Exercise, appetite control, and energy balance

Given the present worldwide epidemic of obesity, it is pertinent to ask how effective exercise could be in helping people to lose weight or to prevent weight gain. There is a widely held belief that exercise is futile for weight reduction because any energy expended in exercise is automatically compensated for by a corresponding increase in energy intake (EI). In other words, exercise elevates the intensity of hunger and drives food consumption. This “commonsense” view appears to originate in an energy-balance model of appetite control, which stipulates that energy expended will drive EI as a consequence of the regulation of energy balance. However, it is very clear that EI (food consumption or eating) is not just a biological matter. Eating does not occur solely to rectify some internal need state. Indeed, an examination of the relation between exercise and appetite control has shown a very weak coupling; most studies have demonstrated that food intake does not immediately rise after exercise, even after very high energy expenditure (EE).[1] The processes of exercise-induced EE and food consumption do not appear to be tightly linked. After exercise, there is only slow and partial compensation for the energy expended. Therefore, exercise can be very useful in helping to bring about weight loss and is even more important in preventing weight gain or weight regain. This editorial explores this issue.

Community voices, votes and action

The diversity of community voices in the SEQ ‘bellwether region’ has grown from a muted murmur in the mid twentieth century supporting provision of urban services, rural conservation and green belts, to the current clamour against over-development, and in favour of protecting local and regional open space, wetlands and natural habitats. This in turn has often resulted in vigorous campaigns against unpopular roads, dams, dumps and tall buildings. In the last twenty years community issues have played a major part in local government elections throughout the region and have even helped unseat (in 1995-1996) a state government which discounted their authenticity and community resolve.

Capital music : personal expression with a public display of song choice

Using information and communication technology devices in public urban places can help to create a personalised space. Looking at a mobile phone screen or listening to music on an MP3 player is a common practice avoiding direct contact with others e.g. whilst using public transport. However, such devices can also be utilised to explore how to build new meaningful connections with the urban space and the collocated people within. We present findings of work-in-progress on Capital Music, a mobile application enabling urban dwellers to listen to music songs as usual, but also allowing them to announce song titles and discover songs currently being listened to by other people in the vicinity. We study the ways that this tool can change or even enhance people’s experience of public urban spaces. Our first user study also found changes in choosing different songs. Anonymous social interactions based on users’ music selection are implemented in the first iteration of the prototype that we studied.

Economics of maritime disasters : essays on the Titanic and Lusitania

This work seeks to fill some of the gap existing in the economics and behavioural economics literature pertaining to the decision making process of individuals under extreme environmental situations (life and death events). These essays specifically examine the sinking’s of the R.M.S. Titanic, on 14th April of 1912, and the R.M.S. Lusitania, on 7th May 1915, using econometric (multivariate) analysis techniques. The results show that even under extreme life and death conditions, social norms matter and are reflected in the survival probabilities of individuals onboard the Titanic. However, results from the comparative analysis of the Titanic and Lusitania show that social norms take time to organise and be effective. In the presence of such time constraints, the traditional “homo economicus” model of individual behaviour becomes evident as a survival of the fittest competition.

Fold back current control and admittance protection scheme for a distribution network containing distributed generators

Islanded operation, protection, reclosing and arc extinguishing are some of the challenging issues related to the connection of converter interfaced distributed generators (DGs) into a distribution network. The isolation of upstream faults in grid connected mode and fault detection in islanded mode using overcurrent devices are difficult. In the event of an arc fault, all DGs must be disconnected in order to extinguish the arc. Otherwise, they will continue to feed the fault, thus sustaining the arc. However, the system reliability can be increased by maximising the DG connectivity to the system: therefore, the system protection scheme must ensure that only the faulted segment is removed from the feeder. This is true even in the case of a radial feeder as the DG can be connected at various points along the feeder. In this paper, a new relay scheme is proposed which, along with a novel current control strategy for converter interfaced DGs, can isolate permanent and temporary arc faults. The proposed protection and control scheme can even coordinate with reclosers. The results are validated through PSCAD/EMTDC simulation and MATLAB calculations.

Advanced analysis of steel frame structures comprising non-compact sections

During the past decade, a significant amount of research has been conducted internationally with the aim of developing, implementing, and verifying "advanced analysis" methods suitable for non-linear analysis and design of steel frame structures. Application of these methods permits comprehensive assessment of the actual failure modes and ultimate strengths of structural systems in practical design situations, without resort to simplified elastic methods of analysis and semi-empirical specification equations. Advanced analysis has the potential to extend the creativity of structural engineers and simplify the design process, while ensuring greater economy and more uniform safety with respect to the ultimate limit state. The application of advanced analysis methods has previously been restricted to steel frames comprising only members with compact cross-sections that are not subject to the effects of local buckling. This precluded the use of advanced analysis from the design of steel frames comprising a significant proportion of the most commonly used Australian sections, which are non-compact and subject to the effects of local buckling. This thesis contains a detailed description of research conducted over the past three years in an attempt to extend the scope of advanced analysis by developing methods that include the effects of local buckling in a non-linear analysis formulation, suitable for practical design of steel frames comprising non-compact sections. Two alternative concentrated plasticity formulations are presented in this thesis: the refined plastic hinge method and the pseudo plastic zone method. Both methods implicitly account for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the methods for the analysis of steel frames comprising non-compact sections has been established by comparison with a comprehensive range of analytical benchmark frame solutions. Both the refined plastic hinge and pseudo plastic zone methods are more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations. For example, the pseudo plastic zone method predicts the ultimate strength of the analytical benchmark frames with an average conservative error of less than one percent, and has an acceptable maximum unconservati_ve error of less than five percent. The pseudo plastic zone model can allow the design capacity to be increased by up to 30 percent for simple frames, mainly due to the consideration of inelastic redistribution. The benefits may be even more significant for complex frames with significant redundancy, which provides greater scope for inelastic redistribution. The analytical benchmark frame solutions were obtained using a distributed plasticity shell finite element model. A detailed description of this model and the results of all the 120 benchmark analyses are provided. The model explicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. Its accuracy was verified by comparison with a variety of analytical solutions and the results of three large-scale experimental tests of steel frames comprising non-compact sections. A description of the experimental method and test results is also provided.

Mechanical properties of thin sol-gel films

This thesis presents a study of the mechanical properties of thin films. The main aim was to determine the properties of sol-gel derived coatings. These films are used in a range of different applications and are known to be quite porous. Very little work has been carried out in this area and in order to study the mechanical properties of sol-gel films, some of the work was carried out on magnetron sputtered metal coatings in order to validate the techniques developed in this work. The main part of the work has concentrated on the development of various bending techniques to study the elastic modulus of the thin films, including both a small scale three-point bending, as well as a novel bi-axial bending technique based on a disk resting on three supporting balls. The bending techniques involve a load being applied to the sample being tested and the bending response to this force being recorded. These experiments were carried out using an ultra micro indentation system with very sensitive force and depth recording capabilities. By analysing the result of these forces and deflections using existing theories of elasticity, the elastic modulus may be determined. In addition to the bi-axial bending study, a finite element analysis of the stress distribution in a disk during bending was carried out. The results from the bi-axial bending tests of the magnetron sputtered films was confirmed by ultra micro indentation tests, giving information of the hardness and elastic modulus of the films. It was found that while the three point bending method gave acceptable results for uncoated steel substrates, it was very susceptible to slight deformations of the substrate. Improvements were made by more careful preparation of the substrates in order to avoid deformation. However the technique still failed to give reasonable results for coated specimens. In contrast, biaxial bending gave very reliable results even for very thin films and this technique was also found to be useful for determination of the properties of sol-gel coatings. In addition, an ultra micro indentation study of the hardness and elastic modulus of sol-gel films was conducted. This study included conventionally fired films as well as films ion implanted in a range of doses. The indentation tests showed that for implantation of H⁺ ions at doses exceeding 3x10¹⁶ ions/cm², the mechanical properties closely resembled those of films that were conventionally fired to 450°C.

The impact of brand and product placements in electronic games

In an environment where it has become increasingly difficult to attract consumer attention, marketers have begun to explore alternative forms of marketing communication. One such form that has emerged is product placement, which has more recently appeared in electronic games. Given changes in media consumption and the growth of the games industry, it is not surprising that games are being exploited as a medium for promotional content. Other market developments are also facilitating and encouraging their use, in terms of both the insertion of brand messages into video games and the creation of brand-centred environments, labelled ‘advergames’. However, while there is much speculation concerning the beneficial outcomes for marketers, there remains a lack of academic work in this area and little empirical evidence of the actual effects of this form of promotion on game players. Only a handful of studies are evident in the literature, which have explored the influence of game placements on consumers. The majority have studied their effect on brand awareness, largely demonstrating that players can recall placed brands. Further, most research conducted to date has focused on computer and online games, but consoles represent the dominant platform for play (Taub, 2004). Finally, advergames have largely been neglected, particularly those in a console format. Widening the gap in the literature is the fact that insufficient academic attention has been given to product placement as a marketing communication strategy overall, and to games in general. The unique nature of the strategy also makes it difficult to apply existing literature to this context. To address a significant need for information in both the academic and business domains, the current research investigates the effects of brand and product placements in video games and advergames on consumer attitude to the brand and corporate image. It was conducted in two stages. Stage one represents a pilot study. It explored the effects of use simulated and peripheral placements in video games on players’ and observers’ attitudinal responses, and whether these are influenced by involvement with a product category or skill level in the game. The ability of gamers to recall placed brands was also examined. A laboratory experiment was employed with a small sample of sixty adult subjects drawn from an Australian east-coast university, some of who were exposed to a console video game on a television set. The major finding of study one is that placements in a video game have no effect on gamers’ attitudes, but they are recalled. For stage two of the research, a field experiment was conducted with a large, random sample of 350 student respondents to investigate the effects on players of brand and product placements in handheld video games and advergames. The constructs of brand attitude and corporate image were again tested, along with several potential confounds. Consistent with the pilot, the results demonstrate that product placement in electronic games has no effect on players’ brand attitudes or corporate image, even when allowing for their involvement with the product category, skill level in the game, or skill level in relation to the medium. Age and gender also have no impact. However, the more interactive a player perceives the game to be, the higher their attitude to the placed brand and corporate image of the brand manufacturer. In other words, when controlling for perceived interactivity, players experienced more favourable attitudes, but the effect was so weak it probably lacks practical significance. It is suggested that this result can be explained by the existence of excitation transfer, rather than any processing of placed brands. The current research provides strong, empirical evidence that brand and product placements in games do not produce strong attitudinal responses. It appears that the nature of the game medium, game playing experience and product placement impose constraints on gamer motivation, opportunity and ability to process these messages, thereby precluding their impact on attitude to the brand and corporate image. Since this is the first study to investigate the ability of video game and advergame placements to facilitate these deeper consumer responses, further research across different contexts is warranted. Nevertheless, the findings have important theoretical and managerial implications. This investigation makes a number of valuable contributions. First, it is relevant to current marketing practice and presents findings that can help guide promotional strategy decisions. It also presents a comprehensive review of the games industry and associated activities in the marketplace, relevant for marketing practitioners. Theoretically, it contributes new knowledge concerning product placement, including how it should be defined, its classification within the existing communications framework, its dimensions and effects. This is extended to include brand-centred entertainment. The thesis also presents the most comprehensive analysis available in the literature of how placements appear in games. In the consumer behaviour discipline, the research builds on theory concerning attitude formation, through application of MacInnis and Jaworski’s (1989) Integrative Attitude Formation Model. With regards to the games literature, the thesis provides a structured framework for the comparison of games with different media types; it advances understanding of the game medium, its characteristics and the game playing experience; and provides insight into console and handheld games specifically, as well as interactive environments generally. This study is the first to test the effects of interactivity in a game environment, and presents a modified scale that can be used as part of future research. Methodologically, it addresses the limitations of prior research through execution of a field experiment and observation with a large sample, making this the largest study of product placement in games available in the literature. Finally, the current thesis offers comprehensive recommendations that will provide structure and direction for future study in this important field.

A life jacket with holes- : a case study of 'temporary engagement' : a strategy used by Education Queensland to employ beginning secondary teachers

This research investigated the impact of Education Queensland's employment policy and practices for beginning secondary teachers appointed on temporary engagement. The context was the public secondary school sector within the state of Queensland, Australia. The study was set within a context of the changing nature of work from full-time permanent employment towards casual, fixed-term contracts, temporary and part-time employment, a trend reflected in the employment patterns for teachers within Australia. Two broad categories of literature relating to the research problem of this thesis were reviewed, namely the beginning teacher and permanency or tenure. The focus in the research literature on beginning teachers was the professional experiences of teachers within the classroom and school. There was a paucity of research that considered the working and industrial conditions of temporary employment for beginning teachers or the personal and professional implications of this form of employment. The review of the context and literature was conceptualised as a Beginning Temporary Teacher Theoretical Framework which served to inform the study. Using a qualitative case study methodology, the research techniques employed for the thesis were semi-structured interview and document analysis. A simultaneously conducted research project in which the researcher participated entitled 'Winning the Lottery? Beginning Teachers on Temporary Engagement' foregrounded this thesis in terms of refining the research question, contributing to the literature and in the selection of the participants. For this case study the perspectives of four distinct yet inter-related categories of professionals were sought. These included four beginning secondary teachers, three school administrators, a Senior Personnel Officer with Education Queensland, and a representative from the Queensland Teachers' Union. The research findings indicated that none of the beginning teachers or other professionals viewed starting a career in teaching on temporary engagement as the ideal. The negative features identified were the differential treatment received and the high level of uncertainty associated with temporary employment. Differential treatment tended to indicate 'less' entitlements, in terms of access to induction and professional development, recreational and sick leave, acceptance by and expectations of other colleagues, and avenues of redress in grievance cases. Moreover, interviews indicated a high level of uncertainty in terms of starting within the teaching profession, commencing at a new school, and a regular income. In addition, frequent changes in schools and/or cohorts of students exacerbated levels of uncertainty. The beginning teachers reported significantly decreased motivation, self-esteem and sense of belonging, and increased stress levels. There was an even more marked negative impact on those beginning teachers who had experienced a higher number of temporary engagements and schools in their first year of teaching. Conversely, strong staff support and a reasonable length of time in the one school improved the quality of the beginning teachers' experiences. The overall impact of being on temporary engagement resulted in delayed permanent position appointments, decreased commitment to particular schools and to Education Queensland as the employing authority, and for two of the beginning teachers, it produced a desire to seek alternative employment. The implementation of Education Queensland's policies relating to working conditions and entitlements for these temporary beginning teachers at the school level was revealed to be less than satisfactory. There was a tendency towards 'just-in- time' management of the beginning teacher on temporary engagement. The beginning teachers received 'less-than-messages' about access to and use of departmental documentation, support through induction and professional development, and their transition from temporary to permanent employment. To ensure a more systematic, supportive and inclusive process for managing the temporary beginning teacher, a conceptual framework entitled 'Continuums of Tension' was developed. The four continuums included permanent employment - temporary employment; system perspective - individual perspective; teaching as a profession - teaching as a job; and the permanent beginning teacher - university graduate. The general principles of the human resource policies of Education Queensland were based on a commitment to permanent employment, a system's perspective, viewing teaching as a profession and a homogeneous group of permanent beginning teachers. Contrasting with this, the beginning teacher on temporary engagement tended to operate from the position of temporary employment and a perspective that was individually based. Their priorities therefore included the 'occupational' aspects of being a temporary teacher striving to become permanent. Thus there existed a tension or contradiction between the general principles of human resource policies within Education Queensland and the employment experiences of beginning teachers on temporary engagement. The study proposed three actions for resolution to address the aforementioned tensions. The actions included: (a) the effective provision and targeted communication of information; (b) support, induction and professional development; and (c) a coordinated approach between Education Queensland, Queensland Teachers' Union, the Universities and the beginning teacher. These actions are fm1her refined to include: (a) an induction kit to suppm1 the individual through the pre-employment to permanent employee phases, (b) an extrapolation of the roles and responsibilities of Education Queensland personnel charged with supporting the beginning temporary teacher, and (c) a series of recommendations to effect a coordinated approach amongst the key stakeholders. The theoretical and conceptual frameworks have provided a means of addressing the identified needs of the beginning teacher on temporary engagement. As such, this study has contributed to the research literature on teacher employment and professionalism and aims to provide a beginning temporary teacher with managed professional and occupational support.

The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.

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.

The differential impact of holocaust trauma across three generations

In the current thesis, the reasons for the differential impact of Holocaust trauma on Holocaust survivors, and the differential intergenerational transmission of this trauma to survivors’ children and grandchildren were explored. A model specifically related to Holocaust trauma and its transmission was developed based on trauma, family systems and attachment theories as well as theoretical and anecdotal conjecture in the Holocaust literature. The Model of the Differential Impact of Holocaust Trauma across Three Generations was tested firstly by extensive meta-analyses of the literature pertaining to the psychological health of Holocaust survivors and their descendants and secondly via analysis of empirical study data. The meta-analyses reported in this thesis represent the first conducted with research pertaining to Holocaust survivors and grandchildren of Holocaust survivors. The meta-analysis of research conducted with children of survivors is the first to include both published and unpublished research. Meta-analytic techniques such as meta-regression and sub-set meta-analyses provided new information regarding the influence of a number of unmeasured demographic variables on the psychological health of Holocaust survivors and descendants. Based on the results of the meta-analyses it was concluded that Holocaust survivors and their children and grandchildren suffer from a statistically significantly higher level or greater severity of psychological symptoms than the general population. However it was also concluded that there is statistically significant variation in psychological health within the Holocaust survivor and descendant populations. Demographic variables which may explain a substantial amount of this variation have been largely under-assessed in the literature and so an empirical study was needed to clarify the role of demographics in determining survivor and descendant mental health. A total of 124 participants took part in the empirical study conducted for this thesis with 27 Holocaust survivors, 69 children of survivors and 28 grandchildren of survivors. A worldwide recruitment process was used to obtain these participants. Among the demographic variables assessed in the empirical study, aspects of the survivors’ Holocaust trauma (namely the exact nature of their Holocaust experiences, the extent of family bereavement and their country of origin) were found to be particularly potent predictors of not only their own psychological health but continue to be strongly influential in determining the psychological health of their descendants. Further highlighting the continuing influence of the Holocaust was the finding that number of Holocaust affected ancestors was the strongest demographic predictor of grandchild of survivor psychological health. Apart from demographic variables, the current thesis considered family environment dimensions which have been hypothesised to play a role in the transmission of the traumatic impact of the Holocaust from survivors to their descendants. Within the empirical study, parent-child attachment was found to be a key determinant in the transmission of Holocaust trauma from survivors to their children and insecure parent-child attachment continues to reverberate through the generations. In addition, survivors’ communication about the Holocaust and their Holocaust experiences to their children was found to be more influential than general communication within the family. Ten case studies (derived from the empirical study data set) are also provided; five Holocaust survivors, three children of survivors and two grandchildren of survivors. These cases add further to the picture of heterogeneity of the survivor and descendant populations in both experiences and adaptations. It is concluded that the legacy of the Holocaust continues to leave its mark on both its direct survivors and their descendants. Even two generations removed, the direct and indirect effects of the Holocaust have yet to be completely nullified. Research with Holocaust survivor families serves to highlight the differential impacts of state-based trauma and the ways in which its effects continue to be felt for generations. The revised and empirically tested Model of the Differential Impact of Holocaust Trauma across Three Generations presented at the conclusion of this thesis represents a further clarification of existing trauma theories as well as the first attempt at determining the relative importance of both cognitive, interpersonal/interfamilial interaction processes and demographic variables in post-trauma psychological health and transmission of traumatic impact.

Learning power and language expressiveness

The topic of the present work is to study the relationship between the power of the learning algorithms on the one hand, and the expressive power of the logical language which is used to represent the problems to be learned on the other hand. The central question is whether enriching the language results in more learning power. In order to make the question relevant and nontrivial, it is required that both texts (sequences of data) and hypotheses (guesses) be translatable from the “rich” language into the “poor” one. The issue is considered for several logical languages suitable to describe structures whose domain is the set of natural numbers. It is shown that enriching the language does not give any advantage for those languages which define a monadic second-order language being decidable in the following sense: there is a fixed interpretation in the structure of natural numbers such that the set of sentences of this extended language true in that structure is decidable. But enriching the original language even by only one constant gives an advantage if this language contains a binary function symbol (which will be interpreted as addition). Furthermore, it is shown that behaviourally correct learning has exactly the same power as learning in the limit for those languages which define a monadic second-order language with the property given above, but has more power in case of languages containing a binary function symbol. Adding the natural requirement that the set of all structures to be learned is recursively enumerable, it is shown that it pays o6 to enrich the language of arithmetics for both finite learning and learning in the limit, but it does not pay off to enrich the language for behaviourally correct learning.

Learning to win process-control games watching game-masters

The present paper focuses on some interesting classes of process-control games, where winning essentially means successfully controlling the process. A master for one of these games is an agent who plays a winning strategy. In this paper we investigate situations in which even a complete model (given by a program) of a particular game does not provide enough information to synthesize—even incrementally—a winning strategy. However, if in addition to getting a program, a machine may also watch masters play winning strategies, then the machine is able to incrementally learn a winning strategy for the given game. Studied are successful learning from arbitrary masters and from pedagogically useful selected masters. It is shown that selected masters are strictly more helpful for learning than are arbitrary masters. Both for learning from arbitrary masters and for learning from selected masters, though, there are cases where one can learn programs for winning strategies from masters but not if one is required to learn a program for the master's strategy itself. Both for learning from arbitrary masters and for learning from selected masters, one can learn strictly more by watching m+1 masters than one can learn by watching only m. Last, a simulation result is presented where the presence of a selected master reduces the complexity from infinitely many semantic mind changes to finitely many syntactic ones.

The impact of holding costs in the housing affordability puzzle

Research is now emerging which exposes the significance and extent to which even small shifts in the regulatory assessment period, and other factors, affect housing affordability. It suggests that the extent of its significance has not been hitherto completely demonstrated.