Rivalry within and between strategic networks : an investigation of the United States Automotive Industry

As a consequence of the increased incidence of collaborative arrangements between firms, the competitive environment characterising many industries has undergone profound change. It is suggested that rivalry is not necessarily enacted by individual firms according to the traditional mechanisms of direct confrontation in factor and product markets, but rather as collaborative orchestration between a number of participants or network members. Strategic networks are recognised as sets of firms within an industry that exhibit denser strategic linkages among themselves than other firms within the same industry. Based on this, strategic networks are determined according to evidence of strategic alliances between firms comprising the industry. As a result, a single strategic network represents a group of firms closely linked according to collaborative ties. Arguably, the collective outcome of these strategic relationships engineered between firms suggest that the collaborative benefits attributed to interorganisational relationships require closer examination in respect to their propensity to influence rivalry in intraindustry environments. Derived in large from the social sciences, network theory allows for the micro and macro examination of the opportunities and constraints inherent in the structure of relationships in strategic networks, establishing a relational approach upon which the conduct and performance of firms can be more fully understood. Research to date has yet to empirically investigate the relationship between strategic networks and rivalry. The limited research that has been completed utilising a network rationale to investigate competitive patterns in contemporary industry environments has been characterised by a failure to directly measure rivalry. Further, this prior research has typically embedded investigation in industry settings dominated by technological or regulatory imperatives, such as the microprocessor and airline industries. These industries, due to the presence of such imperatives, are arguably more inclined to support the realisation of network rivalry, through subscription to prescribed technological standards (eg., microprocessor industry) or by being bound by regulatory constraints dictating operation within particular market segments (airline industry). In order to counter these weaknesses, the proposition guiding research - Are patterns of rivalry predicted by strategic network membership? – is embedded in the United States Light Vehicles Industry, an industry not dominated by technological or regulatory imperatives. Further, rivalry is directly measured and utilised in research, thus distinguishing this investigation from prior research efforts. The timeframe of investigation is 1993 – 1999, with all research data derived from secondary sources. Strategic networks were defined within the United States Light Vehicles Industry based on evidence of horizontal strategic relationships between firms comprising the industry. The measure of rivalry used to directly ascertain the competitive patterns of industry participants was derived from the traditional Herfindahl Index, modified to account for patterns of rivalry observed at the market segment level. Statistical analyses of the strategic network and rivalry constructs found little evidence to support the contention of network rivalry; indeed, greater levels of rivalry were observed between firms comprising the same strategic network than between firms participating in opposing network structures. Based on these results, patterns of rivalry evidenced in the United States Light Vehicle Industry over the period 1993 – 1999 were not found to be predicted by strategic network membership. The findings generated by this research are in contrast to current theorising in the strategic network – rivalry realm. In this respect, these findings are surprising. The relevance of industry type, in conjunction with prevailing network methodology, provides the basis upon which these findings are contemplated. Overall, this study raises some important questions in relation to the relevancy of the network rivalry rationale, establishing a fruitful avenue for further research.

Alternative film production

Typically a film producer expects the director and actors to 'do their job' within a scheduled timeframe. Rather than expecting the creative principals to just deliver, a production model can be tailored to help this creative team produce successful outcomes. This research paper contrasts alternative production models with a traditional (or standard) production and presents possibilities for producers to emphasise the collaborative potential for their production.

Undressing the actor : the erotic relationship with the audience

The intimacy and eroticism of the actor’s relationship with the audience is captured in the ecstatic revelation of the actor “being in the moment.” Drawing on the theories of Freud and Sartre and twenty years of performance praxis, this paper explores the exchange of erotic discourse between stage and spectator that not only heightens the experience of the liveness of theatre, but creates a symbiosis that is silently negotiated, agreed upon and sensuously performed during the suspended timeframe of the theatrical event. The actor draws the audience into the erotic transaction through various dramatic devices: the seduction of the soliloquy, the somatic and verbal discourses, the sensuality of light and costuming. The audience responds with its own paralingual and verbal foreplay: the playfulness of laughter, the slapping of hands and, most significantly, the gaze. While the gaze is often perceived as a form of voyeurism, this paper argues that the gaze of consensual agreement between audience and actor can work to unmask inhibitions enabling the actor to create the truth of the moment in complete abandon.

Integrated sustainable urban infrastructure management: the Brisbane urban growth model

Sustainable urban development and the liveability of a city are increasingly important issues in the context of land use planning and infrastructure management. In recent years, the promotion of sustainable urban development in Australia and overseas is facing various physical, socio-economic and environmental challenges. These challenges and problems arise from the lack of capability of local governments to accommodate the needs of the population and economy in a relatively short timeframe. The planning of economic growth and development is often dealt with separately and not included in the conventional land use planning process. There is also a sharp rise in the responsibilities and roles of local government for infrastructure planning and management. This increase in responsibilities means that local elected officials and urban planners have less time to prepare background information and make decisions. The Brisbane Urban Growth Model has proven initially successful in providing a dynamic platform to ensure timely and coordinated delivery of urban infrastructure. Most importantly, this model is the first step for local governments in moving toward a systematic approach to pursuing sustainable and effective urban infrastructure management.

The Australian response to climate change : business as usual or legal innovation?

Through international agreement to the United Nations Framework Convention on Climate Change and the Kyoto Protocol the global community has acknowledged that climate change is a global problem and sought to achieve reductions in global emissions, within a sufficient timeframe, to avoid dangerous anthropogenic interference with the climate system. The sheer magnitude of emissions reductions required within such an urgent timeframe presents a challenge to conventional regulatory approaches both internationally and within Australia. The phenomenon of climate change is temporally and geographically challenging and it is scientifically complex and uncertain. The purpose of this paper is to analyse the current Australian legal response to climate change and to examine the legal measures which have been proposed to promote carbon trading, energy efficiency, renewable energy, and carbon sequestration initiatives across Australia. As this paper illustrates, the current Australian approach is clearly ineffective and the law as it stands overwhelmingly inadequate to address Australia’s emissions and meet the enormity of the challenges posed by climate change. Consequently, the government should look towards a more effective legal framework to achieve rapid and urgent transformations in the selection of energy sources, energy use and sequestration initiatives across the Australian community.

A dynamic approach to forecast rental growth

Numerous econometric models have been proposed for forecasting property market performance, but limited success has been achieved in finding a reliable and consistent model to predict property market movements over a five to ten year timeframe. This research focuses on office rental growth forecasts and overviews many of the office rent models that have evolved over the past 20 years. A model by DiPasquale and Wheaton is selected for testing in the Brisbane, Australia office market. The adaptation of this study did not provide explanatory variables that could assist in developing a reliable, predictive model of office rental growth. In light of this result, the paper suggests a system dynamics framework that includes an econometric model based on historical data as well as user input guidance for the primary variables. The rent forecast outputs would be assessed having regard to market expectations and probability profiling undertaken for use in simulation exercises. The paper concludes with ideas for ongoing research.

The Figures

This short film, created by David Megarrity and Luke Monsour, experimented within a short timeframe with the challenge of superimposition of hand-drawn backgrounds, non-verbal action, and a short, sharp shoot. The aim was also to find a single piece of standalone music that would act as an unedited soundtrack It won Best Queensland Film at the Woodford Film Festival in 2005, and was screened at Base-Court, Lausanne Switzerland in 2006, and the Westgarth Film Festival 2005. It was acquired by comedy website minimovie in 2007.

Planning of distribution networks for medium voltage and low voltage

Determination of the placement and rating of transformers and feeders are the main objective of the basic distribution network planning. The bus voltage and the feeder current are two constraints which should be maintained within their standard range. The distribution network planning is hardened when the planning area is located far from the sources of power generation and the infrastructure. This is mainly as a consequence of the voltage drop, line loss and system reliability. Long distance to supply loads causes a significant amount of voltage drop across the distribution lines. Capacitors and Voltage Regulators (VRs) can be installed to decrease the voltage drop. This long distance also increases the probability of occurrence of a failure. This high probability leads the network reliability to be low. Cross-Connections (CC) and Distributed Generators (DGs) are devices which can be employed for improving system reliability. Another main factor which should be considered in planning of distribution networks (in both rural and urban areas) is load growth. For supporting this factor, transformers and feeders are conventionally upgraded which applies a large cost. Installation of DGs and capacitors in a distribution network can alleviate this issue while the other benefits are gained. In this research, a comprehensive planning is presented for the distribution networks. Since the distribution network is composed of low and medium voltage networks, both are included in this procedure. However, the main focus of this research is on the medium voltage network planning. The main objective is to minimize the investment cost, the line loss, and the reliability indices for a study timeframe and to support load growth. The investment cost is related to the distribution network elements such as the transformers, feeders, capacitors, VRs, CCs, and DGs. The voltage drop and the feeder current as the constraints are maintained within their standard range. In addition to minimizing the reliability and line loss costs, the planned network should support a continual growth of loads, which is an essential concern in planning distribution networks. In this thesis, a novel segmentation-based strategy is proposed for including this factor. Using this strategy, the computation time is significantly reduced compared with the exhaustive search method as the accuracy is still acceptable. In addition to being applicable for considering the load growth, this strategy is appropriate for inclusion of practical load characteristic (dynamic), as demonstrated in this thesis. The allocation and sizing problem has a discrete nature with several local minima. This highlights the importance of selecting a proper optimization method. Modified discrete particle swarm optimization as a heuristic method is introduced in this research to solve this complex planning problem. Discrete nonlinear programming and genetic algorithm as an analytical and a heuristic method respectively are also applied to this problem to evaluate the proposed optimization method.

Improving self-report measures of speeding

There is continuing debate regarding the psychometric properties of self-report measures of behaviour, particularly in road safety research. Practical considerations often preclude the use of objective assessments, leading to reliance on self-report measures. Acknowledging that such measures are likely to remain commonly used, this pilot project sought not to argue whether self-report measures should continue to be used, but to explore factors associated with how individuals respond to self-reported speeding measures. This paper reports preliminary findings from a qualitative study (focus groups and in-depth interviews) conducted with licensed drivers to explore the operational utility of self-reported speeding behaviour measures. Drawing upon concepts from the Theory of Planned Behaviour (TPB; Ajzen, 1991) and Agency Theory (Bandura, 2001), we identified four dimensions of self-reported speeding: including timeframe, speed zone, degree over the speed limit and, overall frequency of the behaviour, and examined participants’ perceptions of the operational utility of these factors. Issues related to comprehensibility, perceived accuracy, response format and layout were also explored. Results indicated that: heterogeneity in the timeframe of behavioural reflections suggests a need to provide a set timeframe for participants to consider when thinking about their previous speeding behaviour; response categories and formats should be carefully considered to ensure the most accurate representations of the frequency and degree of speeding are captured; the need to clearly articulate “low-level” speeding on self-report measures; and, that self-reports of speeding behaviour are typically context-irrelevant unless stipulated in the question. Limitations and directions for further research are discussed.

A design approach to teaching new product development

The educational unit new product development, taught within the industrial design program at the Queensland University of Technology (QUT) introduces the relationship between product design and commercialisation to third year industrial design undergraduate students. In which, they are exposed for the first time to product strategy development aimed at meeting consumer expectations, whilst at the same time achieving corporate objectives. Delivered content such as intellectual property, market opportunities, competitor analysis and investor requirements are taught within the thirteen week semester timeframe. New product development theory is not a new field. However, the design approach to teaching this theory and more importantly how designers can use it in the design process is novel. This paper provides an overview of the curriculum design of this unit as well as its incremental development over the past four year duration period. Student project outcomes and more importantly the process and tools from this unit are also discussed and presented.

Designing radical business model innovation : a case study

“The process of innovation is often seen as being very linear, with research results, new technologies or user insights being channelled, often prematurely, into specific products and process” (Kyffin and Gardien 2009). It is precisely this perception of innovation-as-linear-process which this paper seeks to challenge. While there are many current theories and much contemporary literature available which discuss the management and catalysts of innovation, what is missing are examples of how innovation occurs from the application of these theories and literature (Wrigley & Bucolo 2010). This paper addresses both this gap and perceptions of the viability of linear innovation by presenting a case study for the commercialisation of a core technology (a cleantech, semi-portable mass-energy generator posited as a direct competitor to conventional energy provision systems), within an 18-month timeframe by the use of the Design-Led Innovation approach: “a process of creating a sustainable competitive advantage by radically changing the customer value proposition” (Bucolo & Matthews 2011).

The role of law in responding to climate change : emerging regulatory, liability and market approaches

Climate change presents as the archetypal environmental problem with short-term economic self-interest operating to the detriment of the long-term sustainability of our society. The scientific reports of the Intergovernmental Panel on Climate Change strongly assert that the stabilisation of emissions in the atmosphere, to avoid the adverse impacts of climate change, requires significant and rapid reductions in ‘business as usual’ global greenhouse gas emissions. The sheer magnitude of emissions reductions required, within this urgent timeframe, will necessitate an unprecedented level of international, multi-national and intra-national cooperation and will challenge conventional approaches to the creation and implementation of international and domestic legal regimes. To meet this challenge, existing international, national and local legal systems must harmoniously implement a strong international climate change regime through a portfolio of traditional and innovative legal mechanisms that swiftly transform current behavioural practices in emitting greenhouse gases. These include the imposition of strict duties to reduce emissions through the establishment of strong command and control regulation (the regulatory approach); mechanisms for the creation and distribution of liabilities for greenhouse gas emissions and climaterelated harm (the liability approach) and the use of innovative regulatory tools in the form of the carbon trading scheme (the market approach). The legal relations between these various regulatory, liability and market approaches must be managed to achieve a consistent, compatible and optimally effective legal regime to respond to the threat of climate change. The purpose of this thesis is to analyse and evaluate the emerging legal rules and frameworks, both international and Australian, required for the effective regulation of greenhouse gas emissions to address climate change in the context of the urgent and deep emissions reductions required to minimise the adverse impacts of climate change. In doing so, this thesis will examine critically the existing and potential role of law in effectively responding to climate change and will provide recommendations on the necessary reforms to achieve a more effective legal response to this global phenomenon in the future.

The evolutionary history of the extinct ratite moa and New Zealand Neogene paleogeography

The ratite moa (Aves: Dinornithiformes) were a speciose group of massive graviportal avian herbivores that dominated the New Zealand (NZ) ecosystem until their extinction �600 years ago. The phylogeny and evolutionary history of this morphologically diverse order has remained controversial since their initial description in 1839. We synthesize mitochondrial phylogenetic information from 263 subfossil moa specimens from across NZ with morphological, ecological, and new geological data to create the first comprehensive phylogeny, taxonomy, and evolutionary timeframe for all of the species of an extinct order. We also present an important new geological/paleogeographical model of late Cenozoic NZ, which suggests that terrestrial biota on the North and South Island landmasses were isolated for most of the past 20–30 Ma. The data reveal that the patterns of genetic diversity within and between differentmoaclades reflect a complex history following a major marine transgression in the Oligocene, affected by marine barriers, tectonic activity, and glacial cycles. Surprisingly, the remarkable morphological radiation of moa appears to have occurred much more recently than previous early Miocene (ca. 15 Ma) estimates, and was coincident with the accelerated uplift of the Southern Alps just ca. 5–8.5 Ma. Together with recent fossil evidence, these data suggest that the recent evolutionary history of nearly all of the iconic NZ terrestrial biota occurred principally on just the South Island.

Saying sorry in the 21st century : public apologies in a digital world

The public apology to the Forgotten Australians in late 2009 was, for many, the culmination of a long campaign for recognition and justice. The groundswell for this apology was built through a series of submissions which documented the systemic institutionalised abuse and neglect experienced by the Forgotten Australians that has resulted, for some, in life-long disadvantage and marginalisation. Interestingly it seems that rather than the official documents being the catalyst for change and prompting this public apology, it was more often the personal stories of the Forgotten Australians that resonated and over time drew out quite a torrent of support from the public leading up to, during and after the public apology, just as had been the case with the ‘Stolen Generation.’ Research suggests (cite) that the ethics of such national apologies only make sense if their personal stories are seen as a collective responsibility of society, and only carry weight if we understand and seek to Nationally address the trauma experienced by such victims. In the case of the Forgotten Australians, the National Library of Australia’s Forgotten Australians and Former Child Migrants Oral History Project and the National Museum’s Inside project demonstrate commitment to the digitisation of the Forgotten Australians’ stories in order to promote a better public understanding of their experiences, and institutionally (and therefore formally) value them with renewed social importance. Our project builds on this work not by making or collecting more stories, but by examining the role of the internet and digital technologies used in the production and dissemination of individuals’ stories that have already been created during the period of time between the tabling of the senate inquiry, Children in Institutional Care (1999 or 2003?) and a formal National apology being delivered in Federal Parliament by PM Kevin Rudd (9 Nov, 2009?). This timeframe also represents the emergent first decade of Internet use by Australians, including the rapid easily accessible digital technologies and social media tools that were at our disposal, along with the promises the technology claimed to offer — that is that more people would benefit from the social connections these technologies allegedly were giving us.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.