The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Investigating knowledge transfer through transnational programs between Indonesian and Australian universities : A conceptual framework

Globalization stimulated demand for transnational higher education. However, little is known about how transnational programs can facilitate knowledge transfer between the partner universities—something that is often implied in the partnership arrangement. For the purpose of this paper transnational programs will be limited to dual degree programs between Indonesian and Australian universities, which, in recent years have been rising. Nevertheless, the discussion and synthesis may have value to other transnational programs. Situating the knowledge transfer in the wider context of globalization of higher education and the current reforms in Indonesian education, the paper acknowledges the tension between the need to generate revenue and the ideals of facilitating knowledge transfer and capacity development for Indonesian universities. Drawing on a detailed review of research findings in the business and education sector literature, this paper presents a conceptual framework that may be used to analyze knowledge transfer between Indonesian and Australian universities. Such investigations delineate the significant drivers underlying transnational programs for supporting knowledge transfer. The proposed framework incorporates the types of knowledge, knowledge transfer mechanisms, and the processes. It also considers how the inter-university antecedents may affect the potential for knowledge transfer between the universities. A discussion of how the framework may be used to implemented knowledge transfer concludes this paper.

Dynamic optimization of migration topology in internet-based distributed genetic algorithms

Distributed Genetic Algorithms (DGAs) designed for the Internet have to take its high communication cost into consideration. For island model GAs, the migration topology has a major impact on DGA performance. This paper describes and evaluates an adaptive migration topology optimizer that keeps the communication load low while maintaining high solution quality. Experiments on benchmark problems show that the optimized topology outperforms static or random topologies of the same degree of connectivity. The applicability of the method on real-world problems is demonstrated on a hard optimization problem in VLSI design.

Transnational higher education programs for facilitating inter-university knowledge transfer : University of Indonesia’s experience

This paper explores the impacts and extent of knowledge transfer (KT) in an undergraduate engineering transnational program with an Australian university partner at the University of Indonesia (UI) using an inter-university KT conceptual framework (Sutrisno, Lisana, & Pillay 2012). For the purpose of this paper, the opportunity for KT in curriculum design is examined. Given the explicit nature of curriculum knowledge, assessing each partner’s curriculum was pivotal in allowing UI to enrich its own curriculum. The KT mechanism of face-to-face contact between Indonesian and Australian academics led to not only transfer of knowledge related to the curriculum of the undergraduate program but also to other cooperation beyond the transnational program in the form of joint research and joint supervision of post-graduate theses. Positive inter-university dynamics, such as trust and willingness to work together between the partners were underpinned by the presence of key actors from both sides at the earlier stages of the partnership. Retrospectively exploring the KT process in the UI’s transnational programs with its Australian partner suggests that there have been both structured and unstructured mechanisms, highlighting the ubiquitous and unbounded nature of KT between universities. While initially successful in facilitating KT, due to rapid succession of persons in charge of the program and the increasing focus on revenue generation, the useful lessons and practices unfortunately are being lost. Although the intention to use the transnational program for KT was always implied, it gradually was overlooked by newer staff members. Based on UI’s experience as the first provider of transnational program in Indonesia and other similar cases in China, seemingly transnational programs driven by short-term immediate financial return are unsuccessful in facilitating KT due to sensitivities to unfavourable economic situation. Those that remain operational and contribute to knowledge exchange between the partners apparently have genuine long-term engagement objective.

Higher education for capacity development or revenue maximisation? Lessons from transnational higher education programs at two Indonesian universities

HE has been changing rapidly due to globalisation that has increased the interconnectedness between nations and people throughout the world (Mok, 2012). As HE has manifested into different forms and governed by competing rationales in recent years, this paper focuses on transnational HE, which is an example of the interconnectedness of universities beyond the national borders. Indonesia is also influenced by the above changes. It took part in free-trade agreements that include HE as a sector to be liberated and accessed by international providers (Nizam, 2006). Indonesian universities found themselves bracing for the global competition for students and simultaneously having to improve their quality in order to survive amidst the growing competition. This competition gave birth to joint transnational HE programs with overseas partners among many Indonesian universities (Macaranas, 2010).

Urban renewal, migration and memories : the affordances of place-based pedagogies for developing immigrant students’ literate repertoires

This paper reports on the new literacy demands in the middle years of schooling project in which the affordances of placed-based pedagogy are being explored through teacher inquiries and classroom-based design experiments. The school is located within a large-scale urban renewal project in which houses are being demolished and families relocated. The original school buildings have recently been demolished and replaced by a large ‘superschool’ which serves a bigger student population from a wider area. Drawing on both quantitative and qualitative data, the teachers reported that the language literacy learning of students (including a majority of students learning English as a second language) involved in the project exceeded their expectations. The project provided the motivation for them to develop their oral language repertoires, by involving them in processes such as conducting interviews with adults for their oral histories, through questioning the project manager in regular meetings, and through reporting to their peers and the wider community at school assemblies. At the same time students’ written and multimodal documentation of changes in the neighbourhood and the school grounds extended their literate and semiotic repertoires as they produced books, reports, films, powerpoints, visual designs and models of structures.

Negotiating teacher identities : dialogic reflections on classroom interaction in a transnational context

This study investigates the development of teacher identity in a transnational context through an analysis of the voices of sixteen preservice teachers from Hong Kong who engage in interaction with primary students in an Australian classroom. The context for this research is the school-based experience undertaken by these preservice English as a second language teachers as part of their short language immersion (SLIM) program in Brisbane, Australia. Such SLIM programs are a genre of study abroad programs which have been gaining in popularity within teacher education in Australia, attended by preservice and inservice teachers from China, Hong Kong, Korea, and other Asian countries. This research is conducted at a time when the imperative to globalise higher education provision is a strategic factor in the educational policies of both Australia and Hong Kong. In Australia, international educational services now constitute the country’s third largest export with more than 400,000 students coming to Australia to study annually. In order to maintain Australia’s current global position as the third most popular Englishspeaking study destination, the government is now focusing on sustainability and the quality of the study experience being offered to international students (Bradley Review, 2008). In Hong Kong, the government sponsors both preservice and inservice English as a second language (ESL) teachers to undertake SLIM programs in Australia and other English-speaking countries, as part of their policy of promoting high levels of English proficiency in Hong Kong classrooms. Transnational teacher education is an important issue to which this study contributes insights into the affordances and constraints of a school-based experience in the transnational context. Second language teacher education has been defined as interventions designed to develop participants’ professional knowledge. In this study, it is argued that participation in a different community of practice helps to foreground tacit theories of second language pedagogy, making them visible and open to review. Questions of pedagogy are also seen as questions of teacher identity, constituting the way that one is in the classroom. I take up a sociocultural and poststructural framework, drawing on the work of James Gee and Mikhail Bakhtin, to theorise the construction of teacher identity as emerging through dialogic relations and socially situated discursive practices. From this perspective, this study investigates whether these teachers engage with different ways of representing themselves through appropriating, adapting or rejecting Discourses prevailing in the Australian classroom. Research suggests that reflecting on dilemmas encountered as lived experiences can extend professional understandings. In this study, the participants engage in a process of dialogic reflection on their intercultural classroom interactions, examining with their peers and their lecturer/researcher selected moments of dissonance that they have faced in the unfamiliar context of an Australian primary classroom. It is argued that the recursive and multivoiced nature of this process of reflection on practice allows participants opportunities to negotiate new understandings of second language teacher identity. Dialogic learning, based on the theories of Bakhtin and Vygotsky, provides the theoretic framing not only for the process of reflection instantiated in this study, but also features in the analysis of the participants’ second language classroom practices. The research design uses a combined discourse analytic and ethnographic approach as a logic-of-inquiry to explore the dialogic relationships which these second language teachers negotiate with their students and their peers in the transnational context. In this way, through discourse analysis of their classroom talk and reflective dialogues, assisted by the analytic tools of speech genres and discourse formats, I explore the participants’ ways of doing and being second language teachers. Thus, this analysis traces the process of ideological becoming of these beginner teachers as shifts in their understandings of teacher and student identities. This study also demonstrates the potential for a nontraditional stimulated recall interview to provide dialogic scaffolding for beginner teachers to reflect productively on their practice.

Transnational field experience : making the familiar strange

This study explores the impact of field experience in Australian primary classrooms on the developing professional identities of Malaysian pre-service teachers. This group of 24 Malaysian students are undertaking their Bachelor of Education in Teaching English as a Foreign Language (BEd TESL) at an Australian university, as part of a transnational twinning program. The globalisation of education has seen an increase in such transnational school experiences for pre-service teachers, with the aim of extending professional experience and intercultural competence by engaging in communities of practice beyond the local (Tsui 2005, Luke 2004). Despite overseas governments, such as Malaysia, having sponsored multimillion dollar twinning programs for their pre-service teachers, there is a lack of research regarding the outcomes of transnational professional practice within such programs. This study adopts a qualitative approach focusing on participants’ narratives as revealed in their reflective writing and through semi-structured interviews. Adopting a Bakhtinian framework, this research uses the concept of ‘voice’ to explore how pre-service teachers negotiate their identities as EFL teachers in response to their lived professional experiences (Bakhtin 1981, 1986). Encountering different cultural and educational practices in their transnational field experiences can lead pre-service teachers to question taken-for-granted practices that they have grown up with. This has been described as a process of making the familiar strange, and can lead to a shift in professional understandings. This study investigates how such questioning occurs and how the transnational field experience is perceived by the participants as contributing to their developing professional identities.

Travelling waves for a velocity–jump model of cell migration and proliferation

Cell invasion, characterised by moving fronts of cells, is an essential aspect of development, repair and disease. Typically, mathematical models of cell invasion are based on the Fisher–Kolmogorov equation. These traditional parabolic models can not be used to represent experimental measurements of individual cell velocities within the invading population since they imply that information propagates with infinite speed. To overcome this limitation we study combined cell motility and proliferation based on a velocity–jump process where information propagates with finite speed. The model treats the total population of cells as two interacting subpopulations: a subpopulation of left–moving cells, $L(x,t)$, and a subpopulation of right–moving cells, $R(x,t)$. This leads to a system of hyperbolic partial differential equations that includes a turning rate, $\Lambda \ge 0$, describing the rate at which individuals in the population change direction of movement. We present exact travelling wave solutions of the system of partial differential equations for the special case where $\Lambda = 0$ and in the limit that $\Lambda \to \infty$. For intermediate turning rates, $0 < \Lambda < \infty$, we analyse the travelling waves using the phase plane and we demonstrate a transition from smooth monotone travelling waves to smooth nonmonotone travelling waves as $\Lambda$ decreases through a critical value $\Lambda_{crit}$. We conclude by providing a qualitative comparison between the travelling wave solutions of our model and experimental observations of cell invasion. This comparison indicates that the small $\Lambda$ limit produces results that are consistent with experimental observations.

Sensitivity of edge detection methods for quantifying cell migration assays

Quantitative imaging methods to analyze cell migration assays are not standardized. Here we present a suite of two–dimensional barrier assays describing the collective spreading of an initially–confined population of 3T3 fibroblast cells. To quantify the motility rate we apply two different automatic image detection methods to locate the position of the leading edge of the spreading population after 24, 48 and 72 hours. These results are compared with a manual edge detection method where we systematically vary the detection threshold. Our results indicate that the observed spreading rates are very sensitive to the choice of image analysis tools and we show that a standard measure of cell migration can vary by as much as 25% for the same experimental images depending on the details of the image analysis tools. Our results imply that it is very difficult, if not impossible, to meaningfully compare previously published measures of cell migration since previous results have been obtained using different image analysis techniques and the details of these techniques are not always reported. Using a mathematical model, we provide a physical interpretation of our edge detection results. The physical interpretation is important since edge detection algorithms alone do not specify any physical measure, or physical definition, of the leading edge of the spreading population. Our modeling indicates that variations in the image threshold parameter correspond to a consistent variation in the local cell density. This means that varying the threshold parameter is equivalent to varying the location of the leading edge in the range of approximately 1–5% of the maximum cell density.

Cell migration and proliferation on homogeneous and non-homogeneous domains : modelling on the scale of individuals and populations

Cell migration is a behaviour critical to many key biological effects, including wound healing, cancerous cell invasion and morphogenesis, the development of an organism from an embryo. However, given that each of these situations is distinctly different and cells are extremely complicated biological objects, interest lies in more basic experiments which seek to remove conflating factors and present a less complex environment within which cell migration can be experimentally examined. These include in vitro studies like the scratch assay or circle migration assay, and ex vivo studies like the colonisation of the hindgut by neural crest cells. The reduced complexity of these experiments also makes them much more enticing as problems to mathematically model, like done here. The primary goal of the mathematical models used in this thesis is to shed light on which cellular behaviours work to generate the travelling waves of invasion observed in these experiments, and to explore how variations in these behaviours can potentially predict differences in this invasive pattern which are experimentally observed when cell types or chemical environment are changed. Relevant literature has already identified the difficulty of distinguishing between these behaviours when using traditional mathematical biology techniques operating on a macroscopic scale, and so here a sophisticated individual-cell-level model, an extension of the Cellular Potts Model (CPM), is been constructed and used to model a scratch assay experiment. This model includes a novel mechanism for dealing with cell proliferations that allowed for the differing properties of quiescent and proliferative cells to be implemented into their behaviour. This model is considered both for its predictive power and used to make comparisons with the travelling waves which result in more traditional macroscopic simulations. These comparisons demonstrate a surprising amount of agreement between the two modelling frameworks, and suggest further novel modifications to the CPM that would allow it to better model cell migration. Considerations of the model’s behaviour are used to argue that the dominant effect governing cell migration (random motility or signal-driven taxis) likely depends on the sort of invasion demonstrated by cells, as easily seen by microscopic photography. Additionally, a scratch assay simulated on a non-homogeneous domain consisting of a ’fast’ and ’slow’ region is also used to further differentiate between these different potential cell motility behaviours. A heterogeneous domain is a novel situation which has not been considered mathematically in this context, nor has it been constructed experimentally to the best of the candidate’s knowledge. Thus this problem serves as a thought experiment used to test the conclusions arising from the simulations on homogeneous domains, and to suggest what might be observed should this non-homogeneous assay situation be experimentally realised. Non-intuitive cell invasion patterns are predicted for diffusely-invading cells which respond to a cell-consumed signal or nutrient, contrasted with rather expected behaviour in the case of random-motility-driven invasion. The potential experimental observation of these behaviours is demonstrated by the individual-cell-level model used in this thesis, which does agree with the PDE model in predicting these unexpected invasion patterns. In the interest of examining such a case of a non-homogeneous domain experimentally, some brief suggestion is made as to how this could be achieved.

Fractional models for the migration of biological cells in complex spatial domains

Travelling wave phenomena are observed in many biological applications. Mathematical theory of standard reaction-diffusion problems shows that simple partial differential equations exhibit travelling wave solutions with constant wavespeed and such models are used to describe, for example, waves of chemical concentrations, electrical signals, cell migration, waves of epidemics and population dynamics. However, as in the study of cell motion in complex spatial geometries, experimental data are often not consistent with constant wavespeed. Non-local spatial models have successfully been used to model anomalous diffusion and spatial heterogeneity in different physical contexts. In this paper, we develop a fractional model based on the Fisher-Kolmogoroff equation and analyse it for its wavespeed properties, attempting to relate the numerical results obtained from our simulations to experimental data describing enteric neural crest-derived cells migrating along the intact gut of mouse embryos. The model proposed essentially combines fractional and standard diffusion in different regions of the spatial domain and qualitatively reproduces the behaviour of neural crest-derived cells observed in the caecum and the hindgut of mouse embryos during in vivo experiments.

Transnational organised environmental crime

Transnational environmental crime must become a government priority, as organised criminal networks continue to exploit the environment with unprecedented profits. Such earnings come at a substantial social, economic and environmental expense for communities and their livelihoods. Indeed, organised environmental crime is identified by the United Nations as a key factor in the impoverishment, displacement and violent conflicts affecting millions of people — notably in developing societies.2 It is widely recognised that organised environmental crime syndicates, motivated by substantial financial rewards, continue to flourish and expand in disadvantaged societies with porous borders, where corruption is widespread and regulation is poor. The theft of biodiversity and the demise of animal species and habitats have resulted not only in financial loss, but also in an increase in “environmental refugees” — people dislocated and forced to migrate due to loss of livelihoods.

Transnational organized crime in Oceania

Oceania has a relatively low level of crime prevalence yet in the smaller and under-developed PICs we have shown that transnational crime has become increasingly common. A risk contained but potentially dangerous if state failure or fragility undermines law enforcement capacities. We predict that as the pace of globalization quickens and the demand for raw materials and resources grows some parts of the Pacific will be prone to criminal enterprises run by both indigenous and foreign crime groups. Australia and New Zealand will remain attractors of illicit goods notably ATS but will in turn be source countries for diminishing fish stock such as beche de mere and abalone as well forest timber. Finally the role of states such as Australia and New Zealand in helping to maintain law enforcement capacities throughout the region will be crucial if organized crime in Oceania is to be kept in check while demand for illicit resources grow.