Competitive advantages as a foundation for social advantage: The role of social enterprise in regional development

The belief that regions play a role in determining national economic development and that advantages are found at the local and regional level has been the focus of economic geography and development studies over the last 10 years. However, this issue has historically been dominated by economic perspectives, industrial firms, and public bodies. In recent years the social economy is starting to receive greater attention in creating regional advantage as well as ameliorating regional disadvantage. The social economy includes the impact of the third sector such as social enterprises. This paper proposes that understanding the role and function of social enterprise will enable a more nuanced understanding of the socio-economic aspects of regional development. Drawing upon Oliver’s (1997) framework for sustainable competitive advantage it is argued that this established management framework provides a valuable foundation for examining the organisational resources that social enterprise need to operate effectively, as well as the socio-economic resources they produce for regional communities.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

Submission to House Standing Committee on Infrastructure and Communications : inquiry into the role and potential of the National Broadband Network

Just as telecommunications has played a key role in the global economy,1 high-speed broadband will have a significant role to play in the future of the digital economy. In particular high-speed broadband will have a role to play in the delivery of applications and services necessary for acquiring, and maintaining into the future Australia and Australians’ appropriate education level; community; health services, information provision and support; government services and engagement and participation by the public in the political process.

Orals ain’t orals : the role of prepared oral presentations in the classroom and beyond. How do instruction and feedback practices guide delivery choices?

Despite an ostensibly technology-driven society, the ability to communicate orally continues to feature as an essential ability for students at school and university, as it is for graduates in the workplace. Pedagogically, one rationale is that the need to develop effective oral communication skills is tied to life-long learning which includes successful participation in future work-related tasks. One tangible way that educators have assessed proficiency in the area of communication is through prepared oral presentations. While much of the literature uses the terms 'oral communication' and 'oral presentation' interchangeably, some writers question the role more formal presentations play in the overall development of oral communication skills. However, such formal speaking tasks continue to be a recognised assessment practice in both the secondary school and academy, and, therefore, worthy of further investigation. Adding to the discussion, this thesis explores the knowledge and skills students bring into the academy from previous educational experiences. It examines some of the teaching and assessment methods used in secondary schools to develop oral communication skills through the use of formal oral presentations. Specifically, it investigates criterion-referenced assessment sheets and how these tools are used as a form of instruction, as well as their role and effectiveness in the evaluation of student ability. The focus is on the student's perspective and includes 12 semi-structured interviews with school students. The purpose of this thesis is to explore key thematics underpinning oral communication and to identify tensions between expectations and practice. While acknowledging the breadth and depth of material available under the heading of 'communication theory', this study specifically draws on an expanded view of the rhetorical tradition to fully interrogate the assumptions supporting the practice of assessing oral presentations. Finally, this thesis recommends reconnecting with an updated understanding of rhetoric as a way of assisting in the development of expressive, articulate and discerning communicators.

The role of the rule of law in virtual communities

Please see the updated published version of this work at http://eprints.qut.edu.au/37850/ There is a severe tendency in cyberlaw theory to delegitimize state intervention in the governance of virtual communities. Much of the existing theory makes one of two fundamental flawed assumptions: that communities will always be best governed without the intervention of the state; or that the territorial state can best encourage the development of communities by creating enforceable property rights and allowing the market to resolve any disputes. These assumptions do not ascribe sufficient weight to the value-laden support that the territorial state always provides to private governance regimes, the inefficiencies that will tend to limit the development utopian communities, and the continued role of the territorial state in limiting autonomy in accordance with communal values...

Active ageing among older adults with lifelong intellectual disabilities : the role of familial and nonfamilial social networks

Little research has examined the extent to which active ageing is facilitated by family and nonfamilial support persons of older adults with intellectual disabilities. This study explores the role played by key unpaid carers/support persons of older adults with lifelong intellectual disabilities in facilitating "active ageing." Little research has examined the extent to which active ageing is facilitated by family and nonfamilial support persons of older adults with intellectual disabilities. This study explores the role played by key unpaid carers/support persons of older adults with lifelong intellectual disabilities in facilitating “active ageing.” All key social network members conceived active ageing to mean ongoing activity. Family and extended family members were found to play a crucial role in facilitating independent living and providing opportunities for recreational pursuits for those living in group homes. Members of religious organizations and group home staff provided the same types of opportunities where family support was absent. The findings suggest the need for improvements in resource provision, staff training, and group home policy and building design.

The α5 neuronal nicotinic acetylcholine receptor subunits plays an important role in the sedative effects of ethanol but does not modulate consumption in mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence. Here, we evaluate the role of 5* nAChR for ethanol-mediated behaviors using α5+/+ and α5-/- mice. We characterized the effect of hypnotic doses of ethanol and investigated drinking behavior using an adapted Drinking-in-the Dark (DID) paradigm that has been shown to induce high ethanol consumption in mice. We found the α5 subunit to be critical in mediating the sedative effects of ethanol. The α5-/- mice showed slower recovery from ethanol-induced sleep, as measured by loss of righting reflex. Additionally the α5-/- mice showed enhanced impairment to ethanol-induced ataxia. We found the initial sensitivity to ethanol and ethanol metabolism to be similar in both α5+/+ and α5-/- mice. Hence the enhanced sedation is likely due to a difference in the acute tolerance of ethanol in mice deficient of the α5 subunit. However the α5 subunit did not play a role in ethanol consumption for ethanol concentrations ranging from 5% to 30% in the DID paradigm. Additionally, varenicline (Chantix®) was effective in reducing ethanol intake in α5-/- mice. Together, our data suggest that the α5 nAChR subunit is important for the sedative hypnotic doses of ethanol but does not play a role in ethanol consumption. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

What is the role of design-led innovation and design-led prototyping in developing novel business models?

Recently, ‘business model’ and ‘business model innovation’ have gained substantial attention in management literature and practice. However, many firms lack the capability to develop a novel business model to capture the value from new technologies. Existing literature on business model innovation highlights the central role of ‘customer value’. Further, it suggests that firms need to experiment with different business models and engage in ‘trail-and-error’ learning when participating in business model innovation. Trial-and error processes and prototyping with tangible artifacts are a fundamental characteristic of design. This conceptual paper explores the role of design-led innovation in facilitating firms to conceive and prototype novel and meaningful business models. It provides a brief review of the conceptual discussion on business model innovation and highlights the opportunities for linking it with the research stream of design-led innovation. We propose design-led business model innovation as a future research area and highlight the role of design-led prototyping and new types of artifacts and prototypes play within it. We present six propositions in order to outline future research avenues.

Stroma regulates increased epithelial lateral cell adhesion in 3D culture : a role for actin/cadherin dynamics

BACKGROUND: Cell shape and tissue architecture are controlled by changes to junctional proteins and the cytoskeleton. How tissues control the dynamics of adhesion and cytoskeletal tension is unclear. We have studied epithelial tissue architecture using 3D culture models and found that adult primary prostate epithelial cells grow into hollow acinus-like spheroids. Importantly, when co-cultured with stroma the epithelia show increased lateral cell adhesions. To investigate this mechanism further we aimed to: identify a cell line model to allow repeatable and robust experiments; determine whether or not epithelial adhesion molecules were affected by stromal culture; and determine which stromal signalling molecules may influence cell adhesion in 3D epithelial cell cultures. METHODOLOGY/PRINCIPAL FINDINGS: The prostate cell line, BPH-1, showed increased lateral cell adhesion in response to stroma, when grown as 3D spheroids. Electron microscopy showed that 9.4% of lateral membranes were within 20 nm of each other and that this increased to 54% in the presence of stroma, after 7 days in culture. Stromal signalling did not influence E-cadherin or desmosome RNA or protein expression, but increased E-cadherin/actin co-localisation on the basolateral membranes, and decreased paracellular permeability. Microarray analysis identified several growth factors and pathways that were differentially expressed in stroma in response to 3D epithelial culture. The upregulated growth factors TGFβ2, CXCL12 and FGF10 were selected for further analysis because of previous associations with morphology. Small molecule inhibition of TGFβ2 signalling but not of CXCL12 and FGF10 signalling led to a decrease in actin and E-cadherin co-localisation and increased paracellular permeability. CONCLUSIONS/SIGNIFICANCE: In 3D culture models, paracrine stromal signals increase epithelial cell adhesion via adhesion/cytoskeleton interactions and TGFβ2-dependent mechanisms may play a key role. These findings indicate a role for stroma in maintaining adult epithelial tissue morphology and integrity.

The role of knowledge intermediaries in developing firm learning capabilities

Regional innovation systems (RISs) literature has emphasized the critical role of interactive learning and knowledge exchange amongst firms and a variety of spatially connected innovation institutions as the foundation of regional innovation. Knowledge intermediaries have been analysed in terms of the technology-transaction services they provide firms and/or knowledge producers such as universities and therefore the role they play in facilitating interaction within the RIS. However, innovation also depends on the capability of the firm to learn. Some studies have suggested that intermediaries also play a role in that regard as participation in intermediary knowledge transfer programmes can contribute to the development of firm capabilities for problem-solving and learning. Our research is based on two case study intermediary programmes involving interviews with facilitators and participants. Our data show that knowledge intermediaries affect organizational learning capabilities by impacting on firms' network relationships, internal and external communication channels and internal learning processes which in turn affect the ability to interpret and use knowledge within the firm. This suggests that the role of knowledge intermediaries might be greater than facilitating interactions in the innovation system, as knowledge intermediation may affect the ability of firms to learn and absorb knowledge from their environment.

Irritable bowel syndrome : the role of gut neuroendocrine peptides

Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 % of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

In defence of Victoria's Children's Court : its value and role in the child protection system

Australian child protection systems have been subject to sustained and significant criticism for many decades. As a central part of that system Children’s Courts have been implicated: three recent inquiries into the child protection system in Victoria all criticised the Family Division of the Children’s Court.1 In the resulting debate two diametrically opposed points of view surfaced about the Children’s Court and the role that legal procedures and professionals should play in child protection matters. On one side bodies like the Children’s Court of Victoria, Victoria Legal Aid (‘VLA’), the Law Institute of Victoria (‘LIV’), and the Federation of Community Legal Centres (‘FCLC’) argued that the Children’s Court plays a vital role in child protection and should continue to play that role.2 On the other side a coalition of human service and child protection agencies called for major change including the removal of the Children’s Court from the child protection system. Victoria’s Department of Human Services (‘DHS’) has been critical of the Court3 as have community sector organisations like Anglicare, Berry Street, MacKillop Family Services and the Salvation Army — all agencies the DHS funds to deliver child protection services.4 Victoria’s Child Safety Commissioner has also called for major reform, publicly labelling the Court a ‘lawyers’ playground’ and recommending abolishing the Court’s involvement in child protection completely.

Paramedics' perceptions of their role in palliative care : analysis of focus group transcripts

Paramedics play an important role in out-of-hospital health care. They provide unscheduled care, assisting both patients with minor injuries and those experiencing life-threatening emergencies. Increasingly, paramedics are called on to manage chronic and complex health needs, including symptom relief for patients at the end of life. However, paramedics may not be well prepared to offer palliative care, as practice guidelines and education tend to focus on the management of acute medical emergencies and major trauma. Emergency medical services that employ paramedics rarely have practice guidelines or protocols that deal specifically with palliative care.

Parent views of play in the Preparatory Year in Queensland

Over the past ten years, Queensland has experienced a period of significant education reform including the introduction in 2007 of a Preparatory Year of schooling for children aged five years. Recently, the development of a new Australian Curriculum represents a further curriculum reform impacting on Prep in Queensland, as Prep is, for the first time, part of the broader school curriculum and specific content is to be taught. The place of play as a context for learning is a current topic of interest during this period of change, and this thesis argues that consideration of parent views with regard to play and its place in Prep is timely and strategic. This thesis reports the findings of a research project that used case study to elicit and describe the ways in which eight parents viewed play in Prep. Analysis of parent interviews identified four themes: (1) parents interpreting play in Prep, (2) play and learning in Prep, (3) the Prep teacher's role in play and (4) parent tensions regarding play and learning in Prep. The results of the study suggest that variation exists in the ways in which parents may view and interpret play in Prep in Queensland. Analysis of the data further suggests that these interpretations may reflect parents' understanding of the Prep program and their attitudes to play and school generally. This thesis suggests that parents may spend limited time in Prep classrooms, which may impact on their understanding of play as a theoretical tenet in Prep and may highlight limitations in parent-teacher partnerships. The results of this study suggest that more attention be given to engaging parents in early childhood programs and eliciting their views on these programs. The results also suggest the importance of early childhood teachers advocating on behalf of play with their teaching colleagues, school leaders and policy makers.

Role of land use and seasonal factors in water quality degradation

Surface water and groundwater are the most important water sources in the natural environment. Land use and seasonal factors play an important role in influencing the quality of these water sources. An in-depth understanding of the role of these two influential factors can help to implement an effective catchment management strategy for the protection of these water sources. This paper discusses the outcomes of an extensive research study which investigated the role of land use and seasonal factors on surface water and groundwater pollution in a mixed land use coastal catchment. The study confirmed that the influence exerted on the water environment by seasonal factors is secondary to that of land use. Furthermore, the influence of land use and seasonal factors on surface water and groundwater quality varies with the pollutant species. This highlights the need to specifically take into consideration the targeted pollutants and the key influential factors for the effective protection of vulnerable receiving water environments.