Differential gene expression in breast cancer cell lines and stroma-tumor differences in microdissected breast cancer biopsies revealed by display array analysis

To examine gene-expression patterning in late-stage breast cancer biopsies, we used a microdissection technique to separate tumor from the surrounding breast tissue or stroma. A DD-PCR protocol was then used to amplify expressed products, which were resolved using PAGE and used as probe to hybridize with representative human arrays and cDNA libraries. The probe derived from the tumor–stroma comparison was hybridized with a gene array and an arrayed cDNA library derived from a GCT of bone; 21 known genes or expressed sequence tags were detected, of which 17 showed differential expression. These included factors associated with epithelial to mesenchymal transition (vimentin), the cargo selection protein (TIP47) and the signal transducer and activator of transcription (STAT3). Northern blot analysis was used to confirm those genes also expressed by representative breast cancer cell lines. Notably, 6 genes of unknown function were restricted to tumor while the majority of stroma-associated genes were known. When applied to transformed breast cancer cell lines (MDA-MB-435 and T47D) that are known to have different metastatic potential, DD array analysis revealed a further 20 genes; 17 of these genes showed differential expression. Use of microdissection and the DD-PCR array protocol allowed us to identify factors whose localized expression within the breast may play a role in abnormal breast development or breast carcinogenesis.

Reimagining learning spaces : A research report for the Queensland Council for Social Science Innovation

The purpose of the Reimagining Learning Spaces project was to conduct an empirical study that would result in findings to inform the design and use of physical school facilities and examine the ways in which these constructions influence pedagogy. The study focused on newly-established school libraries in Queensland, many of which had been established with funding from the Federal Government’s Building the Education Revolution economic stimulus program. To explore the field, the study sought multiple perspectives that included those of school students as well as teacher-librarians and other key school staff, addressing the following focus question: - How does the physical environment of school libraries influence pedagogic practices and learning outcomes? Further research questions that guided the inquiry included: - What are the implications for teacher-librarians when transitioning into a new library learning space? - How do members of the school community (principals, teachers, teacher-librarians and students) experience the creation of a new school library learning space? - How do school students imagine the design and use of engaging library learning spaces? An extensive review explored Australian and international literature based on the research questions, focused on the following major areas: • School library renewal: trends in reimagining the place of libraries in virtual and real space • School libraries as learning spaces: the expanded role of school libraries in whole-school pedagogical support. • The role of teacher-librarians in new times • Built environments and the implications for learning • Learners and learning in newly established spaces • Learning space design: perspectives, research and principles • Pedagogical principles and voices of experience • Transitions to newly created learning spaces Approach Using an innovative qualitative research design, Reimagining Learning Spaces investigated learner and teacher perspectives across three intersecting domains exploring: - Imagined spaces: learners’ imaginative concepts of learning within engaging learning environments; - Emerging spaces: experiences of teacher-librarians in the transition into new spaces for learning, and - Established spaces: learners’ and teachers’ perceptions of ways in which the physical environment influences and shapes pedagogy. Seven schools that had recently benefitted from the BER program became the research sites at which data were collected from teacher-librarians, teachers, school leaders and students. With this range of participants, an appropriately diverse set of data collection tools was developed, including video interviews, drawings, and focus groups. Evocative narrative case studies (Simons 2009) were developed from the data, representing the voices of users of learning spaces. Key findings The study’s findings are presented in this report and complemented by an array of visual materials on the project web site http:// The report includes: • a set of seven cases studies that reveal nuanced experiences of designing and creating school libraries, based on the narrative of key stakeholders (teacher-librarians, teachers, students and principals) • thematic discussion of student imaginings of their ideal school library, based on drawings and narrative of students at the seven case study schools • critical analysis of the case study and student imaginings, focusing on implications for (re)designing school learning spaces and pedagogy, and responding to the study’s overarching research question - .17 recommendations to support: designing, transitioning and reimagining pedagogy; leadership; and policy development

An intuitive dashboard for Bayesian network inference

Current Bayesian network software packages provide good graphical interface for users who design and develop Bayesian networks for various applications. However, the intended end-users of these networks may not necessarily find such an interface appealing and at times it could be overwhelming, particularly when the number of nodes in the network is large. To circumvent this problem, this paper presents an intuitive dashboard, which provides an additional layer of abstraction, enabling the end-users to easily perform inferences over the Bayesian networks. Unlike most software packages, which display the nodes and arcs of the network, the developed tool organises the nodes based on the cause-and-effect relationship, making the user-interaction more intuitive and friendly. In addition to performing various types of inferences, the users can conveniently use the tool to verify the behaviour of the developed Bayesian network. The tool has been developed using QT and SMILE libraries in C++.

Design LED innovation to rejuvenate local food systems and healthy communities : an emerging research agenda

Food Sovereignty (food freedom) is about empowering people to develop their own local food system. Food Sovereignty challenges designers to enable people to innovate the local food system, rather than having a food system which is dictated by corporate interests and failed business ethics. Communities are realising the potential for design to assist in the innovation process, and add strategic value to potentially localise the food system. Design Led Innovation (DLI) offers a strategic framework to address large-scale cultural, systemic and economic changes. The DLI approach empowers communities to take organised action to achieve a healthy, prosperous and happy way of life. DLI can assist with business models in the business world and it is evident this approach can assist with creating social change too. This paper presents on an emerging research agenda aimed to assist designer’s focus from individuals and systems to communities and urban problems. This paper also presents the research proposition that DLI and service design coupled with social entrepreneurial ventures such as local food projects and creative community inventions, have the potential to enable social innovation for healthy and happy communities.

Teaching design thinking and design led innovation to non-designers : a tertiary facilitator multidisciplinary study

This paper aims to address the knowledge gap in regards to the potential intermediary role tertiary institutions can play in developing generic design thinking/design led innovation capabilities in non-designers. Specifically, it investigates the value derived from the contribution of postgraduate design students as facilitators/educators for undergraduate non-design student cohorts. It examines a design immersion workshop designed to encourage the use of design thinking capabilities for project brief development for undergraduate multi-disciplinary student teams involved in a community service learning project for a social enterprise. The workshop was facilitated by design led innovation masters students embedded in industry organisations to research the integration of design led innovation capabilities in business. Data was collected from participating non-design students and postgraduate facilitators’ in the form of reflective journals and semi-structured interviews. The thematic analysis provided insight into the value of design thinking/design led innovation immersion programs for both the postgraduate facilitators and the undergraduate non-design students. The research results will inform a tentative foundation prototype framework to allow for ongoing program developments and research in design thinking/design led innovation integration in higher education, facilitating the development of generic capabilities required to empower future generations for business innovation and active citizenship in the 21st century knowledge economy.

Designing innovative business models: Five emerging meta-models

Business models to date have remained the creation of management, however, it is the belief of the authors that designers should be critically approaching, challenging and creating new business models as part of their practice. This belief portrays a new era where business model constructs become the new design brief of the future and fuel design and innovation to work together at the strategic level of an organisation. Innovation can no longer rely on technology and R&D alone but must incorporate business models. Business model innovation has become a strong type of competitive advantage. As firms choose not to compete only on price, but through the delivery of a unique value proposition in order to engage with customers and to differentiate a company within a competitive market. The purpose of this paper is to explore and investigate business model design through various product and/or service deliveries, and identify common drivers that are catalysts for business model innovation. Fifty companies spanning a diverse range of criteria were chosen, to evaluate and compare commonalities and differences in the design of their business models. The analysis of these business cases uncovered commonalities of the key strategic drivers behind these innovative business models. Five Meta Models were derived from this content analysis: Customer Led, Cost Driven, Resource Led, Partnership Led and Price Led. These five key foci provide a designer with a focus from which quick prototypes of new business models are created. Implications from this research suggest there is no ‘one right’ model, but rather through experimentation, the generation of many unique and diverse concepts can result in greater possibilities for future innovation and sustained competitive advantage.

Early challenges of shifting an Australian manufacturer’s utilisation of design

This paper presents the findings from the initial exploration phase of an 11 month project, identifying the early challenges that a design innovation catalyst faces while initiating a shift in the way a medium sized manufacturing firm utilises design. Ultimately, the overarching aims of the project are to transform the utilisation of design within the participating company from a styling tool to a strategic process through the implementation of a design led approach to innovation. Insights were found through qualitative interviews with company staff and reflective journal entries as part of an Action Research methodology. Challenges identified include managing expectations, conveying the potential of a design innovation catalyst and a design led approach to innovation, and a siloed and risk averse culture. Findings presented in this paper will assist in identifying and understanding the preliminary challenges encountered by a design innovation catalyst when embarking on a design led transformation. Future innovation catalysts can prepare for possible barriers by highlighting considerations, opportunities and challenges when embarking on a design led transformation. Implications of this research are provided as possible approaches to overcoming these challenges.

Can emotion provide a new approach to business model innovation?

Companies require new strategies to drive growth and survival, as the fast pace of change has created the need for greater business flexibility. Therefore, industry leaders are looking to business innovation as a principle source of differentiation and competitive advantage. However, most companies rely heavily on either technology or products to provide business innovation, yet competitors can easily and rapidly surpass these forms of innovation. Business model innovation expands beyond innovation in isolated areas, such as product innovation, to create strategies that incorporate many business avenues to work together to create and deliver value to its customers. Existing literature highlights that a business model’s central role is ‘customer value’. However, the emotional underpinnings of customer value within a business model are not well understood. The integration of customer emotion into business model design and value chain can be viewed as a way to innovate beyond just products, services and processes. This paper investigates the emotional avenues within business strategy and operations, business model innovation and customer engagement. Three propositions are outlined and explored as future research. The significance of this research is to provide companies with a new approach to innovation through a deeper understanding and integration of their customers’ emotions.

From production to purpose : using design led innovation to Build Strategic Potential in a Family-Owned SME

There is an evident need to develop the strategic capabilities of companies from within, to ensure competitive competence in a time where strategy is a necessity. This paper is based on the first 4 months of a longitudinal embedded case study of a family-owned Australian small to medium enterprise, in their journey towards design integration. The first author was embedded as a ‘Design Innovation Catalyst’ to collaborate on overcoming early barriers of strategic development, using design led innovation. Action research methodology, semi-structured interviews with seven out of eight employees and a reflective journal revealed the absence of a shared vision, conflicting drivers and a focus on operational efficiency rather than strategy. Through the Catalyst’s facilitation, a company vision, general awareness, practice and knowledge in strategic development have emerged as the first steps to generating strategic design competence within the firm.

The challenges of adopting design-led innovative strategies in not for profits : the role of consumers, culture and employees

Major changes to regulations, funding and consumer demand in the Australian aged care industry are driving not for profits in this sector to reshape and rethink the services they offer and the ways in which they deliver their services to consumers. Many not for profit organisations facing these new challenges are also facing organisational cultural barriers in the development and implementation of innovative strategies. This paper presents a case study where one organisation, using design led innovation, explored consumer insights and employee values to find new ways to facilitate change.

Design led innovation : shifting from smart follower to digital strategy leader in the Australian airport sector

This paper presents and discusses organisational barriers and opportunities arising from the dissemination of design led innovation within a leading Australian airport corporation. This research is part of a greater action research program which aims to integrate design as a strategic capability through design led innovation within Australian businesses. Findings reveal that there is an opportunity to employ the theoretical framework and tools of design led innovation in practice to build collaborative idea generation by involving customers and stakeholders within the proposal of new to world propositions. The iterative gathering of deep customer insights also provided an opportunity to leverage a greater understanding of stakeholders and customers in strengthening continuing business partnerships through co-design. Challenges to the design led approach include resistance to the exploratory nature of gathering deep customer insights, the testing of long held assumptions and market data, and the disruption of an organisational mindset geared toward risk aversion instilled within the aviation industry. The implication from these findings is that design led innovation can provide the critical platform to allow for a business to grow and sustain internal design capabilities necessary to challenge prevailing assumptions about how its business model operates to deliver value to customers and stakeholders alike. The platform of design led innovation also provides an avenue to support a cultural transformation towards anticipating future needs necessary for establishing a position of leadership within the broader economic environment.

Making sense of purpose, direction and innovation : an embedded design led innovation case study in the Australian mining industry

The mining equipment technology services sector is driven by a reactive and user-centered design approach, with a technological focus on incremental new product development. As Australia moves out of its sustained mining boom, companies need to rethink their strategic position, to become agile to stay relevant in an enigmatic market. This paper reports on the first five months on an embedded case study within an Australian, family-owned mining manufacturer. The first author is currently engaged in a longitudinal design led innovation project, as a catalyst to guide the company’s journey to design integration. The results find that design led innovation could act as a channel for highlighting and exploring company disconnections with the marketplace and offer a customer-centric catalyst for internal change. Data collected for this study is from 12 analysed semistructured interviews, a focus group and a reflective journal, over a five-month period. This paper explores limitations to design integration, and highlights opportunities to explore and leverage entrepreneurial characteristics to stay agile, broaden innovation and future-proof through the next commodity cycle in the mining industry.

De Novo Transcriptome Sequence Assembly and Analysis of RNA Silencing Genes of Nicotiana benthamiana

Background: Nicotiana benthamiana has been widely used for transient gene expression assays and as a model plant in the study of plant-microbe interactions, lipid engineering and RNA silencing pathways. Assembling the sequence of its transcriptome provides information that, in conjunction with the genome sequence, will facilitate gaining insight into the plant's capacity for high-level transient transgene expression, generation of mobile gene silencing signals, and hyper-susceptibility to viral infection. Methodology/Results: RNA-seq libraries from 9 different tissues were deep sequenced and assembled, de novo, into a representation of the transcriptome. The assembly, of16GB of sequence, yielded 237,340 contigs, clustering into 119,014 transcripts (unigenes). Between 80 and 85% of reads from all tissues could be mapped back to the full transcriptome. Approximately 63% of the unigenes exhibited a match to the Solgenomics tomato predicted proteins database. Approximately 94% of the Solgenomics N. benthamiana unigene set (16,024 sequences) matched our unigene set (119,014 sequences). Using homology searches we identified 31 homologues that are involved in RNAi-associated pathways in Arabidopsis thaliana, and show that they possess the domains characteristic of these proteins. Of these genes, the RNA dependent RNA polymerase gene, Rdr1, is transcribed but has a 72 nt insertion in exon1 that would cause premature termination of translation. Dicer-like 3 (DCL3) appears to lack both the DEAD helicase motif and second dsRNA binding motif, and DCL2 and AGO4b have unexpectedly high levels of transcription. Conclusions: The assembled and annotated representation of the transcriptome and list of RNAi-associated sequences are accessible at www.benthgenome.com alongside a draft genome assembly. These genomic resources will be very useful for further study of the developmental, metabolic and defense pathways of N. benthamiana and in understanding the mechanisms behind the features which have made it such a well-used model plant. © 2013 Nakasugi et al.

Description of plant tRNA-derived RNA fragments (tRFs) associated with argonaute and identification of their putative targets

tRNA-derived RNA fragments (tRFs) are 19mer small RNAs that associate with Argonaute (AGO) proteins in humans. However, in plants, it is unknown if tRFs bind with AGO proteins. Here, using public deep sequencing libraries of immunoprecipitated Argonaute proteins (AGO-IP) and bioinformatics approaches, we identified the Arabidopsis thaliana AGO-IP tRFs. Moreover, using three degradome deep sequencing libraries, we identified four putative tRF targets. The expression pattern of tRFs, based on deep sequencing data, was also analyzed under abiotic and biotic stresses. The results obtained here represent a useful starting point for future studies on tRFs in plants. © 2013 Loss-Morais et al.; licensee BioMed Central Ltd.

Construct design for efficient, effective and high-throughput gene silencing in plants

Post-transcriptional silencing of plant genes using anti-sense or co-suppression constructs usually results in only a modest proportion of silenced individuals. Recent work has demonstrated the potential for constructs encoding self-complementary 'hairpin' RNA (hpRNA) to efficiently silence genes. In this study we examine design rules for efficient gene silencing, in terms of both the proportion of independent transgenic plants showing silencing, and the degree of silencing. Using hpRNA constructs containing sense/anti-sense arms ranging from 98 to 853 nt gave efficient silencing in a wide range of plant species, and inclusion of an intron in these constructs had a consistently enhancing effect. Intron-containing constructs (ihpRNA) generally gave 90-100% of independent transgenic plants showing silencing. The degree of silencing with these constructs was much greater than that obtained using either co-suppression or anti-sense constructs. We have made a generic vector, pHANNIBAL, that allows a simple, single PCR product from a gene of interest to be easily converted into a highly effective ihpRNA silencing construct. We have also created a high-throughput vector, pHELLSGATE, that should facilitate the cloning of gene libraries or large numbers of defined genes, such as those in EST collections, using an in vitro recombinase system. This system may facilitate the large-scale determination and discovery of plant gene functions in the same way as RNAi is being used to examine gene function in Caenorhabditis elegans.