and adoption, it is argued, should be similar to that of other social processes, and be subject to the same requirements and criticisms. They will, however, show features peculiar to the institutions developing and selecting technologies, their relation to different social groups, and the forms of knowledge in and about technology. Conventional approaches - organisation and interorganisation theories, and analyses of policy-making - give useful insights but have common limitations. Elements of an analytical framework situating detailed issues and outcomes in a structured historical context are derived from convergent radical critiques. Thus activity on CHP/DH is essentially shaped by the development and relations of energy sector institutions: central and local government, nationalised industries and particularly the electricity industry. Analysis of them is related to the specific character of the British state. A few CHP and DH installations were tried before 1940. During postwar reconstruction, extensive plans for several cities were abandoned or curtailed. In the 1960s and 70s, many small non-CHP DH schemes were installed on housing estates. From the mid-70s, the national potential of CHP/DH has been reappraised, with widespread support and favourable evaluations, but little practical progress. Significant CHP/DH adoption is shown to have been systematically excluded ultimately by the structure of energy provision; centralised production interests dominate and co-ordination is weak. Marginal economics and political commitment have allowed limited development in exceptional circumstances. Periods of upheaval provided greater opportunity and incentive for CHP/DH but restructuring eventually obstructed it. Explanation of these outcomes is shown to require analysis at several levels, from broad context to detailed action.

Importance of tissue transglutaminasenitrosylation in fibroblasts migration and MMPregulation

As an extracellular second messenger, nitric oxide (NO) mediates the modification of proteins through nitrosylation of cysteine andtyrosine residues. Tissue Transglutaminase (TG2) is a Ca2+ activated, sulfhydryl rich protein with 18 free cysteine residues, which catalyzes ε-(γ glutamyl)lysine crosslink between extracellular and intracellular proteins. NO can nitrosylate up to 15 of the cysteine residues in TG2, leading to the irreversible inactivation of the enzyme activity. The interplay between these two agents was revealed for the first time by our study showing that NO inhibited the TG2-induced transcriptional activation of TGFb1and extracellular matrix (ECM) protein synthesis by nitrosylating TG2 in an inactive confirmation with inert catalytic activity. However, nitrosylated TG2 was still able to serve as a novel cell adhesion protein. In the light of our previous findings, in this study we aim to elucidate the NO modified function of TG2 in cell migration using an in vitro model mimicking the tissue matrix remodeling phases of wound healing. Using transfected fibroblasts expressing TG2 under the control of the tetracycline-off promoter, we demonstrate that upregulation of TG2 expression and activity inhibited the cell migration through the activation of TGFβ1. Increased TG2 activity led to arise in the biosynthesis and activity of the gelatinases, MMP-2 andMMP-9, while decreasing the biosynthesis and activity of the col-lagenases MMP-1a and MMP-13. NO donor S-Nitroso-N-acetyl-penicillamine (SNAP) treatment relieved the TG2 obstructed-cellmigration by blocking the TG2 enzyme activity. In addition,decrease in TG2 activity due to nitrosylation led to an inhibition of TGFβ1, which in turn affected the pattern of MMP activation. Recent evidence suggests that, once in complex with fibronectin in the ECM, TG2 can interact with syndecan-4 or integrinβ-1and regulate the cell adhesion. In the other part of this study, the possible role of nitrosylated TG2 on the regulation of cell migration during wound healing was investigated with respect to its interactions with integrin β1 (ITGβ1) and syndecan-4 (SDC4). Treatment with TG2 inhibitor Z-DON resulted in a 50% decrease in the TG2 interaction with ITGB1 and SDC4, while increasing concentrations of SNAP firstly led to a substantial decrease and then completely abolished the TG2/ITGβ1 and TG2/SDC4 complex formation on the cell surface. Taken together, data obtained from this study suggests that nitrosylation of TG2 leads to a change not only in the binding partners of TG2 on cell surface but also in TGFβ1-dependent MMP activation, which give rise to an increase in the migration potential of fibroblasts.