Climate Policy Integration: Towards Operationalization

The climate change debate raises the issue of often identified, but as yet little explored, requirement to incorporate climate policy into other policy sectors, often termed climate “mainstreaming” or climate policy integration (CPI). This paper explores the imperative for CPI, the state of current understanding, and proposals for implementation at the crucial national policy scale. The paper draws on the longer-standing field of environmental policy integration, noting that literature’s scant coverage of climate issues but its greater focus on policy and administrative structures and processes, and concludes that more attention needs to be given to these implementation mechanisms for CPI.Climate change, public policy, environment, sustainable development, international cooperation

The role of Wnt signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is a common malignancy worldwide, causing considerable morbidity and mortality. It is unique among epithelial carcinomas in respect of the fact that it has divergent pathways of tumourigenesis. Low-grade papillary tumours which frequently recur, but seldom convert to muscle invasive tumours harbour mutations that activate the MAPK pathways, as a consequence of oncogenic mutations in FGFR3 or HRAS. However, in contrast, the high-grade muscle invasive tumours that readily metastasise have been shown to have defects in the p53 and retinoblastoma (RB) protein pathways Transgenic mice have allowed us to analyse the molecular basis of initiation, invasion and progression of many human cancers. These mouse models increase our understanding of the disease process as well as providing targets for developing novel therapeutic approaches. In UCC there has been a paucity of models that readily mimic the human disease. Although deregulation of the Wnt signalling pathway has been implicated in urothelial cell carcinoma (UCC), the functional significance is unknown. Recent studies have demonstrated the importance of this pathway in UCC progression, thus I endeavoured to test its importance both as a “driver” mutation, as well as a “progressor” mutation in more established UCC mutations. Thus I targeted expression of an activated form of β-catenin to the urothelium of transgenic mice using Cre-Lox technology. Expression of this activated form of β-catenin led to the formation of localised hyperproliferative lesions by 3 months, which did not progress to malignancy. Furthermore expression in UroIICRE+ β-cateninexon3/+ mice showed marked upregulation of the PTEN tumour suppressor protein that appears to be a direct consequence of activating Wnt signalling in the bladder. I therefore combined PTEN deficiency with β-catenin activation, which resulted in rapid formation of papillary UCC by 6 months. These tumours had increased pAKT signalling and were dependent on mTOR. Importantly in human UCC, there was a significant correlation between high levels of β-catenin and pAKT (and low levels of PTEN) (p<0.01, n=80). Taken together, these data suggest that deregulated Wnt signalling plays a role in driving UCC, and human UCC that have high levels of Wnt and PI3 kinase signalling may be responsive to mTOR inhibition. I next expressed oncogenic K-Ras or H-Ras in the urothelium alone, and in urothelial cells expressing an activated β-catenin. Although Ras activation was not sufficient to drive tumourigenesis, Ras activation combined with β-catenin activation in UroIICRE+ β-cateninexon3/exon3 K-RasG12D/+ and UroIICRE+ β-cateninexon3/exon3 H-RasQ61L mice rapidly developed UCC. These tumours had upregulation of pERK1/2 with minimal levels of pAKT. Importantly in human UCC, there was a significant correlation between high levels of β-catenin and pERK1/2 (p<0.01, n=80). This data further supports the role of deregulated Wnt signalling and its co-operation with Ras in bladder carcinogenesis. I observed upregulated p21 expression in our UroIICRE+ β-cateninexon3/+urothelial lesions and thus postulated that p21 may be acting as a block to tumourigenesis in the lesion. It was highly relevant to observe tumour formation in the double mutant UroIICRE+ β-cateninexon3/exon3 p21-/- mice. FGFR3 gene is frequently mutated in superficial urothelial cell carcinoma (UCC). To test the functional significance of FGFR3 mutations as a “driver” of UCC, expression of mutated Fgfr3 was targeted to the murine urothelium using UroIICRE+ promoter. These FGFR3 mutations (K644E and K644M) had no effect on bladder homeostasis or tumourigenesis up to 18 months of ages. Even when these mutations were combined with β-Catenin or Ras activating mutations, no urothelial dysplasia/hyperplasia or UCC was observed. This suggests that other alterations are required that can cooperate with FGFR3 activation to cause UCC. Interestingly, however, due to sporadic ectopic Cre recombinase expression in the lung and skin of these mice, FGFR3 mutation caused skin papilloma and promoted lung tumourigenesis in cooperation with K-Ras and β-Catenin activation, respectively. This confirmed that the mutant Fgfr3 was functional and that FGFR3 cooperates with other genetic events involving Ras and Wnt pathways to promote tumourigenesis in a context dependent manner and support the hypothesis that activation of FGFR signaling contributes to human cancer

The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC

CORROSION INHIBITION PERFORMANCE BY OCTYLMETHYLIMIDAZOLIUM- BROMIDE OMIBr ON API 5L X52 STEEL IN 1.0M H2SO4

In this study, Ionic Liquid Octyl-Methylimidazolium-Bromide OMIBr will be tested as corrosion inhibitor in 1.0M solution of sulfuric acid (H2SO4) on API 5L X52 using linear polarization method and electrochemical impedance method at temperatures 30◦, 50◦, and 70◦. From Linear Polarization method and Electrochemical Impedance spectroscopy, the polarization resistance and charge transfer resistance increases with injection of OMIBr which confirms the inhibition effect of OMIBr. From electrochemical test, the inhibition efficiency of OMIBr on API 5L x52 in 1.0M H2SO4 has been found to decrease with increasing temperatur

Climate policy integration at national scale

This thesis explores climate policy integration (CPI) particularly looking at the structures and processes at the national policy scale and draws on insights from two developing countries, Pakistan and Malaysia. Climate policy integration is an emerging area of research in scholarly and policy literature that has been advanced as a mechanism for dealing with an integrated climate and development challenge. However, the literature is deficient in terms of coverage of developing countries, evidence of CPI at national scales, exploration of structures and processes and the conditions under which the process of CPI can be most effective. This research attempts to fill this scholarly and practical gap. This thesis presents interdisciplinary research touching on, inter alia, the areas of development policy and economics, sustainable development, environmental policy integration (EPI), public policy, environmental change and history, governance and international relations. Theory construction was formulated using case study and adaptive theory approaches. Empirical evidence was collected qualitatively through review and analysis of literature, document analysis and semi-structured interviews. In order to extend into actual policy systems of national scale, case studies of two developing countries, Pakistan and Malaysia, with contrasting but in some ways similar development challenges, were undertaken. While some of the issues that arise in Pakistan and Malaysia are predictable from a policy integration perspective and often identified in the literature (e.g. silos, question of lead agency), some arise that are less familiar (e.g. the role of information). Climate policy development has occurred in both countries, but with very different foci and priorities, especially regarding mitigation versus adaptation. Key agencies are becoming sensitised to climate change. However, there is a clear disconnect between the high-level political priority being increasingly accorded to climate change in both countries, and the slow rate of agency response and implementation. Mainstreaming or integration is occurring, but incorporation of climate change objectives into all stages of policymaking is still weak. 'Silos' across the policy system are a major issue. The information basis and capacity to develop and justify policy action across sectors is an issue in both countries, but with different emphases. As a process to begin understanding the climate mitigation and adaptation imperatives and costs for each country was only starting to appear, a full aggregate of climate consequences into the all aspects of public policy has still to be made and contradictions between sectoral polices have not been removed. The work contributes a new interpretation of CPI within a public policy and administrative framework. It suggests an integration dynamic that advances low carbon and climate-resilient development and questions the hitherto piece meal and incremental approach that national and global policymakers have internalised to deal with the climate challenge. This views mainstreaming as a vehicle for advancing low carbon and climate-resilient development rather than as an end product of existing practices. This requires a paradigm shift from existing separation of discourses, in particular on EPI and CPI to advance sustainable development. -- provided by Candidate