269 resultados para Synthetase-i Deficiency


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The measurement of Cobb angles on radiographs of patients with spinal deformities is routine practice in spinal clinics. The technique relies on the use and availability of specialist equipment such as a goniometer, cobbometer or protractor. The aim of this study was to validate the use of i-Phone (Apple Inc) combined with Tilt Meter Pro software as compared to a protractor in the measurement of Cobb angles. The i-Phone combined with Tilt Meter Pro software offers a faster alternative to the traditional method of Cobb angle measurement. The use of i-Phone offers a more convenient way of measuring Cobb angles in the outpatient setting. The intra-observer repeatability of the iPhone is equivalent to the protractor in the measurement of Cobb angles.

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Secondary social education in Australia is set to change with the new national history curriculum but integrated social education will continue in the middle years of schooling. Competing discourses of disciplinary and integrated social education approaches create new challenges for pre-service teachers as identification with a teaching area is an important aspect of developing a broader teacher identity. Feedback on a compulsory, final year curriculum studies unit revealed the majority of secondary pre-service teachers identified with at least one social science discipline. However, only a small number listed the integrated social education curriculum of Studies of Society and Environment (SOSE), even though SOSE was an essential part of their brief. More complex identities were revealed in post-teaching practice interviews. In times of curriculum change, attention to pre-service teachers’ disciplinary knowledge is critical in developing a stable subject identity.

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After many years of development BIM (Building Information Modelling) is starting to achieve significant penetration into the building sector of the construction industry. This paper describes the current status of BIM and the drivers that are motivating the change from 2D CAD to BIM within the building sector. The paper then discusses what the implications of the technology underlying BIM may be for the civil construction sector of the construction industry. A project carried out by the Cooperative Research Centre for Construction Innovation is used as an example of this technology as well as several international examples.

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Agent-oriented conceptual modelling (AoCM) approaches in Requirements Engineering (RE) have received considerable attention recently. Semi-formal modeling frameworks such as i* assist analysts in requirements elicitation and reasoning of early-phase RE. AgentSpeak(L) is a widely accepted agent programming language. The Strategic Rationale (SR) model of the i* framework naturally lends itself to AgentSpeak(L) programs. Furthermore, the Strategic Dependency (SD) component of the i* framework prescribes the interaction between the agents in a multi-agent environment. This paper proposes a formal methodology for transforming a SR model to an AgentS- peak(L) agent. The constructed AgentSpeak(L) agents will then form the essential components of a multi-agent system, MAS.

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The theme of this conference comes from the epitaph on the Lewis Carroll’s gravesite. “Is All our Life then But A Dream?” This seems fitting for a time when so much change in the terrain of English makes us feel as if we are somnambulating through a surrealist landscape. Like Lewis Carroll’s Alice, (Carroll, 2003) we might find ourselves at strange tea parties with bureaucratic mad hatters, and just when we think we have a grasp of applying new theory in our teaching, we fall down another rabbit hole, to swim in confusion as some queen calls out, ‘off with their heads!’. The shifting ground in English inevitably moves in response to waves of theory influencing classroom practice. Each new paradigm has claimed to liberate language learners from the flaws of the previous model. Each linguist or literary theorist who shaped the new paradigm no doubt dreamt of a new population emerging from school as more powerfully literate citizens than the previous generation.

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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.

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In recent years concern has been expressed internationally about the future of the library and information services (LIS) profession: recruitment and retention, changing skill sets and declining numbers of people choosing librarianship as a career are all factors contributing to an uncertain future. One area yet explored in any depth is the topic of why LIS studies are not perceived, let alone promoted, as a good first professional qualification for high school graduates. This paper considers the professional literature that examines the uptake of librarianship as a first qualification by school leavers and discusses, in the context of the Australian library sector, the role of professional associations, library schools, National and State Libraries, as well as individual libraries and librarians. Examples of best practice are presented to highlight the opportunities for inspiring and motivating students through well structured and stimulating work experience programs. The topic is relevant to all librarians who are interested in the future of the LIS profession. It is argued that the focus of the present conference on ‘moving up’ and ‘moving on’ can only have real significance when the profession has a more complete understanding of the barriers to and the opportunities for ‘moving in’.

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It has often been argued that young woman’s magazine’s, like Cosmopolitan, Cleo Dolly and Seventeen, constitute a significant instrument in the patriarchal repression of young women - their hegemonic success lying in the fact that they appear to be sites wherein young women are ‘free’ from the elements of coercion so obviously in evidence within other terrains, such as the school and the family. This paper will suggest an alternative approach to these magazines. Rather than locating such texts within an overall model of repression and patriarchal domination, it will be argued here that they can be regarded as practical manuals which enrol young women to do specific kinds of work on themselves. In doing so, they form an effective link between the governmental imperatives aimed at constructing particular personas (such as, for example, ‘the sexually responsible young woman’), and the actual practices whereby these imperatives are operationalised. These manuals do not prevent young women from learning to ‘project a unique self’, they constitute a significant source of practices and techniques through which particular types of self are shaped.

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Teaching to an international audience online can be significantly different as compared to a traditional classroom setting. In a traditional classroom setting, the students are usually removed from their own cultural context and required to operate in the lecturer’s context. International students coming to Malaysia to study are implicitly expected to, and often do, become familiar with the Malaysian culture and style of education. The use of educational technologies as a blended strategy in higher education programs offers challenges and opportunities for all students but this may be different for international students who come from varied backgrounds. With an increasingly competitive global demand for higher education, Malaysian institutions strive to be the hub of educational excellence and a preferred option for international students in coping with the challenges of studying abroad in a different culture. This research will evaluate how undergraduate students perceive their online learning experiences in a Malaysian university. The OLES (Online Learning Environment Survey) will be used to explore the international and domestic students’ perception on e-learning and the findings of the first six OLES scales varying from (Computer Usage, Teacher Support, Student Interaction & Collaboration, Personal Relevance, Authentic Learning, and Student Autonomy) will be reported in this research. An in-depth study will be conducted to compare and contrast the challenges of international students with domestic students. Major difficulties encountered and how these students actually cope with e-learning, as well as the strategies and tools used to overcome the challenges will be investigated.

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While Business Process Management (BPM) is an established discipline, the increased adoption of BPM technology in recent years has introduced new challenges. One challenge concerns dealing with process model complexity in order to improve the understanding of a process model by stakeholders and process analysts. Features for dealing with this complexity can be classified in two categories: 1) those that are solely concerned with the appearance of the model, and 2) those that in essence change the structure of the model. In this paper we focus on the former category and present a collection of patterns that generalize and conceptualize various existing features. The paper concludes with a detailed analysis of the degree of support of a number of state-of-the-art languages and language implementations for these patterns.

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Traffic law enforcement is based on deterrence principles, whereby drivers control their behaviour in order to avoid an undesirable sanction. For “hooning”-related driving behaviours in Queensland, the driver’s vehicle can be impounded for 48 hours, 3 months, or permanently depending on the number of previous hooning offences. It is assumed that the threat of losing something of value, their vehicle, will discourage drivers from hooning. While official data shows that the rate of repeat offending is low, an in-depth understanding of the deterrent effects of these laws should involve qualitative research with targeted drivers. A sample of 22 drivers who reported engaging in hooning behaviours participated in focus group discussions about the vehicle impoundment laws as applied to hooning offences in Queensland. The findings suggested that deterrence theory alone cannot fully explain hooning behaviour, as participants reported hooning frequently, and intended to continue doing so, despite reporting that it is likely that they will be caught, and perceiving the vehicle impoundment laws to be extremely severe. The punishment avoidance aspect of deterrence theory appears important, as well as factors over and above legal issues, particularly social influences. A concerning finding was drivers’ willingness to flee from police in order to avoid losing their vehicle permanently for a third offence, despite acknowledging risks to their own safety and that of others. This paper discusses the study findings in terms of the implications for future research directions, enforcement practices and policy development for hooning and other traffic offences for which vehicle impoundment is applied.

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People with intellectual disability are a relatively new but growing minority group within Australia's ageing population. Disability policies point to the equal right of people with disabilities to a quality of life similar to that of other citizens. Disability services are increasingly required to provide individualised and responsive services, irrespective of age, for people with lifelong disabilities. The present study explored the everyday lives of older people with intellectual disability in Victoria and Queensland, examining their experiences of using disability services and the ways in which services responded to their ageing. The aim of the study was to inform practice and service development for older people with intellectual disability. The findings suggest that services facilitate important social relationships with other service users and staff. Most older people had a sense of belonging and led busy but directionless lives in two disconnected worlds. Their lives were subject to significant external present-focused control. Yet, despite this, neither services nor family members took responsibility for ensuring their sense of continuity or supporting the development of plans about their future. The experiences described suggest an urgent need for, but significant challenges in the implementation of, holistic indivdualised planning similar to the UK concept of person-centred planning.

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With the growth of service industry occupations, managing emotions at work has increased as a topic of interest among scholars and practitioners in organisational behaviour and human resource management(Grandey, 2000). Emotional dissonance occurs when there is discrepancy between organisational sanctioned emotions and actual emotions of employees(Zapf, Vogt, Seifert, Mertini, & Isic, 1999). This discrepancy can be associated with significant levels of psychological ill-health (Zapf, Seifert, Schmutte, Mertini, & Holz, 2001). Policing is consistently ranked among the top five stressful/high-risk occupations (e.g. Coman, Evans, Stanley, & Burrows, 1991). Police officers act as the front-line contact when dealing directly with community members; they are expected to be social workers, teachers, role models, and counsellors. Operational police officers are often required to suppress their actual emotions during their work, in order to perform their job to formally designated procedures and standards.

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The Longitudinal Study of Australian Children (LSAC) is a major national study examining the lives of Australian children, using a cross-sequential cohort design and data from parents, children, and teachers for 5,107 infants (3–19 months) and 4,983 children (4–5 years). Its data are publicly accessible and are used by researchers from many disciplinary backgrounds. It contains multiple measures of children’s developmental outcomes as well as a broad range of information on the contexts of their lives. This paper reports on the development of summary outcome indices of child development using the LSAC data. The indices were developed to fill the need for indicators suitable for use by diverse data users in order to guide government policy and interventions which support young children’s optimal development. The concepts underpinning the indices and the methods of their development are presented. Two outcome indices (infant and child) were developed, each consisting of three domains—health and physical development, social and emotional functioning, and learning competency. A total of 16 measures are used to make up these three domains in the Outcome Index for the Child Cohort and six measures for the Infant Cohort. These measures are described and evidence supporting the structure of the domains and their underlying latent constructs is provided for both cohorts. The factorial structure of the Outcome Index is adequate for both cohorts, but was stronger for the child than infant cohort. It is concluded that the LSAC Outcome Index is a parsimonious measure representing the major components of development which is suitable for non-specialist data users. A companion paper (Sanson et al. 2010) presents evidence of the validity of the Index.

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The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.