Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes

Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

Spontaneous large volume adipose tissue generation from a vascularized pedicled fat flap inside a chamber space

A novel method of spontaneous generation of new adipose tissue from an existing fat flap is described. A defined volume of fat flap based on the superficial inferior epigastric vascular pedicle in the rat was elevated and inset into a hollow plastic chamber implanted subcutaneously in the groin of the rat. The chamber walls were either perforated or solid and the chambers either contained poly(D,L-lactic-co-glycolic acid) (PLGA) sponge matrix or not. The contents were analyzed after being in situ for 6 weeks. The total volume of the flap tissue in all groups except the control groups, where the flap was not inserted into the chambers, increased significantly, especially in the perforated chambers (0.08 ± 0.007 mL baseline compared to 1.2 ± 0.08 mL in the intact ones). Volume analysis of individual component tissues within the flaps revealed that the adipocyte volume increased and was at a maximum in the chambers without PLGA, where it expanded from 0.04 ± 0.003 mL at insertion to 0.5 ± 0.08 mL (1250% increase) in the perforated chambers and to 0.16 ± 0.03 mL (400% increase) in the intact chambers. Addition of PLGA scaffolds resulted in less fat growth. Histomorphometric analysis rather than simple hypertrophy documented an increased number of adipocytes. The new tissue was highly vascularized and no fat necrosis or atypical changes were observed.

Reversible transdifferentiation of blood vascular endothelial cells to a lymphatic-like phenotype in vitro

Blood vascular cells and lymphatic endothelial cells (BECs and LECs, respectively) form two separate vascular systems and are functionally distinct cell types or lineages with characteristic gene expression profiles. Interconversion between these cell types has not been reported. Here, we show that in conventional in vitro angiogenesis assays, human BECs of fetal or adult origin show altered gene expression that is indicative of transition to a lymphatic-like phenotype. This change occurs in BECs undergoing tubulogenesis in fibrin, collagen or Matrigel assays, but is independent of tube formation per se, because it is not inhibited by a metalloproteinase inhibitor that blocks tubulogenesis. It is also reversible, since cells removed from 3D tubules revert to a BEC expression profile upon monolayer culture. Induction of the lymphatic-like phenotype is partially inhibited by co-culture of HUVECs with perivascular cells. These data reveal an unexpected plasticity in endothelial phenotype, which is regulated by contact with the ECM environment and/or cues from supporting cells.

Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44HI/CD24lO/-stem cell phenotype in human breast cancer

We review here the recently emerging relationship between epithelial-mesenchymal transition (EMT) and breast cancer stem cells (BCSC), and provide analyses of published data on human breast cancer cell lines, supporting their utility as a model for the EMT/BCSC state. Genome-wide transcriptional profiling of these cell lines has confirmed the existence of a subgroup with mesenchymal tendencies and enhanced invasive properties ('Basal B'/Mesenchymal), distinct from subgroups with either predominantly luminal ('Luminal') or mixed basal/luminal ('Basal A') features (Neve et al. Cancer Cell, 2006). A literature-derived EMT gene signature has shown specific enrichment within the Basal B subgroup of cell lines, consistent with their over-expression of various EMT transcriptional drivers. Basal B cell lines are found to resemble BCSC, being CD44highCD24low. Moreover, gene products that distinguish Basal B from Basal A and Luminal cell lines (Basal B Discriminators) showed close concordance with those that define BCSC isolated from clinical material, as reported by Shipitsin et al. (Cancer Cell, 2007). CD24 mRNA levels varied across Basal B cell lines, correlating with other Basal B Discriminators. Many gene products correlating with CD24 status in Basal B cell lines were also differentially expressed in isolated BCSC. These findings confirm and extend the importance of the cellular product of the EMT with Basal B cell lines, and illustrate the value of analysing these cell lines for new leads that may improve breast cancer outcomes. Gene products specific to Basal B cell lines may serve as tools for the detection, quantification, and analysis of BCSC/EMT attributes.

Bound to the borders: Representing refugees in the Australian space

This project consists of a novel and an exegesis that explore the use of fiction to counter negative hegemonic representations of refugees in Australia. The possibilities of using Australian spaces, including border spaces, to reveal tensions surrounding refugee belonging and to highlight the reconfiguration of border sites in the Australian imaginary, is a particular focus of this work.

The QUT innovation space : a trans-disciplinary learning environment for entrepreneurship education : final report

In the current climate of global economic volatility, there are increasing calls for training in enterprising skills and entrepreneurship to underpin the systemic innovation required for even medium-term business sustainability. The skills long-recognised as the essential for entrepreneurship now appear on the list of employability skills demanded by industry. The QUT Innovation Space (QIS) was an experiment aimed at delivering entrepreneurship education (EE), as an extra-curricular platform across the university, to the undergraduate students of an Australian higher education institute. It was an ambitious project that built on overseas models of EE studied during an Australian Learning and Teaching Council (ALTC) Teaching Fellowship (Collet, 2011) and implemented those approaches across an institute. Such EE approaches have not been attempted in an Australian university. The project tested resonance not only with the student population, from the perspective of what worked and what didn’t work, but also with every level of university operations. Such information is needed to inform the development of EE in the Australian university landscape. The QIS comprised a physical co-working space, virtual sites (web, Twitter and Facebook) and a network of entrepreneurial mentors, colleagues, and students. All facets of the QIS enabled connection between like-minded individuals that underpins the momentum needed for a project of this nature. The QIS became an innovation community within QUT. This report serves two purposes. First, as an account of the QIS project and its evolution, the report serves to identify the student demand for skills and training as well as barriers and facilitators of the activities that promote EE in an Australian university context. Second, the report serves as a how-to manual, in the tradition of many tomes on EE, outlining the QIS activities that worked as well as those that failed. The activities represent one measure of QIS outcomes and are described herein to facilitate implementation in other institutes. The QIS initially aimed to adopt an incubation model for training in EE. The ‘learning by doing’ model for new venture creation is a highly successful and high profile training approach commonly found in overseas contexts. However, the greatest demand of the QUT student population was not for incubation and progression of a developed entrepreneurial intent, but rather for training that instilled enterprising skills in the individual. These two scenarios require different training approaches (Fayolle and Gailly, 2008). The activities of the QIS evolved to meet that student demand. In addressing enterprising skills, the QIS developed the antecedents of entrepreneurialism (i.e., entrepreneurial attitudes, motivation and behaviours) including high-level skills around risk-taking, effective communication, opportunity recognition and action-orientation. In focusing on the would-be entrepreneur and not on the (initial) idea per se, the QIS also fostered entrepreneurial outcomes that would never have gained entry to the rigid stage-gated incubation model proposed for the original QIS framework. Important lessons learned from the project for development of an innovation community include the need to: 1. Evaluate the context of the type of EE program to be delivered and the student demand for the skills training (as noted above). 2. Create a community that builds on three dimensions: a physical space, a virtual environment and a network of mentors and partners. 3. Supplement the community with external partnerships that aid in delivery of skills training materials. 4. Ensure discovery of the community through the use of external IT services to deliver advertising and networking outlets. 5. Manage unrealistic student expectations of billion dollar products. 6. Continuously renew and rebuild simple activities to maintain student engagement. 7. Accommodate the non-university end-user group within the community. 8. Recognise and address the skills bottlenecks that serve as barriers to concept progression; in this case, externally provided IT and programming skills. 9. Use available on-line and published resources rather than engage in constructing project-specific resources that quickly become obsolete. 10. Avoid perceptions of faculty ownership and operate in an increasingly competitive environment. 11. Recognise that the continuum between creativity/innovation and entrepreneurship is complex, non-linear and requires different training regimes during the different phases of the pipeline. One small entity, such as the QIS, cannot address them all. The QIS successfully designed, implemented and delivered activities that included events, workshops, seminars and services to QUT students in the extra-curricular space. That the QIS project can be considered successful derives directly from the outcomes. First, the QIS project changed the lives of emerging QUT student entrepreneurs. Also, the QIS activities developed enterprising skills in students who did not necessarily have a business proposition, at the time. Second, successful outcomes of the QIS project are evidenced as the embedding of most, perhaps all, of the QIS activities in a new Chancellery-sponsored initiative: the Leadership Development and Innovation Program hosted by QUT Student Support Services. During the course of the QIS project, the Brisbane-based innovation ecosystem underwent substantial change. From a dearth of opportunities for the entrepreneurially inclined, there is now a plethora of entities that cater for a diversity of innovation-related activities. While the QIS evolved with the landscape, the demand endpoint of the QIS activities still highlights a gap in the local and national innovation ecosystems. The freedom to experiment and to fail is not catered for by the many new entities seeking to build viable businesses on the back of the innovation push. The onus of teaching the enterprising skills, which are the employability skills now demanded by industry, remains the domain of the higher education sector.

A finite volume scheme with preconditioned Lanczos method for two-dimensional space-fractional reaction–diffusion equations

Fractional differential equations have been increasingly used as a powerful tool to model the non-locality and spatial heterogeneity inherent in many real-world problems. However, a constant challenge faced by researchers in this area is the high computational expense of obtaining numerical solutions of these fractional models, owing to the non-local nature of fractional derivatives. In this paper, we introduce a finite volume scheme with preconditioned Lanczos method as an attractive and high-efficiency approach for solving two-dimensional space-fractional reaction–diffusion equations. The computational heart of this approach is the efficient computation of a matrix-function-vector product f(A)bf(A)b, where A A is the matrix representation of the Laplacian obtained from the finite volume method and is non-symmetric. A key aspect of our proposed approach is that the popular Lanczos method for symmetric matrices is applied to this non-symmetric problem, after a suitable transformation. Furthermore, the convergence of the Lanczos method is greatly improved by incorporating a preconditioner. Our approach is show-cased by solving the fractional Fisher equation including a validation of the solution and an analysis of the behaviour of the model.

The role of active locomotion in space perception

It has been shown that active control of locomotion increases accuracy and precision of nonvisual space perception, but psychological mechanisms of this enhancement are poorly understood. The present study explored a hypothesis that active control of locomotion enhances space perception by facilitating crossmodal interaction between visual and nonvisual spatial information. In an experiment, blindfolded participants walked along a linear path under one of the following two conditions: (1) They walked by themselves following a guide rope; and (2) they were led by an experimenter. Subsequently, they indicated the walked distance by tossing a beanbag to the origin of locomotion. The former condition gave participants greater control of their locomotion, and thus represented a more active walking condition. In addition, before each trial, half the participants viewed the room in which they performed the distance perception task. The other half remained blindfolded throughout the experiment. Results showed that although the room was devoid of any particular cues for walked distances, visual knowledge of the surroundings improved the precision of nonvisual distance perception. Importantly, however, the benefit of preview was observed only when participants walked more actively. This indicates that active control of locomotion allowed participants to better utilize their visual memory of the environment for perceiving nonvisually encoded distance, suggesting that active control of locomotion served as a catalyst for integrating visual and nonvisual information to derive spatial representations of higher quality.

Mastery motivation in children with intellectual disability : Is there evidence for a Down syndrome behavioural phenotype?

The main purpose of the current study was to provide empirical evidence to support or refute assumptions of phenotypic deficits in motivation for children with Down syndrome. Children with moderate intellectual disability associated with etiologies other than Down syndrome were recruited in an extension of a previous study that involved children with Down syndrome and typically developing children. The participants were 29 children with moderate intellectual disability and 33 children with Down syndrome who were matched on mental age to 33 typically developing children, aged 3 to 8 years. Mastery motivation was assessed on task measures of curiosity, preference for challenge, and persistence, as well as parental reports. There were no significant group differences on the mastery motivation tasks. Parental ratings of mastery motivation differed, with typically developing children generally being rated more highly than each of the disability groups. The view that motivational deficits are part of the Down syndrome behavioural phenotype was not supported.

SCRAMSPACE : Radical-Farming Scramjet for access to space

Scramjet-based launch systems offer considerable promise for safe, reliable and economical access to space. A general Scramjets introduction is first provided, followed by the specifics of Australian Scramjet Research and the recent progress in inlet-injection radical-farming scramjets as part of the SCRAMSPACE program. Through both flight and ground tests, leveraging Australias world leadership in scramjet R&D, the SCRAMSPACE project is designed to answer key scientific and technological questions and build an industry-ready talent pool for a future Australian space industry. An extensive descriptions of all phases of the development of the SCRAMSPACE I scramjet-powered free-flight experiment are described in these lecture notes.

Serial explant culture provides novel insights into the potential location and phenotype of corneal endothelial progenitor cells

The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploiting this concept remain unclear. In the course of evaluating methods for growing corneal endothelial cells, we have noted a case where remarkable growth was achieved using a serial explant culture technique. Over the course of 7 months, a single explant of corneal endothelium, acquired from cadaveric human tissue, was sequentially seeded into 7 culture plates and on each occasion produced a confluent cell monolayer. Sample cultures were confirmed as endothelial in origin by positive staining for glypican-4. On each occasion, small cells, closest to the tissue explant, developed into a highly compact layer with an almost homogenous structure. This layer was resistant to removal with trypsin and produced continuous cell outgrowth during multiple culture periods. The small cells gave rise to larger cells with phase-bright cell boundaries and prominent immunostaining for both nestin and telomerase. Nestin and telomerase were also strongly expressed in small cells immediately adjacent to the wound site, following transfer of the explant to another culture plate. These findings are consistent with the theory that progenitor cells for the corneal endothelium reside within the limbus and provide new insights into expected expression patterns for nestin and telomerase within the differentiation pathway.

Art spaces, public space, and the link to community development

Recent literature credits community art spaces with both enhancing social interaction and engagement and generating economic revitalization. This article argues that the ability of art spaces to realize these outcomes is linked to their role as public spaces and that their community development potential can be expanded with greater attention to this role. An analysis of the public space characteristics is useful because it encourages consideration of sometimes overlooked issues, particularly the effect of the physical environment on outcomes related to community development. I examine the relationship between public space and community development at various types of art spaces including artist cooperatives, ethnic-specific art spaces, and city-sponsored art centers in central city and suburban locations. This study shows that through their programming and other activities, art spaces serve various public space roles related to community development. However, the ability of many to perform as public spaces is hindered by facility design issues and poor physical connections in their surrounding area. This article concludes with proposals for enhancing the community development role of the art spaces through their function as public spaces.

Indigenous epistemology : creating an international Indigenous higher education space in the wake of the western “university of excellence”

Interest in the participation of Indigenous peoples in higher education has, in recent times, gained momentum with an increasing number of advocates challenging the global history of culturally inept policies and practices imposed within the western higher education system. To address the challenges being presented by Indigenous communities and other groups (often relegated under the banner of disadvantaged or equity) Western Universities are promoting a shift toward inclusive policies and practices. Frustrated with the offerings of the Western Higher Education system, a global movement of Indigenous academics, Elders and knowledge holders are developing strategies to meet the educational needs of their own communities, in order to find a way forward. The mobilization of Elders and Indigenous academics has resulted in the development of a global higher education network which is proving to be a significant force in changing the position of Indigenous participation in higher education. The World Indigenous Network Higher Education Consortium (WINHEC) has presented a significant challenge to those barriers within the western higher education system that has historically demonstrated an inability to develop culturally inclusive practices within their institutions. This paper examines the development of a world Indigenous higher education movement and its contribution to the history of the “university” within the context of western higher education institutions. Outlined in this examination will be a synopsis of the development of the “University of Excellence” and the creation of an international Indigenous space within higher education.

Exploring Bodies in Time and Space

While the body, time and space are fundamental to human experience, comparatively little attention has been given to the connections between them. Here scholars from a wide range of disciplines explore important themes of embodied life in time and space across cultures, activities and bodymind states. Motivated by a common desire to deepen and extend our comprehension of these phenomena and the connections and conversations between them, this book emerged from intense inter-disciplinary dialogue during the 1st Global Conferences on Time, Space and the Body and Body Horror. A plenitude of theoretical approaches and media are deployed to investigate assumptions and pose problems, to creatively deconstruct and reconstruct the terms through which experience is rendered meaningful, pleasurable, and functional. These investigations, pursued through various research methods in fields of the arts, social and psychological sciences and humanities, invite readers into a genuinely pluralistic conversation around the most basic and profound aspects of being.

Introduction : Understanding Connections between Time, Space and the Body

The experiences and constructs of time, space and bodies saturate human discourse—naturally enough, since they are fundamental to existence—yet there has long been a tendency for the terms to be approached somewhat independently, belying the depth of their interconnections. It was a desire to address that apparent shortcoming that inspired this book, and the interdisciplinary meetings from which it was born, the 1st Global Conferences on ‘Time, Space and the Body’ and ‘Body Horror’ held in Sydney in February 2013. Following the lively, often provocative, exchange of ideas throughout those meetings, the writing here crosses conventional boundaries inhabiting everyday life and liminal experiences, across cultures, life circumstances, and bodily states. Through numerous theoretical frameworks and with reference to a variety of media, the authors problematize or deconstruct commonplace assumptions to reveal challenging new perspectives on the diverse cultures and communities which make our world. If there is an overarching theme of this collection it is diversity itself. The writers here come from numerous academic fields, but a good number of them also draw on first-hand cultural production in the arts: photography, sculpture and fine art instillation, for example. Of course, however laudable it might be, there is a potential problem in such diversity: does it produce fruitful dialogue moving toward creative, workable syntheses or simply a cacophony of competing, incomprehensible, barely comprehending voices? To a large degree this depends upon the intellectual, existential ambitions as well as the old-fashioned goodnatured tolerance of both writers and readers. But we hope three unifying characteristics are discernable in the following chapters viewed as a whole: firstly, a genuine concern for the world humans inhabit and the communities they form as bodies in space and time; secondly, an emphasis upon the experience of the human subject, exemplified perhaps by the number of chapters drawing on phenomenology; thirdly, an adventurous, explorative impulse associated with an underlying sense that being, since it is inseparable from the body’s temporality, is always becoming, and here the presence of poststructuralist influences is unmistakable, often explicit. Our challenge as editors has been to present the enormous variety of subjects and views in a way that would render the book coherent and at the same time encourage readers to make explorations themselves into realms they might usually consider beyond their field of interest. To that end we have divided the book into six sections around loosely defined themes, each offering different angles on how time and/or space unfold in and around bodies.