The role of law in responding to climate change : emerging regulatory, liability and market approaches

Climate change presents as the archetypal environmental problem with short-term economic self-interest operating to the detriment of the long-term sustainability of our society. The scientific reports of the Intergovernmental Panel on Climate Change strongly assert that the stabilisation of emissions in the atmosphere, to avoid the adverse impacts of climate change, requires significant and rapid reductions in ‘business as usual’ global greenhouse gas emissions. The sheer magnitude of emissions reductions required, within this urgent timeframe, will necessitate an unprecedented level of international, multi-national and intra-national cooperation and will challenge conventional approaches to the creation and implementation of international and domestic legal regimes. To meet this challenge, existing international, national and local legal systems must harmoniously implement a strong international climate change regime through a portfolio of traditional and innovative legal mechanisms that swiftly transform current behavioural practices in emitting greenhouse gases. These include the imposition of strict duties to reduce emissions through the establishment of strong command and control regulation (the regulatory approach); mechanisms for the creation and distribution of liabilities for greenhouse gas emissions and climaterelated harm (the liability approach) and the use of innovative regulatory tools in the form of the carbon trading scheme (the market approach). The legal relations between these various regulatory, liability and market approaches must be managed to achieve a consistent, compatible and optimally effective legal regime to respond to the threat of climate change. The purpose of this thesis is to analyse and evaluate the emerging legal rules and frameworks, both international and Australian, required for the effective regulation of greenhouse gas emissions to address climate change in the context of the urgent and deep emissions reductions required to minimise the adverse impacts of climate change. In doing so, this thesis will examine critically the existing and potential role of law in effectively responding to climate change and will provide recommendations on the necessary reforms to achieve a more effective legal response to this global phenomenon in the future.

Prediction of transcriptional regulatory interactions in bacteria : a comparative genomics approach

Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.

Molecular mechanisms of cisplatin resistance in lung cancer

Cisplatin is one of the most potent anticancer agents, displaying significant clinical activity against a variety of solid tumours. To date, cisplatin-based combination treatment remains the most effective systemic chemotherapy for non-small cell lung cancer (NSCLC) patients. Unfortunately, the outcome of cisplatin therapy in NSCLC has reached a plateau due to the development of both intrinsic and acquired resistance that have become a major obstacle in the use of cisplatin in the clinical setting. The molecular mechanisms that underlie chemoresistance are largely unknown. Mechanisms of acquired resistance to cisplatin include reduced intracellular accumulation of the drug, enhanced drug inactivation by metallothionine and glutathione, increased repair activity of DNA damage, and altered expression of oncogenes and regulatory proteins. Cisplatin-induced cytotoxicity is mediated through the induction of apoptosis and cell cycle arrest as a result of cisplatin-DNA adduct formation, which in turn, activates multiple signaling pathways and mediators. These include p53, Bcl-2 family, caspases, cyclins, CDKs, MAPK and PI3K/Akt. Increased expression of anti-apoptotic genes and mutations in the intrinsic apoptotic pathway may also contribute to the inability of cells to detect DNA damage or to induce apoptosis. This chapter will provide an insight into the mechanisms involved in cisplatin resistance and a better understanding of the molecular basis of the cellular response to cisplatin-based chemotherapy in lung cancer.

Regulatory interplay between pap operons in uropathogenic Escherichia coli

Pathogenic bacteria have a large repertoire of surface organelles involved in adherence, motility and protein export, but how individual bacteria co-ordinate surface organelle expression to prevent interference and excessive immune stimulation is unclear. Phase variation is a mechanism by which expression of surface factors is limited to a fraction of the bacterial population; however, the presence of multiple homologous surface structures controlled by related mechanisms and regulators antagonizes the independent expression achieved by phase variation. To investigate whether other mechanisms have evolved to sort out the bacterial cell surface, we examined regulatory cross-talk between multiple phase-variable pyelonephritis-associated pili (pap) operons in Escherichia coli isolates associated with urinary tract infections. Allelic variation identified in the regulatory regions and regulators acts synergistically to limit coexpression of homologous fimbrial operons. In particular, there is evidence that papI is under positive selection and PapI variants displayed differences in their capacity to activate related pap operons. Alleles of the high-affinity binding site for PapB were shown to contain a variable number of (T/A)3 repeats occurring every 9 bp that altered the sensitivity of pap operon activation. Taken together with other examples of surface organelle cross-talk, we illustrate how this regulation could promote sequential expression.

Is climate change litigation an effective strategy for promoting greater action to address climate change? What other legal mechanisms might be appropriate?

In recent times a widespread consensus on the reality and gravity of anthropogenic climate change has emerged. Perceived inadequacies in the Australian government’s legal and policy responses to climate change issues have resulted in environmental activists increasingly turning to the courts as a strategy to promote greater action to address adverse climate impacts. The efficacy of this strategy for achieving climate goals is limited by the time and expense of litigating, the restrictions inherent in environmental law administrative challenges, and the possibility that judicial decisions may be overruled by the legislature. To date, climate change litigation in Australia has met with varied success, yet its significance extends beyond the court room as an important mechanism for raising public, political and commercial awareness about climate change issues. Ultimately, however, the types of far-reaching changes needed to mitigate and manage adverse climate impacts require strong regulatory backing. The most effective approach to addressing the complex challenges posed by climate change is a coordinated suite of regulatory measures spearheaded by the Federal Government.

The impact of change on careers in the 21st century : what do individuals need to do

There is a growing literature (Arthur, Inkson, & Pringle, 1999; Collin & Young, 2000; Hall & Associates, 1996; Peiperl, Arthur,& Anand, 2002) about the changing workplace and the consequent changes to our understanding of the place of career in individuals’ lives (Richardson, 1996, 2000) - “Careers are becoming more varied and more difficult to manage for both individuals and organisations” (Arnold et al, 2005, p. 523). This chapter will present the background to the changes in the world of work and the changes which inevitably impact individuals’ careers. It will then focus on the close relationship between career development and lifelong learning and the importance of ongoing professional learning for individuals to maintain employability in a changing work world.

Structural differentiation and corporate venturing : the moderating role of formal and informal integration mechanisms

Research has suggested that corporate venturing is crucial to strategic renewal and firm performance, yet scholars still debate the appropriate organizational configurations to facilitate the creation of new businesses in existing organizations. Our study investigates the effectiveness of combining structural differentiation with formal and informal organizational as well as top management team integration mechanisms in establishing an appropriate context for venturing activities. Our findings suggest that structural differentiation has a positive effect on corporate venturing. In addition, our study indicates that a shared vision has a positive effect on venturing in a structurally differentiated context. Socially integrated senior teams and cross-functional interfaces, however, are ineffective integration mechanisms for establishing linkages across differentiated units and for successfully pursuing corporate venturing.

A comparative study – regulatory requirements on subdivisions for increasing passive cooling

This is the third in a series of reports planned for this project. The aim of this research is to conduct a comparative study of current legislation or guidelines at the federal, state and local government levels to confirm if any natural ventilation criteria are required at the subdivision development stage of planning. It also seeks to discover if there are any other incentives, statutory planning or development principles that encourage developers to orient subdivision lots to maximize natural ventilation for the dwellings. Findings from the research in this report are intended to contribute to the discussion on the development of an enhanced lot rating methodology for sustainable subdivisions as documented in other reports in this series.

Final report : a software diagnostic tool for evaluating distress mechanisms in bridges exposed to aggressive environments

Durability issues of reinforced concrete construction cost millions of dollars in repair or demolition. Identification of the causes of degradation and a prediction of service life based on experience, judgement and local knowledge has limitations in addressing all the associated issues. The objective of this CRC CI research project is to develop a tool that will assist in the interpretation of the symptoms of degradation of concrete structures, estimate residual capacity and recommend cost effective solutions. This report is a documentation of the research undertaken in connection with this project. The primary focus of this research is centred on the case studies provided by Queensland Department of Main Roads (QDMR) and Brisbane City Council (BCC). These organisations are endowed with the responsibility of managing a huge volume of bridge infrastructure in the state of Queensland, Australia. The main issue to be addressed in managing these structures is the deterioration of bridge stock leading to a reduction in service life. Other issues such as political backlash, public inconvenience, approach land acquisitions are crucial but are not within the scope of this project. It is to be noted that deterioration is accentuated by aggressive environments such as salt water, acidic or sodic soils. Carse, 2005, has noted that the road authorities need to invest their first dollars in understanding their local concretes and optimising the durability performance of structures and then look at potential remedial strategies.

Towards a rule-based matrix for evaluating distress mechanisms in bridges

The effective management of bridge stock involves making decisions as to when to repair, remedy, or do nothing, taking into account the financial and service life implications. Such decisions require a reliable diagnosis as to the cause of distress and an understanding of the likely future degradation. Such diagnoses are based on a combination of visual inspections, laboratory tests on samples and expert opinions. In addition, the choice of appropriate laboratory tests requires an understanding of the degradation mechanisms involved. Under these circumstances, the use of expert systems or evaluation tools developed from “realtime” case studies provides a promising solution in the absence of expert knowledge. This paper addresses the issues in bridge infrastructure management in Queensland, Australia. Bridges affected by alkali silica reaction and chloride induced corrosion have been investigated and the results presented using a mind mapping tool. The analysis highights that several levels of rules are required to assess the mechanism causing distress. The systematic development of a rule based approach is presented. An example of this application to a case study bridge has been used to demonstrate that preliminary results are satisfactory.