The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.

Re-envisioning sovereignty : the end of Westphalia?

Fables of sovereignty / Wayne Hudson Sovereignty discourse and practice : past and future / Joseph Camilleri Guises of sovereignty / Gerry Simpson Westphalian and Islamic concepts of sovereignty in the Middle East / Amin Saikal Wither sovereignty in Southeast Asia today? / See Seng Tan Ambivalent sovereignty : China and re-imagining the Westphalian ideal / Yongjin Zhang Confronting terrorism : dilemmas of principle and practice regarding sovereignty / Brian L. Job Sovereignty in the 21st century : security, immigration, and refugees / Howard Adelman State sovereignty and international refugee protection / Robyn Lui Do no harm : towards a Hippocratic standard for international civilisation / Neil Arya Sovereignty and the global politics of the environment : beyond Westphalia? / Lorraine Elliott Westphalian sovereignty in the shadow of international justice? a fresh coat of paint for a tainted concept / Jackson Nyamuya Maogoto Development assistance and the hollow sovereignty of the weak / Roland Rich Corruption and transparency in governance and development : reinventing sovereignty for promoting good governance / C. Raj Kumar Re-envisioning economic sovereignty : developing countries and the International Monetary Fund / Ross P. Buckley Trust, legitimacy, and the sharing of sovereignty / William Maley Sovereignty as indirect rule / Barry Hindess Indigenous sovereignty / Paul Keal Civil society in a post-statist circumstance / Jan Aart Scholte.

Householder experiences with resource monitoring technology in sustainable homes

The use of feedback technologies, in the form of products such as Smart Meters, is increasingly seen as the means by which 'consumers' can be made aware of their patterns of resource consumption, and to then use this enhanced awareness to change their behaviour to reduce the environmental impacts of their consumption. These technologies tend to be single-resource focused (e.g. on electricity consumption only) and their functionality defined by persons other than end-users (e.g. electricity utilities). This paper presents initial findings of end-users' experiences with a multi-resource feedback technology, within the context of sustainable housing. It proposes that an understanding of user context, supply chain management and market diffusion issues are important design considerations that contribute to technology 'success'.

GVS : A flexible, low-end, 3D visualisation framework for enhancing conceptual groundwater models for community, management and simulations

In this paper we discuss an advanced, 3D groundwater visualisation and animation system that allows scientists, government agencies and community groups to better understand the groundwater processes that effect community planning and decision-making. The system is unique in that it has been designed to optimise community engagement. Although it incorporates a powerful visualisation engine, this open-source system can be freely distributed and boasts a simple user interface allowing individuals to run and investigate the models on their own PCs and gain intimate knowledge of the groundwater systems. The initial version of the Groundwater Visualisation System (GVS v1.0), was developed from a coastal delta setting (Bundaberg, QLD), and then applied to a basalt catchment area (Obi Obi Creek, Maleny, QLD). Several major enhancements have been developed to produce higher quality visualisations, including display of more types of data, support for larger models and improved user interaction. The graphics and animation capabilities have also been enhanced, notably the display of boreholes, depth logs and time-series water level surfaces. The GVS software remains under continual development and improvement

Attack of the creationist reverberators! Or: the end of the world (as we know it)

This special issue of Popular Communication examines the impact of the global financial crisis and recession on differnt aspects of global and regional media and the cultural industries, changing practices of media production, as well as media consumption, and the interplay of economic challenges and technological change.

"As ideias são mais importantes que os produtos", diz Paul Makeham" [Ideas are more important than products, says Paul Makeham]

This interview with Paul Makeham was conducted in 2010 by Felipe Carneiro from Brazilian business magazine Exame. Structured around Exame's "seven questions" format ("Sete Perguntas"), the interview ranges across topics relating to the creative economy, including the increasingly important role of creativity in business, and the role of education in promoting creativity.