p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Developing a model of embedding academic numeracy in university programs : a case study from nursing

This is a study of the academic numeracy of nursing students. This study develops a theoretical model for the design and delivery of university courses in academic numeracy. The following objectives are addressed: 1. To investigate nursing students' current knowledge of academic numeracy; 2. To investigate how nursing students’ knowledge and skills in academic numeracy can be enhanced using a developmental psychology framework; and 3. To utilise data derived from meeting objectives 1 and 2 to develop a theoretical model to embed academic numeracy in university programs. This study draws from Valsiner’s Human Development Theory (Valsiner, 1997, 2007). It is a quasi-experimental intervention case study (Faltis, 1997) and takes a multimethod approach using pre- and post-tests; observation notes; and semi-structured teaching sessions to document a series of microgenetic studies of student numeracy. Each microgenetic study is centered on the lived experience of students becoming more numerate. The method for this section is based on Vygotsky’s double stimulation (Valsiner, 2000a; 2007). Data collection includes interviews on students’ past experience with mathematics; their present feelings and experiences and how these present feelings and experiences are transformed. The findings from this study have provided evidence that the course developed for nursing students, underpinned by an appropriate framework, does improve academic numeracy. More specifically, students improved their content knowledge of and confidence in mathematics in areas that were directly related to their degree. The study used Valsiner’s microgenetic approach to development to trace the course as it was being taught and two students’ personal academic numeracy journeys. It highlighted particularly troublesome concepts, then outlined scaffolding and pathways used to develop understanding. This approach to academic numeracy development was summarised into a four-faceted model at the university, program, course and individual level. This model can be applied successfully to similar contexts. Thus the thesis advances both theory and practice in this under-researched and under-theorised area.

Competition and innovation : independent production in the Chinese TV industry

Independent television production is recognised for its capacity to generate new kinds of program content, as well as deliver innovation in formats. Globally, the television industry is entering into the post-broadcasting era where audiences are fragmented and content is distributed across multiple platforms. The effects of this convergence are now being felt in China, as it both challenges old statist models and presents new opportunities for content innovation. This thesis discusses the status of independent production in China, making relevant comparisons with independent production in other countries. Independent television production has become an important element in the reform of broadcasting in China in the past decade. The first independent TV production company was registered officially in 1994. While there are now over 4000 independent companies, the term „independent. does not necessarily constitute autonomy. The question the thesis addresses is: what is the status and nature of independence in China? Is it an appropriate term to use to describe the changing environment, or is it a misnomer? The thesis argues that Chinese independents operate alongside the mainstream state-owned system; they are „dependent. on the mainstream. Therefore independent television in China is a relative term. By looking at several companies in Beijing, mainly in entertainment, TV drama and animation, the thesis shows how the sector is injecting fresh ideas into the marketplace and how it plays an important role in improving innovation in many aspects of the television industry. The thesis shows how independent television companies in China are looking to protect their property rights. It demonstrates that far from being at the cutting edge, independents are reliant on a system that has many inbuilt structural problems. The thesis outlines many of the challenges facing 'independents'.

'Homes for Life' : a critical ecological study of an independent living project

In this paper, an ‘ecological’ lens is applied to an independent living project aiming to provide ‘homes for life’ for adult children with disabilities. The qualities of the project as ecological praxis are highlighted along with the implications for an open-ended enquiry into ecologies for and of the interior. In terms of the ecological concern for intimate modes of being, interior design is shown to be well placed through its association with environments in which people spend most of their life and through powerful concepts such as ‘interiority’ and ‘home’ which link to fundamental existential notions of ‘self ’ and ‘identity’. However, despite the interior being a significant generative force, this has not happened to the exclusion of other disciplines. Ignoring territorial urges to claim areas and concepts as one’s own, the paper describes how the project has actively encouraged design disciplines to trespass in each other’s territories. Ecologies for and of the interior, while recognising the need for discipline emphasis, also demand an integrated and collective approach through what is in effect transdisciplinary practice.

Participatory content creation and collective intelligence in Rio de Janeiro's favelas [Virtual presentation]

This proposal combines ethnographic techniques and discourse studies to investigating a collective of people engaged with audiovisual productions who collaborate in Curta Favela’s workshops in Rio de Janeiro’s favelas. ‘Favela’ is often translated simply as ‘slum’ or ‘shantytown’, but these terms connote negative characteristics such as shortage, poverty, and deprivation referring to favelas which end up stigmatizing these low income suburbs. Curta Favela (Favela Shorts) is an independent project which all participants join to use photography and participatory audiovisual production as a tool for social change and raising consciousness. As cameras are not affordable for favelas dwellers, Curta Favela’s volunteers teach favela residents how they can use their mobile phones and compact cameras to take pictures and make movies, and afterwards, how they can edit the data using free editing video software programs and publish it on the Internet. To record audio, they use their mp3 or mobile phones. The main aim of this study is to shed light not only on how this project operates, but also to highlight how collective intelligence can be used as a way of fighting against the lack of basic resources.

Participatory content creation and collective intelligence in Rio de Janeiro's favelas

This proposal combines ethnographic techniques and discourse studies to investigate a collective of people engaged with audiovisual productions who collaborate in Curta Favela’s workshops in Rio de Janeiro’s favelas. ‘Favela’ is often translated simply as ‘slum’ or ‘shantytown’, but these terms connote negative characteristics such as shortage, poverty, and deprivation which end up stigmatizing these low income suburbs. Curta Favela (Favela Shorts) is an independent project in which all participants join to use photography and participatory audiovisual production as tools for social change and to raise consciousness. As cameras are not affordable for favela dwellers, Curta Favela’s volunteers teach favela residents how they can use their mobile phones and compact cameras to take pictures and make movies, and afterwards, how they can edit the data using free editing video software programs and publish it on the Internet. To record audio, they use their mp3 or mobile phones. The main aim of this study is to shed light not only on how this project operates, but also to highlight how collective intelligence can be used as a way of fighting against a lack of basic resources.

Skins for smokes and the use of cultural content and imagery

[Extract] For just $5.29 Australians can now purchase "Skins" from local, independent grocers to cover their cigarette packet with the Aboriginal or Torres Strait Islander flag. We argue that this use of cultural content and copyright' imagery on cigarette packets negates health promotion efforts, such as Australia's recent introduction of plain packaging laws and the subsequent dismissal of a legal challenge from the tobacco industry.

From Aussiewood Movies to Guerrilla Filmmaking: Independent Filmmaking and Contemporary Australian Cinema

Independent filmmaking within the context of Australian cinema is a multifaceted subject. In comparison to the United States, where production can be characterised as bifurcated between major studio production and so-called “indie” or independent production without the backing of the majors, since the 1970s and until recently the vast majority of Australian feature film production has been independent filmmaking. Like most so-called national cinemas, most Australian movies are supported by both direct and indirect public subvention administered by state and federal government funding bodies, and it could be argued that filmmakers are, to a certain degree, “dependent” on official mandates. As this chapter demonstrates national production slates are subjected to budget restraints and cut-backs, official cultural policies (for example pursuing international co-productions and local content quotas) and shifts in policy directions among others. Therefore, within the context of Australian cinema, feature film production operating outside the public funding system could be understood as “independent”. However, as is the case for most English-language national cinemas, independence has long been defined in terms of autonomy from Hollywood, and – as alluded to above – as Australia becomes more dependent upon international inputs into production, higher budget movies are becoming less independent from Hollywood. As such, this chapter argues that independence in Australian cinema can be viewed as having two poles: independence from direct government funding and independence from Hollywood studios. With a specific focus on industry and policy contexts, this chapter explores key issues that constitute independence for Australian cinema. In so doing it examines the production characteristics of four primary domains of contemporary independent filmmaking in Australia, namely: “Aussiewood” production; government-backed low-to-mid budget production; co-productions; and guerrilla filmmaking.

Embedding EfS in teacher education : an introductory guide to using the systems change model

Welcome to this introductory guide on using a systems change model to embed Education for Sustainability (EfS) into teacher education. Pressing sustainability issues such as climate change, biodiversity loss and depletion of non-renewable resources pose new challenges for education. The importance of education in preparing future citizens to engage in sustainable living practices and help create a more sustainable world is widely acknowledged. As a result many universities around the world are beginning to recognize the need to integrate EfS into their teacher education programs. However, evidence indicates that there is little or no core EfS knowledge or pedagogy in pre-service teacher courses available to student teachers in a thorough and systematic fashion. Instead efforts are fragmented and individually or, at best, institutionally-based and lacking a systems approach to change, an approach that is seen as essential to achieving a sustainable society (Henderson & Tilbury, 2004). The result is new teachers are graduating without the necessary knowledge or skills to teach in ways that enable them to prepare their students to cope well with the new and emerging challenges their communities face. This guide has been prepared as part of a teaching and learning research project that applied a systems change approach to embedding the learning and teaching of sustainability into pre-service teacher education. The processes, outcomes and lessons learnt from this project are presented here as a guide for navigating pathways to systemic change in the journey of re-orienting teacher education towards sustainability. The guide also highlights how a systems change approach can be used to successfully enact change within a teacher education system. If you are curious about how to introduce and embed EfS into teacher education – or have tried other models and are looking for a more encompassing, transformative approach – this guide is designed to help you. The material presented in this guide is designed to be flexible and adaptive. However you choose to use the content, our aim is to help you and your students develop new perspectives, promote discussion and to engage with a system-wide approach to change.

Progression of human breast cancer cells from hormone-dependent to hormone-independent growth both in vitro and in vivo

We have isolated a series of sublines of the hormone-dependent MCF-7 human breast cancer cell line after selection both in vivo and in vitro for growth in the presence of subphysiological concentrations of estrogens. These sublines represent a model system for study of the processes leading to hormonal autonomy. The cells form growing tumors in ovariectomized athymic nude mice in the absence of estrogen supplementation but retain some responsivity to estrogen as determined by stimulation of the rate of tumor growth in vivo and by induction of progesterone receptor. An ovarian-independent but hormone-responsive phenotype may occur early in the natural progression to hormone-independent and unresponsive growth in breast cancer. We observed no change in the affinity or decrease in the level of expression of estrogen receptors and progesterone receptors among the sublines and the parental cells. Epidermal growth factor receptors are not overexpressed in ovarian-independent cells. Thus, altered hormone receptor expression may be a late event in the acquisition of a hormone-independent and unresponsive phenotype. Sublines isolated by in vivo but not in vitro selection are more invasive than the parental cells both in vivo and across an artificial basement membrane in vitro. Thus, as yet unknown tumor-host interactions may be important in the development of an invasive phenotype. Furthermore, acquisition of the ovarian-independent and invasive phenotypes can occur independently.

Re-thinking ancillary: Australian screen content in education

The use of Australian screen content in Australian schools and universities is undergoing rapid change due to digital and online distribution capacity on the supply side and digital and online affordance embedded in student cultures. This paper examines the ways in which Australian screen content and its distribution are beginning to adapt to educational usage. Issues facing content rights holders, distribution companies and emerging digital platforms reflect broad-based digital disruption patterns. Learning opportunities that can coincide with the growth in uptake of Australian screen content in Australia's education sector are not immune to the challenges posed by emerging digital consumption behaviours and issues of sustainability. At the same time, the growth in the use of digital and online screen content learning resources, under current copyright conditions, poses significant increases in the underlying cost structure for educational interests. This paper examines the innovations occurring in both the supply and the demand sides of Australian screen content and the expanded learning opportunities arising out of emerging digital affordances. Precedents in the UK are explored that demonstrate how stronger connections can be forged between nationally produced film and media content and a national curriculum. While addressing recent issues arising out of the Australian Law Review Commission's inquiry into copyright in the digital economy, the purpose of this discussion is not to assess policy debates about fair use versus fair dealing. What is clear, however, is that independent research is required that draws upon research-based evidence with an aim to better understanding the needs of the education sector against the transformative shifts taking place in digital-based learning materials and their modes of delivery.

Embedding sustainability in a real-world context: Developing a world class early learning centre

This symposium describes what is possible when early childhood professionals work with designers to develop a vision for an exemplary early childhood centre with a focus on Education for Sustainability (EfS). The symposium provides insights into cross-disciplinary initiatives between QUT Early childhood and Design staff and students, who have worked together with the iconic Lone Pine Koala Sanctuary in Brisbane, to explore imperatives around EfS, including leadership and professionalism. This practical, real world project has seen all stakeholders engage in a focus on sustainability which has opened new ways of thinking about early childhood centre design. Cross-disciplinarity has created space to re-think the potential of the disciplines to interweave, and in so doing opened different ways for thinking about early childhood centres – their operation and their function. For the first time in Queensland, this project creates strategic alliances between EfS, childcare, business and sustainable design. EfS is essential for addressing local and global environmental issues and early childhood EfS research has been gaining international momentum, with governments nominating this area as having significant capacity to empower communities and promote change. While models for collaboration exist in the early childhood programs in Reggio Emilia, we offer sustainability as a unique and contemporary focus with immense potential to generate international and national interest. To date Early Childhood degree students enrolled in a leadership and management unit/subject have worked collaboratively with Design students to explore the sustainable design of the proposed Lone Pine early childhood centre. Providing students with a ‘real world’ project sees them re-positioned from ‘novice’ to ‘professional’, where their knowledge, expertise and perspectives are simultaneously validated and challenged. These learning experiences are enabling students to practice a new model of early childhood leadership, one that is vital for leading in an increasingly complex world. The symposium will be comprised of three discrete, though interconnected presentations, that work together to tell the story of this project. Three key facets of the project will be explored during the 90 minute session, as the perspectives of key stakeholders are shared. The first presentation (A/Prof Julie Davis, Dr Lyndal O’Gorman& Dr Megan Gibson) will outline the role of QUT School of Early Childhood staff and students, with attention to the ways in which the project was embedded in students’ work in the final year of their degree program of study. The second presentation (Ms Lindy Osborne) will provide insights into the Design students’ collaborative work in the project. Finally, the key role of the Lone Pine Koala Sanctuary and their commitment for EfS (Ms Peta Wilson & Dr Sue Elliott) will map out the philosophy that underpins the project. Together, the authors will conclude key project outcomes that have been achieved through this real-world, cross-disciplinary work.

Shifting the Focus. Incorporating knowledge about Aboriginal engineering into main stream content

BACKGROUND OR CONTEXT The concept of 'Aboriginal engineering' has had little exposure in conventional engineering education programs, despite more than 40,000 years of active human engagement with the diverse Australian environment. The work reported in this paper began with the premise that Indigenous Student Support Through Indigenous Perspectives Embedded in Engineering Curricula (Goldfinch, et al 2013) would provide a clear and replicable means of encouraging Aboriginal teenagers to consider a career in engineering. Although that remains a key outcome of this OLT project, the direction taken by the research had led to additional insights and perspectives that have wide implications for engineering education more generally. There has only been passing reference to the achievements of Aboriginal engineering in current texts, and the very absence of such references was a prompt to explore further as our work developed. PURPOSE OR GOAL Project goals focused on curriculum-based change, including development of a model for inclusive teaching spaces, and study units employing key features of the model. As work progressed we found we needed to understand more about the principles and practices informing the development of pre-contact Aboriginal engineering strategies for sustaining life and society within the landscape of this often harsh continent. We also found ourselves being asked 'what engineering did Aboriginal cultures have?' Finding that there are no easy-to- access answers, we began researching the question, while continuing to engage with specific curriculum trials. APPROACH Stakeholders in the project had been identified as engineering educators, potential Aboriginal students and Aboriginal communities local to Universities involved in the project. We realised, early on, that at least one more group was involved - all the non-Aboriginal students in engineering classes. This realisation, coupled with recognition of the need to understand Aboriginal engineering as a set of viable, long term practices, altered the focus of our efforts. Rather than focusing primarily on finding ways to attract Aboriginal engineering students, the shift has been towards evolving ways of including knowledge about Aboriginal practices and principles in relevant engineering content. DISCUSSION This paper introduces the model resulting from the work of this project, explores its potential influence on engineering curriculum development and reports on implementation strategies. The model is a static representation of a dynamic and cyclic approach to engaging with Aboriginal engineering through contact with local communities in regard to building knowledge about the social beliefs underlying Aboriginal engineering principles and practices. Ways to engage engineering educators, students and the wider community are evolving through the continuing work of the project team and will be reported in more detail in the paper. RECOMMENDATIONS/IMPLICATIONS/CONCLUSION While engineering may be considered by some to be agnostic in regard to culture and social issues, the work of this project is drawing attention to the importance of including such issues into curriculum materials at a number of levels of complexity. The paper will introduce and explore the central concepts of the research completed to date, as well as suggesting ways in which engineering educators can extend their knowledge and understanding of Aboriginal engineering principles in the context of their own specialisations.

Embedding Of Non-Simple Lie-Groups, Coupling-Constant Relations And Non-Uniqueness Of Models Of Unification

A general derivation of the coupling constant relations which result on embedding a non-simple group like SU L (2) @ U(1) in a larger simple group (or graded Lie group) is given. It is shown that such relations depend only on the requirement (i) that the multiplet of vector fields form an irreducible representation of the unifying algebra and (ii) the transformation properties of the fermions under SU L (2). This point is illustrated in two ways, one by constructing two different unification groups containing the same fermions and therefore have same Weinberg angle; the other by putting different SU L (2) structures on the same fermions and consequently have different Weinberg angles. In particular the value sin~0=3/8 is characteristic of the sequential doublet models or models which invoke a large number of additional leptons like E 6, while addition of extra charged fermion singlets can reduce the value of sin ~ 0 to 1/4. We point out that at the present time the models of grand unification are far from unique.

Approximation algorithm for maximum independent set in planar traingle-free graphs

The maximum independent set problem is NP-complete even when restricted to planar graphs, cubic planar graphs or triangle free graphs. The problem of finding an absolute approximation still remains NP-complete. Various polynomial time approximation algorithms, that guarantee a fixed worst case ratio between the independent set size obtained to the maximum independent set size, in planar graphs have been proposed. We present in this paper a simple and efficient, O(|V|) algorithm that guarantees a ratio 1/2, for planar triangle free graphs. The algorithm differs completely from other approaches, in that, it collects groups of independent vertices at a time. Certain bounds we obtain in this paper relate to some interesting questions in the theory of extremal graphs.