Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Fungal spore fragmentation as a function of airflow rates and fungal generation methods

The aim of this study was to characterise and quantify the fungal fragment propagules derived and released from several fungal species (Penicillium, Aspergillus niger and Cladosporium cladosporioides) using different generation methods and different air velocities over the colonies. Real time fungal spore fragmentation was investigated using an Ultraviolet Aerodynamic Particle Sizer (UVASP) and a Scanning Mobility Particle Sizer (SMPS). The study showed that there were significant differences (p < 0.01) in the fragmentation percentage between different air velocities for the three generation methods, namely the direct, the fan and the fungal spore source strength tester (FSSST) methods. The percentage of fragmentation also proved to be dependant on fungal species. The study found that there was no fragmentation for any of the fungal species at an air velocity ≤ 0.4 m/s for any method of generation. Fluorescent signals, as well as mathematical determination also showed that the fungal fragments were derived from spores. Correlation analysis showed that the number of released fragments measured by the UVAPS under controlled conditions can be predicted on the basis of the number of spores, for Penicillium and Aspergillus niger, but not for Cladosporium cladosporioides. The fluorescence percentage of fragment samples was found to be significantly different to that of non-fragment samples (p < 0.0001) and the fragment sample fluorescence was always less than that of the non-fragment samples. Size distribution and concentration of fungal fragment particles were investigated qualitatively and quantitatively, by both UVAPS and SMPS, and it was found that the UVAPS was more sensitive than the SMPS for measuring small sample concentrations, and the results obtained from the UVAPS and SMAS were not identical for the same samples.

Combining ganglion cell topology and data of patients with glaucoma to determine a structure-function map

PURPOSE: To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. METHODS: Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P < 0.05) correlation coefficient within 40 degrees of the angle predicted by GROW for each location was computed. Before correlation, both functional and structural data were normalized by either normative data or the fellow eye in each participant. RESULTS: The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P < 0.001) when both field and rim area data were normalized with the fellow eye. CONCLUSIONS: A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data.

The function of property in creating an effective legal regime for trade in environmental offsets

Market-based environmental regulation is becoming increasingly common within international and national frameworks. Environmental offset and trading regimes are part of the market-based instrument revolution. This paper proposes that environmental market mechanisms could be used to introduce an ethic of land holder responsibility. In order for market based regimes to attract sufficient levels of stakeholder engagement, participants within such scheme require an incentive to participate and furthermore need to feel a sense of security about investing in such processes. A sense of security is often associated with property based interests. This paper explores the property related issues connected with environmental offset and trading scheme initiatives. Relevant property-related considerations include land tenure considerations, public versus private management of land choices, characteristics and powers associated with property interests, theories defining property and the recognition of legal proprietal interests. The Biodiversity Banking Scheme in New South Wales is then examined as a case study followed by a critique on the role of environmental markets.

Investigating erythemal UV exposure and vitamin D production in the urban canyon

Exposure to ultraviolet radiation (UV) results in both damaging and beneficial health outcomes. Excessive UV exposure has been linked to many skin and eye problems, but moderate exposure induces vitamin D production. It has been reported that humans receive 90-95% of their vitamin D from production that starts after UV exposure. Although it is possible to acquire vitamin D through dietary supplementation, the average person receives very little in this manner. Therefore, since most people acquire their vitamin D from synthesis after exposure to UV from sunlight, it is very important to understand the different environments in which people encounter UV. This project measured UV radiation and in-vitro vitamin D production in the urban canyon and at a nearby suburban location. The urban canyon is an environment consisting of tall buildings and tropospheric air pollution, which have an attenuating effect on UV. Typically, UV measurements are collected in areas outside the urban canyon, meaning that at times studies and public recommendations do not accurately represent the amount of UV reaching street-level in highly urbanized areas. Understanding of UV exposure in urban canyons becomes increasingly important as the number of people working and living in large cities steadily increases worldwide. This study was conducted in the central business district (CBD) of Brisbane, Australia, which models the urban canyons of large cities around the world in that it boasts a great number of tall buildings, including many skyscrapers, meaning that most areas only see a small amount of direct sunlight each day. During the winter of 2007 measurements of UV radiation and in-vitro vitamin D production were collected in the CBD and at a suburban site approximately 2.5km outside the CBD. Air pollution data was obtained from a central CBD measurement site. Data analysis showed that urban canyon measurements of both UV radiation and in-vitro vitamin D production were significantly lower than those collected at the suburban site. These results will aid both future researchers and policy makers in better understanding human UV exposure in Brisbane’s CBD and other urban canyons around the world.

In the mouth of the imagination : positioning children as co-researchers and co-artists to create a professional children's theatre production

In recent decades a number of Australian artists and teacher/artists have given serious attention to the creation of performance forms and performance engagement models that respect children’s intelligence, engage with themes of relevance, avoid the cliche´s of children’s theatre whilst connecting both sincerely and playfully with current understandings of the way in which young children develop and engage with the world. Historically a majority of performing arts companies touring Australian schools or companies seeking schools to view a performance in a dedicated performance venue engage with their audiences in what can be called a ‘drop-in drop-out’ model. A six-month practice-led research project (The Tashi Project) which challenged the tenets of the ‘drop-in drop-out’ model has been recently undertaken by Sandra Gattenhof and Mark Radvan in conjunction with early childhood students from three Brisbane primary school classrooms who were positioned as co-researchers and co-artists. The children, researchers and performers worked in a complimentary relationship in both the artistic process and the development of product.

Documentary practice in a participatory culture

Debates concerning the veracity, ethics and politics of the documentary form circle endlessly around the function of those who participate in it, and the meaning attributed to their participation. Great significance is attached to the way that documentary filmmakers do or do not participate in the world they seek to represent, just as great significance is attached to those subjects whose participation extends beyond playing the part of eyewitness or expert, such that they become part of the very filmmaking process itself. This Ph.D. explores the interface between documentary practice and participatory culture by looking at how their practices, discursive fields and histories intersect, but also by looking at how participating in one might mean participating in the other. In short, the research is an examination of participatory culture through the lens of documentary practice and documentary criticism. In the process, however, this examination of participatory culture will in turn shed light on documentary thinking, especially the meaning and function of ‘the participant’ in contemporary documentary practice. A number of ways of conceiving of participation in documentary practice are discussed in this research, but one of the ideas that gives purpose to that investigation is the notion that the participant in contemporary documentary practice is someone who belongs to a participatory culture in particular. Not only does this mean that those subjects who play a part in a documentary are already informed by their engagement with a range of everyday media practices before the documentary apparatus arrives, the audience for such films are similarly informed and engaged. This audience have their own expectations about how they should be addressed by media producers in general, a fact that feeds back into their expectations about participatory approaches to documentary practice too. It is the ambition of this research to get closer to understanding the relationship between participants in the audience, in documentary and ancillary media texts, as well as behind the camera, and to think about how these relationships constitute a context for the production and reception of documentary films, but also how this context might provide a model for thinking about participatory culture itself. One way that documentary practice and participatory culture converge in this research is in the kind of participatory documentary that I call the ‘Camera Movie’, a narrow mode of documentary filmmaking that appeals directly to contemporary audiences’ desires for innovation and participation, something that is achieved in this case by giving documentary subjects control of the camera. If there is a certain inevitability about this research having to contend with the notion of the ‘participatory documentary’, the ‘participatory camera’ also emerges strongly in this context, especially as a conduit between producer and consumer. Making up the creative component of this research are two documentaries about the reality television event Band In A Bubble, and participatory media practices more broadly. The single-screen film, Hubbub , gives form to the collective intelligence and polyphonous voice of contemporary audiences who must be addressed and solicited in increasingly innovative ways. One More Like That is a split-screen, DVD-Video with alternate audio channels selected by a user who thereby chooses who listens and who speaks in the ongoing conversation between media producers and media consumers. It should be clear from the description above that my own practice does not extend to highly interactive, multi-authored or web-enabled practices, nor the distributed practices one might associate with social media and online collaboration. Mine is fundamentally a single authored, documentary video practice that seeks to analyse and represent participatory culture on screen, and for this reason the Ph.D. refrains from a sustained discussion of the kinds of collaborative practices listed above. This is not to say that such practices don’t also represent an important intersection of documentary practice and participatory culture, they simply represent a different point of intersection. Being practice-led, this research takes its procedural cues from the nature of the practice itself, and sketches parameters that are most enabling of the idea that the practice sets the terms of its own investigation.

Learning through collaboration and co-production in the Singapore film industry : opportunities for development

Co-production and strategic partnerships may generate valuable learning opportunities for firms to access to the knowledge and expertise of their partners. Such sharing and transfer of knowledge has become an increasingly common way for organising corporate finance and resources. However, not all collaborations result in a net positive experience for both partners. It can be a zero-sum game in which the partner learning the fastest dominates the relationship. In some cases, failure to gain access to partner knowledge results in unequal benefits accruing from such alliances. By examining the Singapore film industry from a learning perspective and taking into account particular forms of alliances, the study contributes to our understanding of the potential benefit and challenges of coproduction as a strategy for development.

Digital media literacy : connecting young people’s identities, creative production and learning about video games

This chapter outlines examples of classroom activities that aim to make connections between young people’s everyday experiences with video games and the formal high school curriculum. These classroom activities were developed within the emerging field of digital media literacy. Digital media literacy combines elements of ‘traditional’ approaches to media education with elements of technology and information education (Buckingham, 2007; Warschauer, 2006). It is an educational field that has gained significant attention in recent years. For example, digital media literacy has become a significant objective for media policy makers in response to the increased social and cultural roles of new media technologies and controversies associated with young people’s largely unregulated online participation. Media regulators, educational institutions and independent organizations1 in the United States, Canada, the United Kingdom and Australia have developed digital media literacy initiatives that aim to provide advice to parents, teachers and young people.

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.

An analysis and comparison of rural land sales

Rural land prices, in developed, free trade real estate markets, are influenced not only by prevailing economic conditions but also physical factors such as climate, topography and soil type. In broad acre farming and grazing operations, both commodity price and yields determine farm income. Yields, in turn, are a function of climate, topography and soil type. The strength of a rural land market is influenced by the overall rural economy in a Country, State or region. These differences in rural land markets can also vary within smaller regions. It has been held that rural land, in relative safe production areas, is less effected by adverse economic and climatic factors than land in more marginal agricultural areas. This paper will analyse rural land sales in both traditional cropping areas and marginal cropping areas for the period 1975 to 1996. The analysis will determine the overall trend in rural land prices over the period, compare the average annual return between marginal and established farming areas and determine which economic and production factors have influenced this change. The impact of this analysis will also be discussed in relation to rural land appraisal.

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.