Inquiries, empirical research and regulatory failure

The paper reveals that regulatory failure, often chronic, has characterised the regulatory environments of charities across time and locale. The analysis of the primary literature identifies common issues and suggested remedies pertaining to the regulatory failures of charities. These issues may well be appropriate for consideration by the commission and participants given their persistence in various inquiries for nearly four centuries. Such inquiries also considered other issues not directly referred to in this paper, to also include them would exponentially increase the already unwieldy size of this paper.

Identity verification in conveyancing : the failure of current legislative and regulatory measures, and recommendations for change

"Defrauding land titles systems impacts upon us all. Those who deal in land include ordinary citizens, big business, small business, governments, not-for-profit organisation, deceased estates...Fraud here touches almost everybody." the thesis presented in this paper is that the current and disparate steps taken by jurisdictions to alleviate land fraud associated with identity-based crimes are inadequate. The centrepiece of the analysis is the consideration of two scenarios that have recently occurred. One is the typical scenario where a spouse forges the partner's signature to obtain a mortgage from a financial institution. The second is atypical. It involves a sophisticated overseas fraud duping many stakeholders involved in the conveyancing process. After outlining these scenarios, we will examine how identity verification requirements of the United Kingdom, Ontario, the Australian states, and New Zealand would have been applied to these two frauds. Our conclusion is that even though some jurisdictions may have prevented the frauds from occurring, the current requirements are inadequate. We use the lessons learnt to propose what we consider core principles for identity verification in land transactions.

Effects of speeding and headway related variable message signs on driver behaviour and attitudes

This research project examined objective measures of driver behaviour and road users' perceptions on the usefulness and effectiveness of three specific VMS (Variable Message Signs) interventions to improve speeding and headway behaviours. The interventions addressed speeding behaviour alone (intervention 1), headway behaviour alone (intervention 2) and a combination of speeding and headway behaviour (intervention 3). Six VMS were installed along a segment of the Bruce Highway, with a series of three signs for each of the northbound and southbound traffic. Speeds and headway distances were measured with loop detectors installed before and after each VMS. Messages addressing speeding and headway were devised for display on the VMS. A driver could receive a message if they were detected as exceeding the posted speed limit (of 90km/hr) or if the distance to the vehicle in front was less than 2.0s. In addition to the on-road objective measurement of speeding and headway behaviours, the research project elicited self-reported responses to the speeding and headway messages from a sample of drivers via a community-based survey. The survey sought to examine the drivers' beliefs about the effectiveness of the signs and messages, and their views about the role, use, and effectiveness of VMS more generally.

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.

Corporate fraud and misconduct : investigative and regulatory priorities

This article investigates the profile of the companies that have been investigated for corporate fraud and misconduct. Our definition of fraud includes financial statement fraud, market misconduct fraud such as insider trading or false disclosures, and managerial fraud. The particular evidence presented relates to those instances of corporate fraud and misconduct investigated by the Australian corporate regulatory, Australian Securities and Investments Commission (ASIC), and relates to sanctions for fraud, misconduct or compliance breaches. Using data compiled from the public announcements in the ASIC reports over the period 2004-2008, we categorise the type of fraud and misconduct breaches ASIC chooses to report and investigate.

The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration

Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into various cell types and have been used widely in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with the activation of the PI3K/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functinalities. Biomaterials have been modified in their properties, surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

Property : a regulatory instrument for protecting private and public interests in the environment

Property in an elusive concept. In many respects it has been regarded as a source of authority to use, develop and make decisions about whatever is the subject matter of this right of ownership. This is true whether the holder of this right of ownership is a private entity or a public entity. Increasingly a right of ownership of this kind has been recognised not only as a source of authority but also as a mechanism for restricting or limiting and perhaps even prohibiting existing or proposed activities that impact upon the environment. It is increasingly therefore an instrument of regulation as much as an instrument of authorisation. The protection and conservation of the environment are ultimately a matter of the public interest. This is not to suggest that the individual holders of rights of ownership are not interested in protecting the environment. It is open to them to do so in the exercise of a right of ownership as a source of authorisation. However a right of ownership – whether private or public – has become increasingly the mechanism according to which the environment is protected and conserved through the use of rights of ownership as a means of regulation. This paper addressed these issues from a doctrinal as well as a practical perspective in how the environment is managed.

Regulatory Impact Assessment of Potential Duplication of Governance and Reporting Standards for Charities

On 25 January 2013, the Council of Australian Governments (COAG) released a Regulatory Impact Assessment (RIA) for consultation on ways to reduce regulatory duplication between the proposed Commonwealth governance and reporting standards and existing state and territory requirements.

Interim financial reporting in the Asia-Pacific region : a review of regulatory requirements

This paper addresses the question of how interim financial reporting regulation varies across the Asia-Pacific region. Using a content analysis method, the study investigates the relevant regulations in eight selected countries in the Asia-Pacific region which differ in a number of country-level attributes. We find that the regulations in the region show considerable variation in terms of the form of regulatory enforcement, reporting lag, audit requirements, and reporting form. By providing the first in-depth review of the nature of differences in interim financial reporting in key countries in the Asia-Pacific region, the findings of this study will be of interest to investors, regulators and researchers in their quest for international “convergence” in financial reporting practices.

Regulatory compliance as a means to achieve environmental sustainability at some large coastal developments in Queensland

The growing public concern about the complexity, cost and uncertain efficacy of the statuary environmental impact assessment process applying to large-scale projects in Queensland is reviewed. This is based on field data gathered over the past six years sat large-scale marina developments that access major environmental reserves along the coast. An ecological design proposal to broaden the process consisted with both government aspirations and regional ecological parameters - termed Regional Landscape Strategies - would allow the existing Environmental Impact Asessment to be modified alone potentially more practicable and effective lines.

Regulatory options for gender equity in health research

It is clear that where a disease affects men and women differently, research on potential therapies or cures should include both men and women and should examine whether the therapy is effective and safe for both sexes. In this paper we consider whether there is an appropriate role for law in regulating to ensure an examination of these sex- and gender-specific aspects in health research. We consider the relative advantages and disadvantages of pursuing a regulatory approach to achieving gender equity in the field of women's health by exploring first, the meaning of gender equity, and second, the regulatory mechanisms that might be best suited to promoting the goal of gender equity. Within our examination of different regulatory forms and mechanisms, we also interrogate the shift from gender-neutral provisions relating to sex in favor of generalized notions of fairness that remove any specific consideration of sex.

High temperature reduces apple fruit colour via modulation of the anthocyanin regulatory complex

The biosynthesis of anthocyanin in many plants is affected by environmental conditions. In apple (Malus×domestica Borkh.), concentrations of fruit anthocyanins are lower under hot climatic conditions. We examined the anthocyanin accumulation in the peel of maturing 'Mondial Gala' and 'Royal Gala' apples, grown in both temperate and hot climates, and using artificial heating of on-tree fruit. Heat caused a dramatic reduction of both peel anthocyanin concentration and transcripts of the genes of the anthocyanin biosynthetic pathway. Heating fruit rapidly reduced expression of the R2R3 MYB transcription factor (MYB10) responsible for coordinative regulation for red skin colour, as well as expression of other genes in the transcriptional activation complex. A single night of low temperatures is sufficient to elicit a large increase in transcription of MYB10 and consequently the biosynthetic pathway. Candidate genes that can repress anthocyanin biosynthesis did not appear to be responsible for reductions in anthocyanin content. We propose that temperature-induced regulation of anthocyanin biosynthesis is primarily caused by altered transcript levels of the activating anthocyanin regulatory complex.

Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

Background Transcription factors (TFs) co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1) leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA, it does provide a tool to characterise cis-regulatory sequences that are necessary for transcription activation in a complex list of co-ordinately regulated genes.

EMT and MET in carcinoma : clinical observations, regulatory pathways and new models

The articles collected here in this special edition Epithelial-Mesenchymal (EMT) and Mesenchymal-Epithelial Transitions (MET) in Cancer provide a snapshot of the very rapidly progressing cinemascope of the involvement of these transitions in carcinoma progression. Pubmed analysis of EMT and cancer shows an exponential increase in the last few years in the number of papers and reviews published under these terms (Fig. 1). The last few years have seen these articles appearing in high calibre journals including Nature, Nature Cell Biology, Cancer Cell, PNAS, JNCI, JCI, and Cell, signaling the acceptance and quality of work in this field.