Neuromelanin (NM) is a dark polymer pigment present in specific populations of catecholaminergic neurons in the brain. Interest in this pigment has rekindled in recent years because of a hypothesised link between NM and the especial vulnerability of NM-containing neurons to cell death in Parkinson???s disease (PD). Many aspects of the biology of NM are yet to be characterised. It is not known if NM like the similar melanin of the skin is synthesised via an enzymatic pathway or solely through autoxidation as has traditionally been thought. Examination of the ultrastructure of NM granules showed that in contrast to peripheral melanosomes, an electron-lucent lipid component was present that represented 30% of pigment volume. The identity of the lipid component of NM has remained unclear since it was first suggested that NM contained lipid in the 1960???s. NM lipid was biochemically isolated from the substantia nigra of 32 human brains. Using reversed-phase high performance liquid chromatography, atmospheric pressure chemical ionisation mass spectrometry and 1H- and 13C NMR techniques, it was shown for the first time that the NM lipid is the polyisoprenoid dolichol. The age-related development and regulation of NM has not previously been described. Optical density and area measurements of unstained NM in ventral substantia nigra neurons spanning the ages of 24 weeks to 95 years old demonstrated three developmental phases. NM was not present at birth and initiation of pigmentation began at approximately 3 years of age, followed by a period of increasing pigment granule number and colouration until age 20. In PD brain, the ultrastructure of NM demonstrated that the amount of lipid did not change. However, filipin staining showed a reduction of cholesterol in PD NM containing neurons. In addition, immunogold staining of ??-synuclein demonstrated that this protein redistributed to the NM lipid in PD brain. The finding of phases in the development of NM, and the identification of lipid species in NM suggest that NM biology is regulated. This thesis has also demonstrated changes in the lipid and associated proteins in PD, suggesting NM???s chemical composition alters which may have functional consequences that contribute to PD.

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of vascular occlusive disorders such as atherosclerosis and restenosis, in part due to its regulation of smooth muscle cell (SMC) phenotype. The molecular mechanisms regulating the expression of PDGF-receptor-?? (PDGF-R-??), which binds all known dimeric forms of PDGF except PDGF-DD, are poorly understood. Here it is demonstrated that PDGF-R-?? protein and transcriptional regulation in SMCs is under the positive regulatory influence of the zinc finger nuclear protein, Sp1. An atypical G-rich Sp1-binding element from -61 to -52 bp (-61G10 - 52) upstream of the transcriptional start site, was identified in the PDGF-R-?? promoter via electrophoretic mobility shift, competition and supershift analysis. Mutation of this sequence ablated endogenous Sp1 binding and activation of the PDGF-R-?? promoter. In addition to Sp1 regulation of PDGF-R-??, it was shown that fibroblast growth factor-2 (FGF-2) represses PDGF-R-?? transcription, mRNA and protein expression in SMCs. The FGF-2-induced inhibition of PDGF-R-?? was rescued by block of extracellular signal-regulated kinase-1/2 (ERK1/2) signaling. Interestingly, mutation of the aforementioned novel Sp1-response-element blocked FGF-2-induced repression of PDGF-R-?? transcription. FGF-2 was also shown to stimulate Sp1 phosphorylation in an ERK1/2-dependent manner, enhancing its interaction with the PDGF-R-?? promoter. Further analysis revealed that mutations of residues Thr453 and Thr739 in Sp1 resulted in loss of FGF-2-mediated repression of PDGF-R-?? transcription. These findings demonstrate that FGF-2 stimulates ERK1/2- dependent Sp1 phosphorylation, thereby repressing PDGF-R-?? transcription via Sp1 binding the -61/-52 element in the PDGF-R-?? promoter. Thus, phosphorylation triggered by FGF-2, switches Sp1 from an activator to a repressor of PDGF-R-?? transcription, a finding previously unreported in any Sp1-dependent gene. It is also shown in this thesis that the proto-oncogene Ets-1 controls PDGF-R-?? transcription and mRNA expression in SMCs. Mutational, electrophoretic mobility shift and chromatin immunoprecipitation assays revealed the existence of a reverse Ets binding motif (-45TTCC-42) in the proximal region of the PDGFR- ?? promoter which bound both recombinant and endogenous Ets-1. Ets-1- inducible PDGF-R-?? expression was dependent upon the integrity of both the - 45TTCC-42 motif and the previously identified -61G10 -52 element, which resides upstream of -45TTCC-42 and mediates Sp1 induction. Hydrogen peroxide (H2O2) at nanomolar concentrations, stimulated levels of Ets-1 and increased PDGF-R- ?? transcription and mRNA expression without affecting Sp1 expression. Disruption of the -45TTCC-42 motif or -61G10 -52 element blocked H2O2 activation of the PDGF-R-?? promoter. These studies identify a functional Ets motif in the PDGF-R-?? promoter which plays a pivotal role in agonist-inducible PDGF-R-?? transcription. The interplay between transcription factors such as Sp1 and Ets- 1 in the promoter of genes can exert profound influences on gene regulation. Modulating gene expression affects biological processes such as SMC proliferation and phenotype changes, which contributes to changes in vessel integrity, a hallmark of atherosclerosis. This study provides a greater insight in the functional consequences of Sp1 and Ets-1 interplay in PDGF-R-?? gene regulation and in general, provides a greater understanding of the functional regulation of cooperating transcription factors.

It is known in many gold operations that less than 2% of the cyanide consumed accounts for the gold and silver dissolution. The majority of the cyanide is consumed by minerals contained in the gold ore to produce many different cyanide soluble complexes or used in converting cyanide to other related species such as thiocyanate and cyanate. The high costs associated with cyanide and thiocyanate detoxification and excessive cyanide utilisation encountered when treating ores with high cyanide consumption constitutes a significant proportion of the overall processing costs. This study examines the possibility of recovering free cyanide from thiocyanate using a process based on the Acidification-Volatilisation-Regeneration (AVR) circuit in conjunction with a pre-concentration stage using commercially available ionexchange resin. From thermodynamic modelling based on the STABCAL program it was found that it was thermodynamically possible to recover cyanide from thiocyanate if the oxidation of cyanide to cyanate can be stopped. Addition of copper to the system found that the majority of the thiocyanate exists as copper(I) thiocyanate (CuSCN) solid. Using ion-exchange resins can be an effective way to concentrate thiocyanate from tailing solutions or slurries. Four different models were successfully used to model the equilibria between thiocyanate and chloride on commercial ion-exchange resins. By normalising the equilibria data when applying the Mass action law the equilibria becomes independent of ionic strength within the range of concentration considered. An advantage of this is that only one unique equilibrium constant is used to describe the ion-exchange process. The electrochemical and kinetic studies showed that the reaction between thiocyanate and hydrogen peroxide is catalysed by hydrogen ions. Secondly under acidic conditions the rate of cyanide recovery by the AVR circuit was faster than at higher pH conditions. The overall reaction of thiocyanate with respect to the concentration of thiocyanate and hydrogen peroxide is an overall third order reaction. The derived third order rate expression is first order with respect to thiocyanate concentration and second order with respect to hydrogen peroxide concentration. Previous studies showed that the production of cyanide inhibits the reactions between thiocyanate and hydrogen peroxide, but by removing cyanide from the reaction by air stripping, this was not observed. Addition of copper to the system did not show a catalytic effect on the reaction but it was found that copper (II) ions suppresses competing reactions that occurred without affecting the reaction between thiocyanate and hydrogen peroxide.

In this thesis, multiple-response sequences (MRSs) are examined. These are a language classroom practice in which two or more students respond to a teacher???s question or other elicitation. The study uses tools of Conversation Analysis to investigate over 38 hours of classroom talk- in-interaction in TESOL classes comprising monolingual adult Korean learners. Classes were recorded on audio and video in Seoul, South Korea and Sydney, Australia. About 1050 cases of MRSs were found and analysed. In the study, four distinct major types of multiple responses (MRs) are identified. These are: the identical MR, in which two or more students provide the same response; the complementary MR, in which two or more students??? responses provide essent ially the same meaning, but in different forms; the collaborative MR, in which two or more students collectively provide various parts of the response in the construction of a single response; and the competitive MR, in which two or more students provide responses that diverge from one another. The study also examines complex MRs, which are combinations of the basic four types, and expanded sequences, in which MRs occur in preparatory stage or post-expansion sequences. It was found that the teacher and students can produce highly complex, co-ordinated and orderly talk in the course of MRSs. The study also considers MRSs as a potential locus for second language learning. The relevance of this study to some major theories of second language acquisition is discussed, in particular in relation to social interaction in the classroom.Finally, some suggestions for future research in the area are presented.

Since the early stages of the Hawke government, Australia???s taxation system has been modified with a view to attracting additional capital into the domestic venture capital market. In December 2002, the Howard government enacted the Taxation Laws Amendment (Venture Capital) Act 2002 (Cth) and the Venture Capital Act 2002 (Cth). This legislative package created a prospective concession primarily aimed at qualifying limited partnerships who participate in the Australian venture capital market. Subject to a rather stringent qualification criteria, such partnerships are treated as fiscally transparent for the purposes of Australian taxation law. In addition, the gains made upon the disposal of portfolio investments by these partnerships may not be subject to Australian capital gains tax (&quotCGT&quot) or otherwise assessable as ordinary income. The central concept of these measures is the venture capital limited partnership (&quotVCLP&quot), and other fund of fund organisational forms which are founded on the limited partnership. For this reason, the provisions of the Taxation Laws Amendment (Venture Capital) Act 2002 (Cth) and the Venture Capital Act 2002 (Cth) are collectively identified as the &quotVCLP Concessions&quot. This thesis has been prepared as a rigorous assessment of the VCLP Concessions. It draws upon an analysis of the nature and structure of venture capital investing to determine whether the particular features of the VCLP Concessions appropriately cater for the needs of prospective foreign investors. The efficacy and appropriateness of the VCLP Concessions from a policy perspective is also examined. Recommendations are provided which, if enacted, would address regions of structural inconsistency and improve the functioning of this concessional regime.

Issue Addressed: Access block (the prolonged wait for an inpatient hospital bed after emergency department (ED) treatment) is regarded as one of the major issues currently facing emergency medicine both in Australia and internationally. At this tertiary referral hospital review of existing data has indicated that access block has continued to increase in recent years, with a sharp rise in emergency access problems since July 1999 and is now identified as a system wide problem. Objective: This research thesis sought to explore four main areas of inquiry concerning access issues within this hospital. The first objective was to determine the current bed capacity of this hospital and identify the percentage of access block within this system. The second objective was to seek an understanding of hospital clinicians??? experiences of access block and to identify the factors they perceive directly influence patient access to acute in-patient care. The third objective was to identify change strategies to improve patient access. The final objective was to determine whether collaborative participation and involvement of clinicians would lead to a change in hospital culture and foster a collective ownership of access block as a hospital wide problem. Method: In a participatory action research inquiry, hospital clinicians within this hospital were invited to be co-researchers. The process of concurrent investigation and action followed a five- part sequence of entry, issue identification, planning, action and reflection. Both qualitative and quantitative research methods were used including in-depth semi structured interviews, focus groups, process mapping, control charts and statistical analysis. Results: The research findings revealed a consistently high level of access block experienced by this hospital with bed occupancy rates in excess of 90%. During the study, hospital clinicians??? became actively involved in identifying major access issues. Six main delay categories evolved: Access delays due to limited imaging and diagnostic services, patient transport delays, barriers within the patient discharges process, insufficient access and availability to transitional, hostel, rehabilitation and nursing home beds and delays due to poor internal processes within the wards. Multi-disciplinary working parties were formed to implement six intervention strategies identified by the hospital clinicians. These included: the development of a patient access database and hospital wide alert system for code red status, the design of a pharmacy discharge prescription tracking system, the establishment of a patient discharge lounge, a quality study of the aged care assessment team within the ED and the formation of a transport working group to evaluate an electronic transport booking system within the hospital. Conclusion: In recording the qualitative process involved in gaining hospital clinicians??? perceptions of the problem of access block some indicators of engagement and empowerment were documented. The success of this participatory action approach is based on the simple principal that those that are doing the job are in the best position to change or improve it.

This study extends research on the information content of qualified audit opinions in more developed markets to the emerging capital market in China. It investigates the market reaction to audit opinions of listed Chinese companies on the Shanghai Stock Exchange. A sample of 3128 company/year observations was included, with 386 modified audit opinions and 2742 unqualified audit opinions during the investigation period 1999 to 2003. The variable of interest is audit opinions. Control variables include those used in studies of developed countries, such as earnings surprise, concurrent bad news disclosure, audit report delay, leverage, the presence of loss and firm size. Also included are variables controlling for specific Chinese institutional characteristics, such as ???special treatment???, as well as bull and bear market indicators. When all modified audit opinions are combined, this study does not find evidence that the modified audit opinions have significant information value to Chinese investors. However, when modified audit opinions are classified by type, the market is found to significantly react to qualified audit opinions with explanatory notes and disclaimer audit opinions, which are the severest audit opinions investigated in this study. When the entire sample is partitioned by year, a significant stock price revision to modified audit opinions is documented in 2003. This study also examined in the Chinese context the Melumad and Ziv (1997) model of stock price response to avoidable and unavoidable modified audit opinions. Consistent with Melumad and Ziv (1997) predictions, the market reaction to avoidable audit reports is unclear, while investors view unavoidable audit reports as necessarily negative information. In conclusion, this study finds mixed evidence in support of the notion that the Chinese stock market views audit opinions as valuable information.

Introduction: In previous decades, the basis of child health and survival strategy in the developing countries has been the promotion of breastfeeding. However, transmission of HIV through breast milk to infants in the postnatal period has caused uncertainty over the best feeding technique. Previous policies in Uganda promoted breastfeeding even among HIV positive mothers without offering an informed choice of feeding mode. Consequently, the Ugandan Ministry of Health developed and adopted policy guidelines on feeding of infants and young children in the context of HIV/AIDS in 2001. However, little is known about their impact on infant feeding behaviour in Bushenyi district. Methods: This cross-sectional study conducted in Bushenyi district, Uganda, compared 94 HIV positive and 100 HIV negative mothers with infants aged less than 12 months on infant feeding practice, on the predictors of the different modes of infant feeding practice, and adherence to Ugandan infant feeding guidelines. Results: All HIV negative and 55% of HIV positive mothers were breastfeeding their infants aged less than 12 months. Among breastfeeding mothers, 85% of the HIV negative were breastfeeding non-exclusively. Of concern to the possibility of HIV transmission, 61% of the HIV positive mothers who were breastfeeding were doing so non-exclusively. Adherence to Ugandan infant feeding guidelines was higher in HIV positive mothers (67%) than in HIV negative mothers (41%). HIV negative mothers were more likely to be adherent if the mothers??? youngest infant was not a first-born (OR= 0.30, 95% CI = 0.10 ??? 0.88) and if they were aware of HIV transmission during pregnancy (OR = 2.60, 95% CI = 1.02 ??? 6.66). The single most predictive factor of adherence among HIV positive mothers was attendance at an infant feeding counselling session (OR= 5.63, 95% CI = 2.15???14.73). Conclusions: Counselling support is necessary for mothers to make infant feeding choices that are viable and sustainable. The self-reported method of assessing adherence in our study could have been sub-optimal and may therefore overestimate the adherent proportions reported here. Addressing development of better assessment methods and methods for improving adherence to guidelines is crucial for preventive strategies. Recommendations: Increase coverage of infant feeding counselling by introducing peer counsellors in the community.

The main aims of the investigation conducted here are to draw out important debates in theory and in the South African social context over the concepts of responsibility and accountability for human rights abuse, and to look at how these were present within, and impacted on, discussions within and around the Truth and Reconciliation Commission. The TRC did not specifically discuss or define theoretical concepts of responsibility or accountability. However, I argue that it is possible to draw out some important features of its implicit approach ??? particularly in terms of its emphasis on collective responsibility and social context (in addition to individual responsibility), and its emphasis on moral arguments for individuals and collectives to accept responsibility and hold themselves accountable by contributing to future change. This ambitious and complex approach raised some important theoretical issues, which have been discussed and debated in the theoretical literature. These include: the relationship between individual responsibility, collective responsibility and the influence of ???the system???; the nature of collective responsibility; the nature of morality; the distinction between moral and political responsibility; and how individuals and collectives can or should be held accountable. In South Africa, these theoretical debates inter-mingled with a range of other factors, including individual and collective interests, motives and political perspectives. From an analysis of the existing literature on the TRC and original interviews conducted with key informants, I draw out three main opposing views which I argue arose in the South African social context about responsibility and accountability, and what the TRC could and should have done to address these. In a detailed analysis of the TRC???s hearings and Final Report, I draw out how theoretical debates, and these three opposing views, were present within and impacted on the TRC???s work. I argue that it was impossible for the TRC to satisfy everyone and resolve these debates, and that its approach led to unrealistic expectations of its work and its role more generally. This has impacted negatively on how the TRC was and is perceived.

This thesis considers the colonial literary relationship between the ???centre??? and the ???margin??? in the field of post-colonial counter-discourse. As such, this thesis investigates the possibility of disrupting the dominance of Empire, which is often rhetorically constructed through the certainty of the parent and child binary relationship. By analysing the orphan???s affiliational associations, which exist beyond the traditional binary of parent and child in the colonial relationship, I argue that the orphan, as both figure and trope, becomes a site of resistance to the dominant colonial discourse. Re-reading Charles Dickens???s Great Expectations with two Australian re-writings of his text in mind ??? Peter Carey???s Jack Maggs and Gail Jones???s Sixty Lights ??? this thesis investigates the particular case of post-colonial counter-discursive practice, and explores the way in which the orphan figure in each re-writing inscribes their expectations and thereby refigures the power hierarchy between the canonical European text and the post-colonial re-writing. In order to do so, I have organised this thesis into four main chapters, each of which develops a specific interrogation of the orphan figure in light of post-colonial theory and criticism. So, chapter one considers the colonial figure and the trope of parent and child, investigating the influence that this trope wields in casting the racialised colonial Other as ???savage??? and ???primitive???, but, ultimately, ???child-like???. Chapter two furthers this observation by highlighting the disruptive affect of such naturalised perspectives of the colonial Other???evidenced in post-colonial theory through the motion of the key concepts of ambivalence and abjection. And, it is in this context that chapters three and four stand as direct examinations of the disruptive affect of the orphan figure. Discussing Peter Carey???s Jack Maggs and Gail Jones???s Sixty Lights (respectively), these last two chapters formalise the subversive agency assumed by the orphan, and locate it in the very practice of ???writing back to the centre???.