Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

Balls up : the converse blank canvas project

Research background: For decades the Chuck Taylor All Star basketball shoe (first designed in 1921 by Converse, an American shoe company), has been an iconic item of fashion apparel, particularly for the youth oriented market - as a form of self expression and identify, adolescents have for generations been customising their Converse sneakers to create innovative and unique footwear. Although originally developed purely for sport, sneakers gradually crossed over into fashion and the majority of athletic shoes are now purchased for street fashion or leisure wear. Artisan Gallery (Brisbane), in conjunction with the exhibition Reboot: Function, Fashion and the Sneaker, a history of the sneaker, selected 20 designers to customise and re-design the classic Converse Chuck Taylor All Stars shoe and in doing so highlighted the diversity of forms possible for creative outcomes. As Artisan Gallery Curator Kirsten Fitzpatrick states “the ‘sports show’, designed to coincide with the Olympics, is also about exploring the sneaker as a platform for creativity... and (one) of the more bazaar creations was Dean Brough's deconstructed shoes to make men’s underwear.” The exhibition ran from 21 June – 16 August 2012: http://artisan-ideaskillproduct.blogspot.com.au/2012/06/converse-blank-canvas-project.html Research question: Even though the sneaker is a fashion item, it still is fundamentally used for foot protection and historically was aligned to ball sports, principally Basketball - as a fashion designers/practitioner how can I connect (in a whimsical manner) this history of usage for ball sports to the sneaker and re-design and re-use all the physical elements of the shoe to produce a unique wearable item of clothing - the selected medium for this challenge and experimentation was the classic archetypal men’s white boxer shorts. Artisan Statement BALLS UP - The Converse Sneaker, it’s almost impossible to imagine a better rounded item to maintain peak performance for all types of ball sports. Gentlemen, your other most precious balls also deserve this level of comfort and support to sustain the hard times – the Converse Boxer, balls up, bats out, get ready to play hard. Research contribution: The project highlighted some of the unique and diverse creative manifestations that are possible from the classic sneaker. From a fashion practitioners’ perspective, the design outcomes (men’s boxer short made from converse sneakers) demonstrated the strong association to iconic fashion apparel, and recognised the connection to wearability and comfort that is requisite in both footwear and men’s underwear. Research significance: The exhibition was viewed by in excess of 1000 people and generated exceptional media coverage and public exposure/impact. As Artisan Gallery Curator Kirsten Fitzpatrick states “20 of Brisbane's best designers were given the opportunity to customise their own Converse Sneakers, with The Converse Blank Canvas Project.” And to be selected in this category demonstrates the calibre of importance for design prominence.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Developing authentic professional knowledge through transformative community engagement in an interdisciplinary service learning project

This showcase presents a preliminary analysis of a community service learning project designed to align more authentically with contemporary society and emerging constructs of professional knowledge. As described in the paper, the project involves a multidisciplinary group of students working collaboratively with a community organisation to find creative presponses to challenging issues concerning the organisation's identity, how it interfaces with stakeholders, and how it evidences its inclusive practice. Of particular interest is how the interdisciplinary practice of the students within a service learning context encouraged reconsideration of their world0view and their rols as future professionals. Also highlighted is the need for greater congruence between the goals of the project and the structural elements of the curriculum.

‘Wanna do more math’: engaging underachieving Indigenous learners the YuMi Deadly way.

The Accelerating Indigenous Mathematics (AIM) Program offered by the YuMi Deadly Centre from QUT accelerates the mathematics learning of underperforming students in Years 8 - 10 by a) apportioning Years 2-10 Australian Curriculum: Mathematics content into three years, and b) provides a teaching approach that accelerates the mathematical learning. The philosophy of the YuMi Deadly teaching approach for mathematics is one that requires a ‘body’, ‘hand’, ‘mind’ pedagogy. This presentation will provide examples of the “‘body’, ‘hand’, ‘mind’” mathematics pedagogy. In AIM classrooms, mathematics is presented this approach is having a positive impact. Students are willing ‘to have a go’ without shame; and they develop the desire to learn and improve their numeracy.

Finitude (V03)

WHAT: An interactive installation with full body interface, digital projection, multi-touch sensitive screen surfaces, interactive 3D gaming software, motorised dioramas, 4.1 spatial sound & new furniture forms - investigating the cultural dimensions of sustainability through the lens of 'time'. “Time is change, time is finitude. Humans are a finite species. Every decision we make today brings that end closer, or alternatively pushes it further away. Nothing can be neutral”. Tony Fry DETAILS: Each participant/viewer lies comfortably on their back. Directly above them is a semi-transparent Perspex screen that displays projected 3D imagery and is simultaneously sensitive to the lightest of finger touches. Depending upon the ever changing qualities of the projected image on this screen the participant can see through its surface to a series of physical dioramas suspended above, lit by subtle LED spotlighting. This diorama consists of a slowly rotating series of physical environments, which also include several animatronic components, allowing the realtime composition of whimsical ‘landscapes’ of both 'real' and 'virtual' media. Through subtle, non-didactic touch-sensitive interactivity the participant then has influence over both the 3D graphic imagery, the physical movements of the diorama and the 4 channel immersive soundscape, creating an uncanny blend of physical and virtual media. Five speakers positioned around the room deliver a rich interactive soundscape that responds both audibly and physically to interactions.

Creating fashion professionals for the 21st century : a tale of pedagogical tensions and emerging challenges

The ‘Fashion Tales’ Conference identifies three fashion discourses: that of making, that of media, and that of scholarship. We propose a fourth, which provides a foundational base for the others: the discourse of fashion pedagogy. We begin with the argument that to thrive in any of these discourses, all fashion graduates require the ability to navigate the complexities of the 21st century fashion industry. Fashion graduates emerge into a professional world which demands a range of high level capabilities above and beyond those traditionally acknowledged by the discipline. Professional education in fashion must transform itself to accommodate these imperatives. In this paper, we document a tale of fashion learning, teaching and scholarship – the tale of a highly successful future-orientated boutique university-based undergraduate fashion course in Queensland, Australia. The Discipline consistently maintains the highest student satisfaction and lowest attrition of any course in the university, achieves extremely competitive student satisfaction scores when compared with other courses nationally and internationally, and reports outstanding graduate employment outcomes. The core of the article addresses how the course effectively balances five key pedagogical tensions identified from the findings of in-depth focus groups with graduating students, and interviews with teaching staff. The pedagogical tensions are: high concept/ authenticity; high disciplinarity/ interdisciplinarity; high rigour/ play; high autonomy/ scaffolding; and high individuality/ community, where community can be further divided into high challenge and high support. We discuss each of these tensions and how they are characterised within the course, using rich descriptions given by the students. We also draw upon the wider andragogical and learning futures literatures to link the tensions with what is already known about excellence in 21st century higher and further education curriculum and pedagogic practice. We ask: as the fashion industry becomes truly globalised, virtualised, and diversified, and as initial professional training for the industry becomes increasingly massified and performatised, what are the best teaching approaches to produce autonomous, professionally capable, enterprising and responsible graduates into the future? Can the pedagogical balances described in this case study be maintained in the light of these powerful external forces, and if so, how?

Pulse Gauntlets

To feel another person’s pulse is an intimate and physical interaction. In these prototypes we use near field communications to extend the tangible reach of our heart beat, so another person can feel our heart beat at a distance. The work is an initial experiment in near field haptic interaction, and is used to explore the quality of interactions resulting from feeling another persons pulse. The work takes the form of two feathered white gauntlets, to be worn on the fore arm. Each of the gauntlets contain a pulse sensor, radio transmitter and vibrator. The pulse of the wearer is transmitted to the other feathered gauntlet and transformed into haptic feedback. When there are two wearers, their heart beats are exchanged. To be felt by of each other without physical contact.

Shut up & write! Facilitating informal learning in doctoral education

Providing help for research degree writing within a formal structure is difficult because research students come into their degree with widely varying needs and levels of experience. Providing writing assistance within a less structured learning context is an approach which has been trialled in higher education with promising results (Boud, Cohen & Sampson, 2001; Stracke, 2010; Devendish et al., 2009). While semi structured approaches have been the subject of study, little attention has been paid to the processes of informal learning which exist within doctoral education. In this paper we explore a 'writing movement' which has started to be taken up at various locations in Australia through the auspices of social media (Twitter and Facebook). 'Shut up and Write' is a concept first used in the cafe scene in San Francisco, where writers converge at a specific time and place and write together, without showing each other the outcomes, temporarily transforming writing from a solitary practice to a social one. In this paper we compare the experience of facilitating shut up and write sessions in two locations: RMIT University and Queensland University of Technology. The authors describe the set up and functioning of the different groups and report on feedback from regular participants, both physical and virtual. We suggest that informal learning practices can be exploited to assist research students to orientate themselves to the university environment and share vital technical skills, with very minimal input from academic staff. This experience suggests there is untapped potential within these kinds of activities to promote learning within the research degree experience which is sustainable and builds a stronger sense of community.

Learning landscapes 2.0 : warning - assembly required

Twenty first century learners operate in organic, immersive environments. A pedagogy of student-centred learning is not a recipe for rooms. A contemporary learning environment is like a landscape that grows, morphs, and responds to the pressures of the context and micro-culture. There is no single adaptable solution, nor a suite of off-the-shelf answers; propositions must be customisable and infinitely variable. They must be indeterminate and changeable; based on the creation of learning places, not restrictive or constraining spaces. A sustainable solution will be un-fixed, responsive to the life cycle of the components and materials, able to be manipulated by the users; it will create and construct its own history. Learning occurs as formal education with situational knowledge structures, but also as informal learning, active learning, blended learning social learning, incidental learning, and unintended learning. These are not spatial concepts but socio-cultural patterns of discovery. Individual learning requirements must run free and need to be accommodated as the learner sees fit. The spatial solution must accommodate and enable a full array of learning situations. It is a system not an object. Three major components: 1. The determinate landscape: in-situ concrete 'plate' that is permanent. It predates the other components of the system and remains as a remnant/imprint/fossil after the other components of the system have been relocated. It is a functional learning landscape in its own right; enabling a variety of experiences and activities. 2. The indeterminate landscape: a kit of pre-fabricated 2-D panels assembled in a unique manner at each site to suit the client and context. Manufactured to the principles of design-for-disassembly. A symbiotic barnacle like system that attaches itself to the existing infrastructure through the determinate landscape which acts as a fast growth rhizome. A carapace of protective panels, infinitely variable to create enclosed, semi-enclosed, and open learning places. 3. The stations: pre-fabricated packages of highly-serviced space connected through the determinate landscape. Four main types of stations; wet-room learning centres, dry-room learning centres, ablutions, and low-impact building services. Entirely customised at the factory and delivered to site. The stations can be retro-fitted to suit a new context during relocation. Principles of design for disassembly: material principles • use recycled and recyclable materials • minimise the number of types of materials • no toxic materials • use lightweight materials • avoid secondary finishes • provide identification of material types component principles • minimise/standardise the number of types of components • use mechanical not chemical connections • design for use of common tools and equipment • provide easy access to all components • make component size to suite means of handling • provide built in means of handling • design to realistic tolerances • use a minimum number of connectors and a minimum number of types system principles • design for durability and repeated use • use prefabrication and mass production • provide spare components on site • sustain all assembly and material information

Bouncing back : the role of design and making in understanding and dealing with adversity

The Bouncing Back Project, which began after the Queensland flood event in January 2011, has organically grown through a number of reiterations as per the diagram above. In the August 2011 it resulted in the physical construction of an Emergency Shelter [designed by GreenLeaf Engineers] in Sydney at the Customs House in Circular Quay and a conference paper publication at the AASA conference. To date this research has progressed without any research grant funding and has resulted in significant media interest. During the construction of the Emergency Shelter we collected a wide range of multimedia data which is being compilled into a documentary focusing on the architecture students’ experience throughout the iterations of Bouncing Back.

Speaker linking using complete-linkage clustering

Speaker diarization determines instances of the same speaker within a recording. Extending this task to a collection of recordings for linking together segments spoken by a unique speaker requires speaker linking. In this paper we propose a speaker linking system using linkage clustering and state-of-the-art speaker recognition techniques. We evaluate our approach against two baseline linking systems using agglomerative cluster merging (AC) and agglomerative clustering with model retraining (ACR). We demonstrate that our linking method, using complete-linkage clustering, provides a relative improvement of 20% and 29% in attribution error rate (AER), over the AC and ACR systems, respectively.

Speaker attribution of multiple telephone conversations using a complete-linkage clustering approach

In this paper we propose and evaluate a speaker attribution system using a complete-linkage clustering method. Speaker attribution refers to the annotation of a collection of spoken audio based on speaker identities. This can be achieved using diarization and speaker linking. The main challenge associated with attribution is achieving computational efficiency when dealing with large audio archives. Traditional agglomerative clustering methods with model merging and retraining are not feasible for this purpose. This has motivated the use of linkage clustering methods without retraining. We first propose a diarization system using complete-linkage clustering and show that it outperforms traditional agglomerative and single-linkage clustering based diarization systems with a relative improvement of 40% and 68%, respectively. We then propose a complete-linkage speaker linking system to achieve attribution and demonstrate a 26% relative improvement in attribution error rate (AER) over the single-linkage speaker linking approach.

Re-use of domain knowledge to provide confidence for adoption of off-site manufacturing for construction in Australia

Many construction industry decision-makers believe there is a lack of off-site manufacture (OSM) adoption for non-residential construction in Australia. Identification of construction business process was considered imperative in order to assist decision-makers to increase OSM utilisation. The premise that domain knowledge can be re-used to provide an intervention point in the construction process led a team of researchers to construct simple base-line process models for the complete construction process, segmented into six phases. Sixteen domain knowledge industry experts were asked to review the construction phase base-line models to answer the question “Where in the process illustrated by this base-line model phase is an OSM task?”. Through an iterative and generative process a number of off-site manufacture intervention points were identified and integrated into the process models. The re-use of industry expert domain knowledge provided suggestions for new ways to do basic tasks thus facilitating changes to current practice. It is expected that implementation of the new processes will lead to systemic industry change and thus a growth in productivity due to increased adoption of OSM.