Mineralized human primary osteoblast matrices as a model system to analyse interactions of prostate cancer cells with the bone microenvironment

Prostate cancer metastasis is reliant on the reciprocal interactions between cancer cells and the bone niche/micro-environment. The production of suitable matrices to study metastasis, carcinogenesis and in particular prostate cancer/bone micro-environment interaction has been limited to specific protein matrices or matrix secreted by immortalised cell lines that may have undergone transformation processes altering signaling pathways and modifying gene or receptor expression. We hypothesize that matrices produced by primary human osteoblasts are a suitable means to develop an in vitro model system for bone metastasis research mimicking in vivo conditions. We have used a decellularized matrix secreted from primary human osteoblasts as a model for prostate cancer function in the bone micro-environment. We show that this collagen I rich matrix is of fibrillar appearance, highly mineralized, and contains proteins, such as osteocalcin, osteonectin and osteopontin, and growth factors characteristic of bone extracellular matrix (ECM). LNCaP and PC3 cells grown on this matrix, adhere strongly, proliferate, and express markers consistent with a loss of epithelial phenotype. Moreover, growth of these cells on the matrix is accompanied by the induction of genes associated with attachment, migration, increased invasive potential, Ca2+ signaling and osteolysis. In summary, we show that growth of prostate cancer cells on matrices produced by primary human osteoblasts mimics key features of prostate cancer bone metastases and thus is a suitable model system to study the tumor/bone micro-environment interaction in this disease.

What will the Apple iPad deliver for newspapers?

The launch of the Apple iPad in January 2010 was one of the most anticipated and publicised launched of a new technological device in recent history. Positioning itself as between a smart phone and a PC, but with the attributes of both, Apple have sought to develop a new market niche with the iPad for tablet PC devices, and early signs are that market expectations are being met.. The iPad’s launch was potentially fortuitous for the newspaper industry worldwide, as it offered the potential to address its two recurring problems: the slow but inexorable decline of print media circulation, and the inability to satisfactorily monetise online readerships. As a result, the Apple iPad has benefited from an enormous amount of free publicity in newspapers, as they develop their own applications (apps) for the device. This paper reports on findings from work undertaken through Smart Services CRC into potential take-up and likely uses of the iPad, and their implications for the news media industry. It reports on focus group analysis undertaken in the mid-2010 using “customer job mapping” methodologies, that draw attention to current gaps in user behaviour in terms of available devices, in order to anticipate possibilities beyond the current “three screens” of PC, mobile phone and television.

New media services : ratings and recommendations websites in the travel and tourism industry

The travel and hospitality industry is one which relies especially crucially on word of mouth, both at the level of overall destinations (Australia, Queensland, Brisbane) and at the level of travellers’ individual choices of hotels, restaurants, sights during their trips. The provision of such word-of-mouth information has been revolutionised over the past decade by the rise of community-based Websites which allow their users to share information about their past and future trips and advise one another on what to do or what to avoid during their travels. Indeed, the impact of such user-generated reviews, ratings, and recommendations sites has been such that established commercial travel advisory publishers such as Lonely Planet have experienced a pronounced downturn in sales ¬– unless they have managed to develop their own ways of incorporating user feedback and contributions into their publications. This report examines the overall significance of ratings and recommendation sites to the travel industry, and explores the community, structural, and business models of a selection of relevant ratings and recommendations sites. We identify a range of approaches which are appropriate to the respective target markets and business aims of these organisations, and conclude that there remain significant opportunities for further operators especially if they aim to cater for communities which are not yet appropriately served by specific existing sites. Additionally, we also point to the increasing importance of connecting stand-alone ratings and recommendations sites with general social media spaces like Facebook, Twitter, and LinkedIn, and of providing mobile interfaces which enable users to provide updates and ratings directly from the locations they happen to be visiting. In this report, we profile the following sites: * TripAdvisor, the international market leader for travel ratings and recommendations sites, with a membership of some 11 million users; * IgoUgo, the other leading site in this field, which aims to distinguish itself from the market leader by emphasising the quality of its content; * Zagat, a long-established publisher of restaurant guides which has translated its crowdsourcing model from the offline to the online world; * Lonely Planet’s Thorn Tree site, which attempts to respond to the rise of these travel communities by similarly harnessing user-generated content; * Stayz, which attempts to enhance its accommodation search and booking services by incorporating ratings and reviews functionality; and * BigVillage, an Australian-based site attempting to cater for a particularly discerning niche of travellers; * Dopplr, which connects travel and social networking in a bid to pursue the lucrative market of frequent and business travellers; * Foursquare, which builds on its mobile application to generate a steady stream of ‘check-ins’ and recommendations for hospitality and other services around the world; * Suite 101, which uses a revenue-sharing model to encourage freelance writers to contribute travel writing (amongst other genres of writing); * Yelp, the global leader in general user-generated product review and recommendation services. In combination, these profiles provide an overview of current developments in the travel ratings and recommendations space (and beyond), and offer an outlook for further possibilities. While no doubt affected by the global financial downturn and the reduction in travel that it has caused, travel ratings and recommendations remain important – perhaps even more so if a reduction in disposable income has resulted in consumers becoming more critical and discerning. The aggregated word of mouth from many tens of thousands of travellers which these sites provide certainly has a substantial influence on their users. Using these sites to research travel options has now become an activity which has spread well beyond the digirati. The same is true also for many other consumer industries, especially where there is a significant variety of different products available – and so, this report may also be read as a case study whose findings are able to be translated, mutatis mutandis, to purchasing decisions from household goods through consumer electronics to automobiles.

What will the Apple iPad deliver for newspapers?

The launch of the Apple iPad in January 2010 was one of the most anticipated and publicised launched of a new technological device in recent history. Positioning itself as between a smart phone and a PC, but with the attributes of both, Apple have sought to develop a new market niche with the iPad for tablet PC devices, and early signs are that market expectations are being met.. The iPad’s launch was potentially fortuitous for the newspaper industry worldwide, as it offered the potential to address its two recurring problems: the slow but inexorable decline of print media circulation, and the inability to satisfactorily monetise online readerships. As a result, the Apple iPad has benefited from an enormous amount of free publicity in newspapers, as they develop their own applications (apps) for the device. This paper reports on findings from work undertaken through Smart Services CRC into potential take-up and likely uses of the iPad, and their implications for the news media industry. It reports on focus group analysis undertaken in the mid-2010 using “customer job mapping” methodologies, that draw attention to current gaps in user behaviour in terms of available devices, in order to anticipate possibilities beyond the current “three screens” of PC, mobile phone and television.

Where money and meanings meet : theorizing the emergence of new values in media and education

Recent developments in technology, globalization, and consumer activism have challenged the "broadcasting model" of natonally bounded, vertically integrated, monopolistic, expert-paradigm media industries, dedicated to supplying leisure entertainment to more or less passive consumers. Instead, attention has turned to globally traded formats, social network markets, consumer-created content, multiplatform "publication," and a semiotic long tail where niche representations can be as valuable as blockbusters. Such chenges are just as much a challenge to education as they are to business models. And education, both formal and informal, is a dynamic agent in these processes, participation, and creative content require a rethink of "studies" just as much as of "media."

Tips for generating a media release and media coverage : how the media ate up my research on Aussie horror movies

The focus of this paper is preparing research for dissemination by mainstream print, broadcast, and online media. While the rise of the blogosphere and social media is proving an effective way of reaching niche audiences, my own research reached such an audience through traditional media. The first major study of Australian horror cinema, my PhD thesis A Dark New World: Anatomy of Australian Horror Films, generated strong interest from horror movie fans, film scholars, and filmmakers. I worked closely with the Queensland University of Technology’s (QUT) public relations unit to write two separate media releases circulated on October 13, 2008 and October 14, 2009. This chapter reflects upon the process of working with the media and provides tips for reaching audiences, particularly in terms of strategically planning outcomes. It delves into the background of my study which would later influence my approach to the media, the process of drafting media releases, and key outcomes and benefits from popularising research. A key lesson from this experience is that redeveloping research for the media requires a sharp writing style, letting go of academic justification, catchy quotes, and an ability to distil complex details into easy-to-understand concepts. Although my study received strong media coverage, and I have since become a media commentator, my experiences also revealed a number of pitfalls that are likely to arise for other researchers keen on targeting media coverage.

Review of Apple iPad news applications : new media service

The launch of the Apple iPad on January 2010 has seen considerable interest from the newspaper and publishing industry in developing content and business models for the tablet PC device that can address the limits of both the print and online news and information media products. It is early days in the iPad’s evolution, and we wait to see what competitor devices will emerge in the near future. It is apparent, however, that it has become a significant “niche��� product, with considerable potential for mass market expansion over the next few years, possibly at the expense of netbook sales. The scope for the iPad and tablet PCs to become a “fourth screen” for users, alongside the TV, PC and mobile phone, is in early stages of evolution. The study used five criteria to assess iPad apps: • Content: timeliness; archive; personalisation; content depth; advertisements; the use of multimedia; and the extent to which the content was in sync with the provider brand. • Useability: degree of static content; ability to control multimedia; file size; page clutter; resolution; signposts; and customisation. • Interactivity: hyperlinks; ability to contribute content or provide feedback to news items; depth of multimedia; search function; ability to use plug-ins and linking; ability to highlight, rate and/or save items; functions that may facilitate a community of users. • Transactions capabilities: ecommerce functionality; purchase and download process; user privacy and transaction security. • Openness: degree of linking to outside sources; reader contribution processes; anonymity measures; and application code ownership.

Strategic management of technology in construction : a framework and case study

This case study analyzes a firm's technology strategy for its fit or match with the requirements of the industry environment in which it operates. Understanding the relationships between market characteristics and technology strategies can assist managers in making complex and difficult decisions regarding their use of technology to improve competitive performance. Using the technology strategy framework, managers can map their own capabilities for comparison with the more appropriate or superior approach to technology in that industry environment. Alternatively, firms seeking to transition from one industry niche or environment to another could identify and move to acquire the required capabilities. The dynamics of industry competition, both domestic and international, emphasize the need for improved management of the strategic fit between technical capabilities and industry environment.

Investigation into the introduction of clonal strains of Pseudomonas aeruginosa to the cystic fibrosis population by consumption of raw salad vegetables

Most salad vegetables are eaten fresh by consumers. However, raw vegetables may pose a risk of transmitting opportunistic bacteria to immunocompromised people, including cystic fibrosis (CF) patients. In particular, CF patients are vulnerable to chronic Pseudomonas aeruginosa lung infections and this organism is the primary cause of morbidity and mortality in this group. Clonal variants of P. aeruginosa have been identified as emerging threats to people afflicted with CF; however it has not yet been proven from where these clones originate or how they are transmitted. Due to the organisms‟ aquatic environmental niche, it was hypothesised that vegetables may be a source of these clones. To test this hypothesis, lettuce, tomatoes, mushrooms and bean sprout packages (n = 150) were analysed from a green grocer, supermarket and farmers‟ market within the Brisbane region, availability permitting. The internal and external surfaces of the vegetables were separately analysed for the presence of clonal strains of P. aeruginosa using washings and homogenisation techniques, respectively. This separation was in an attempt to establish which surface was contaminated, so that recommendations could be made to decrease or eliminate P. aeruginosa from these foods prior to consumption. Soil and water samples (n = 17) from local farms were also analysed for the presence of P. aeruginosa. Presumptive identification of isolates recovered from these environmental samples was made based on growth on Cetrimide agar at 42°C, presence of the cytochrome-oxidase enzyme and inability to ferment lactose. P. aeruginosa duplex real-time polymerase chain reaction assay (PAduplex) was performed on all bacterial isolates presumptively identified as P. aeruginosa. Enterobacterial repetitive intergenic consensus strain typing PCR (ERIC-PCR) was subsequently performed on confirmed bacterial isolates. Although 72 P. aeruginosa were isolated, none of these proved to be clonal strains. The significance of these findings is that vegetables may pose a risk of transmitting sporadic strains of P. aeruginosa to people afflicted with CF and possibly, other immunocompromised people.

The last post? Tracking the Australasian to Aussie Post, 1864-2002

Aussie Post, the flagship of ocker Australiana, folded in January 2002. Post began life as the Australasian, a middlebrow magazine steeped in a nineteenth century civics of stable citizenship with a modicum of diversionary leisure. The transformation began when the Australasian became Australasian Post in 1946 under George Johnston's brief 15-week editorship. Johnston's idealistic vision of Post as a voice of post-war Australian modernity was soon overtaken by commercial imperatives as Post's identity wavered between its civic antecedents and a new low-brow populism, a niche it had finally settled into by the mid-1950s. This tension between staid civics and risqué populism shaped the magazine's long evolution into its final realisation of the pictorial general interest genre. This paper, based on a close examination of the magazines themselves, tracks Post's generic evolution and focuses on the struggle to redefine the magazine’s identity during the post-war period when the axis of Australian identity was reluctantly shifting from the staid traditions of Rule Britannia to the flashy modernity of Pax Americana.

Biomashups: the new world of exploratory bioinformatics?

Bioinformatics is dominated by online databases and sophisticated web-accessible tools. As such, it is ideally placed to benefit from the rapid, purpose specific combination of services achievable via web mashups. The recent introduction of a number of sophisticated frameworks has greatly simplified the mashup creation process, making them accessible to scientists with limited programming expertise. In this paper we investigate the feasibility of mashups as a new approach to bioinformatic experimentation, focusing on an exploratory niche between interactive web usage and robust workflows, and attempting to identify the range of computations for which mashups may be employed. While we treat each of the major frameworks, we illustrate the ideas with a series of examples developed under the Popfly framework

Influence of culture conditions on the molecular signature of mesenchymal stem cells

Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche��� required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.

Diversity in action : minority group media and social change

My thesis consists of a creative work plus an exegesis. This exegesis uses case study research to investigate three Brisbane-based media organisations and the role they play in encouraging social inclusion and other positive social change for specific disadvantaged and stigmatised minority groups. Bailey, Cammaerts and Carpentier’s theoretical approach to alternative media forms the basis of this research. Bailey et al. (2008, p. 156) view alternative media organisations as having four important roles, two media-centred and two society-centred, which must all be considered to best understand them: • serving their communities • acting as an alternative to mainstream media discourses • promoting and advocating democratisation in the media and through the media in society • functioning as a crossroads in civil society. The first case study, about community radio station 4RPH (Radio for the Print Handicapped), centres on promoting social inclusion for people with a print disability through access to printed materials (primarily mainstream print media) in an audio format. The station also provides important opportunities for members of this group to produce media and, to a lesser extent, provides disability-specific information and discussions. The second case study, about gay print and online magazine Queensland Pride, focuses on promoting social inclusion and combating the discrimination and repression of people who identify as lesbian, gay, bisexual or transgender. Central issues include the representation (including sexualised representation) of a subculture and niche target market, and the impact of commercialisation on this free publication. The third case study, about community radio station 98.9FM, explores the promotion of social inclusion for peoples whose identity, cultures, issues, politics and contributions are often absent or misrepresented in the mainstream media. This radio station provides “a first level of service” (Meadows & van Vuuren, 1998, p. 104) to these people, but also informs and entertains those in the majority society. The findings of this research suggest that there are two key mechanisms that help these media organisations to effect social change: first, strengthening the minority community and serving its needs, and second, fostering connections with the broader society.

Value management : an extension of quantity surveying services in Malaysia

Value Management (VM) initially started in early 1940s in the US manufacturing industry has increasingly becoming popular within the construction industry community internationally. It has been widely accepted as an important tool in the management of projects. The structured, systematic and multi-disciplinary approach in decision making process is a niche for VM in delivering better value for money project to the client investment. It would appear to be gaining some momentum as an essential management tool in the Malaysian construction sector especially in the quantity surveying practice. Quantity surveyors increasing involvement in VM provides an opportunity for the profession to re-model some of its traditional services in a more positive light and develop leading-edge skills and promote the profession. International practice has associated VM to be part of services offered in the quantity surveying practice; especially in UK has proven to be a natural progression of QS profession. The introduction of VM as early 1980’s in Malaysia combined with increasing demand for construction project to facilitate nation progress is shedding a positive light for quantity surveying profession to take lead in developing VM as one of their niche area. Therefore, the quantity surveying profession having the opportunity to take lead of this service which reflect their traditional attributes for providing the best value-for-money advise to the client. This paper shall discuss on the development of VM in Malaysia and the challenges VM face services in QS firm to remain ahead of their competitors.