Freedom of information implications of information sharing networks for critical infrastructure protection

Protection of “critical infrastructure” has become a major issue for govern- ments worldwide. Yet in Australia, as in many other countries, including the United States, an estimated 90% of critical infrastructure is privately owned or operated commercially – in other words, critical infrastructure protection is not the exclusive domain of government. As a result, information sharing between government and the private sector has become a vitally important component of effective risk management. However, establishing effective arrangements of this kind between the public and private sector needs to take account of existing regimes of access and public disclosure which relate to government-held documents; in particular, that which is established by freedom of information (FOI) legislation. This article examines the extent to which the current Commonwealth FOI regime is likely to act as an impediment to the private sector operators of critical infrastructure participat- ing in government-operated information sharing arrangements. By examining developments in other jurisdictions, principally the United States, the article considers whether amendments to the current Australian FOI regime are necessary to ensure effective participation, consistent with the underlying object and purpose of FOI.

Valuing brand equity of a geographic region

There is much anecdotal evidence and academic argument that the location of a business influences its value. That is, some businesses appear to be worth more than others because of their location. This is particularly so in the tourism industry. Within the domain of the destination literature, many factors can be posited on why business valuation varies, ranging from access to markets, availability of labor, climate, and surrounding services. Given that business value is such a fundamental principle that underpins the viability of the tourist industry through its relationship with pricing, business acquisition, and investment, it is surprising that scant research has sought to quantify the relative premium associated with geographic locations. This study proposes a novel way in which to estimate geographic brand premium. Specifically, the approach translates valuation techniques from financial economics to quantify the incremental value derived from businesses operating in a particular geographic region, and produces a geographic brand premium. The article applies the technique to a well-known tourist destination in Australia, and the results are consistent with a positive value of brand equity in the key industries and are of a plausible order of magnitude. The article carries strong implications for business and tourism operators in terms of valuation, pricing, and investment, but more generally, the approach is potentially useful to local authorities and business associations when deciding how much resource and effort should be devoted to brand protection.

The use of Creative Commons licensing to enable open access to public sector information and publicly funded research results : an overview of recent Australian developments

This chapter provides an account of the use of Creative Commons (CC) licensing as a legally and operationally effective means by which governments can implement systems to enable open access to and reuse of their public sector information (PSI). It describes the experience of governments in Australia in applying CC licences to PSI in a context where a vast range of material and information produced, collected, commissioned of funded by government is subject to copyright. By applying CC licences, governments can give effect to their open access policies and create a public domain of PSI which is available for resue by other governmental agencies and the community at large.

Explaining usage of process modeling grammars : comparing three theoretical models in the study of two grammars

Our objective was to determine the factors that lead users to continue working with process modeling grammars after their initial adoption. We examined the explanatory power of three theoretical models of IT usage by applying them to two popular process modeling grammars. We found that a hybrid model of technology acceptance and expectation-confirmation best explained user intentions to continue using the grammars. We examined differences in the model results, and used them to provide three contributions. First, the study confirmed the applicability of IT usage models to the domain of process modeling. Second, we discovered that differences in continued usage intentions depended on the grammar type instead of the user characteristics. Third, we suggest implications and practice.

Modelling and execution of asset management process via workflow automation

An Asset Management (AM) life-cycle constitutes a set of processes that align with the development, operation and maintenance of assets, in order to meet the desired requirements and objectives of the stake holders of the business. The scope of AM is often broad within an organization due to the interactions between its internal elements such as human resources, finance, technology, engineering operation, information technology and management, as well as external elements such as governance and environment. Due to the complexity of the AM processes, it has been proposed that in order to optimize asset management activities, process modelling initiatives should be adopted. Although organisations adopt AM principles and carry out AM initiatives, most do not document or model their AM processes, let alone enacting their processes (semi-) automatically using a computer-supported system. There is currently a lack of knowledge describing how to model AM processes through a methodical and suitable manner so that the processes are streamlines and optimized and are ready for deployment in a computerised way. This research aims to overcome this deficiency by developing an approach that will aid organisations in constructing AM process models quickly and systematically whilst using the most appropriate techniques, such as workflow technology. Currently, there is a wealth of information within the individual domains of AM and workflow. Both fields are gaining significant popularity in many industries thus fuelling the need for research in exploring the possible benefits of their cross-disciplinary applications. This research is thus inspired to investigate these two domains to exploit the application of workflow to modelling and execution of AM processes. Specifically, it will investigate appropriate methodologies in applying workflow techniques to AM frameworks. One of the benefits of applying workflow models to AM processes is to adapt and enable both ad-hoc and evolutionary changes over time. In addition, this can automate an AM process as well as to support the coordination and collaboration of people that are involved in carrying out the process. A workflow management system (WFMS) can be used to support the design and enactment (i.e. execution) of processes and cope with changes that occur to the process during the enactment. So far few literatures can be found in documenting a systematic approach to modelling the characteristics of AM processes. In order to obtain a workflow model for AM processes commonalities and differences between different AM processes need to be identified. This is the fundamental step in developing a conscientious workflow model for AM processes. Therefore, the first stage of this research focuses on identifying the characteristics of AM processes, especially AM decision making processes. The second stage is to review a number of contemporary workflow techniques and choose a suitable technique for application to AM decision making processes. The third stage is to develop an intermediate ameliorated AM decision process definition that improves the current process description and is ready for modelling using the workflow language selected in the previous stage. All these lead to the fourth stage where a workflow model for an AM decision making process is developed. The process model is then deployed (semi-) automatically in a state-of-the-art WFMS demonstrating the benefits of applying workflow technology to the domain of AM. Given that the information in the AM decision making process is captured at an abstract level within the scope of this work, the deployed process model can be used as an executable guideline for carrying out an AM decision process in practice. Moreover, it can be used as a vanilla system that, once being incorporated with rich information from a specific AM decision making process (e.g. in the case of a building construction or a power plant maintenance), is able to support the automation of such a process in a more elaborated way.

Fiji pre-service primary teachers' understanding of physical science : a cultural perspective

Science and technology are promoted as major contributors to national development. Consequently, improved science education has been placed high on the agenda of tasks to be tackled in many developing countries, although progress has often been limited. In fact there have been claims that the enormous investment in teaching science in developing countries has basically failed, with many reports of how efforts to teach science in developing countries often result in rote learning of strange concepts, mere copying of factual information, and a general lack of understanding on the part of local students. These generalisations can be applied to science education in Fiji. Muralidhar (1989) has described a situation in which upper primary and middle school students in Fiji were given little opportunity to engage in practical work; an extremely didactic form of teacher exposition was the predominant method of instruction during science lessons. He concluded that amongst other things, teachers' limited understanding, particularly of aspects of physical science, resulted in their rigid adherence to the text book or the omission of certain activities or topics. Although many of the problems associated with science education in developing countries have been documented, few attempts have been made to understand how non-Western students might better learn science. This study addresses the issue of Fiji pre-service primary teachers' understanding of a key aspect of physical science, namely, matter and how it changes, and their responses to learning experiences based on a constructivist epistemology. Initial interviews were used to probe pre-service primary teachers' understanding of this domain of science. The data were analysed to identify students' alternative and scientific conceptions. These conceptions were then used to construct Concept Profile Inventories (CPI) which allowed for qualitative comparison of the concepts of the two ethnic groups who took part in the study. This phase of the study also provided some insight into the interaction of scientific information and traditional beliefs in non-Western societies. A quantitative comparison of the groups' conceptions was conducted using a Science Concept Survey instrument developed from the CPis. These data provided considerable insight into the aspects of matter where the pre-service teachers' understanding was particularly weak. On the basis of these preliminary findings, a six-week teaching program aimed at improving the students' understanding of matter was implemented in an experimental design with a group of students. The intervention involved elements of pedagogy such as the use of analogies and concept maps which were novel to most of those who took part. At the conclusion of the teaching programme, the learning outcomes of the experimental group were compared with those of a control group taught in a more traditional manner. These outcomes were assessed quantitatively by means of pre- and post-tests and a delayed post-test, and qualitatively using an interview protocol. The students' views on the various teaching strategies used with the experimental group were also sought. The findings indicate that in the domain of matter little variation exists in the alternative conceptions held by Fijian and Indian students suggesting that cultural influences may be minimal in their construction. Furthermore, the teaching strategies implemented with the experimental group of students, although largely derived from Western research, showed considerable promise in the context of Fiji, where they appeared to be effective in improving the understanding of students from different cultural backgrounds. These outcomes may be of significance to those involved in teacher education and curriculum development in other developing countries.

Re-thinking home economics : from modern to postmodern accounts of pedagogical bodies

Two perceptions of the marginality of home economics are widespread across educational and other contexts. One is that home economics and those who engage in its pedagogy are inevitably marginalised within patriarchal relations in education and culture. This is because home economics is characterised as women's knowledge, for the private domain of the home. The other perception is that only orthodox epistemological frameworks of inquiry should be used to interrogate this state of affairs. These perceptions have prompted leading theorists in the field to call for non-essentialist approaches to research in order to re-think the thinking that has produced this cul-de-sac positioning of home economics as a body of knowledge and a site of teacher practice. This thesis takes up the challenge of working to locate a space outside the frame of modernist research theory and methods, recognising that this shift in epistemology is necessary to unsettle the idea that home economics is inevitably marginalised. The purpose of the study is to reconfigure how we have come to think about home economics teachers and the profession of home economics as a site of cultural practice, in order to think it otherwise (Lather, 1991). This is done by exploring how the culture of home economics is being contested from within. To do so, the thesis uses a 'posthumanist' approach, which rejects the conception of the individual as a unitary and fixed entity, but instead as a subject in process, shaped by desires and language which are not necessarily consciously determined. This posthumanist project focuses attention on pedagogical body subjects as the 'unsaid' of home economics research. It works to transcend the modernist dualism of mind/body, and other binaries central to modernist work, including private/public, male/female,paid/unpaid, and valued/unvalued. In so doing, it refuses the simple margin/centre geometry so characteristic of current perceptions of home economics itself. Three studies make up this work. Studies one and two serve to document the disciplined body of home economics knowledge, the governance of which works towards normalisation of the 'proper' home economics teacher. The analysis of these accounts of home economics teachers by home economics teachers, reveals that home economics teachers are 'skilled' yet they 'suffer' for their profession. Further,home economics knowledge is seen to be complicit in reinforcing the traditional roles of masculinity and femininity, thereby reinforcing heterosexual normativity which is central to patriarchal society. The third study looks to four 'atypical'subjects who defy the category of 'proper' and 'normal' home economics teacher. These 'atypical' bodies are 'skilled' but fiercely reject the label of 'suffering'. The discussion of the studies is a feminist poststructural account, using Russo's (1994) notion of the grotesque body, which is emergent from Bakhtin's (1968) theory of the carnivalesque. It draws on the 'shreds' of home economics pedagogy,scrutinising them for their subversive, transformative potential. In this analysis, the giving and taking of pleasure and fun in the home economics classroom presents moments of surprise and of carnival. Foucault's notion of the construction of the ethical individual shows these 'atypical' bodies to be 'immoderate' yet striving hard to be 'continent' body subjects. This research captures moments of transgression which suggest that transformative moments are already embodied in the pedagogical practices of home economics teachers, and these can be 'seen' when re-looking through postmodemist lenses. Hence, the cultural practices ofhome economics as inevitably marginalised are being contested from within. Until now, home economics as a lived culture has failed to recognise possibilities for reconstructing its own field beyond the confines of modernity. This research is an example of how to think about home economics teachers and the profession as a reconfigured cultural practice. Future research about home economics as a body of knowledge and a site of teacher practice need not retell a simple story of oppression. Using postmodemist epistemologies is one way to provide opportunities for new ways of looking.

Art in early childhood : the discourse of 'proper' teaching

This thesis is a problematisation of the teaching of art to young children. To problematise a domain of social endeavour, is, in Michel Foucault's terms, to ask how we come to believe that "something ... can and must be thought" (Foucault, 1985:7). The aim is to document what counts (i.e., what is sayable, thinkable, feelable) as proper art teaching in Queensland at this point ofhistorical time. In this sense, the thesis is a departure from more recognisable research on 'more effective' teaching, including critical studies of art teaching and early childhood teaching. It treats 'good teaching' as an effect of moral training made possible through disciplinary discourses organised around certain epistemic rules at a particular place and time. There are four key tasks accomplished within the thesis. The first is to describe an event which is not easily resolved by means of orthodox theories or explanations, either liberal-humanist or critical ones. The second is to indicate how poststructuralist understandings of the self and social practice enable fresh engagements with uneasy pedagogical moments. What follows this discussion is the documentation of an empirical investigation that was made into texts generated by early childhood teachers, artists and parents about what constitutes 'good practice' in art teaching. Twenty-two participants produced text to tell and re-tell the meaning of 'proper' art education, from different subject positions. Rather than attempting to capture 'typical' representations of art education in the early years, a pool of 'exemplary' teachers, artists and parents were chosen, using "purposeful sampling", and from this pool, three videos were filmed and later discussed by the audience of participants. The fourth aspect of the thesis involves developing a means of analysing these texts in such a way as to allow a 're-description' of the field of art teaching by attempting to foreground the epistemic rules through which such teacher-generated texts come to count as true ie, as propriety in art pedagogy. This analysis drew on Donna Haraway's (1995) understanding of 'ironic' categorisation to hold the tensions within the propositions inside the categories of analysis rather than setting these up as discursive oppositions. The analysis is therefore ironic in the sense that Richard Rorty (1989) understands the term to apply to social scientific research. Three 'ironic' categories were argued to inform the discursive construction of 'proper' art teaching. It is argued that a teacher should (a) Teach without teaching; (b) Manufacture the natural; and (c) Train for creativity. These ironic categories work to undo modernist assumptions about theory/practice gaps and finding a 'balance' between oppositional binary terms. They were produced through a discourse theoretical reading of the texts generated by the participants in the study, texts that these same individuals use as a means of discipline and self-training as they work to teach properly. In arguing the usefulness of such approaches to empirical data analysis, the thesis challenges early childhood research in arts education, in relation to its capacity to deal with ambiguity and to acknowledge contradiction in the work of teachers and in their explanations for what they do. It works as a challenge at a range of levels - at the level of theorising, of method and of analysis. In opening up thinking about normalised categories, and questioning traditional Western philosophy and the grand narratives of early childhood art pedagogy, it makes a space for re-thinking art pedagogy as "a game oftruth and error" (Foucault, 1985). In doing so, it opens up a space for thinking how art education might be otherwise.

Getting that piece of paper : mental health nurses' experience of undertaking doctoral studies in Victoria, Australia

The aim of this study was to explore the experience of mental health nurses undertaking doctoral studies. The study was conducted in Victoria, Australia. A descriptive exploratory approach to inquiry was used for this study. Participants were mental health nurses who had successfully completed a doctoral qualification. Eligibility for inclusion required participants to be residing in Victoria (irrespective of where their doctoral studies were undertaken) and to have conducted their research within the domain of mental health and/or currently employed in the field of mental health nursing. Of the 20 potential participants invited, 16 accepted the invitation. Five emergent themes were explicated from narrative analyses. These themes were being a trail blazer, positioning for professional advancement, achieving a balance between competing priorities, maintaining a commitment to the development of the profession, and a point of affirmation. An understanding of the experience of undertaking doctoral studies can be used to influence the development of strategies to encourage more mental health nurses to consider undertaking a doctoral degree.

A snapshot of Australian nurse practitioners’ extended practice activities

Introduction The Australian Nurse Practitioner Project (AUSPRAC) was initiated to examine the introduction of nurse practitioners into the Australian health service environment. The nurse practitioner concept was introduced to Australia over two decades ago and has been evolving since. Today, however, the scope of practice, role and educational preparation of nurse practitioners is well defined (Gardner et al, 2006). Amendments to specific pre-existing legislation at a State level have permitted nurse practitioners to perform additional activities including some once in the domain of the medical profession. In the Australian Capital Territory, for example 13 diverse Acts and Regulations required amendments and three new Acts were established (ACT Health, 2006). Nurse practitioners are now legally authorized to diagnose, treat, refer and prescribe medications in all Australian states and territories. These extended practices differentiate nurse practitioners from other advanced practice roles in nursing (Gardner, Chang & Duffield, 2007). There are, however, obstacles for nurse practitioners wishing to use these extended practices. Restrictive access to Medicare funding via the Medicare Benefit Scheme (MBS) and the Pharmaceutical Benefit Scheme (PBS) limit the scope of nurse practitioner service in the private health sector and community settings. A recent survey of Australian nurse practitioners (n=202) found that two-thirds of respondents (66%) stated that lack of legislative support limited their practice. Specifically, 78% stated that lack of a Medicare provider number was ‘extremely limiting’ to their practice and 71% stated that no access to the PBS was ‘extremely limiting’ to their practice (Gardner et al, in press). Changes to Commonwealth legislation is needed to enable nurse practitioners to prescribe medication so that patients have access to PBS subsidies where they exist; currently patients with scripts which originated from nurse practitioners must pay in full for these prescriptions filled outside public hospitals. This report presents findings from a sub-study of Phase Two of AUSPRAC. Phase Two was designed to enable investigation of the process and activities of nurse practitioner service. Process measurements of nurse practitioner services are valuable to healthcare organisations and service providers (Middleton, 2007). Processes of practice can be evaluated through clinical audit, however as Middleton cautions, no direct relationship between these processes and patient outcomes can be assumed.

Queensland Aborigines, multiple realities and the social sources of suffering. Part 2: Suicide, spirits and symbolism

This is the second part of a paper that explores a range of magico-religious experiences such as immaterial voices and visions, in terms of local cultural, moral and socio-political circumstances in an Aboriginal town in rural Queensland. This part of the paper explores the political and cultural symbolism and meaning of suicide. It charts the saliency of suicide amongst two groups of kin and cohorts and the social meaningfulness and problematic of the voices and visions in relation to suicide, to identity and family forms and to funerals and a heavily drinking lifestyle. I argue that voices and visions are used to reinterpret social experience and to establish meaning and that tragically suicide evokes connectivity rather than anomie and here cannot be understood merely as an individualistic act or evidence of individual pathology. Rather it is about transformation and crossing a threshold to join an enduring domain of Aboriginality. In this life world, where family is the highest social value and where a relational view of persons holds sway, the individualistic practice of psychiatric and other helping professions, is a considerable problem.

Codes of conduct for mobile device use in meetings : an exploratory analysis

The present paper addresses the findings of a preliminary investigation into policy and codes of conduct pertaining to the use of laptops and PDA’s in business meetings. The purpose of this study was to conduct a review of policies or codes of conduct pertaining to the use of laptops and PDAs in meetings. The investigation included academic literature, policy searches in the public domain of the Internet, as well as personal contact with target industries (large corporations – N=1000 + employees). The results highlight the dearth of policy and codes of conducts pertaining to the use of laptops and PDA’s in business meetings. Consequently, given the growing interdependence between mobile technologies and the contemporary workplace, there exists an opportunity for communication professionals to further research and develop policy and codes of conduct in this area. Implications for corporate communication policies and practices are also discussed.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

Towards a model for the analysis and description of mathematical knowledge and understanding

Mathematics education literature has called for an abandonment of ontological and epistemological ideologies that have often divided theory-based practice. Instead, a consilience of theories has been sought which would leverage the strengths of each learning theory and so positively impact upon contemporary educational practice. This research activity is based upon Popper’s notion of three knowledge worlds which differentiates the knowledge shared in a community from the personal knowledge of the individual, and Bereiter’s characterisation of understanding as the individual’s relationship to tool-like knowledge. Using these notions, a re-conceptualisation of knowledge and understanding and a subsequent re-consideration of learning theories are proposed as a way to address the challenge set by literature. Referred to as the alternative theoretical framework, the proposed theory accounts for the scaffolded transformation of each individual’s unique understanding, whilst acknowledging the existence of a body of domain knowledge shared amongst participants in a scientific community of practice. The alternative theoretical framework is embodied within an operational model that is accompanied by a visual nomenclature with which to describe consensually developed shared knowledge and personal understanding. This research activity has sought to iteratively evaluate this proposed theory through the practical application of the operational model and visual nomenclature to the domain of early-number counting, addition and subtraction. This domain of mathematical knowledge has been comprehensively analysed and described. Through this process, the viability of the proposed theory as a tool with which to discuss and thus improve the knowledge and understanding with the domain of mathematics has been validated. Putting of the proposed theory into practice has lead to the theory’s refinement and the subsequent achievement of a solid theoretical base for the future development of educational tools to support teaching and learning practice, including computer-mediated learning environments. Such future activity, using the proposed theory, will advance contemporary mathematics educational practice by bringing together the strengths of cognitivist, constructivist and post-constructivist learning theories.

The factor V HR2 haplotype: Prevalence and association of the A4070G and A6755G polymorphisms

Recently, a polymorphism was identified in exon 25 of the factor V gene that is possibly a functional candidate for the HR2 haplotype. This haplotype is characterized by a single base substitution named R2 (A4070G) in the B domain of the protein. A mutation (A6755G; 2194Asp→Gly) located near the C terminus has been hypothesized to influence protein folding and glycosylation, and might be responsible for the shift in factor V isoform (FV1 / FV2) ratio. This study investigated the prevalence of these two factor V HR2 haplotype polymorphisms in a cohort of normal blood donors, patients with osteoarthritis and women with complications during pregnancy, and in families of factor V Leiden individuals. A high allele frequency for the two polymorphisms was found in the blood donor group (6.2% R2, 5.6% A6755G). No significant difference in allele frequency was observed in the clinical groups (obstetric complications and osteoarthritis, 4.1-4.9% for the two polymorphisms) when compared with that of healthy blood donors. We confirm that the factor V A6755G polymorphism shows strong linkage to the R2 allele, although it is not exclusively inherited with the exon 13 A4070G variant and can occur independently. © 2001 Lippincott Williams & Wilkins.