Design, synthesis and development of PDE5 inhibitors

This research project is concerned with the design, synthesis and development of new phosphodiesterase 5 (PDE5) inhibitors with improved selectivities and lower toxicities. Two series of a 5 member and a 6 member ring fused heterocyclic compounds were designed, and synthesized. By alteration of starting materials and fragments, two virtual libraries, each is consisted of close to hundred compounds, were obtained successfully. The screening of sexual stimulation activity with rabbits demonstrated both groups of compounds were able to stimulate rabbit penile erection significantly. The following toxicity studies revealed 2-(substituted-sulfonylphenyl)-imidazo [1,5-a]-1,3,5-triazine-4-(3H)-one group possessed an unacceptable toxicity with oral LD50 about 200mg/kg; while 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group showed an acceptable toxicity with oral LD50 over 2000mg/kg. The continued bioactivity studies showed yonkenafil, the representative of 2-(substituted-sulfonylphenyl)-pyrrolo[2,3-d]pyrimidin-4-one group, has a better selectivity towards PDE5 and PDE6 than sildenafil and a better overall profile of sexual stimulation on animals than sildenafil. Chronic toxicity studies of yonkenafil further confirmed yonkenafil did not cause any serious side effect and damage on animal models and most actions were explainable. Based on evidences of the above studies, yonkenafil were recommended to enter clinical trials by the regulation authority of China, SFDA. Currently yonkenafil has been through the Phase I clinical trials and ready to progress into Phase II. Hopefully, yonkenafil will provide an alternative to the ED patients in the future.

Polish EU accession in comparative perspective:macroeconomics, finance and the government

This book is a collection of papers that focusses on the macroeconomic and financial aspects of EU accession of its largest new member, Poland, seen in comparative perspective. Two main themes are covered. One relates to empirical estimations, evaluating the effects of integration on fiscal balance, prices, seigniorage wealth and FDI flows. The second theme relates to institutional reform and policy recommendations. Discussion focuses on how transparency and fiscal rules, including those implied by EU accession, may help to reduce the deficit bias in fiscal policy; what is the institutional framework for low inflation and how to make the insurance sector regulation more efficient, including its implications for insurance offer for small and medium-size enterprises. Last but not least, the Irish model of development and the role of the foreign direct investment in it is discussed, including the applicability of the Irish policy in Poland and other new EU member states.

Enhanced renewable energy adoption for sustainable development in India:interpretive structural modeling approach

Poverty alleviation and social upliftment of rural India is closely linked with the availability and use of energy for development. At the same time, sustainable supply of clean and affordable renewable energy sources is required if development is to be sustainable, so that it does not cause any environmental problems. The purpose of this paper is to determine the key variables of renewable energy implementation for sustainable development, on which the top management should focus. In this paper, an interpretive structural modeling (ISM) - based approach has been employed to model the implementation variables of renewable energy for sustainable development. These variables have been categorized under ‘enablers’ that help to increase the implementation of renewable energy for sustainable development. A major finding of this research is that public awareness regarding renewable energy for sustainable development is a very significant enabler. In this paper, an interpretation of variables of renewable energy for sustainable development in terms of their driving and dependence powers has been examined. For better results, top management should focus on improving the high-driving power enablers such as leadership, strategic planning, public awareness, top management support, availability of finance, government support, and support from interest groups.

The Greater London Authority:problems of strategy integration

The Act that established the Greater London Authority (GLA) incorporated many of New Labour's aspirations for modern governance. Among those aspirations was the notion of policy integration, or 'joining up'. The Mayor of Greater London was required to develop a number of strategies, broadly in the planning and environmental policy domains, and to ensure that those strategies meshed into a coherent overall strategy for promoting London's economic, social and environmental well-being. How would this work in practice, given the need for coordination between the GLA and a number of related functional bodies, and given the political imperative for the GLA to make an impact quickly? Through our analysis of the strategy development and integration efforts of the GLA in its first nine months, we have gleaned new insights into the highly complex and difficult process of policy integration. We argue that the high aspirations of the Act for policy integration have not been met, policy integration instead being narrowly interpreted as the coordination of strategies to the Mayor's political agenda. Finally,we reflect on the likelihood of the GLA, as currently constituted, evolving to meet the functional requirement of policy integration.

Low-emission vehicle adoption in a UK local authority fleet:economic barriers and air quality benefits

Local air quality was one of the main stimulants for low carbon vehicle development during the 1990s. Issues of national fuel security and global air quality (climate change) have added pressure for their development, stimulating schemes to facilitate their deployment in the UK. In this case study, Coventry City Council aimed to adopt an in-house fleet of electric and hybrid-electric vehicles to replace business mileage paid for in employee's private vehicles. This study made comparisons between the proposed vehicle technologies, in terms of costs and air quality, over projected scenarios of typical use. The study found that under 2009 conditions, the electric and hybrid fleet could not compete on cost with the current business model because of untested assumptions, but certain emissions were significantly reduced >50%. Climate change gas emissions were most drastically reduced where electric vehicles were adopted because the electricity supply was generated by renewable energy sources. The study identified the key cost barriers and benefits to adoption of low-emission vehicles in current conditions in the Coventry fleet. Low-emission vehicles achieved significant air pollution-associated health cost and atmospheric emission reductions per vehicle, and widespread adoption in cities could deliver significant change. © The Author 2011. Published by Oxford University Press. All rights reserved.