An additional step towards modelling the mechanical behaviour of sugar cane bagasse

A better understanding of the behaviour of prepared cane and bagasse, especially the ability to model the mechanical behaviour of bagasse as it is squeezed in a milling unit to extract juice, would help identify how to improve the current milling process; for example to reduce final bagasse moisture. Previous investigations have proven with certainty that juice flow through bagasse obeys Darcy’s permeability law, that the grip of the rough surface of the grooves on the bagasse can be represented by the Mohr- Coulomb failure criterion for soils, and that the internal mechanical behaviour of the bagasse can be represented by critical state behaviour similar to that of sand and clay. Current Finite Element Models (FEM) available in commercial software have adequate permeability models. However, commercial software does not contain an adequate mechanical model for bagasse. Progress has been made in the last ten years towards implementing a mechanical model for bagasse in finite element software code. This paper builds on that progress and carries out a further step towards obtaining an adequate material model. In particular, the prediction of volume change during shearing of normally consolidated final bagasse is addressed.

Police misconduct and crime : bad apples or systems failure?

There is a debate in the research literature whether to view police misconduct and crime as acts of individuals perceived as 'rotten apples' or as an indication of systems failure in the police force. Based on an archival analysis of court cases where police employees were prosecuted, this paper attempts to explore the extent of rotten apples versus systems failure in the police. Exploratory research of 57 prosecuted police officers in Norway indicate that there were more rotten apple cases than system failure cases. The individual failures seem to be the norm rather than the exception of ethical breaches, therefore enhancing the rotten apple theory. However as exploratory research, police crime may still be explained at the organizational level as well.

Socio-economic differences in takeaway food consumption among adults

To examine socioeconomic differences in the frequency and types of takeaway foods consumed. Cross-sectional postal survey. Participants were asked about their usual consumption of overall takeaway food (< four times a month, or ≥ four times a month) and 22 specific takeaway food items (< once a month, or ≥ once a month): these latter foods were grouped into “healthy” and “less healthy” choices. Socioeconomic position was measured using education and equivalised household income and differences in takeaway food consumption were assessed by calculating prevalence ratios using log binomial regression. Adults aged 25–64 years from Brisbane, Australia were randomly selected from the electoral roll (N = 903, 63.7% response rate). Compared with their more educated counterparts, the least educated were more regular consumers of overall takeaway food, fruit/vegetable juice, and less regular consumers of sushi. For the “less healthy” items, the least educated more regularly consumed potato chips, savoury pies, fried chicken, and non-diet soft drinks; however, the least educated were less likely to consume curry. Household income was not associated with overall takeaway consumption. The lowest income group were more regular consumers of fruit/vegetable juice compared with the highest income group. Among the “less healthy” items, the lowest income group were more regular consumers of fried fish, ice-cream, and milk shakes, while curry was consumed less regularly. The frequency and types of takeaway foods consumed by socioeconomically disadvantaged groups may contribute to inequalities in overweight/obesity and chronic disease.

The rise of co-creative consumers : user experience sharing behaviour in online communities

This thesis examines consumer initiated value co-creation behaviour in the context of convergent mobile online services using a Service-Dominant logic (SD logic) theoretical framework. It focuses on non-reciprocal marketing phenomena such as open innovation and user generated content whereby new viable business models are derived and consumer roles and community become essential to the success of business. Attention to customers. roles and personalised experiences in value co-creation has been recognised in the literature (e.g., Prahalad & Ramaswamy, 2000; Prahalad, 2004; Prahalad & Ramaswamy, 2004). Similarly, in a subsequent iteration of their 2004 version of the foundations of SD logic, Vargo and Lusch (2006) replaced the concept of value co-production with value co-creation and suggested that a value co-creation mindset is essential to underpin the firm-customer value creation relationship. Much of this focus, however, has been limited to firm initiated value co-creation (e.g., B2B or B2C), while consumer initiated value creation, particularly consumer-to-consumer (C2C) has received little attention in the SD logic literature. While it is recognised that not every consumer wishes to make the effort to engage extensively in co-creation processes (MacDonald & Uncles, 2009), some consumers may not be satisfied with a standard product, instead they engage in the effort required for personalisation that potentially leads to greater value for themselves, and which may benefit not only the firm, but other consumers as well. Literature suggests that there are consumers who do, and as a result initiate such behaviour and expend effort to engage in co-creation activity (e.g., Gruen, Osmonbekov and Czaplewski, 2006; 2007 MacDonald & Uncles, 2009). In terms of consumers. engagement in value proposition (co-production) and value actualisation (co-creation), SD logic (Vargo & Lusch, 2004, 2008) provides a new lens that enables marketing scholars to transcend existing marketing theory and facilitates marketing practitioners to initiate service centric and value co-creation oriented marketing practices. Although the active role of the consumer is acknowledged in the SD logic oriented literature, we know little about how and why consumers participate in a value co-creation process (Payne, Storbacka, & Frow, 2008). Literature suggests that researchers should focus on areas such as C2C interaction (Gummesson 2007; Nicholls 2010) and consumer experience sharing and co-creation (Belk 2009; Prahalad & Ramaswamy 2004). In particular, this thesis seeks to better understand consumer initiated value co-creation, which is aligned with the notion that consumers can be resource integrators (Baron & Harris, 2008) and more. The reason for this focus is that consumers today are more empowered in both online and offline contexts (Füller, Mühlbacher, Matzler, & Jawecki, 2009; Sweeney, 2007). Active consumers take initiatives to engage and co-create solutions with other active actors in the market for their betterment of life (Ballantyne & Varey, 2006; Grönroos & Ravald, 2009). In terms of the organisation of the thesis, this thesis first takes a „zoom-out. (Vargo & Lusch, 2011) approach and develops the Experience Co-Creation (ECo) framework that is aligned with balanced centricity (Gummesson, 2008) and Actor-to-Actor worldview (Vargo & Lusch, 2011). This ECo framework is based on an extended „SD logic friendly lexicon. (Lusch & Vargo, 2006): value initiation and value initiator, value-in-experience, betterment centricity and betterment outcomes, and experience co-creation contexts derived from five gaps identified from the SD logic literature review. The framework is also designed to accommodate broader marketing phenomena (i.e., both reciprocal and non-reciprocal marketing phenomena). After zooming out and establishing the ECo framework, the thesis takes a zoom-in approach and places attention back on the value co-creation process. Owing to the scope of the current research, this thesis focuses specifically on non-reciprocal value co-creation phenomena initiated by consumers in online communities. Two emergent concepts: User Experience Sharing (UES) and Co-Creative Consumers are proposed grounded in the ECo framework. Together, these two theorised concepts shed light on the following two propositions: (1) User Experience Sharing derives value-in-experience as consumers make initiative efforts to participate in value co-creation, and (2) Co-Creative Consumers are value initiators who perform UES. Three research questions were identified underpinning the scope of this research: RQ1: What factors influence consumers to exhibit User Experience Sharing behaviour? RQ2: Why do Co-Creative Consumers participate in User Experience Sharing as part of value co-creation behaviour? RQ3: What are the characteristics of Co-Creative Consumers? To answer these research questions, two theoretical models were developed: the User Experience Sharing Behaviour Model (UESBM) grounded in the Theory of Planned Behaviour framework, and the Co-Creative Consumer Motivation Model (CCMM) grounded in the Motivation, Opportunity, Ability framework. The models use SD logic consistent constructs and draw upon multiple streams of literature including consumer education, consumer psychology and consumer behaviour, and organisational psychology and organisational behaviour. These constructs include User Experience Sharing with Other Consumers (UESC), User Experience Sharing with Firms (UESF), Enjoyment in Helping Others (EIHO), Consumer Empowerment (EMP), Consumer Competence (COMP), and Intention to Engage in User Experience Sharing (INT), Attitudes toward User Experience Sharing (ATT) and Subjective Norm (SN) in the UESBM, and User Experience Sharing (UES), Consumer Citizenship (CIT), Relating Needs of Self (RELS) and Relating Needs of Others (RELO), Newness (NEW), Mavenism (MAV), Use Innovativeness (UI), Personal Initiative (PIN) and Communality (COMU) in the CCMM. Many of these constructs are relatively new to marketing and require further empirical evidence for support. Two studies were conducted to underpin the corresponding research questions. Study One was conducted to calibrate and re-specify the proposed models. Study Two was a replica study to confirm the proposed models. In Study One, data were collected from a PC DIY online community. In Study Two, a majority of data were collected from Apple product online communities. The data were examined using structural equation modelling and cluster analysis. Considering the nature of the forums, the Study One data is considered to reflect some characteristics of Prosumers and the Study Two data is considered to reflect some characteristics of Innovators. The results drawn from two independent samples (N = 326 and N = 294) provide empirical support for the overall structure theorised in the research models. The results in both models show that Enjoyment in Helping Others and Consumer Competence in the UESBM, and Consumer Citizenship and Relating Needs in CCMM have significant impacts on UES. The consistent results appeared in both Study One and Study Two. The results also support the conceptualisation of Co-Creative Consumers and indicate Co-Creative Consumers are individuals who are able to relate the needs of themselves and others and feel a responsibility to share their valuable personal experiences. In general, the results shed light on "How and why consumers voluntarily participate in the value co-creation process?. The findings provide evidence to conceptualise User Experience Sharing behaviour as well as the Co-Creative Consumer using the lens of SD logic. This research is a pioneering study that incorporates and empirically tests SD logic consistent constructs to examine a particular area of the logic – that is consumer initiated value co-creation behaviour. This thesis also informs practitioners about how to facilitate and understand factors that engage with either firm or consumer initiated online communities.

DispoMaps

The gathering of people in everyday life is intertwined with travelling to negotiated locations. As a result, mobile phones are often used to rearrange meetings when one or more participants are late or cannot make it on time. Our research is based on the hypothesis that the provision of location data can enhance the experience of people who are meeting each other in different locations. Disposable Maps allows users to select contacts from their phone’s address book who then receive up-to-date location data. The utilisation of peer-to-peer notifications and the application of unique URLs for location storage and presentation enable location sharing whilst ensuring users’ location privacy. In contrast to other location sharing services like Google Latitude, Disposable Maps enables ad hoc location sharing to actively selected location receivers for a fixed period of time in a specific given situation.

Use of the iPhone for Cobb angle measurement in scoliosis

Purpose: The Cobb technique is the universally accepted method for measuring the severity of spinal deformities. Traditionally, Cobb angles have been measured using protractor and pencil on hardcopy radiographic films. The new generation of mobile phones make accurate angle measurement possible using an integrated accelerometer, providing a potentially useful clinical tool for assessing Cobb angles. The purpose of this study was to compare Cobb angle measurements performed using an Apple iPhone and traditional protractor in a series of twenty Adolescent Idiopathic Scoliosis patients. Methods: Seven observers measured major Cobb angles on twenty pre-operative postero-anterior radiographs of Adolescent Idiopathic Scoliosis patients with both a standard protractor and using an Apple iPhone. Five of the observers repeated the measurements at least a week after the original measurements. Results: The mean absolute difference between pairs of iPhone/protractor measurements was 2.1°, with a small (1°) bias toward lower Cobb angles with the iPhone. 95% confidence intervals for intra-observer variability were ±3.3° for the protractor and ±3.9° for the iPhone. 95% confidence intervals for inter-observer variability were ±8.3° for the iPhone and ±7.1° for the protractor. Both of these confidence intervals were within the range of previously published Cobb measurement studies. Conclusions: We conclude that the iPhone is an equivalent Cobb measurement tool to the manual protractor, and measurement times are about 15% less. The widespread availability of inclinometer-equipped mobile phones and the ability to store measurements in later versions of the angle measurement software may make these new technologies attractive for clinical measurement applications.

Studying the mobile : locating the field

Book Description: The iPhone represents an important moment in both the short history of mobile media and the long history of cultural technologies. Like the Walkman of the 1980s, it marks a juncture in which notions about identity, individualism, lifestyle and sociality require rearticulation. this book explores not only the iPhone’s particular characteristics, uses and "affects," but also how the "iPhone moment" functions as a barometer for broader patterns of change. In the iPhone moment, this study considers the convergent trajectories in the evolution of digital and mobile culture, and their implications for future scholarship. Through the lens of the iPhone—as a symbol, culture and a set of material practices around contemporary convergent mobile media—the essays collected here explore the most productive theoretical and methodological approaches for grasping media practice, consumer culture and networked communication in the twenty-first century.

ACE research briefing paper 002: learning and adaptation in the business creation process

This year marks the completion of data collection for year three (Wave 3) of the CAUSEE study. This report uses data from the first three years and focuses on the process of learning and adaptation in the business creation process. Most start-ups need to change their business model, their product, their marketing plan, their market or something else about the business to be successful. PayPal changed their product at least five times, moving from handheld security, to enterprise apps, to consumer apps, to a digital wallet, to payments between handhelds before finally stumbling on the model that made the a multi-billion dollar company revolving around email-based payments. PayPal is not alone and anecdotes abounds of start-ups changing direction: Sysmantec started as an artificial intelligence company, Apple started selling plans to build computers and Microsoft tried to peddle compilers before licensing an operating system out of New Mexico. To what extent do Australian new ventures change and adapt as their ideas and business develop? As a longitudinal study, CAUSEE was designed specifically to observe development in the venture creation process. In this research briefing paper, we compare development over time of randomly sampled Nascent Firms (NF) and Young Firms(YF), concentrating on the surviving cases. We also compare NFs with YFs at each yearly interval. The 'high potential' over sample is not used in this report.

The composition of sugarcane juices dervied from burnt cane and whole green cane crop

There has been substantial interest within the Australian sugar industry in product diversification as a means to reduce its exposure to fluctuating raw sugar prices and in order to increase its commercial viability. In particular, the industry is looking at fibrous residues from sugarcane harvesting (trash) and from sugarcane milling (bagasse) for cogeneration and the production of biocommodities, as these are complementary to the core process of sugar production. A means of producing surplus residue (biomass) is to process whole sugarcane crop. In this paper, the composition of different juices derived from different harvesting methods, viz. burnt cane with all trash extracted (BE), green cane with half of the trash extracted (GE), and green cane (whole sugarcane crop) with trash unextracted (GU), were investigated and the results and comparison presented. The determination of electrical conductivity, inorganic composition, and organic acids indicate that both GU and GE cane juice contain a higher proportion of soluble inorganic ions and ionisable organic acids, compared to BE cane juice. It is important to note that there are considerably higher levels of Na ions and citric acid, but relatively low P levels in the GU samples. A higher level of reducing sugars was analysed in the GU samples than the BE samples due to the higher proportion of impurities found naturally in sugarcane tops and leaves. The purity of the first expressed juice (FEJ) of GU cane was on average higher than that of FEJ of BE cane. Results also show that GU juices appear to contain higher levels of proteins and polysaccharides, with no significant difference in starch levels.

Optimisation of process parameters for the removal of hydroxycinnamic acids in sugar solutions

Colour is one of the most important parameters in sugar quality and its presence in raw sugar plays a key role in the marketing strategy of sugar industries worldwide. This study investigated the degradation of a mixture of colour precursors using the Fenton oxidation process. These colour precursors are caffeic acid, p–coumaric acid and ferulic acid, which are present in cane juice. Results showed that with a Fe(II) to H2O2 molar ratio of 1:15 in an aqueous system at 25 °C, 77% of the total phenolic acid content was removed at pH 4.72. However, in a synthetic juice solution which contained 13 mass % sucrose (35 °C, pH 5.4), only 60% of the total phenolic acid content was removed.

A mill design concept for reducing bagasse moisture

This paper describes the development and testing of a novel mill design to reduce the moisture content of bagasse. It takes advantage of gravity to separate juice from bagasse by pushing bagasse upwards while juice drains downwards under gravity. The potential of the design to reduce bagasse moisture content has not been adequately established. The prototype mill had limited power available that prevented typical delivery nip compactions from being achieved. Tests conducted did show a reduction in bagasse moisture but that moisture reduction is less than expected under ideal conditions. Work on the mill design has ceased, at least for the foreseeable future. The design does have potential to reduce bagasse moisture content but presents some engineering challenges to establish a reliable, low maintenance design alternative.

An enhanced mill extraction model

An enhanced mill extraction model has been developed to calculate mill performance parameters and to predict the extraction performance of a milling unit. The model takes into account the fibre suspended in juice streams and calculates filling ratio, reabsorption factor, imbibition coefficient, and separation efficiency using more complete definitions than those used in previous extraction models. A mass balance model is used to determine the fibre, brix and moisture mass flows between milling units so that a complete milling train, including the return stream from the juice screen, is modelled. Model solutions are presented to determine the effect of different levels of fibre in juice and efficiency of fibre separation in the juice screen on brix extraction. The model provides more accurate results than earlier models leading to better understanding and improvement of the milling process.

The effect of mill orientation angle on bagasse moisture content

THIS PAPER DESCRIBES an experimental investigation to explore a concept designed to reduce the moisture content of bagasse. It takes advantage of gravity to separate juice from bagasse by feeding bagasse upwards into the nip of the mill while juice drains downwards under gravity. The investigation found that orienting the feed to a mill upwards does reduce bagasse moisture content and that the benefit is expected to be greater than two units of moisture. While an advantage was found in orienting the feed up to 50° above the horizontal, no extra benefit was found in increasing the angle higher (up to 60° was explored) and so a 50° orientation was identified as the preferred angle for this design concept.

Evaluation of the iPhone with an acrylic sleeve versus the Scoliometer for rib hump measurement in scoliosis

Background. Vertebral rotation found in structural scoliosis contributes to trunkal asymmetry which is commonly measured with a simple Scoliometer device on a patient's thorax in the forward flexed position. The new generation of mobile 'smartphones' have an integrated accelerometer, making accurate angle measurement possible, which provides a potentially useful clinical tool for assessing rib hump deformity. This study aimed to compare rib hump angle measurements performed using a Smartphone and traditional Scoliometer on a set of plaster torsos representing the range of torsional deformities seen in clinical practice. Methods. Nine observers measured the rib hump found on eight plaster torsos moulded from scoliosis patients with both a Scoliometer and an Apple iPhone on separate occasions. Each observer repeated the measurements at least a week after the original measurements, and were blinded to previous results. Intra-observer reliability and inter-observer reliability were analysed using the method of Bland and Altman and 95% confidence intervals were calculated. The Intra-Class Correlation Coefficients (ICC) were calculated for repeated measurements of each of the eight plaster torso moulds by the nine observers. Results. Mean absolute difference between pairs of iPhone/Scoliometer measurements was 2.1 degrees, with a small (1 degrees) bias toward higher rib hump angles with the iPhone. 95% confidence intervals for intra-observer variability were +/- 1.8 degrees (Scoliometer) and +/- 3.2 degrees (iPhone). 95% confidence intervals for inter-observer variability were +/- 4.9 degrees (iPhone) and +/- 3.8 degrees (Scoliometer). The measurement errors and confidence intervals found were similar to or better than the range of previously published thoracic rib hump measurement studies. Conclusions. The iPhone is a clinically equivalent rib hump measurement tool to the Scoliometer in spinal deformity patients. The novel use of plaster torsos as rib hump models avoids the variables of patient fatigue and discomfort, inconsistent positioning and deformity progression using human subjects in a single or multiple measurement sessions.

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.