Hypoxia-inducible factor (HIF) network:insights from mathematical models

Oxygen is a crucial molecule for cellular function. When oxygen demand exceeds supply, the oxygen sensing pathway centred on the hypoxia inducible factor (HIF) is switched on and promotes adaptation to hypoxia by up-regulating genes involved in angiogenesis, erythropoiesis and glycolysis. The regulation of HIF is tightly modulated through intricate regulatory mechanisms. Notably, its protein stability is controlled by the oxygen sensing prolyl hydroxylase domain (PHD) enzymes and its transcriptional activity is controlled by the asparaginyl hydroxylase FIH (factor inhibiting HIF-1).To probe the complexity of hypoxia-induced HIF signalling, efforts in mathematical modelling of the pathway have been underway for around a decade. In this paper, we review the existing mathematical models developed to describe and explain specific behaviours of the HIF pathway and how they have contributed new insights into our understanding of the network. Topics for modelling included the switch-like response to decreased oxygen gradient, the role of micro environmental factors, the regulation by FIH and the temporal dynamics of the HIF response. We will also discuss the technical aspects, extent and limitations of these models. Recently, HIF pathway has been implicated in other disease contexts such as hypoxic inflammation and cancer through crosstalking with pathways like NF?B and mTOR. We will examine how future mathematical modelling and simulation of interlinked networks can aid in understanding HIF behaviour in complex pathophysiological situations. Ultimately this would allow the identification of new pharmacological targets in different disease settings.

Scenario planning:teaching how to anticipate perceived environmental uncertainty within strategy development

Scenario Planning is a strategy tool with growing popularity in both academia and practical situations. Current practices in the teaching of scenario planning are largely based on existing literature which utilises scenario planning to develop strategies for the future, primarily considering the assessment of perceived macro-external environmental uncertainties. However there is a body of literature hitherto ignored by scenario planning researchers, which suggests that Perceived Environmental Uncertainty (PEU) influences micro-external or industrial environmental as well as the internal environment of the organisation. This paper provides a review of the most dominant theories on scenario planning process, demonstrates the need to consider PEU theory within scenario planning and presents how this can be done. The scope of this paper is to enhance the scenario planning process as a tool taught for Strategy Development. A case vignette is developed based on published scenarios to demonstrate the potential utilisation of the proposed process.

A micro gas turbines for UK domestic combined heat and power

Various micro-radial compressor configurations were investigated using one-dimensional meanline and computational fluid dynamics (CFD) techniques for use in a micro gas turbine (MGT) domestic combined heat and power (DCHP) application. Blade backsweep, shaft speed, and blade height were varied at a constant pressure ratio. Shaft speeds were limited to 220 000 r/min, to enable the use of a turbocharger bearing platform. Off-design compressor performance was established and used to determine the MGT performance envelope; this in turn was used to assess potential cost and environmental savings in a heat-led DCHP operating scenario within the target market of a detached family home. A low target-stage pressure ratio provided an opportunity to reduce diffusion within the impeller. Critically for DCHP, this produced very regular flow, which improved impeller performance for a wider operating envelope. The best performing impeller was a low-speed, 170 000 r/min, low-backsweep, 15° configuration producing 71.76 per cent stage efficiency at a pressure ratio of 2.20. This produced an MGT design point system efficiency of 14.85 per cent at 993 W, matching prime movers in the latest commercial DCHP units. Cost and CO2 savings were 10.7 per cent and 6.3 per cent, respectively, for annual power demands of 17.4 MWht and 6.1 MWhe compared to a standard condensing boiler (with grid) installation. The maximum cost saving (on design point) was 14.2 per cent for annual power demands of 22.62 MWht and 6.1 MWhe corresponding to an 8.1 per cent CO2 saving. When sizing, maximum savings were found with larger heat demands. When sized, maximum savings could be made by encouraging more electricity export either by reducing household electricity consumption or by increasing machine efficiency.

The environmental impacts of technical change

The thesis is concerned with relationships between profit, technology and environmental change. Existing work has concentrated on only a few questions, treated at either micro or macro levels of analysis. And there has been something of an impasse since the neoclassical and neomarxist approaches are either in direct conflict (macro level), or hardly interact (micro level). The aim of the thesis was to bypass this impasse by starting to develop a meso level of analysis that focusses on issues largely ignored in the traditional approaches - on questions about distribution. The first questions looked at were descriptive - what were the patterns of distribution over time of the variability in types and rates of environmental change, and in particular, was there any evidence of periodization? Two case studies were used to examine these issues. The first looked at environmental change in the iron and steel industry since 1700, and the second studied pollution in five industries in the basic processing sector. It was established that environmental change has been markedly periodized, with an apparently fairly regular `cycle length' of about fifty years. The second questions considered were explanatory - whether and how this periodization could be accounted for by reference to variations in aspects of profitability and technical change. In the iron and steel industry, it was found that diffusion rates and the rate of nature of innovation were periodized on the same pattern as was environmental change. And the same sort of variation was also present in the realm of profits, as evidenced by cyclical changes in output growth. Simple theoretical accounts could be given for all the empirically demonstrable links, and it was suggested that the most useful models at this meso level of analysis are provided by structural change models of economic development.

Perceived environmental uncertainty in scenario planning

Scenarioplanning is a strategy tool with growing popularity in both academia and practical situations. Current practices of scenarioplanning are largely based on existing literature which utilises scenarioplanning to develop strategies for the future, primarily considering the assessment of perceived macro-external environmentaluncertainties. However there is a body of literature hitherto ignored by scenarioplanning researchers, which suggests that PerceivedEnvironmentalUncertainty (PEU) influences the micro-external as well as the internal environment of the organisation. This paper reviews the most dominant theories on scenarioplanning process and PEU, developing three propositions for the practice of scenarioplanning process. Furthermore, it shows how these propositions can be integrated in the scenarioplanning process in order to improve the development of strategy.