Dopamine and visually regulated eye growth in chick

Retinal image properties such as contrast and spatial frequency play important roles in the development of normal vision. For example, visual environments comprised solely of low contrast and/or low spatial frequencies induce myopia. The visual image is processed by the retina and it then locally controls eye growth. In terms of the retinal neurotransmitters that link visual stimuli to eye growth, there is strong evidence to suggest involvement of the retinal dopamine (DA) system. For example, effectively increasing retinal DA levels by using DA agonists can suppress the development of form-deprivation myopia (FDM). However, whether visual feedback controls eye growth by modulating retinal DA release, and/or some other factors, is still being elucidated. This thesis is chiefly concerned with the relationship between the dopaminergic system and retinal image properties in eye growth control. More specifically, whether the amount of retinal DA release reduces as the complexity of the image degrades was determined. For example, we investigated whether the level of retinal DA release decreased as image contrast decreased. In addition, the effects of spatial frequency, spatial energy distribution slope, and spatial phase on retinal DA release and eye growth were examined. When chicks were 8-days-old, a cone-lens imaging system was applied monocularly (+30 D, 3.3 cm cone). A short-term treatment period (6 hr) and a longer-term treatment period (4.5 days) were used. The short-term treatment tests for the acute reduction in DA release by the visual stimulus, as is seen with diffusers and lenses, whereas the 4.5 day point tests for reduction in DA release after more prolonged exposure to the visual stimulus. In the contrast study, 1.35 cyc/deg square wave grating targets of 95%, 67%, 45%, 12% or 4.2% contrast were used. Blank (0% contrast) targets were included for comparison. In the spatial frequency study, both sine and square wave grating targets with either 0.017 cyc/deg and 0.13 cyc/deg fundamental spatial frequencies and 95% contrast were used. In the spectral slope study, 30% root-mean-squared (RMS) contrast fractal noise targets with spectral fall-off of 1/f0.5, 1/f and 1/f2 were used. In the spatial alignment study, a structured Maltese cross (MX) target, a structured circular patterned (C) target and the scrambled versions of these two targets (SMX and SC) were used. Each treatment group comprised 6 chicks for ocular biometry (refraction and ocular dimension measurement) and 4 for analysis of retinal DA release. Vitreal dihydroxyphenylacetic acid (DOPAC) was analysed through ion-paired reversed phase high performance liquid chromatography with electrochemical detection (HPLC-ED), as a measure of retinal DA release. For the comparison between retinal DA release and eye growth, large reductions in retinal DA release possibly due to the decreased light level inside the cone-lens imaging system were observed across all treated eyes while only those exposed to low contrast, low spatial frequency sine wave grating, 1/f2, C and SC targets had myopic shifts in refraction. Amongst these treatment groups, no acute effect was observed and longer-term effects were only found in the low contrast and 1/f2 groups. These findings suggest that retinal DA release does not causally link visual stimuli properties to eye growth, and these target induced changes in refractive development are not dependent on the level of retinal DA release. Retinal dopaminergic cells might be affected indirectly via other retinal cells that immediately respond to changes in the image contrast of the retinal image.

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.

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.

Bringing the internet down to earth : emerging spaces of locative media

Web 1.0 referred to the early, read-only internet; Web 2.0 refers to the ‘read-write web’ in which users actively contribute to as well as consume online content; Web 3.0 is now being used to refer to the convergence of mobile and Web 2.0 technologies and applications. One of the most important developments in mobile 3.0 is geography: with many mobile phones now equipped with GPS, mobiles promise to “bring the internet down to earth” through geographically-aware, or locative media. The internet was earlier heralded as “the death of geography” with predictions that with anyone able to access information from anywhere, geography would no longer matter. But mobiles are disproving this. GPS allows the location of the user to be pinpointed, and the mobile internet allows the user to access locally-relevant information, or to upload content which is geotagged to the specific location. It also allows locally-specific content to be sent to the user when the user enters a specific space. Location-based services are one of the fastest-growing segments of the mobile internet market: the 2008 AIMIA report indicates that user access of local maps increased by 347% over the previous 12 months, and restaurant guides/reviews increased by 174%. The central tenet of cultural geography is that places are culturally-constructed, comprised of the physical space itself, culturally-inflected perceptions of that space, and people’s experiences of the space (LeFebvre 1991). This paper takes a cultural geographical approach to locative media, anatomising the various spaces which have emerged through locative media, or “the geoweb” (Lake 2004). The geoweb is such a new concept that to date, critical discourse has treated it as a somewhat homogenous spatial formation. In order to counter this, and in order to demonstrate the dynamic complexity of the emerging spaces of the geoweb, the paper provides a topography of different types of locative media space: including the personal/aesthetic in which individual users geotag specific physical sites with their own content and meanings; the commercial, like the billboards which speak to individuals as they pass in Minority Report; and the social, in which one’s location is defined by the proximity of friends rather than by geography.

Integrated versus non-integrated management and care for clients with co-occurring mental health and substance use disorders : a qualitative systematic review of randomised controlled trials

The purpose of this paper is to conduct a qualitative review of randomised controlled trials in relation to the treatment of adults with co-occurring mental health and substance use disorder (MH/SUD). In particular, integrated approaches are compared with non-integrated approaches to treatment. Ten articles were identified for inclusion in the review. The findings are equivocal with regard to the superior efficacy of integrated approaches to treatment, although the many limitations of the studies need to be considered in our understanding of this finding. Clearly, this is an extremely challenging client group to engage and maintain in intervention research, and the complexity and variability of the problems render control particularly difficult. The lack of available evidence to support the superiority of integration is discussed in relation to these challenges. Much remains to be investigated with regard to integrated management and care for people with co-occurring and MH/SUD, particularly for specific combinations of dual diagnosis and giving consideration to the level of inter-relatedness between the disorders.

Power law distributions in pattern dynamics of attacker-defender dyads in the team sport of Rugby Union : phenomena in a region of self-organized criticality?

In the region of self-organized criticality (SOC) interdependency between multi-agent system components exists and slight changes in near-neighbor interactions can break the balance of equally poised options leading to transitions in system order. In this region, frequency of events of differing magnitudes exhibits a power law distribution. The aim of this paper was to investigate whether a power law distribution characterized attacker-defender interactions in team sports. For this purpose we observed attacker and defender in a dyadic sub-phase of rugby union near the try line. Videogrammetry was used to capture players’ motion over time as player locations were digitized. Power laws were calculated for the rate of change of players’ relative position. Data revealed that three emergent patterns from dyadic system interactions (i.e., try; unsuccessful tackle; effective tackle) displayed a power law distribution. Results suggested that pattern forming dynamics dyads in rugby union exhibited SOC. It was concluded that rugby union dyads evolve in SOC regions suggesting that players’ decisions and actions are governed by local interactions rules.

Deepening our understanding about school leadership : learning from educators and non-educators

Increasingly, leadership is argued as a way forward to improve performance and practice in a variety of contexts. School leadership is no different. There is little doubt that in the current globalised world characterized by change and complexity, effective school leadership is a key requirement. The contribution of this chapter is framed around a synthesis of current research, writing and theoretical insights regarding leadership. It draws upon three bodies of writing, Firstly, it begins by distilling several key themes and trends regarding educational leadership from the current research and writing. Secondly, it reports on the findings of a current research project carried out by the authors that explored the leadership stories of ten outstanding leaders from non-educational settings in Australia. Finally, it concludes by referring to some of the paradoxes and tensions inherent in the work of school leaders. It is argued that understanding and endeavouring to reconcile these dilemmas is a pre-requisite for school leaders as they continue to operate in an environment fraught with change and complexity.

Quality assurance in higher education : for whom and of what?

Over the past two decades the quality assurance of higher education institutions has captured a growing interest as evidenced by the increasing number of national and transnational bodies engaged in this area. Yet as the first decade of the 21st century draws to a close, higher education systems and thus the regimes designed to ensure their quality are faced with significant complexity. Issues of accountability, authority and responsibility are paramount when responding to industry bodies, to globalisation and the transnational provision of higher education and to the use of market mechanisms. In this paper we raise some of the challenges for quality assurance for higher education presented by this growing complexity through the question, quality assurance in higher education, for whom and of what, highlighting our concern for a need to expand the centrality of accountability to include authority and responsibility as part of the quality assurance regimes for higher education

Achieving effective supervision

Supervision probably does have benefits both for the maintenance and improvement of clinical skills and for job satisfaction, but the data are very thin and almost non-existent in the area of alcohol and other drugs ser vices. Because of the potential complexity of objectives and roles in super vision, a structured agreement appears to be an important part of the effective supervision relationship. Because sessions can degenerate easily into unstructured socialization, agendas and session objectives may also be important. While a working alliance based on mutual respect and trust is an essential base for the supervision relationship, procedures for direct observation of clinical skills, demonstration of new procedures and skills practice with detailed feedback appear critical to super vision’s impact on practice. To ensure effective supervision, there needs not only to be a minimum of personnel and resources, but also a compatibility with the values and procedures of management and staff, access to supervision training and consultation and sufficient incentives to ensure it continues.

Patterns of query reformulation during web searching

Query reformulation is a key user behavior during Web search. Our research goal is to develop predictive models of query reformulation during Web searching. This article reports results from a study in which we automatically classified the query-reformulation patterns for 964,780 Web searching sessions, composed of 1,523,072 queries, to predict the next query reformulation. We employed an n-gram modeling approach to describe the probability of users transitioning from one query-reformulation state to another to predict their next state. We developed first-, second-, third-, and fourth-order models and evaluated each model for accuracy of prediction, coverage of the dataset, and complexity of the possible pattern set. The results show that Reformulation and Assistance account for approximately 45% of all query reformulations; furthermore, the results demonstrate that the first- and second-order models provide the best predictability, between 28 and 40% overall and higher than 70% for some patterns. Implications are that the n-gram approach can be used for improving searching systems and searching assistance.

Historical timelines : analyzing multimodal text design

The recent focus on literacy in Social Studies has been on linguistic design, particularly that related to the grammar of written and spoken text. When students are expected to produce complex hybridized genres such as timelines, a focus on the teaching and learning of linguistic design is necessary but not sufficient to complete the task. Theorizations of new literacies identify five interrelated meaning making designs for text deconstruction and reproduction: linguistic, spatial, visual, gestural, and audio design. Honing in on the complexity of timelines, this paper casts a lens on the linguistic, visual, spatial, and gestural designs of three pairs of primary school aged Social Studies learners. Drawing on a functional metalanguage, we analyze the linguistic, visual, spatial, and gestural designs of their work. We also offer suggestions of their effect, and from there consider the importance of explicit instruction in text design choices for this Social Studies task. We conclude the analysis by suggesting the foci of explicit instruction for future lessons.

The studio sans frontières : the open-studio as an answer to the challenges of teaching contemporary art

Since at least the 1960s, art has assumed a breadth of form and medium as diverse as social reality itself. Where once it was marginal and transgressive for artists to work across a spectrum of media, today it is common practice. In this ‘post-medium’ age, fidelity to a specific branch of media is a matter of preference, rather than a code of practice policed by gallerists, curators and critics. Despite the openness of contemporary art practice, the teaching of art at most universities remains steadfastly discipline-based. Discipline-based art teaching, while offering the promise of focussed ‘mastery’ of a particular set of technical skills and theoretical concerns, does so at the expense of a deeper and more complex understanding of the possibilities of creative experimentation in the artist’s studio. By maintaining an hermetic approach to medium, it does not prepare students sufficiently for the reality of art making in the twenty-first century. In fact, by pretending that there is a select range of techniques fundamental to the artist’s trade, discipline-based teaching can often appear to be more engaged with the notion of skills preservation than purposeful art training. If art schools are to survive and prosper in an increasingly vocationally-oriented university environment, they need to fully synthesise the professional reality of contemporary art practice into their approach to teaching and learning. This paper discusses the way in which the ‘open’ studio approach to visual art study at QUT endeavours to incorporate the diversity and complexity of contemporary art while preserving the sense of collective purpose that discipline-based teaching fosters. By allowing students to independently develop their own art practices while also applying collaborative models of learning and assessment, the QUT studio program aims to equip students with a strong sense of self-reliance, a broad awareness and appreciation of contemporary art, and a deep understanding of studio-based experimentation unfettered by the boundaries of traditional media: all skills fundamental to the practice of contemporary art.

Wrapped fragments : Drapery, the eighteenth century portrait bust and the male subject

The depiction of drapery (generalised cloth as opposed to clothing) is a well-established convention of Neo-Classical sculpture and is often downplayed by art historians as of purely rhetorical value. It can be argued however that sculpted drapery has served a spectrum of expressive ends, the variety and complexity of which are well illustrated by a study of its use in portrait sculpture. For the Neo-Classical portrait bust, drapery had substantial iconographic and political meaning, signifying the new Enlightenment notions of masculine authority. Within the portrait bust, drapery also served highly strategic aesthetic purposes, alleviating the abruptness of the truncated format and the compromising visual consequences of the “cropped” body. With reference to Joseph Nollekens’ portraits of English statesman Charles James Fox and the author’s own sculptural practice, this paper analyses the Neo-Classical use of drapery to propose that rendered fabric, far from mere stylistic flourish, is a highly charged visual signifier with much scope for exploration in contemporary sculptural practice.

Monitoring the Performance of Complex Projects from Multiple Perspectives over Multiple Time Frames

When complex projects go wrong they can go horribly wrong with severe financial consequences. We are undertaking research to develop leading performance indicators for complex projects, metrics to provide early warning of potential difficulties. The assessment of success of complex projects can be made by a range of stakeholders over different time scales, against different levels of project results: the project’s outputs at the end of the project; the project’s outcomes in the months following project completion; and the project’s impact in the years following completion. We aim to identify leading performance indicators, which may include both success criteria and success factors, and which can be measured by the project team during project delivery to forecast success as assessed by key stakeholders in the days, months and years following the project. The hope is the leading performance indicators will act as alarm bells to show if a project is diverting from plan so early corrective action can be taken. It may be that different combinations of the leading performance indicators will be appropriate depending on the nature of project complexity. In this paper we develop a new model of project success, whereby success is assessed by different stakeholders over different time frames against different levels of project results. We then relate this to measurements that can be taken during project delivery. A methodology is described to evaluate the early parts of this model. Its implications and limitations are described. This paper describes work in progress.

Estimation and compensation of clipping noise in OFDMA systems

We propose an efficient and low-complexity scheme for estimating and compensating clipping noise in OFDMA systems. Conventional clipping noise estimation schemes, which need all demodulated data symbols, may become infeasible in OFDMA systems where a specific user may only know his own modulation scheme. The proposed scheme first uses equalized output to identify a limited number of candidate clips, and then exploits the information on known subcarriers to reconstruct clipped signal. Simulation results show that the proposed scheme can significantly improve the system performance.