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.

From vision to reality : views of primary school principals on inclusive education in New South Wales, Australia

This paper discusses the findings of a research study that used semi-structured interviews to explore the views of primary school principals on inclusive education in New South Wales, Australia. Content analysis of the transcript data indicates that principals’ attitudes towards inclusive education and their success in engineering inclusive practices within their school are significantly affected by their own conception of what “inclusion” means, as well as the characteristics of the school community, and the attitudes and capacity of staff. In what follows, we present two parallel conversations that arose from the interview data to illustrate the main conceptual divisions existing between our participants’ conceptions of inclusion. First, we discuss the act of “being inclusive” which was perceived mainly as an issue of culture and pedagogy. Second, we consider the mechanics of “including,” which reflected a more instrumentalist position based on perceptions of individual student deficit, the level of support they may require and the amount of funding they can attract.

Archival analysis of enterprise resource planning systems : the current state and future directions

Research on Enterprise Resource Planning (ERP) Systems is becoming a well-established research theme in Information Systems (IS) research. Enterprise Resource Planning Systems, given its unique differentiations with other IS applications, have provided an interesting backdrop to test and re-test some of the key and fundamental concepts in IS. While some researchers have tested well-established concepts of technology acceptance, system usage and system success in the context of ERP Systems, others have researched how new paradigms like cloud computing and social media integrate with ERP Systems. Moreover, ERP Systems provided the context for cross disciplinary research such as knowledge management, project management and business process management research. Almost after two-decades since its inception in IS research, this paper provides a critique of 198 papers published on ERP Systems since 2006-2012. We observe patterns on ES research, provide comparisons to past studies and provide future research directions.

Ensuring student success : establishing a community of practice for culturally and linguistically diverse preservice teachers

This paper discusses the primacy of communities of practice within learning contexts at university and during practicum for culturally and linguistically diverse preservice teachers. The study illustrates that learning occurs when there are adequate opportunities for participation and practice. Data from interviews with 28 culturally and linguistically diverse preservice teachers illustrate that tensions created by social, cultural differences impact upon modes of identification and dimensions of practice (Lave & Wenger, 1991; Wenger, 1998). The study concludes by reiterating the importance of establishing proactive communities of practice to ensure success in learning and practice for this group of preservice teachers.

Normative requirements for business process compliance

Norms regulate the behaviour of their subjects and define what is legal and what is illegal. Norms typically describe the conditions under which they are applicable and the normative effects as a results of their applications. On the other hand, process models specify how a business operation or service is to be carried out to achieve a desired outcome. Norms can have significant impact on how business operations are conducted and they can apply to the whole or part of a business process. For example, they may impose conditions on the different aspects of a process (e.g., perform tasks in a specific sequence (control-flow), at a specific time or within a certain time frame (temporal aspect), by specific people (resources)). We propose a framework that provides the formal semantics of the normative requirements for determining whether a business process complies with a normative document (where a normative document can be understood in a very broad sense, ranging from internal policies to best practice policies, to statutory acts). We also present a classification of normal requirements based on the notion of different types of obligations and the effects of violating these obligations.

Performance configurations over time: implications for growth-and profit-oriented strategies

Entrepreneurship research and practice places emphasis on company growth as a measure of entrepreneurial success. In many cases, there has been a tendency to give growth a very central role, with some researchers even seeing growth as the very essence of entrepreneurship (Cole, 1949; Sexton, 1997; Stevenson & Gumpert, 1991). A large number of empirical studies of the performance of young and/or small firms use growth as the dependent variable (see reviews by Ardishvili, Cardozo, Harmon, & Vadakath, 1998; Delmar, 1997; Wiklund, 1998). By contrast, the two most prominent views of strategic management – strategic positioning (Porter, 1980) and the resource-based view (Barney, 1991; Wernerfelt, 1984) – are both concerned with achieving competitive advantage and regard achieving economic rents and profitability relative to other competitors as the central measures of firm performance. Strategic entrepreneurship integrates these two perspectives and is simultaneously concerned with opportunity seeking and advantage seeking (Hitt, Ireland, Camp, & Sexton, 2002; Ireland, Hitt, & Sirmon, 2003). Consequently, both company growth and relative profitability are together relevant measures of firm performance in the domain of strategic entrepreneurship.

Let's talk about failures : why was the game for children not a success?

A significant proportion of research in the field of human-computer interaction has been devoted to game design. Yet, a multitude of good ideas and enthusiastic game design initiatives exist, where the games never see the light of day. Unfortunately, the causes of these failures remain often unexplored and unpublished. The challenges faced by researchers and practitioners are particularly complex when designing games for special target groups, such as children, or for a serious purpose. The HCI community would benefit from a discussion on these issues in order to avoid researchers and practitioners to repeat mistakes. We want to learn from projects that started with a promising idea, but failed or faced severe challenges. This workshop will be the first at CHI focusing on 'failed game projects'. In particular, workshop participants are encouraged to discuss issues that typically received little attention in publications and hereby contribute to the discussion on failures in the design, development and evaluation of games for and or with children. As a result, the community will benefit from these insights and lessons-learned, which will enhance the design of future (serious) games with/for children.

L’internationalisation des jeunes entreprises de hautes technologies : Le rôle des compétences internationales des fondateurs [The internationalization of new technology based firms : the role of the international skills of founding teams]

Extending recent research on the importance of specific resources and skills for the internationalization of start-ups, this article tests a negative binomial model on a sample of 520 recently created high technology firms from the UK and Germany. The results show that previous international experience of entrepreneurs facilitates the rapid penetration of foreign markets, especially when the company features a clear and deliberate strategic intent of internationalization from the outset. This research provides one of the first empirical studies linking the influence of entrepreneurial teams to a high probability of success in the internationalization of high-technology ventures.

An analysis of corporate related-party disclosure in the Asia-Pacific region

Related-party (RP) transactions are said to be commonly used opportunistically in business and contribute to corporate failures. While periodic disclosure is widely accepted as an effective means of monitoring such transactions, research is scant, particularly in countries where business dealings may be more susceptible to corruption. This study investigates the nature and extent of corporate RP disclosures across six countries in the Asia-Pacific region. The key finding indicates that companies in countries with stronger regulatory enforcement, shareholders’ protection, and control for corruption, have more transparent RP disclosures. This evidence potentially contributes to reforms aimed at strengthening RP disclosure and compliance.

Principles of Taxation Law 2013

Taxation law can be an incredibly complex subject to absorb, particularly when time is limited. Written specifically for students, Principles of Taxation Law 2013 brings much needed clarity to this area of law. Utilising many methods to make this often daunting subject achievable, particular features of the 2013 edition include: • seven parts: overview and structure, principles of income, deductions and offsets, timing issues, investment and business entities, tax avoidance and administration, and indirect taxes; • clearly structured chapters within those parts grouped under helpful headings; • flowcharts, diagrams and tables, end of chapter practice questions, and case summaries; • an appendix containing all of the up to date and relevant rates; and • the online self-testing component mentor, which provides questions for students of both business and law. Every major aspect of the Australian tax system is covered, with chapters on topics such as goods and services tax, superannuation, offsets, partnerships, capital gains tax, trusts, company tax and tax administration. All chapters have been thoroughly revised. Principles of Taxation Law 2013 is the perfect tool to guide the reader from their initial exposure to the subject to success in taxation law exams.

Contemporary Australian masculinities and De Certeau’s concept of la perruqe in Christos Tsiolkas’ novel The Slap (2008)

This paper will focus on how Christos Tsiolkas the author of The Slap (2008) invites us to view the complex range of private lives of his male characters living in suburban Melbourne through their daily routines, conversations and innermost thoughts. On the surface most appear to be participating in and achieving a certain level of success in their lives. However, this novel reveals when we agitate and dig below the “practices of everyday life” there is often a disquiet simmering away under the facade of family harmony, male bravado and contentment. This paper will argue that as a result of dissatisfaction with the established order of their lives, each man has managed to create another level of meaning for himself, his own form of la perruque (De Certeau 2011: 29),the concept of living proposed by Michel De Certeau. A treatment of the characters in this article draws on, and is used to illustrate the paradigm.

Relationship between CEO salaries and performance of banks in Australia and Germany

Purpose: The purpose of this paper was to examine the relationship between CEO salaries and firm performance in the banking sector. Design/methodology/approach: The data relating to a six year period (2007 - 2012) was gathered from databases and the websites of the major banks in Australia and Germany. The data was subjected to Regression and Pearson Correlation Analysis to test if there was a positive correlation between total salary including incentive bonuses against the variables indicating the performance of the firm. Findings: The tests indicate a weak relationship between the CEO salary package and the key indicators of a firm's performance in Australian banks but a strong relationship in the German banks. Research limitations/implications: This study was limited in that it only covers the major banks in Australia and Germany and may therefore not be relevant to different countries with different economic climates. Practical implications: This study provides additional evidence to support the continued debate regarding the need to have greater accountability for CEO salary packages linked to actual performance measures of firms. Originality/value: This paper adds to the literature in so far as it compares two different Countries of the banking sector in a global market

Cloud computing : how does it differ from IT outsourcing and what are the implications for practice and research?

The purpose of this paper is to provide an evolutionary perspective of cloud computing (CC) by integrating two previously disparate literatures: CC and information technology outsourcing (ITO). We review the literature and develop a framework that highlights the demand for the CC service, benefits, risks, as well as risk mitigation strategies that are likely to influence the success of the service. CC success in organisations and as a technology overall is a function of (i) the outsourcing decision and supplier selection, (ii) contractual and relational governance, and (iii) industry standards and legal framework. Whereas CC clients have little control over standards and/or the legal framework, they are able to influence other factors to maximize the benefits while limiting the risks. This paper provides guidelines for (potential) cloud computing users with respect to the outsourcing decision, vendor selection, service-level-agreements, and other issues that need to be addressed when opting for CC services. We contribute to the literature by providing an evolutionary and holistic view of CC that draws on the extensive literature and theory of ITO. We conclude the paper with a number of research paths that future researchers can follow to advance the knowledge in this field.

Exploiting Web 2.0 technologies to forge live connectedness in class

The economics of supporting learning has seen institutional encouragement of a wide range of blended learning initiatives in face to face and online teaching and learning. This has become one of the key drivers for the adoption of technology in teaching, in a manner occassionally guilty of putting the cart before the horse. Learning spaces are increasingly equipped with a dizzying array of technological options testifying to institutional and governmental investment and commitment in supporting face to face blended learning (QUT, 2011, C/4.2). Yet innovation within traditional learning and teaching models faces a number of challenges both at an institutional level and at the teaching coal face. Web 2.0 technologies present a vast array of opportunities to harness and capture the attention of students in engaging learning opportunitites. This presentation will explore technologies supportive of active learning pedagogies.

Does project culture matter? A comparative study of two major hospital projects

Purpose - Cultural issues in the construction industry have attracted growing attention from both practitioners and academia. However, there are few studies on culture issues at the project level. The influence of project culture has not traditionally been on the research radar. This research aims to investigate the impacts of project culture on the performance of construction projects. Design/methodology/approach - A case study approach, utilising questionnaire surveys, in-depth interviews and review of project documents, was employed to investigate project culture and its associated impacts in two major hospital projects. Findings - The results indicated that project culture played an important role in achieving harmonious relationships between project participants and better project outcomes in terms of schedule, functionality, satisfaction with the process, satisfaction with the relationships, environmental issues addressed commercial success, further business opportunities and overall performance. Case 1 outperformed Case 2 in these performance indicators. Similarly, it became clear that the project’s culture should be developed from the outset and sustained during the project period. Furthermore, it was also highlighted that the project culture should be translated to all levels of the supply chain i.e. sub-contractors and suppliers. Practical implications – The findings enabled the client to understand the role of project culture and actively commit towards the development and maintenance of the project culture from very early on. It also helps project teams to understand how to deal with cultural issues at the project level. Originality/value- This study is one of limited empirical studies that offer in-depth insights of how project culture affects the performance of construction projects. It is also the first study of hospital projects on the research topic.