A Hybrid AUV design for shallow water reef navigation

The highly unstructured nature of coral reef environments makes them difficult for current robotic vehicles to efficiently navigate. Typical research and commercial platforms have limited autonomy within these environments and generally require tethers and significant external infrastructure. This paper outlines the development of a new robotic vehicle for underwater monitoring and surveying in highly unstructured environments and presents experimental results illustrating the vehicle’s performance. The hybrid AUV design developed by the CSIRO robotic reef monitoring team realises a compromise between endurance, manoeuvrability and functionality. The vehicle represents a new era in AUV design specifically focused at providing a truly low-cost research capability that will progress environmental monitoring through unaided navigation, cooperative robotics, sensor network distribution and data harvesting.

A New robot for environmental monitoring on the Great Barrier Reef

A vast amount of research into autonomous underwater navigation has, and is, being conducted around the world. However, typical research and commercial platforms have limited autonomy and are generally unable to navigate efficiently within coral reef environments without tethers and significant external infrastructure. This paper outlines the development and presents experimental results into the performance evaluation of a new robotic vehicle for underwater monitoring and surveying in highly unstructured environments. The hybrid AUV design developed by the CSIRO robotic reef monitoring team realises a compromise between endurance, manoeuvrability and functionality. The vehicle represents a new era in AUV design specifically focused at providing a truly lowcost research capability that will progress environmental monitoring through unaided navigation, cooperative robotics, sensor network distribution and data harvesting.

Specifying and enforcing a fine-grained information flow policy : model and experiments

In this paper we present a model for defining and enforcing a fine-grained information flow policy. We describe how the policy can be enforced on a typical computer and present experiments using the proposed model. A key feature of the model is that it allows the expression of rules which detail precisely which information elements are allowed to mix together. For example, the model allows the expression of a policy which forbids a doctor from mixing the personal medical details of the patients. The enforcement mechanisms tracks and records information flows within the system so that dynamic changes to the policy can be made with respect to information elements which may have propagated to different locations in the system.

Port of Brisbane stormwater quality : stage 1 rainfall simulation to evaluate pollutant build-up and wash-off from selected land uses

Background: The quality of stormwater runoff from ports is significant as it can be an important source of pollution to the marine environment. This is also a significant issue for the Port of Brisbane as it is located in an area of high environmental values. Therefore, it is imperative to develop an in-depth understanding of stormwater runoff quality to ensure that appropriate strategies are in place for quality improvement. ---------------- The Port currently has a network of stormwater sample collection points where event based samples together with grab samples are tested for a range of water quality parameters. Whilst this information provides a ‘snapshot’ of the pollutants being washed from the catchment/s, it does not allow for a quantifiable assessment of total contaminant loads being discharged to the waters of Moreton Bay. It also does not represent pollutant build-up and wash-off from the different land uses across a broader range of rainfall events which might be expected. As such, it is difficult to relate stormwater quality to different pollutant sources within the Port environment. ----------------- Consequently, this would make the source tracking of pollutants to receiving waters extremely difficult and in turn the ability to implement appropriate mitigation measures. Also, without this detailed understanding, the efficacy of the various stormwater quality mitigation measures implemented cannot be determined with certainty. --------------- Current knowledge on port stormwater runoff quality Currently, little knowledge exists with regards to the pollutant generation capacity specific to port land uses as these do not necessarily compare well with conventional urban industrial or commercial land use due to the specific nature of port activities such as inter-modal operations and cargo management. Furthermore, traffic characteristics in a port area are different to a conventional urban area. Consequently, as data inputs based on an industrial and commercial land uses for modelling purposes is questionable. ------------------ A comprehensive review of published research failed to locate any investigations undertaken with regards to pollutant build-up and wash-off for port specific land uses. Furthermore, there is very limited information made available by various ports worldwide about the pollution generation potential of their facilities. Published work in this area has essentially focussed on the water quality or environmental values in the receiving waters such as the downstream bay or estuary. ----------------- The Project: The research project is an outcome of the collaborative Partnership between the Port of Brisbane Corporation (POBC) and Queensland University of Technology (QUT). A key feature of this Partnership is the undertaking of ‘cutting edge’ research to strengthen the environmental custodianship of the Port area. This project aims to develop a port specific stormwater quality model to allow informed decision making in relation to stormwater quality improvement in the context of the increased growth of the Port. --------------- Stage 1 of the research project focussed on the assessment of pollutant build-up and wash-off using rainfall simulation from the current Port of Brisbane facilities with the longer-term objective of contributing to the development of ecological risk mitigation strategies for future expansion scenarios. Investigation of complex processes such as pollutant wash-off using naturally occurring rainfall events has inherent difficulties. These can be overcome using simulated rainfall for the investigations. ----------------- The deliverables for Stage 1 included the following: * Pollutant build-up and wash-off profiles for six primary land uses within the Port of Brisbane to be used for water quality model development. * Recommendations with regards to future stormwater quality monitoring and pollution mitigation measures. The outcomes are expected to deliver the following benefits to the Port of Brisbane: * The availability of Port specific pollutant build-up and wash-off data will enable the implementation of customised stormwater pollution mitigation strategies. * The water quality data collected would form the baseline data for a Port specific water quality model for mitigation and predictive purposes. * To be at the cutting-edge in terms of water quality management and environmental best practice in the context of port infrastructure. ---------------- Conclusions: The important conclusions from the study are: * It confirmed that the Port environment is unique in terms of pollutant characteristics and is not comparable to typical urban land uses. * For most pollutant types, the Port land uses exhibited lower pollutant concentrations when compared to typical urban land uses. * The pollutant characteristics varied across the different land uses and were not consistent in terms of the land use. Hence, the implementation of stereotypical structural water quality improvement devices could be of limited value. * The <150m particle size range was predominant in suspended solids for pollutant build-up as well as wash-off. Therefore, if suspended solids are targeted as the surrogate parameter for water quality improvement, this specific particle size range needs to be removed. ------------------- Recommendations: Based on the study results the following preliminary recommendations are made: * Due to the appreciable variation in pollutant characteristics for different port land uses, any water quality monitoring stations should preferably be located such that source areas can be easily identified. * The study results having identified significant pollutants for the different land uses should enable the development of a more customised water quality monitoring and testing regime targeting the critical pollutants. * A ‘one size fits all’ approach may not be appropriate for the different port land uses due to the varying pollutant characteristics. As such, pollution mitigation will need to be specifically tailored to suit the specific land use. * Any structural measures implemented for pollution mitigation to be effective should have the capability to remove suspended solids of size <150m. * Based on the results presented and the particularly the fact that the Port land uses cannot be compared to conventional urban land uses in relation to pollutant generation, consideration should be given to the development of a port specific water quality model.

Port of Brisbane stormwater quality : stage 2 development of a port specific water quality model

Background: The quality of stormwater runoff from ports is significant as it can be an important source of pollution to the marine environment. This is also a significant issue for the Port of Brisbane as it is located in an area of high environmental values. Therefore, it is imperative to develop an in-depth understanding of stormwater runoff quality to ensure that appropriate strategies are in place for quality improvement, where necessary. To this end, the Port of Brisbane Corporation aimed to develop a port specific stormwater model for the Fisherman Islands facility. The need has to be considered in the context of the proposed future developments of the Port area. ----------------- The Project: The research project is an outcome of the collaborative Partnership between the Port of Brisbane Corporation (POBC) and Queensland University of Technology (QUT). A key feature of this Partnership is that it seeks to undertake research to assist the Port in strengthening the environmental custodianship of the Port area through ‘cutting edge’ research and its translation into practical application. ------------------ The project was separated into two stages. The first stage developed a quantitative understanding of the generation potential of pollutant loads in the existing land uses. This knowledge was then used as input for the stormwater quality model developed in the subsequent stage. The aim is to expand this model across the yet to be developed port expansion area. This is in order to predict pollutant loads associated with stormwater flows from this area with the longer term objective of contributing to the development of ecological risk mitigation strategies for future expansion scenarios. ----------------- Study approach: Stage 1 of the overall study confirmed that Port land uses are unique in terms of the anthropogenic activities occurring on them. This uniqueness in land use results in distinctive stormwater quality characteristics different to other conventional urban land uses. Therefore, it was not scientifically valid to consider the Port as belonging to a single land use category or to consider as being similar to any typical urban land use. The approach adopted in this study was very different to conventional modelling studies where modelling parameters are developed using calibration. The field investigations undertaken in Stage 1 of the overall study helped to create fundamental knowledge on pollutant build-up and wash-off in different Port land uses. This knowledge was then used in computer modelling so that the specific characteristics of pollutant build-up and wash-off can be replicated. This meant that no calibration processes were involved due to the use of measured parameters for build-up and wash-off. ---------------- Conclusions: Stage 2 of the study was primarily undertaken using the SWMM stormwater quality model. It is a physically based model which replicates natural processes as closely as possible. The time step used and catchment variability considered was adequate to accommodate the temporal and spatial variability of input parameters and the parameters used in the modelling reflect the true nature of rainfall-runoff and pollutant processes to the best of currently available knowledge. In this study, the initial loss values adopted for the impervious surfaces are relatively high compared to values noted in research literature. However, given the scientifically valid approach used for the field investigations, it is appropriate to adopt the initial losses derived from this study for future modelling of Port land uses. The relatively high initial losses will reduce the runoff volume generated as well as the frequency of runoff events significantly. Apart from initial losses, most of the other parameters used in SWMM modelling are generic to most modelling studies. Development of parameters for MUSIC model source nodes was one of the primary objectives of this study. MUSIC, uses the mean and standard deviation of pollutant parameters based on a normal distribution. However, based on the values generated in this study, the variation of Event Mean Concentrations (EMCs) for Port land uses within the given investigation period does not fit a normal distribution. This is possibly due to the fact that only one specific location was considered, namely the Port of Brisbane unlike in the case of the MUSIC model where a range of areas with different geographic and climatic conditions were investigated. Consequently, the assumptions used in MUSIC are not totally applicable for the analysis of water quality in Port land uses. Therefore, in using the parameters included in this report for MUSIC modelling, it is important to note that it may result in under or over estimations of annual pollutant loads. It is recommended that the annual pollutant load values given in the report should be used as a guide to assess the accuracy of the modelling outcomes. A step by step guide for using the knowledge generated from this study for MUSIC modelling is given in Table 4.6. ------------------ Recommendations: The following recommendations are provided to further strengthen the cutting edge nature of the work undertaken: * It is important to further validate the approach recommended for stormwater quality modelling at the Port. Validation will require data collection in relation to rainfall, runoff and water quality from the selected Port land uses. Additionally, the recommended modelling approach could be applied to a soon-to-be-developed area to assess ‘before’ and ‘after’ scenarios. * In the modelling study, TSS was adopted as the surrogate parameter for other pollutants. This approach was based on other urban water quality research undertaken at QUT. The validity of this approach should be further assessed for Port land uses. * The adoption of TSS as a surrogate parameter for other pollutants and the confirmation that the <150 m particle size range was predominant in suspended solids for pollutant wash-off gives rise to a number of important considerations. The ability of the existing structural stormwater mitigation measures to remove the <150 m particle size range need to be assessed. The feasibility of introducing source control measures as opposed to end-of-pipe measures for stormwater quality improvement may also need to be considered.

Clarification of cane juice for fermentation

Fermentation feedstocks in the sugar industry are based on cane juice, B molasses or final molasses. Brazil has been producing ethanol by directing sugarcane juice to fermentation directly or using lower quality juice as a diluent with B molasses to prepare the fermentation broth. One issue that has received only limited interest particularly from outside Brazil is the most appropriate conditions for clarification of the juice going to fermentation. Irrespective of whether the juice supply is the total flow from the milling tandem or a diffuser station or a part of the total flow, removal of the insoluble solids is essential. However, the standard defecation process used by sugar factories around the world to clarify juice can introduce unwanted calcium ions and remove other nutrients such as phosphorus and nitrogen that are considered essential for the fermentation process. An investigation was undertaken by SRI to assess the effects on the constituents of cane juice when subjected to the typical clarification process in an Australian factory and what conditions would be needed to provide a clarified juice suitable for fermentation. Typical juices from one factory were clarified in laboratory trials under a range of pH conditions and the resulting clarified juices analysed. The results indicated that pH had a major effect on the residual concentrations of key constituents in the clarified juice and that the selected clarification conditions are determined by the nominated quality criteria of clarified juice feedstock for fermentation. Further trials were conducted in overseas factories to confirm the results obtained in Australia. It became apparent that the preferred specifications for clarified juice going to fermentation varied from country to country. Each supplier of fermentation technology had criteria applying to clarified juice feedstock that would have a major impact on the standard of clarification required to achieve compliance with the criteria.

Gender equity in the professoriate : a cohort study of new women professors in Australia

According to statistics and trend data, women continue to be substantially under- represented in the Australian professoriate, and growth in their representation has been slow despite the plethora of equity programs. While not disputing these facts, we propose that examining gender equity by cohort provides a complementary perspective on the status of gender equity in the professoriate. Based on over 500 survey responses, we detected substantial similarities between women and men who were appointed as professors or associate professors between 2005 and 2008. There were similar proportions of women and men appointed via external or internal processes or by invitation. Additionally, similar proportions of women and men professors expressed a marked preference for research over teaching. Furthermore, there were similar distributions between the genders in the age of appointment to the professoriate. However, a notable gender difference was that women were appointed to the professoriate on average 1.9 years later than mens. This later appointment provides one reason for the lower representation of women compared to men in the professoriate. It also raises questions of the typical length of time that women and men remain in the (paid) professoriate and reasons why they might leave it. A further similarity between women and men in this cohort was their identification of motivation and circumstances as key factors in their career orientation. However, substantially more women identified motivation than circumstances and the situation was reversed for men. The open-ended survey responses also provided confirmation that affirmative action initiatives make a difference to women’s careers.

Robust image hashing using higher order spectral features

Robust image hashing seeks to transform a given input image into a shorter hashed version using a key-dependent non-invertible transform. These image hashes can be used for watermarking, image integrity authentication or image indexing for fast retrieval. This paper introduces a new method of generating image hashes based on extracting Higher Order Spectral features from the Radon projection of an input image. The feature extraction process is non-invertible, non-linear and different hashes can be produced from the same image through the use of random permutations of the input. We show that the transform is robust to typical image transformations such as JPEG compression, noise, scaling, rotation, smoothing and cropping. We evaluate our system using a verification-style framework based on calculating false match, false non-match likelihoods using the publicly available Uncompressed Colour Image database (UCID) of 1320 images. We also compare our results to Swaminathan’s Fourier-Mellin based hashing method with at least 1% EER improvement under noise, scaling and sharpening.

An innovative modelling approach to assess stormwater pollutant loads from the Port of Brisbane, Australia

Port land uses are subjected to unique anthropogenic activities compared to typical urban land uses. This uniqueness results in distinctive stormwater quality characteristics. Such distinction in stormwater quality has made conventional approaches used for pollutant load estimations inaccurate. This is also the case for the Port of Brisbane (PoB). The study discussed in the paper was conducted to estimate the pollutant contributions from Port specific land uses at PoB. For estimation, software modules embedded in Mike URBAN were used. An innovative approach was adopted in modelling where the conventional model calibration step was not needed to be performed to generate suitable site specific parameters. Instead, equations and site specific parameters that replicate pollutant build-up and wash-off were generated from an extensive field investigation. Models were simulated incorporating site specific parameters from six different Port specific land uses and rainfall events from three representative years. Outcomes of the modelling exercise were used to identify the distinct pollutant contributions from different Port land uses.

Advice-implicative interrogatives : building 'client-centered" support in a children's helpline

Interactional research on advice giving has described advice as normative and asymmetric. In this paper we examine how these dimensions of advice are softened by counselors on a helpline for children and young people through the use of questions. Through what we term ‘‘adviceimplicative interrogatives,’’ counselors ask clients about the relevance or applicability of a possible future course of action. The allusion to this possible action by the counselor identifies it as normatively relevant, and displays the counselor’s epistemic authority in relation to dealing with a client’s problems. However, the interrogative format mitigates the normative and asymmetric dimensions typical of advice sequences by orienting to the client’s epistemic authority in relation to their own lives, and delivering advice in a way that is contingent upon the client’s accounts of their experiences, capacities, and understandings. The demonstration of the use of questions in advice sequences offers an interactional specification of the ‘‘client-centered’’ support that is characteristic of prevailing counseling practice. More specifically, it shows how the values of empowerment and child-centered practice, which underpin services such as Kids Helpline, are embodied in specific interactional devices. Detailed descriptions of this interactional practice offer fresh insights into the use of interrogatives in counseling contexts, and provide practitioners with new ways of thinking about, and discussing, their current practices.

Reliability analysis with suspended items

Reliability analysis has several important engineering applications. Designers and operators of equipment are often interested in the probability of the equipment operating successfully to a given age - this probability is known as the equipment's reliability at that age. Reliability information is also important to those charged with maintaining an item of equipment, as it enables them to model and evaluate alternative maintenance policies for the equipment. In each case, information on failures and survivals of a typical sample of items is used to estimate the required probabilities as a function of the item's age, this process being one of many applications of the statistical techniques known as distribution fitting. In most engineering applications, the estimation procedure must deal with samples containing survivors (suspensions or censorings); this thesis focuses on several graphical estimation methods that are widely used for analysing such samples. Although these methods have been current for many years, they share a common shortcoming: none of them is continuously sensitive to changes in the ages of the suspensions, and we show that the resulting reliability estimates are therefore more pessimistic than necessary. We use a simple example to show that the existing graphical methods take no account of any service recorded by suspensions beyond their respective previous failures, and that this behaviour is inconsistent with one's intuitive expectations. In the course of this thesis, we demonstrate that the existing methods are only justified under restricted conditions. We present several improved methods and demonstrate that each of them overcomes the problem described above, while reducing to one of the existing methods where this is justified. Each of the improved methods thus provides a realistic set of reliability estimates for general (unrestricted) censored samples. Several related variations on these improved methods are also presented and justified. - i

Art in early childhood : the discourse of 'proper' teaching

This thesis is a problematisation of the teaching of art to young children. To problematise a domain of social endeavour, is, in Michel Foucault's terms, to ask how we come to believe that "something ... can and must be thought" (Foucault, 1985:7). The aim is to document what counts (i.e., what is sayable, thinkable, feelable) as proper art teaching in Queensland at this point ofhistorical time. In this sense, the thesis is a departure from more recognisable research on 'more effective' teaching, including critical studies of art teaching and early childhood teaching. It treats 'good teaching' as an effect of moral training made possible through disciplinary discourses organised around certain epistemic rules at a particular place and time. There are four key tasks accomplished within the thesis. The first is to describe an event which is not easily resolved by means of orthodox theories or explanations, either liberal-humanist or critical ones. The second is to indicate how poststructuralist understandings of the self and social practice enable fresh engagements with uneasy pedagogical moments. What follows this discussion is the documentation of an empirical investigation that was made into texts generated by early childhood teachers, artists and parents about what constitutes 'good practice' in art teaching. Twenty-two participants produced text to tell and re-tell the meaning of 'proper' art education, from different subject positions. Rather than attempting to capture 'typical' representations of art education in the early years, a pool of 'exemplary' teachers, artists and parents were chosen, using "purposeful sampling", and from this pool, three videos were filmed and later discussed by the audience of participants. The fourth aspect of the thesis involves developing a means of analysing these texts in such a way as to allow a 're-description' of the field of art teaching by attempting to foreground the epistemic rules through which such teacher-generated texts come to count as true ie, as propriety in art pedagogy. This analysis drew on Donna Haraway's (1995) understanding of 'ironic' categorisation to hold the tensions within the propositions inside the categories of analysis rather than setting these up as discursive oppositions. The analysis is therefore ironic in the sense that Richard Rorty (1989) understands the term to apply to social scientific research. Three 'ironic' categories were argued to inform the discursive construction of 'proper' art teaching. It is argued that a teacher should (a) Teach without teaching; (b) Manufacture the natural; and (c) Train for creativity. These ironic categories work to undo modernist assumptions about theory/practice gaps and finding a 'balance' between oppositional binary terms. They were produced through a discourse theoretical reading of the texts generated by the participants in the study, texts that these same individuals use as a means of discipline and self-training as they work to teach properly. In arguing the usefulness of such approaches to empirical data analysis, the thesis challenges early childhood research in arts education, in relation to its capacity to deal with ambiguity and to acknowledge contradiction in the work of teachers and in their explanations for what they do. It works as a challenge at a range of levels - at the level of theorising, of method and of analysis. In opening up thinking about normalised categories, and questioning traditional Western philosophy and the grand narratives of early childhood art pedagogy, it makes a space for re-thinking art pedagogy as "a game oftruth and error" (Foucault, 1985). In doing so, it opens up a space for thinking how art education might be otherwise.

Crosstalk between developmental and tumour-specific signalling pathways : kallikrein-related serine peptidases and nodal in prostrate cancer

Prostate cancer is an important male health issue. The strategies used to diagnose and treat prostate cancer underscore the cell and molecular interactions that promote disease progression. Prostate cancer is histologically defined by increasingly undifferentiated tumour cells and therapeutically targeted by androgen ablation. Even as the normal glandular architecture of the adult prostate is lost, prostate cancer cells remain dependent on the androgen receptor (AR) for growth and survival. This project focused on androgen-regulated gene expression, altered cellular differentiation, and the nexus between these two concepts. The AR controls prostate development, homeostasis and cancer progression by regulating the expression of downstream genes. Kallikrein-related serine peptidases are prominent transcriptional targets of AR in the adult prostate. Kallikrein 3 (KLK3), which is commonly referred to as prostate-specific antigen, is the current serum biomarker for prostate cancer. Other kallikreins are potential adjunct biomarkers. As secreted proteases, kallikreins act through enzyme cascades that may modulate the prostate cancer microenvironment. Both as a panel of biomarkers and cascade of proteases, the roles of kallikreins are interconnected. Yet the expression and regulation of different kallikreins in prostate cancer has not been compared. In this study, a spectrum of prostate cell lines was used to evaluate the expression profile of all 15 members of the kallikrein family. A cluster of genes was co-ordinately expressed in androgenresponsive cell lines. This group of kallikreins included KLK2, 3, 4 and 15, which are located adjacent to one another at the centromeric end of the kallikrein locus. KLK14 was also of interest, because it was ubiquitously expressed among the prostate cell lines. Immunohistochemistry showed that these 5 kallikreins are co-expressed in benign and malignant prostate tissue. The androgen-regulated expression of KLK2 and KLK3 is well-characterised, but has not been compared with other kallikreins. Therefore, KLK2, 3, 4, 14 and 15 expression were all measured in time course and dose response experiments with androgens, AR-antagonist treatments, hormone deprivation experiments and cells transfected with AR siRNA. Collectively, these experiments demonstrated that prostatic kallikreins are specifically and directly regulated by the AR. The data also revealed that kallikrein genes are differentially regulated by androgens; KLK2 and KLK3 were strongly up-regulated, KLK4 and KLK15 were modestly up-regulated, and KLK14 was repressed. Notably, KLK14 is located at the telomeric end of the kallikrein locus, far away from the centromeric cluster of kallikreins that are stimulated by androgens. These results show that the expression of KLK2, 3, 4, 14 and 15 is maintained in prostate cancer, but that these genes exhibit different responses to androgens. This makes the kallikrein locus an ideal model to investigate AR signalling. The increasingly dedifferentiated phenotype of aggressive prostate cancer cells is accompanied by the re-expression of signalling molecules that are usually expressed during embryogenesis and foetal tissue development. The Wnt pathway is one developmental cascade that is reactivated in prostate cancer. The canonical Wnt cascade regulates the intracellular levels of β-catenin, a potent transcriptional co-activator of T-cell factor (TCF) transcription factors. Notably, β-catenin can also bind to the AR and synergistically stimulate androgen-mediated gene expression. This is at the expense of typical Wnt/TCF target genes, because the AR:β-catenin and TCF:β-catenin interactions are mutually exclusive. The effect of β-catenin on kallikrein expression was examined to further investigate the role of β-catenin in prostate cancer. Stable knockdown of β-catenin in LNCaP prostate cancer cells attenuated the androgen-regulated expression of KLK2, 3, 4 and 15, but not KLK14. To test whether KLK14 is instead a TCF:β-catenin target gene, the endogenous levels of β-catenin were increased by inhibiting its degradation. Although KLK14 expression was up-regulated by these treatments, siRNA knockdown of β-catenin demonstrated that this effect was independent of β-catenin. These results show that β-catenin is required for maximal expression of KLK2, 3, 4 and 15, but not KLK14. Developmental cells and tumour cells express a similar repertoire of signalling molecules, which means that these different cell types are responsive to one another. Previous reports have shown that stem cells and foetal tissues can reprogram aggressive cancer cells to less aggressive phenotypes by restoring the balance to developmental signalling pathways that are highly dysregulated in cancer. To investigate this phenomenon in prostate cancer, DU145 and PC-3 prostate cancer cells were cultured on matrices pre-conditioned with human embryonic stem cells (hESCs). Soft agar assays showed that prostate cancer cells exposed to hESC conditioned matrices had reduced clonogenicity compared with cells harvested from control matrices. A recent study demonstrated that this effect was partially due to hESC-derived Lefty, an antagonist of Nodal. A member of the transforming growth factor β (TGFβ) superfamily, Nodal regulates embryogenesis and is re-expressed in cancer. The role of Nodal in prostate cancer has not previously been reported. Therefore, the expression and function of the Nodal signalling pathway in prostate cancer was investigated. Western blots confirmed that Nodal is expressed in DU145 and PC-3 cells. Immunohistochemistry revealed greater expression of Nodal in malignant versus benign glands. Notably, the Nodal inhibitor, Lefty, was not expressed at the mRNA level in any prostate cell lines tested. The Nodal signalling pathway is functionally active in prostate cancer cells. Recombinant Nodal treatments triggered downstream phosphorylation of Smad2 in DU145 and LNCaP cells, and stably-transfected Nodal increased the clonogencity of LNCaP cells. Nodal was also found to modulate AR signalling. Nodal reduced the activity of an androgen-regulated KLK3 promoter construct in luciferase assays and attenuated the endogenous expression of AR target genes including prostatic kallikreins. These results demonstrate that Nodal is a novel example of a developmental signalling molecule that is reexpressed in prostate cancer and may have a functional role in prostate cancer progression. In summary, this project clarifies the role of androgens and changing cellular differentiation in prostate cancer by characterising the expression and function of the downstream genes encoding kallikrein-related serine proteases and Nodal. Furthermore, this study emphasises the similarities between prostate cancer and early development, and the crosstalk between developmental signalling pathways and the AR axis. The outcomes of this project also affirm the utility of the kallikrein locus as a model system to monitor tumour progression and the phenotype of prostate cancer cells.

Calculating shades of meaning in semantic spaces

This thesis introduces the problem of conceptual ambiguity, or Shades of Meaning (SoM) that can exist around a term or entity. As an example consider President Ronald Reagan the ex-president of the USA, there are many aspects to him that are captured in text; the Russian missile deal, the Iran-contra deal and others. Simply finding documents with the word “Reagan” in them is going to return results that cover many different shades of meaning related to "Reagan". Instead it may be desirable to retrieve results around a specific shade of meaning of "Reagan", e.g., all documents relating to the Iran-contra scandal. This thesis investigates computational methods for identifying shades of meaning around a word, or concept. This problem is related to word sense ambiguity, but is more subtle and based less on the particular syntactic structures associated with or around an instance of the term and more with the semantic contexts around it. A particularly noteworthy difference from typical word sense disambiguation is that shades of a concept are not known in advance. It is up to the algorithm itself to ascertain these subtleties. It is the key hypothesis of this thesis that reducing the number of dimensions in the representation of concepts is a key part of reducing sparseness and thus also crucial in discovering their SoMwithin a given corpus.

Fabrication using a rapid prototyping system and in vitro characterization of PEG-PCL-PLA scaffolds for tissue engineering

n the field of tissue engineering new polymers are needed to fabricate scaffolds with specific properties depending on the targeted tissue. This work aimed at designing and developing a 3D scaffold with variable mechanical strength, fully interconnected porous network, controllable hydrophilicity and degradability. For this, a desktop-robot-based melt-extrusion rapid prototyping technique was applied to a novel tri-block co-polymer, namely poly(ethylene glycol)-block-poly(epsi-caprolactone)-block-poly(DL-lactide), PEG-PCL-P(DL)LA. This co-polymer was melted by electrical heating and directly extruded out using computer-controlled rapid prototyping by means of compressed purified air to build porous scaffolds. Various lay-down patterns (0/30/60/90/120/150°, 0/45/90/135°, 0/60/120° and 0/90°) were produced by using appropriate positioning of the robotic control system. Scanning electron microscopy and micro-computed tomography were used to show that 3D scaffold architectures were honeycomb-like with completely interconnected and controlled channel characteristics. Compression tests were performed and the data obtained agreed well with the typical behavior of a porous material undergoing deformation. Preliminary cell response to the as-fabricated scaffolds has been studied with primary human fibroblasts. The results demonstrated the suitability of the process and the cell biocompatibility of the polymer, two important properties among the many required for effective clinical use and efficient tissue-engineering scaffolding.