The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Seeing is understanding : the effect of visualisation in understanding programming concepts

How and why visualisations support learning was the subject of this qualitative instrumental collective case study. Five computer programming languages (PHP, Visual Basic, Alice, GameMaker, and RoboLab) supporting differing degrees of visualisation were used as cases to explore the effectiveness of software visualisation to develop fundamental computer programming concepts (sequence, iteration, selection, and modularity). Cognitive theories of visual and auditory processing, cognitive load, and mental models provided a framework in which student cognitive development was tracked and measured by thirty-one 15-17 year old students drawn from a Queensland metropolitan secondary private girls’ school, as active participants in the research. Seventeen findings in three sections increase our understanding of the effects of visualisation on the learning process. The study extended the use of mental model theory to track the learning process, and demonstrated application of student research based metacognitive analysis on individual and peer cognitive development as a means to support research and as an approach to teaching. The findings also forward an explanation for failures in previous software visualisation studies, in particular the study has demonstrated that for the cases examined, where complex concepts are being developed, the mixing of auditory (or text) and visual elements can result in excessive cognitive load and impede learning. This finding provides a framework for selecting the most appropriate instructional programming language based on the cognitive complexity of the concepts under study.

Vision, functional and cognitive determinants of motor vehicle incidents in older drivers

Background: The proportion of older individuals in the driving population is predicted to increase in the next 50 years. This has important implications for driving safety as abilities which are important for safe driving, such as vision (which accounts for the majority of the sensory input required for driving), processing ability and cognition have been shown to decline with age. The current methods employed for screening older drivers upon re-licensure are also vision based. This study, which investigated social, behavioural and professional aspects involved with older drivers, aimed to determine: (i) if the current visual standards in place for testing upon re-licensure are effective in reducing the older driver fatality rate in Australia; (ii) if the recommended visual standards are actually implemented as part of the testing procedures by Australian optometrists; and (iii) if there are other non-standardised tests which may be better at predicting the on-road incident-risk (including near misses and minor incidents) in older drivers than those tests recommended in the standards. Methods: For the first phase of the study, state-based age- and gender-stratified numbers of older driver fatalities for 2000-2003 were obtained from the Australian Transportation Safety Bureau database. Poisson regression analyses of fatality rates were considered by renewal frequency and jurisdiction (as separate models), adjusting for possible confounding variables of age, gender and year. For the second phase, all practising optometrists in Australia were surveyed on the vision tests they conduct in consultations relating to driving and their knowledge of vision requirements for older drivers. Finally, for the third phase of the study to investigate determinants of on-road incident risk, a stratified random sample of 600 Brisbane residents aged 60 years and were selected and invited to participate using an introductory letter explaining the project requirements. In order to capture the number and type of road incidents which occurred for each participant over 12 months (including near misses and minor incidents), an important component of the prospective research study was the development and validation of a driving diary. The diary was a tool in which incidents that occurred could be logged at that time (or very close in time to which they occurred) and thus, in comparison with relying on participant memory over time, recall bias of incident occurrence was minimised. Association between all visual tests, cognition and scores obtained for non-standard functional tests with retrospective and prospective incident occurrence was investigated. Results: In the first phase,rivers aged 60-69 years had a 33% lower fatality risk (Rate Ratio [RR] = 0.75, 95% CI 0.32-1.77) in states with vision testing upon re-licensure compared with states with no vision testing upon re-licensure, however, because the CIs are wide, crossing 1.00, this result should be regarded with caution. However, overall fatality rates and fatality rates for those aged 70 years and older (RR=1.17, CI 0.64-2.13) did not differ between states with and without license renewal procedures, indicating no apparent benefit in vision testing legislation. For the second phase of the study, nearly all optometrists measured visual acuity (VA) as part of a vision assessment for re-licensing, however, 20% of optometrists did not perform any visual field (VF) testing and only 20% routinely performed automated VF on older drivers, despite the standards for licensing advocating automated VF as part of the vision standard. This demonstrates the need for more effective communication between the policy makers and those responsible for carrying out the standards. It may also indicate that the overall higher driver fatality rate in jurisdictions with vision testing requirements is resultant as the tests recommended by the standards are only partially being conducted by optometrists. Hence a standardised protocol for the screening of older drivers for re-licensure across the nation must be established. The opinions of Australian optometrists with regard to the responsibility of reporting older drivers who fail to meet the licensing standards highlighted the conflict between maintaining patient confidentiality or upholding public safety. Mandatory reporting requirements of those drivers who fail to reach the standards necessary for driving would minimise potential conflict between the patient and their practitioner, and help maintain patient trust and goodwill. The final phase of the PhD program investigated the efficacy of vision, functional and cognitive tests to discriminate between at-risk and safe older drivers. Nearly 80% of the participants experienced an incident of some form over the prospective 12 months, with the total incident rate being 4.65/10 000 km. Sixty-three percent reported having a near miss and 28% had a minor incident. The results from the prospective diary study indicate that the current vision screening tests (VA and VF) used for re-licensure do not accurately predict older drivers who are at increased odds of having an on-road incident. However, the variation in visual measurements of the cohort was narrow, also affecting the results seen with the visual functon questionnaires. Hence a larger cohort with greater variability should be considered for a future study. A slightly lower cognitive level (as measured with the Mini-Mental State Examination [MMSE]) did show an association with incident involvement as did slower reaction time (RT), however the Useful-Field-of-View (UFOV) provided the most compelling results of the study. Cut-off values of UFOV processing (>23.3ms), divided attention (>113ms), selective attention (>258ms) and overall score (moderate/ high/ very high risk) were effective in determining older drivers at increased odds of having any on-road incident and the occurrence of minor incidents. Discussion: The results have shown that for the 60-69 year age-group, there is a potential benefit in testing vision upon licence renewal. However, overall fatality rates and fatality rates for those aged 70 years and older indicated no benefit in vision testing legislation and suggests a need for inclusion of screening tests which better predict on-road incidents. Although VA is routinely performed by Australian optometrists on older drivers renewing their licence, VF is not. Therefore there is a need for a protocol to be developed and administered which would result in standardised methods conducted throughout the nation for the screening of older drivers upon re-licensure. Communication between the community, policy makers and those conducting the protocol should be maximised. By implementing a standardised screening protocol which incorporates a level of mandatory reporting by the practitioner, the ethical dilemma of breaching patient confidentiality would also be resolved. The tests which should be included in this screening protocol, however, cannot solely be ones which have been implemented in the past. In this investigation, RT, MMSE and UFOV were shown to be better determinants of on-road incidents in older drivers than VA and VF, however, as previously mentioned, there was a lack of variability in visual status within the cohort. Nevertheless, it is the recommendation from this investigation, that subject to appropriate sensitivity and specificity being demonstrated in the future using a cohort with wider variation in vision, functional performance and cognition, these tests of cognition and information processing should be added to the current protocol for the screening of older drivers which may be conducted at licensing centres across the nation.

A phenomenological explication of dream interpretation among rural and urban Nguni people

Psychologists investigating dreams in non-Western cultures have generally not considered the meanings of dreams within the unique meaning-structure of the person in his or her societal context. The majority of dream studies in African societies are no exception. Researchers approaching dreams within rural Xhosa and Zulu speaking societies have either adopted an anthropological or a psychodynamic orientation. The latter approach particularly imposes a Western perspective in the interpretation of dream material. There have been no comparable studies of dream interpretation among urban blacks participating in the African Independent Church Movement. The present study focuses on the rural Xhosa speaking people and the urban black population who speak one of the Nguni languages and identify with the African Independent Church Movement. The study is concerned with understanding the meanings of dreams within the cultural context in which they occur. The specific aims of the study are: 1. To explicate the indigenous system of dream interpretation as revealed by acknowledged dream experts. 2. To examine the commonalities and the differences between the interpretation of dreams in two groups, drawn from a rural and urban setting respectively. 3. To elaborate upon the life-world of the participants by the interpretations gained from the above investigation. One hundred dreams and interpretations are collected from two categories of participants referred to as the Rural Group and the Urban Group. The Rural Group is made up of amagqira [traditional healers] and their clients, while the Urban Group consists of prophets and members of the African Independent Churches. Each group includes acknowledged dream experts. A phenomenological methodology is adopted in explicating the data. The methodological precedure involves a number of rigorous stages of expl ication whereby the original data is reduced to Constituent Profiles leading to the construction of a Thematic Index File. By searching and reflect ing upon the data, interpretative themes are identified. These themes are explicated to provide a rigorous description of the interpretative-reality of each group. Themes explicated w i thin the Rural Group are: the physiognomy of the dreamer's life-world as revealed by ithongo, the interpretation of ithongo as revealed through action, the dream relationship as an anticipatory mode-of-existence, iphupha as disclosing a vulnerable mode-of-being, human bodiliness as revealed in dream interpretations and the legitimation of the interpretative-reality within the life-world. Themes explicated within the Urban Group are: the phys iognomy of the dreamer's life-world revealed in their dream-existence, the interpretative-reality revealed through the enaction of dreams, tension between the newer Christian-based cosomology and the traditional cultural-based cosmology, a moral imperative, prophetic perception and human bodiliness, as revealed in dream interpretations and the legitimation of the interpretative-reality within the life-world. The essence of the interpretative-reality of both groups is very similar and is expressed in the notion of relatedness to a cosmic mode-of-being. The cosmic mode-of-being includes a numinous dimension which is expressed through divine presence in the form of ancestors, Holy Spirit or God. These notions cannot be apprehended by theoretical constructs alone but may be grasped and given form in meaning-disclosing intuitions which are expressed in the lifeworld in terms of bodiliness, revelatory knowledge, action and healing. Some differences b e tween the two groups are evident and reveal some conflict between the monotheistic Christian cosmology and the traditional cosmology. Unique aspects of the interpetative-reality of the Urban Group are expressed in terms of difficulties in the urban social environment and the notion of a moral imperative. It is observed that cul tural self-expression based upon traditional ideas continues to play a significant role in the urban environment. The apparent conflict revealed between the respective cosmologies underlies an integration of the aditional meanings with Christian concepts. This finding is consistent with the literature suggesting that the African Independent Church is a syncretic movement. The life-world is based upon the immediate and vivid experience of the numinous as revealed in the dream phenomenon. The participants' approach to dreams is not based upon an explicit theory, but upon an immediate and pathic understanding of the dream phenomenon. The understanding is based upon the interpreter's concrete understanding of the life-world, which includes the possibility of cosmic integration and continuity between the personal and transpersonal realms of being. The approach is characterized as an expression of man's primordial attunement with the cosmos. The approach of the participants to dreams may not b e consistent with a Western rational orientation, but neverthele ss, it is a valid approach . The validity is based upon the immediate life-world of experience which is intelligible, coherent, and above all, it is meaning-giving in revealing life-possibility within the context of human existence.

Incorporating interdependence in risk likelihood analysis to enhance diagnostics in condition monitoring

This research is aimed at addressing problems in the field of asset management relating to risk analysis and decision making based on data from a Supervisory Control and Data Acquisition (SCADA) system. It is apparent that determining risk likelihood in risk analysis is difficult, especially when historical information is unreliable. This relates to a problem in SCADA data analysis because of nested data. A further problem is in providing beneficial information from a SCADA system to a managerial level information system (e.g. Enterprise Resource Planning/ERP). A Hierarchical Model is developed to address the problems. The model is composed of three different Analyses: Hierarchical Analysis, Failure Mode and Effect Analysis, and Interdependence Analysis. The significant contributions from the model include: (a) a new risk analysis model, namely an Interdependence Risk Analysis Model which does not rely on the existence of historical information because it utilises Interdependence Relationships to determine the risk likelihood, (b) improvement of the SCADA data analysis problem by addressing the nested data problem through the Hierarchical Analysis, and (c) presentation of a framework to provide beneficial information from SCADA systems to ERP systems. The case study of a Water Treatment Plant is utilised for model validation.

Developing a best practice framework for implementing public private partnerships (PPP) in Hong Kong

Public Private Partnership (PPP) is a well established methodology for procuring public works projects. By incorporating the private sector’s expertise, efficiency, innovation, business sense, risk sharing, financing etc. into public works projects, the quality of public services and facilities can be uplifted. Like many jurisdictions, Hong Kong is also keen to take aboard this methodology which is so familiar but yet so distant. Although they have been one of the first jurisdictions to utilise the private sector in public works projects, their comfortable financial reserves has meant that there has been no urge to push the movement until recently. PPP has become increasingly popular amongst governments. The Hong Kong Special Administrative Region (HKSAR) government is no exception. Some of the more active works departments have commissioned studies to investigate the best ways to deliver these projects, others have even trialed the method themselves. The efficiency Unit of the HKSAR government has also become an active arm in conducting research in this area. Although so, the information that is currently available is still very broad. Building from their works there is a need to develop a best practice framework for implementing PPP projects in Hong Kong by incorporating international experiences. To develop a best practice framework will require thorough investigation into the benefits, difficulties and critical success factor of PPP. PPP should also be compared with other procurement methods. In order to do so it is important to clearly understand the local situation by an analysis of projects conducted to date. Lessons learnt can further be derived from other countries and incorporated to those derived locally. Finally the best conditions in terms of project nature, complexity, types, and scales for adopting PPP should be derived. The aim and objectives of this study were achieved via a comprehensive literature review, in-depth case analyses, interview survey with experts from both Hong Kong and overseas, and finally a large scale data collection was conducted via a questionnaire survey with PPP practitioners. These findings were further triangulated before they were used as the basis to form the best practice framework presented in this thesis. The framework was then further validated by PPP experts to ensure it is comprehensive, objective, reliable and practical. This study has presented a methodology that can be adopted for future studies. It has also updated our knowledge on the development trends of PPP as well as opened up the experiences of other jurisdictions. The findings have shown that the local industry is familiar with “what” should be done in PPP projects but they are unsure of “how” these goals can be achieved. This framework has allowed this further knowledge to be delivered to PPP practitioners. As a result, the development of this framework can help to resolve the current economic crisis by encouraging more developments and business opportunities for the private sector. In addition, the correct projects can be delivered by PPP, the advantages of PPP can be maximised, and the general public can benefit from the private sector’s participation.

Bearing-only SLAM : a vision-based navigation system for autonomous robots

To navigate successfully in a previously unexplored environment, a mobile robot must be able to estimate the spatial relationships of the objects of interest accurately. A Simultaneous Localization and Mapping (SLAM) sys- tem employs its sensors to build incrementally a map of its surroundings and to localize itself in the map simultaneously. The aim of this research project is to develop a SLAM system suitable for self propelled household lawnmowers. The proposed bearing-only SLAM system requires only an omnidirec- tional camera and some inexpensive landmarks. The main advantage of an omnidirectional camera is the panoramic view of all the landmarks in the scene. Placing landmarks in a lawn field to define the working domain is much easier and more flexible than installing the perimeter wire required by existing autonomous lawnmowers. The common approach of existing bearing-only SLAM methods relies on a motion model for predicting the robot’s pose and a sensor model for updating the pose. In the motion model, the error on the estimates of object positions is cumulated due mainly to the wheel slippage. Quantifying accu- rately the uncertainty of object positions is a fundamental requirement. In bearing-only SLAM, the Probability Density Function (PDF) of landmark position should be uniform along the observed bearing. Existing methods that approximate the PDF with a Gaussian estimation do not satisfy this uniformity requirement. This thesis introduces both geometric and proba- bilistic methods to address the above problems. The main novel contribu- tions of this thesis are: 1. A bearing-only SLAM method not requiring odometry. The proposed method relies solely on the sensor model (landmark bearings only) without relying on the motion model (odometry). The uncertainty of the estimated landmark positions depends on the vision error only, instead of the combination of both odometry and vision errors. 2. The transformation of the spatial uncertainty of objects. This thesis introduces a novel method for translating the spatial un- certainty of objects estimated from a moving frame attached to the robot into the global frame attached to the static landmarks in the environment. 3. The characterization of an improved PDF for representing landmark position in bearing-only SLAM. The proposed PDF is expressed in polar coordinates, and the marginal probability on range is constrained to be uniform. Compared to the PDF estimated from a mixture of Gaussians, the PDF developed here has far fewer parameters and can be easily adopted in a probabilistic framework, such as a particle filtering system. The main advantages of our proposed bearing-only SLAM system are its lower production cost and flexibility of use. The proposed system can be adopted in other domestic robots as well, such as vacuum cleaners or robotic toys when terrain is essentially 2D.

A 'deleterious' effect? : Australian legal education and the production of the legal identity

A body of critical legal scholarship argues that, by the time they have completed their studies, students who enter legal education holding social ideals and intending to use their legal education to achieve social change, have become cynical about the ability of the law to do so and no longer possess such ideals. This is explained by critical scholars to be the result of a process of ideological indoctrination, aimed at ensuring that graduates uphold the narrow and conservative interests of the legal profession and capitalist society, being exercised by law schools acting as adjuncts of the legal profession, and exercised upon the passive body of the law student. By using Foucault’s work on knowledge, power, and the subject to interrogate the assumptions upon which this narrative is based, this thesis intends to suggest a way of thinking differently to the approach taken by many critical legal scholars. It then uses an analytics of government (based on Foucault’s notion of ‘governmentality’) to consider the construction of the legal identity differently. It examines the ways in which the governance of the legal identity is rationalised, programmed, and implemented, in three Queensland law schools. It also looks at the way that five prescriptive texts to ‘surviving’ law school suggest students establish and practise a relation to themselves in order to construct their own legal identities. Overall, this analysis shows that governance is not simply conducted in the profession’s interests, but occurs due to a complex arrangement of different practices, which can lead to the construction of skilled legal professional identities as well as ethical lawyer-citizens that hold an interest in justice. The implications of such an analytics provide the basis for original ways of understanding legal education, and legal education scholarship.

Host searching behaviour of Diachasmimorpha kraussii (Fullaway) (Hymenoptera: Braconidae: Opiinae), a polyphagous parasitoid of Dacinae fruit flies (Diptera: Tephritidae)

Diachasmimorpha kraussii (Hymenoptera: Braconidae: Opiinae) is a koinobiont larval parasitoid of dacine fruit flies of the genus Bactrocera (Diptera: Tephritidae) in its native range (Australia, Papua New Guinea, Solomon Islands). The wasp is a potentially important control agent for pest fruit flies, having been considered for both classical and inundative biological control releases. I investigated the host searching, selection and utilisation mechanisms of the wasp against native host flies within its native range (Australia). Such studies are rare in opiine research where the majority of studies, because of the applied nature of the research, have been carried out using host flies and environments which are novel to the wasps. Diachasmimorpha kraussii oviposited equally into maggots of four fruit fly species, all of which coexist with the wasp in its native range (Australia), when tested in a choice trial using a uniform artificial diet media. While eggs laid into Bactrocera tryoni and B. jarvisi developed successfully through to adult wasps, eggs laid into B. cucumis and B. cacuminata were encapsulated. These results suggest that direct larval cues are not an important element in host selection by D. kraussii. Further exploring how D. kraussii locates suitable host larvae, I investigated the role of plant cues in host searching and selection. This was examined in a laboratory choice trial using uninfested fruit or fruit infested with either B. tryoni or B. jarvisi maggots. The results showed a consistent preference ranking among infested fruits by the wasp, with guava and peach most preferred, but with no response to uninfested fruits. Thus, it appears the wasp uses chemical cues emitted in response to fruit fly larval infestation for host location, but does not use cues from uninfested fruits. To further tease apart the role of (i) suitable and non-suitable maggots, (ii) infested and uninfested fruits of different plant species, and (iii) adult flies, in wasp host location and selection, I carried out a series of behavioural tests where I manipulated these attributes in a field cage. These trials confirmed that D. kraussii did not respond to cues in uninfested fruits, that there were consistent preferences by the wasps for different maggot infested fruits, that fruit preference did not vary depending on whether the maggots were physiologically suitable or not suitable for wasp offspring development, and finally, that adult flies appear to play a secondary role as indicators of larval infestation. To investigate wasp behaviour in an unrestrained environment, I concurrently observed diurnal foraging behaviours of both the wasp and one of its host fly in a small nectarine orchard. Wasp behaviour, both spatially and temporally, was not correlated with adult fruit fly behaviour or abundance. This study reinforced the point that infested fruit seems to be the primary cue used by foraging wasps. Wasp and fly feeding and mating was not observed in the orchard, implying these activities are occurring elsewhere. It is highly unlikely that these behaviours were happening within the orchard during the night as both insects are diurnal. As the final component of investigating host location, I carried out a habitat preference study for the wasp at the landscape scale. Using infested sentinel fruits, I tested the parasitism rate of B. tryoni in eucalyptus sclerophyll forest, rainforest and suburbia in South East Queensland. Although, rainforest is the likely endemic habitat of both B. tryoni and D. kraussii, B. tryoni abundance is significantly greater in suburban environments followed by eucalyptus sclerophyll forest. Parasitism rate was found to be higher in suburbia than in the eucalyptus sclerophyll forest, while no parasitism was recorded in the rainforest. This result suggests that wasps orient within the landscape towards areas of high host density and are not restricted by habitat types. Results from the different experiments suggest that host searching, selection and utilisation behaviour of D. kraussii are strongly influenced by cues associated with fruit fly larval feeding. Cues from uninfested fruits, the host larvae themselves, and the adult host flies play minimal roles. The discussion focuses on the fit of D. kraussii to Vinson’s classical parasitoid host location model and the implications of results for biological control, including recommendations for host and plant preference screening protocols and release regimes.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

Modulation of the SHBG signalling axis

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Who is publishing in the Journal of Sociology? an analysis of author trends 1965–2008

This paper presents the author characteristics of papers published in The Australian Sociological Association (TASA) journal, the Journal of Sociology (formerly the Australian and New Zealand Journal of Sociology) between 1965 and 2008. The aim of the paper is empirically to identify trends in authorship. The review examines all articles published in the period (excluding book reviews). The rationale of the study is to reveal trends in who publishes in the journal in terms of authors’ academic rank, gender, institution, and country. A table of those who have published the greatest number of papers is also presented. Findings show that over time the gap between the proportion of males and females publishing has closed; more PhD students and research fellows are publishing in the journal in recent decades; the highest proportion of authors consistently come from the Australian National University and The University of Queensland; and most authors are located in Australia. Information such as this can inform editorial practices and serve to inform the membership and readership on the nature of the journal.

Alternative schooling programs for at risk youth : three case studies

This thesis develops a critical realist explanatory critique of alternative schooling programs for youth at risk taking place at three case study sites. Throughout the thesis the author pursues the question, \Are alternative provisions of schooling working academically and socially for youth at risk?. The academic lens targets literacy learning and associated pedagogies. Social outcomes are posited as positive social behaviours and continued engagement in learning. A four phased analysis, drawing on critical realism, interpretive and subject specific theories is used to elicit explanations for the research question. An overall framework is a critical realist methodology as set out by Danermark, Ekstrom, Jakobsen and Karlsson (2002, p. 129). Consequently phase one describes the phenomena of alternative schooling programs taking place at three case study sites. This is reported first as staff narratives that are resolved into imaginable historical causal components of \generative events., \prior schooling structures., \models of alternative schooling., \purpose., \individual agency., and \relations with linked community organisations.. Then transcendental questions are posed about each component using retroduction to uncover structures, underlying mechanisms and powers, and individual agency. In the second phase the researcher uses modified grounded theory methodology to theoretically redescribe causal categories related to a \needed different teaching and administrative approach. that emerged from the previous critique. A transcendental question is then applied to this redescription. The research phenomena are again theoretically redescribed in the third phase, this time using three theoretically based constructs associated with literacy and literacy pedagogies; the NRS, the 4 Resources Model, and Productive Pedagogies. This redescription is again questioned in terms of its core or \necessary. components. The fourth phase makes an explanatory critique by comparing and critiquing all previous explanations, recontextualising them in a wider macro reality of alternative schooling. Through this critical realist explanatory critiquing process, a response emerges not only to whether alternative provisions of schooling are working, but also how they are working, and how they are not working, with realistically based implications for future improvement.

The failure of Australian legislation on indirect discrimination to detect the systemic racism which prevents Aboriginal people from fully participating in the workforce

Government figures put the current indigenous unemployment rate at around 23%, 3 times the unemployment rate for other Australians. This thesis aims to assess whether Australian indirect discrimination legislation can provide a remedy for one of the causes of indigenous unemployment - the systemic discrimination which can result from the mere operation of established procedures of recruitment and hiring. The impact of those practices on indigenous people is examined in the context of an analysis of anti-discrimination legislation and cases from all Australian jurisdictions from the time of the passing of the Racial Discrimination Act by the Commonwealth in 1975 to the present. The thesis finds a number of reasons why the legislation fails to provide equality of opportunity for indigenous people seeking to enter the workforce. In nearly all jurisdictions it is obscurely drafted, used mainly by educated middle class white women, and provides remedies which tend to be compensatory damages rather than change to recruitment policy. White dominance of the legal process has produced legislative and judicial definitions of "race" and "Aboriginality" which focus on biology rather than cultural difference. In the commissions and tribunals complaints of racial discrimination are often rejected on the grounds of being "vexatious" or "frivolous", not reaching the required standard of proof, or not showing a causal connection between race and the conduct complained of. In all jurisdictions the cornerstone of liability is whether a particular employment term, condition or practice is reasonable. The thesis evaluates the approaches taken by appellate courts, including the High Court, and concludes that there is a trend towards an interpretation of reasonableness which favours employer arguments such as economic rationalism, the maintenance of good industrial relations, managerial prerogative to hire and fire, and the protection of majority rights. The thesis recommends that separate, clearly drafted legislation should be passed to address indigenous disadvantage and that indigenous people should be involved in all stages of the process.

Members abroad - Australia : Paul Sanders

I have been an academic since joining the University of Natal in 1998 and, following a period as a visiting lecturer in Brisbane in 2001, I joined the staff at QUT on an ongoing basis in 2003. I was appointed as Architecture Co-ordinator in 2006, and this role involves the leadership of the architectur discipline of 17 full time academics. I am currently enrolled in a PhD course in the field of urban morphology. This research proposes a theory on the relevance of mapping the evolutionary aspects of historical urban form to develop a measure for evaluating architecural elements and deriving parameters for new buildings. My participation in a QUT design team contributed to a recent successful invited competition bid for an Urban Transit Centre in Hangzhou, China. The Centre will include retail, business, entertainment, residential and service components at the heart of the Binjiang district on the 11.5ha core area with 32ha surrounding urban design precinct. The project has received the approval to commence and is to be implemented over the next three years!