Developing a three-dimensional in-vitro cell culture model for studying breast and prostate cancer using starPEG-heparin hydrogels

Introduction Hydrogels prepared from poly(ethylene glycol) (PEG) and maleimide-functionalized heparin provide a potential matrix for use in developing three dimensional (3D) models. We have previously demonstrated that these hydrogels support the cultivation of human umbilical vein endothelial cells (HUVECs) (1). We extend this body of work to study the ability to create an extracellular matrix (ECM)-like model to study breast and prostate cancer cell growth in 3D. Also, we investigate the ability to produce a tri-culture mimicking tumour angiogenesis with cancer spheroids, HUVECs and mesenchymal stem cells (MSC). Materials and Methods The breast cancer cell lines, MCF-7 and MDA-MB-231, and prostate cancer cell lines, LNCaP and PC3, were seeded into starPEG-heparin hydrogels and grown for 14 Days to analyse the effects of varying hydrogel stiffness on spheroid development. Resulting hydrogel constructs were analyzed via Alamar Blue assays, light microscopy, and immunofluorescence staining for cytokeratin 8/18, Ki67 and E-Cadherin. Cancer cell lines were then pre-grown in hydrogels for 5-7 days and then re-seeded into starPEG-heparin hydrogels functionalised with RGD, SDF-1, bFGF and VEGF as spheroids with HUVECs and MSC and grown for 14 days as a tri-culture in Endothelial Cell Growth Medium (ECGM; Promocell). Cell lines were also seeded as a single cell suspension into the functionalised tri-culture system. Cultures were fixed in 4% paraformaldehyde and analysed via immunostaining for Von Willebrand Factor and CD31, as well as the above mentioned markers, and observed using confocal microscopy. Results Cultures prepared in MMP-cleavable starPEG-heparin hydrogels display spheroid formation in contrast to adherent growth on tissue culture plastic. Small differences were visualised in cancer spheroid growth between different gel stiffness across the range of cell lines. Cancer cell lines were able to be co-cultivated with HUVECs and MSC. HUVEC tube formation and cancer line spheroid formation occured after 3-4 days. Interaction was visualised between tumours and HUVECs via confocal microscopy. Slightly increased interaction was seen between cancer tumours and micro-vascular tubes when seeded as single cells compared with the pre-formed spheroid approach. Further studies intend to utilise cytokine gradients to further optimise the ECM environment of in situ tumour angiogenesis. Discussion and Conclusions Our results confirm the suitability of hydrogels constructed from starPEG-heparin for HUVECs and MSC co-cultivation with cancer cell lines to study cell-cell and cell-matrix interactions in a 3D environment. This represents a step forward in the development of 3D culture models to study the pathomechanisms of breast and prostate cancer. References 1. Tsurkan MV, Chwalek K, Prokoph S, Zieris A, Levental KR, Freudenberg U, Werner C. Advanced Materials. 25, 2606-10, 2013. Disclosures The authors declare no conflicts of interest

Literacy and Digital Culture in the Early Years

In this chapter we present data drawn from observations of kindergarten children using iPads and talk with the children, their parents/guardians and teachers. We identify a continuum of practices that extends from ‘educational apps’ teaching handwriting, sight words and so forth to uses of the iPad as a device for multimodal literacy development and substantive conversation around children’s creative work. At the current time high stakes testing and the implementation of the Australian Curriculum are prompting new public and professional conversations about literacy and digital technology. The iPad is construed as both cause of and solution to problems of traditional literacy education. In this context we describe the literacies enabled by educational software available on iPads. We higlight the time constraints which bore on teachers' capacity to enact their visions of literacy education through the iPad platform and suggest ways of reflecting on responses to this constraint.

Foreign news coverage in five African newspapers

One of the principal arguments that dominated intellectual debate in the 19805 concerned the imbalance in the quantity and quality of world news, in particular news from developing countries. African delegates at the United Nations Educational, Scientific and Cultural Organisation (UNESCO), supported by other developing countries, argued that most of the news disseminated by the major Western news agencies was unfavourable to developing countries in qualitative and quantitative terms. Not only did Western news media pay little attention to news of developing countries, it was also argued that the few items that made the news tended to focus on negative events such as crises, wars, coups, riots, street demonstrations, diseases, poverty, pestilence, etc. More than 20 years after the intellectual debate received attention in academic journals, this study set out to examine systematically how African newspapers report the world. The researchers investigate the relative degree of balance and imbalance in the coverage of world news by Nigerian and Ghanaian newspapers. The study also examines Nigerian and Ghanaian journalists’ perceptions of world news coverage by local and foreign newspapers.

Development and parameterization of a rain- and fire-driven model for exploring elephant effects in African savannas

We describe the development and parameterization of a grid-based model of African savanna vegetation processes. The model was developed with the objective of exploring elephant effects on the diversity of savanna species and structure, and in this formulation concentrates on the relative cover of grass and woody plants, the vertical structure of the woody plant community, and the distribution of these over space. Grid cells are linked by seed dispersal and fire, and environmental variability is included in the form of stochastic rainfall and fire events. The model was parameterized from an extensive review of the African savanna literature; when available, parameter values varied widely. The most plausible set of parameters produced long-term coexistence between woody plants and grass, with the tree-grass balance being more sensitive to changes in parameters influencing demographic processes and drought incidence and response, while less sensitive to fire regime. There was considerable diversity in the woody structure of savanna systems within the range of uncertainty in tree growth rate parameters. Thus, given the paucity of height growth data regarding woody plant species in southern African savannas, managers of natural areas should be cognizant of different tree species growth and damage response attributes when considering whether to act on perceived elephant threats to vegetation. © 2007 Springer Science+Business Media B.V.

A model-framed evaluation of elephant effects on tree and fire dynamics in African savannas

There is a concern that high densities of elephants in southern Africa could lead to the overall reduction of other forms of biodiversity. We present a grid-based model of elephant-savanna dynamics, which differs from previous elephant-vegetation models by accounting for woody plant demographics, tree-grass interactions, stochastic environmental variables (fire and rainfall), and spatial contagion of fire and tree recruitment. The model projects changes in height structure and spatial pattern of trees over periods of centuries. The vegetation component of the model produces long-term tree-grass coexistence, and the emergent fire frequencies match those reported for southern African savannas. Including elephants in the savanna model had the expected effect of reducing woody plant cover, mainly via increased adult tree mortality, although at an elephant density of 1.0 elephant/km2, woody plants still persisted for over a century. We tested three different scenarios in addition to our default assumptions. (1) Reducing mortality of adult trees after elephant use, mimicking a more browsing-tolerant tree species, mitigated the detrimental effect of elephants on the woody population. (2) Coupling germination success (increased seedling recruitment) to elephant browsing further increased tree persistence, and (3) a faster growing woody component allowed some woody plant persistence for at least a century at a density of 3 elephants/km2. Quantitative models of the kind presented here provide a valuable tool for exploring the consequences of management decisions involving the manipulation of elephant population densities. © 2005 by the Ecological Society of America.

Culture in Business Process Management: How cultural values determine BPM success

There is consensus among practitioners and academics that culture is a critical factor that is able to determine success or failure of BPM initiatives. Yet, culture is a topic that seems difficult to grasp and manage. This may be the reason for the overall lack of guidance on how to address this topic in practice. We have conducted in-depth research for more than three years to examine why and how culture is relevant to BPM. In this chapter, we introduce a framework that explains the role of culture in BPM. We also present the relevant cultural values that compose a BPM culture, and we introduce a tool to examine the supportiveness of organizational cultures for BPM. Our research results provide the basis for further empirical analyses on the topic and support practitioners in the management of culture as an important factor in BPM initiatives.

The culture of young women's drinking: Implications for developing effective policing strategies. Report to National Drug Strategy Law Enforcement Committee

Alcohol-related mortality and morbidity represents a substantial financial burden on communities across the world. Adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk of acute alcoholrelated harm at least once in the previous 12 months (Australian Institute of Health and Welfare [AIHW], 2011). Excessive alcohol consumption has long been seen as a male problem; however, a gradual shift towards a social acceptance of female drunkenness has narrowed the gap in drinking quantity and style between men and women (Grucza, Bucholz, Rice, & Bierut, 2008). The presented data point to the vulnerability of women to the consequences of acute alcohol intoxication and indicate that alcohol-related offending by women is on the rise. Taken together, these findings reveal that alcohol-related harms and aggression for young women are becoming more prevalent and problematic. This report addressed these issues from a policing perspective...

3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

The ethics of corporate governance: A (South)African perspective

Purpose – The purpose of this paper is to review the developments in South African corporate governance since the end of apartheid, with a view to identifying themes and points of convergence and/or divergence with other models. Design/methodology/approach – The paper presents a critical review of South African corporate governance in the context of political and economic developments. Where relevant, aspects of corporate governance theory (in particular the stakeholder and shareholder debate) are considered in the South African context. Findings – South African corporate governance can be seen to broadly follow Anglo‐American examples with the notable exception of the stakeholder approach of the two King reports. This approach emphasises the responsibilities of companies to various stakeholders and encourages stakeholder engagement as an integral element of company strategy. There has not, however, been any substantial incorporation of stakeholder interests into formal corporate governance structures such as board structure and financial reporting. Practical implications – The ongoing consideration of corporate governance developments in South Africa is important for its continued development in the country and the region. Originality/value – A review of South African corporate governance is timely given the probable release of the third King report in 2009, together with new company legislation.

A commentary on the global position of South African accounting research

The South African designation of Chartered Accountant is comparable to similar designations in most developed countries. However, the research outputs of Accountancy academics in South Africa seem to lag far behind those of their counterparts abroad. This article discusses the results of several inquiries into the status of South African Accounting research in a global context, and identifies several reasons and possible remedies for low research output.

A humanistic approach to South African accounting education

Humanistic psychologist Carl Rogers made a distinction between traditional approaches and humanistic `learner-centred\' approaches to education. The traditional approach holds that educators impart their knowledge to willing and able recipients; whereas the humanistic approach holds that educators act as facilitators who assist learners in their learning processes. As a learning theory, humanism refers to the belief in the innate ability of humans to learn, and the creation of an environment in which students are given `Freedom to Learn\'. South African accounting education has, by and large, followed the traditional approach rather than the humanistic approach. This article attempts to expand on the existing references to a humanistic approach through a more detailed exposition and application of the educational theory of Carl Rogers in the context of South African accounting education. The prospects of a humanistic approach in accounting education are then discussed and some practical strategies provided in relation to a specific third-year undergraduate accounting unit offered in South Africa.

Using culture to manage the transition into university: Conceptualising the dynamics of withdrawal and engagement

This conceptual paper explored the purposes of using culture in the process of coping with stress by looking how first year undergraduate students used cultural elements and activities to aid their transition into university. Results supported two key conceptualisations of the use of culture. Firstly, results indicated that students used culture either for withdrawal purposes, i.e., for escaping from the stressful situation, or for engagement purposes, i.e., for actively engaging with the stressful situation. Secondly, the results suggested three different forms of using culture to engage with stressful situations: mood management, learning, and personal interaction. While the results of the study resonate with the distinction between avoidance versus approach-oriented coping strategies that are widely explored in the stress and coping literature, they also suggest that the relationship between withdrawal and engagement might be dynamic with those two strategies serving distinct purposes in the process of coping with stress. The paper thus suggests that there is a need to develop process-oriented models of coping that would allow identifying patterns in the way people fluctuate between withdrawal and engagement that support and facilitate their personal growth and development.