A two-compartment mechanochemical model of the roles of transforming growth factor-beta and tissue tension in dermal wound healing

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor-beta (TGF-beta) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF-beta and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF-beta in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF-beta significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures.

Closing the gap : the next steps for the interaction of corporate reputation and psychological contract development

With an increasing body of literature linking the human resource management and marketing fields, one area receiving increased academic attention is how an organisation’s corporate reputation can be managed to attract potential recruits and shape their employment expectations through their psychological contracts. This paper seeks to enhance current models which focus on the interrelationship of corporate reputation and psychological contract theory. It is argued that a number of factors need to be considered in order the build a firmer foundation for such a theory. Firstly, a common understanding of the psychological contract needs to be established such that the focus on either expectations or promises is clarified. Secondly, the included components of the psychological contract need to be considered in light of their empirical founding and their relationship with one another. Thirdly, the interrelationship of corporate reputation, employer branding, identity and image needs to be explicated within the context of how they both influence and interrelate with the psychological contract. The final consideration surrounds the opportunity for potential employees to be considered within the corporate reputation literature as a significant stakeholder group.

Tracking employees’ twists and turns : a mixed methods approach to assessing change in the psychological contract

The psychological contract has emerged over the past 60 years as a key analytical device for both academics and practitioners to conceptualise and explain the employment relationship. However, despite the recognised import of this field, some authors suggest it has fallen into a ‘methodological rut’ and is neglecting to empirically assess basic theoretical tenets of the concept – such as the temporal and individualised, subjective nature of the construct. This paper describes the research design of a longitudinal, mixed methods study to explore development and change in the psychological contract and outline how the use of individual growth modelling can be a powerful tool in analysing the type of quantitative data collected. Finally, by briefly outlining the benefits of this approach, the paper seeks to offer an alternative methodology to explore the dynamic and intra-individual processes within the psychological contract domain.

Expectations, obligations or promises? A conceptual review and revision of the beliefs comprising the psychological contract

The psychological contract is a frequently deployed construct to examine the dynamics of the employee-employer exchange relationship. While there is consensus that the contract comprises employee and employer beliefs regarding this relationship, the various belief types are not conceptually well-defined and understood. Over time, the contract has been conceptualised as comprising expectations, obligations, promises or some combination therein. While most contemporary researchers focus solely upon promises, the justifications for this position are unpersuasive. This paper theoretically describes the various belief types, identifies their interrelationships and proposes a reconceptualisation of the beliefs constituting the contract. Specifically, it is demonstrated that the extant promise-based belief framework provides too restrictive a theoretical base for a comprehensive understanding of individuals’ psychological contracts.

The hydrodynamic and capture/retention performance of a gross pollutant trap

This research shows that gross pollutant traps (GPTs) continue to play an important role in preventing visible street waste—gross pollutants—from contaminating the environment. The demand for these GPTs calls for stringent quality control and this research provides a foundation to rigorously examine the devices. A novel and comprehensive testing approach to examine a dry sump GPT was developed. The GPT is designed with internal screens to capture gross pollutants—organic matter and anthropogenic litter. This device has not been previously investigated. Apart from the review of GPTs and gross pollutant data, the testing approach includes four additional aspects to this research, which are: field work and an historical overview of street waste/stormwater pollution, calibration of equipment, hydrodynamic studies and gross pollutant capture/retention investigations. This work is the first comprehensive investigation of its kind and provides valuable practical information for the current research and any future work pertaining to the operations of GPTs and management of street waste in the urban environment. Gross pollutant traps—including patented and registered designs developed by industry—have specific internal configurations and hydrodynamic separation characteristics which demand individual testing and performance assessments. Stormwater devices are usually evaluated by environmental protection agencies (EPAs), professional bodies and water research centres. In the USA, the American Society of Civil Engineers (ASCE) and the Environmental Water Resource Institute (EWRI) are examples of professional and research organisations actively involved in these evaluation/verification programs. These programs largely rely on field evaluations alone that are limited in scope, mainly for cost and logistical reasons. In Australia, evaluation/verification programs of new devices in the stormwater industry are not well established. The current limitations in the evaluation methodologies of GPTs have been addressed in this research by establishing a new testing approach. This approach uses a combination of physical and theoretical models to examine in detail the hydrodynamic and capture/retention characteristics of the GPT. The physical model consisted of a 50% scale model GPT rig with screen blockages varying from 0 to 100%. This rig was placed in a 20 m flume and various inlet and outflow operating conditions were modelled on observations made during the field monitoring of GPTs. Due to infrequent cleaning, the retaining screens inside the GPTs were often observed to be blocked with organic matter. Blocked screens can radically change the hydrodynamic and gross pollutant capture/retention characteristics of a GPT as shown from this research. This research involved the use of equipment, such as acoustic Doppler velocimeters (ADVs) and dye concentration (Komori) probes, which were deployed for the first time in a dry sump GPT. Hence, it was necessary to rigorously evaluate the capability and performance of these devices, particularly in the case of the custom made Komori probes, about which little was known. The evaluation revealed that the Komori probes have a frequency response of up to 100 Hz —which is dependent upon fluid velocities—and this was adequate to measure the relevant fluctuations of dye introduced into the GPT flow domain. The outcome of this evaluation resulted in establishing methodologies for the hydrodynamic measurements and gross pollutant capture/retention experiments. The hydrodynamic measurements consisted of point-based acoustic Doppler velocimeter (ADV) measurements, flow field particle image velocimetry (PIV) capture, head loss experiments and computational fluid dynamics (CFD) simulation. The gross pollutant capture/retention experiments included the use of anthropogenic litter components, tracer dye and custom modified artificial gross pollutants. Anthropogenic litter was limited to tin cans, bottle caps and plastic bags, while the artificial pollutants consisted of 40 mm spheres with a range of four buoyancies. The hydrodynamic results led to the definition of global and local flow features. The gross pollutant capture/retention results showed that when the internal retaining screens are fully blocked, the capture/retention performance of the GPT rapidly deteriorates. The overall results showed that the GPT will operate efficiently until at least 70% of the screens are blocked, particularly at high flow rates. This important finding indicates that cleaning operations could be more effectively planned when the GPT capture/retention performance deteriorates. At lower flow rates, the capture/retention performance trends were reversed. There is little difference in the poor capture/retention performance between a fully blocked GPT and a partially filled or empty GPT with 100% screen blockages. The results also revealed that the GPT is designed with an efficient high flow bypass system to avoid upstream blockages. The capture/retention performance of the GPT at medium to high inlet flow rates is close to maximum efficiency (100%). With regard to the design appraisal of the GPT, a raised inlet offers a better capture/retention performance, particularly at lower flow rates. Further design appraisals of the GPT are recommended.

The formation of, and change in, the psychological contracts of graduates entering the Queensland public sector

The workplace is evolving and the predicted impact of demographic changes (Salt, 2009; Taylor, 2005) has seen organisations focus on strategic workforce planning. As part of this, many organisations have established or expanded formalised graduate programs to attract graduates and transition them effectively into organisations (McDermott, Mangan, & O'Connor, 2005; Terjesen, Freeman, & Vinnicombe, 2007). The workplace context is also argued to be changing because of the divergence in preferences and priorities across the different generations in the workplace - a topic which is prolific in the popular culture media but is yet to be fully developed in the academic literature (Jorgenson, 2003). The public sector recruits large numbers of graduates and maintains well established graduate programs. Like the workplace context, the public sector is seen to be undergoing a transition to more closely align its practices and processes with that of the private sector (Haynes & Melville Jones, 1999; N. Preston, 1995). Consequently, questions have been raised as to how new workforce entrants see the public sector and its associated attractiveness as an employment option. This research draws together these issues and reviews the formation of, and change in, the psychological contracts of graduates across ten Queensland public sector graduate programs. To understand the employment relationship, the theories of psychological contract and public service motivation are utilised. Specifically, this research focuses on graduates' and managers' expectations over time, the organisational perspective of the employment relationship and how ideology influences graduates' psychological contract. A longitudinal mixed method design, involving individual interviews and surveys, is employed along with significant researcher-practitioner collaboration throughout the research process. A number of important qualitative and quantitative findings arose from this study and there was strong triangulation between results from the two methods. Prior to starting with the organisation, graduates found it difficult to articulate their expectations; however, organisational experience rapidly brought these to the fore. Of the expectations that became salient, most centred on their relationship with their supervisor. Without experience and quality information on which to base their expectations, graduates tended to over-rely on sectoral stereotypes which negatively impacted their psychological contracts. Socialisation only limited affected graduates' psychological contracts and public service motivation. The graduate survey, measured thrice throughout the first 12 months of the graduate program, revealed that the psychological contract and public service motivation results followed a similar trajectory of beginning at mediocre levels, declining between times one and two and increasing between times two and three (although this is not back to original levels). Graduates attributed these to a number of sectoral, organisational, team, supervisory and individual factors. On a theoretical level, this research provides support for the notion of ideology within the psychological contract although it raises some important questions about how it is conceptualised. Additionally, support is given for the manager to be seen as the primary organisational counterpart to the employee in future theoretical and practical work. The research also argues to extend current notions of time within the psychological contract as this seems to be the most divergent and combustible issue across the generations in terms of how the workplace is perceived. A number of practical implications also transpire from the study and the collaborative foundation was highly successful. It is anticipated that this research will make a meaningful contribution to both the theory and practice of the employment relationship with particular regard to graduates entering the public sector.

The role of emotional labour and role stress on burnout and psychological strain in high contact service employees

This study examines the relationships between job demands (in the form of role stressors and emotional management) and employee burnout amongst high contact service employees. Employees in customer facing roles are frequently required to manage overwhelming, conflicting or ambiguous demands, which they may feel ill-equipped to handle. Simultaneously, they must manage the emotions they display towards customers, suppressing some, and expressing others, be they genuine or contrived. If the in-role effort required of employees exceeds their inherent capacity to cope, burnout may result. Burnout, in turn, can have serious detrimental consequences for the psychological well being of employees. We find that both emotional management and role stressors impact burnout. We also confirm that burnout predicts psychological strain. In line with the Job Demands and Resources Model, we examine the mitigating impact of perceived support on these relationships but do not find a significant mitigating impact.

Departures from tradition : the early years learning framework for Australia

In 2009, the Commonwealth Government of Australia published the first national learning framework for use with children aged birth to five years. The framework marks a departure from tradition in that it emphasizes intentional teaching, learning as well as child development, a particular type of play-based learning, outcomes, and equity. This article analyzes aspects of the document that depart from well established approaches to early childhood education in Australia and identifies challenges for educators who are required to use the document. It concludes that ongoing and supportive professional learning opportunities must accompany the introduction and enactment of the document.

Hoodie-wearing Hamlet mixes horror with humour in a play for our times [REVIEW]

Hamlet By Shakespeare. La Boite Theatre Company, Brisbane, February 10 LA Boite Theatre Company begins this year's season with a new look, a new logo and a new interpretation of Hamlet directed by artistic director David Berthold. In this production, Berthold contemporises Shakespeare's tragedy by focusing on the family relationships and introducing modern references in the set, sound and costume design: this Hamlet wears jeans and a hoodie.

Environmental aspects and challenges of oilseed produced biodiesel in Southeast Asia

Research on alternative fuel for the vehemently growing number of automotivesis intensified due to environmental reasons rather than turmoil in energy price and supply. From the policy and steps to emphasis the use of biofuel by governments all around the world, this can be comprehended that biofuel have placed itself as a number one substitute for fossil fuels. These phenomena made Southeast Asia a prominent exporter of biodiesel. But thrust in biodiesel production from oilseeds of palm and Jatropha curcas in Malaysia, Indonesia and Thailand is seriously threatening environmental harmony. This paper focuses on this critical issue of biodiesels environmental impacts, policy, standardization of this region as well as on the emission of biodiesel in automotive uses. To draw a bottom line on feasibilities of different feedstock of biodiesel, a critical analysis on oilseed yield rate, land use, engine emissions and oxidation stability is reviewed. Palm oil based biodiesel is clearly ahead in all these aspects of feasibility, except in the case of NOx where it lags from conventional petro diesel.

Dropout from internet-based treatment for psychological disorders

Purpose: The purpose of this review was to present an in-depth analysis of literature identifying the extent of dropout from Internet-based treatment programmes for psychological disorders, and literature exploring the variables associated with dropout from such programmes. ----- ----- Methods: A comprehensive literature search was conducted on PSYCHINFO and PUBMED with the keywords: dropouts, drop out, dropout, dropping out, attrition, premature termination, termination, non-compliance, treatment, intervention, and program, each in combination with the key words Internet and web. A total of 19 studies published between 1990 and April 2009 and focusing on dropout from Internet-based treatment programmes involving minimal therapist contact were identified and included in the review. ----- ----- Results: Dropout ranged from 2 to 83% and a weighted average of 31% of the participants dropped out of treatment. A range of variables have been examined for their association with dropout from Internet-based treatment programmes for psychological disorders. Despite the numerous variables explored, evidence on any specific variables that may make an individual more likely to drop out of Internet-based treatment is currently limited. ----- ----- Conclusions: This review highlights the need for more rigorous and theoretically guided research exploring the variables associated with dropping out of Internet-based treatment for psychological disorders.

Dialogical mindfulness in supervision role-play

Aims: This exploratory pilot study investigated Mindfulness-based Role-play (MBRP) supervision to find out how therapists would experience the approach, and to what extent they would find it useful, particularly in relation to empathy toward clients. Method: Thirteen therapists participated in a workshop, introducing mindfulness and MBRP supervision, and subsequently had one individual MBRP supervision session. Data collection and analysis: Qualitative data were collected by means of semi-structured interviews and analysed with regard to participants' supervision experiences by means of a modified version of the Consensual Qualitative Research method. Findings: Participants predominantly had positive emotional and cognitive responses to their supervision experiences. The main supervision outcomes were empathy with the client's emotional experience, enhanced awareness of functioning as a therapist, and thoughts about how to proceed in therapy. A subset of participants also reported observed effects in therapy with clients. Conclusions: Even taking into account the methodological limitations of the study, these findings are promising and suggest that further research into the MBRP supervision approach is warranted.

Alternative dispute resolution : are apology and forgiveness simply two sides of the one coin?

Alternative dispute resolution (a.d.r.) processes are entrenched in western style legal systems. Forms of dispute resolution are utilised within schools and health systems; built in to commercial contracts; found in workplaces, clubs and organisations; and accepted in general day-to-day community disputes. The a.d.r. literature includes references to ‘apology’, but is largely silent on ‘forgiveness’. Where an apology is offered as part of a dispute resolution process, practice suggests that formalised ‘forgiveness’ rarely follows. Mediators may agree there is a meaningful place for apology in dispute resolution processes, but are most unlikely to support a view that forgiveness, as a conscious act, has an equivalent place. Yet, if forgiveness is not limited to the ‘pardoning of an offence’, but includes a ‘giving up of resentment’, or the relinquishing of a grudge, then forgiveness may play an underestimated role in dispute management. In the context of some day-to-day dispute management practice, this paper questions whether forgiveness should follow an apology; and concludes that meaningful resolutions can be reached without any formal element of ‘forgiveness’ or absolution. However, dispute management practitioners need to be aware of the latent role other aspects of forgiveness may play for the disputing parties.

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.

Ecological aspects of biosecurity surveillance design for the detection of multiple invasive animal species

Complex surveillance problems are common in biosecurity, such as prioritizing detection among multiple invasive species, specifying risk over a heterogeneous landscape, combining multiple sources of surveillance data, designing for specified power to detect, resource management, and collateral effects on the environment. Moreover, when designing for multiple target species, inherent biological differences among species result in different ecological models underpinning the individual surveillance systems for each. Species are likely to have different habitat requirements, different introduction mechanisms and locations, require different methods of detection, have different levels of detectability, and vary in rates of movement and spread. Often there is a further challenge of a lack of knowledge, literature, or data, for any number of the above problems. Even so, governments and industry need to proceed with surveillance programs which aim to detect incursions in order to meet environmental, social and political requirements. We present an approach taken to meet these challenges in one comprehensive and statistically powerful surveillance design for non-indigenous terrestrial vertebrates on Barrow Island, a high conservation nature reserve off the Western Australian coast. Here, the possibility of incursions is increased due to construction and expanding industry on the island. The design, which includes mammals, amphibians and reptiles, provides a complete surveillance program for most potential terrestrial vertebrate invaders. Individual surveillance systems were developed for various potential invaders, and then integrated into an overall surveillance system which meets the above challenges using a statistical model and expert elicitation. We discuss the ecological basis for the design, the flexibility of the surveillance scheme, how it meets the above challenges, design limitations, and how it can be updated as data are collected as a basis for adaptive management.