910 resultados para major histocompatibility complex


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Risks and uncertainties are inevitable in engineering projects and infrastructure investments. Decisions about investment in infrastructure such as for maintenance, rehabilitation and construction works can pose risks, and may generate significant impacts on social, cultural, environmental and other related issues. This report presents the results of a literature review of current practice in identifying, quantifying and managing risks and predicting impacts as part of the planning and assessment process for infrastructure investment proposals. In assessing proposals for investment in infrastructure, it is necessary to consider social, cultural and environmental risks and impacts to the overall community, as well as financial risks to the investor. The report defines and explains the concept of risk and uncertainty, and describes the three main methodology approaches to the analysis of risk and uncertainty in investment planning for infrastructure, viz examining a range of scenarios or options, sensitivity analysis, and a statistical probability approach, listed here in order of increasing merit and complexity. Forecasts of costs, benefits and community impacts of infrastructure are recognised as central aspects of developing and assessing investment proposals. Increasingly complex modelling techniques are being used for investment evaluation. The literature review identified forecasting errors as the major cause of risk. The report contains a summary of the broad nature of decision-making tools used by governments and other organisations in Australia, New Zealand, Europe and North America, and shows their overall approach to risk assessment in assessing public infrastructure proposals. While there are established techniques to quantify financial and economic risks, quantification is far less developed for political, social and environmental risks and impacts. The report contains a summary of the broad nature of decision-making tools used by governments and other organisations in Australia, New Zealand, Europe and North America, and shows their overall approach to risk assessment in assessing public infrastructure proposals. While there are established techniques to quantify financial and economic risks, quantification is far less developed for political, social and environmental risks and impacts. For risks that cannot be readily quantified, assessment techniques commonly include classification or rating systems for likelihood and consequence. The report outlines the system used by the Australian Defence Organisation and in the Australian Standard on risk management. After each risk is identified and quantified or rated, consideration can be given to reducing the risk, and managing any remaining risk as part of the scope of the project. The literature review identified use of risk mapping techniques by a North American chemical company and by the Australian Defence Organisation. This literature review has enabled a risk assessment strategy to be developed, and will underpin an examination of the feasibility of developing a risk assessment capability using a probability approach.

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Major infrastructure assets are often governed by a mix of public and private organizations, each fulfilling a specific and separate role i.e. policy, ownership, operation or maintenance. This mix of entities is a legacy of Public Choice Theory influenced NPM reforms of the late 20th century. The privatization of the public sector has resulted in agency theory based ‘self-interest’ relationships and governance arrangements for major infrastructure assets which emphasize economic efficiency but which do not do not advance non-economic public values and the collective Public Interest. The community is now requiring that governments fulfill their stewardship role of also satisfying non-economic public values such as sustainability and intergenerational responsibility. In the 21st century governance arrangements which minimize individual self-interest alone and look to also pursue the interests of other stakeholders have emerged. Relational contracts, Public-Private Partnerships (PPP’s) and hybrid mixes of organizations from the state, market and network modes (Keast et al 2006) provide options for governance which better meet the interests of contractors, government and the community there is emerging a body of research which extends the consideration of the immediate governance configuration to the metagovernance environment constituted by hierarchy, regulation, industry standards, trust, culture and values. Stewardship theory has reemerged as a valuable aid in the understanding of the features of governance configurations which establish relationships between principal and agent which maximize the agent acting in the interests of the principal, even to the detriment of the agent. This body of literature suggests that an improved stewardship outcome from infrastructure governance configurations can be achieved by the application of the emerging options as to the immediate governance configuration, and the surrounding metagovernance environment. Stewardship theory provides a framework for the design of the relationships within that total governance environment, focusing on the achievement of a better, complete stewardship outcome. This paper explores the directions future research might take in seeking to improve the understanding of the design of the governance of major, critical infrastructure assets.

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The learner licence is an important component of the graduated driver licensing system. This research describes the driving and licensing experiences of learner drivers in Queensland and New South Wales licensed prior to the changes made to the system in mid-2007. The sample consisted of 392 participants who completed a telephone interview just after they obtained their provisional licence. The results suggest that learner drivers in the two states had many similar experiences when they were obtaining a learner licence. However, once a learner licence was obtained, there were differences in the amount of practice, the supervisor learners practised with, the type of vehicle they used and the amount of unlicensed driving. This paper provides important baseline descriptive data that can be used to measure the impact of the changes that were introduced to the learner licence phase in mid-2007 in both of these states.

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Due to the popularity of modern Collaborative Virtual Environments, there has been a related increase in their size and complexity. Developers therefore need visualisations that expose usage patterns from logged data, to understand the structures and dynamics of these complex environments. This chapter presents a new framework for the process of visualising virtual environment usage data. Major components, such as an event model, designer task model and data acquisition infrastructure are described. Interface and implementation factors are also developed, along with example visualisation techniques that make use of the new task and event model. A case study is performed to illustrate a typical scenario for the framework, and its benefits to the environment development team.

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The innovation diffusion and knowledge management literature strongly supports the importance of communities of practice (COP) for enabling knowledge about how to use and adopt innovation initiatives. One of the most powerful tools for innovation diffusion is word-of-mouth wisdom from committed individuals who mentor and support each other. Close proximity for face-to-face interaction is highly effective, however, many organisations are geographically dispersed with projects being virtual linked sub-organisations using ICT to communicate. ICT has also introduced a useful facilitating technology for developing knowledge networks. This paper presents findings from a research program concentrating on ICT innovation diffusion in the Australian construction industry. One way in which ICT diffusion is taking place was found to be through within-company communities of practice. We undertook in-depth unstructured interviews with three of the major 10 to 15 contractors in Australia to discuss their ICT diffusion strategies. We discovered that in all three cases,within company networked communities of practice was a central strategy. Further, effective diffusion of ICT groupware tools can be critical in developing COP where they are geographically dispersed.

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Having flexible notions of the unit (e.g., 26 ones can be thought of as 2.6 tens, 1 ten 16 ones, 260 tenths, etc.) should be a major focus of elementary mathematics education. However, often these powerful notions are relegated to computations where the major emphasis is on "getting the right answer" thus procedural knowledge rather than conceptual knowledge becomes the primary focus. This paper reports on 22 high-performing students' reunitising processes ascertained from individual interviews on tasks requiring unitising, reunitising and regrouping; errors were categorised to depict particular thinking strategies. The results show that, even for high-performing students, regrouping is a cognitively complex task. This paper analyses this complexity and draws inferences for teaching.

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This study employs BP neural network to simulate the development of Chinese private passenger cars. Considering the uncertain and complex environment for the development of private passenger cars, indicators of economy, population, price, infrastructure, income, energy and some other fields which have major impacts on it are selected at first. The network is proved to be operable to simulate the progress of chinese private passenger cars after modeling, training and generalization test. Based on the BP neural network model, sensitivity analysis of each indicator is carried on and shows that the sensitivity coefficients of fuel price change suddenly. This special phenomenon reveals that the development of Chinese private passenger cars may be seriously affected by the recent high fuel price. This finding is also consistent with facts and figures

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Due to the popularity of modern Collaborative Virtual Environments, there has been a related increase in their size and complexity. Developers therefore need visualisations that expose usage patterns from logged data, to understand the structures and dynamics of these complex environments. This chapter presents a new framework for the process of visualising virtual environment usage data. Major components, such as an event model, designer task model and data acquisition infrastructure are described. Interface and implementation factors are also developed, along with example visualisation techniques that make use of the new task and event model. A case study is performed to illustrate a typical scenario for the framework, and its benefits to the environment development team.

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With increasingly complex engineering assets and tight economic requirements, asset reliability becomes more crucial in Engineering Asset Management (EAM). Improving the reliability of systems has always been a major aim of EAM. Reliability assessment using degradation data has become a significant approach to evaluate the reliability and safety of critical systems. Degradation data often provide more information than failure time data for assessing reliability and predicting the remnant life of systems. In general, degradation is the reduction in performance, reliability, and life span of assets. Many failure mechanisms can be traced to an underlying degradation process. Degradation phenomenon is a kind of stochastic process; therefore, it could be modelled in several approaches. Degradation modelling techniques have generated a great amount of research in reliability field. While degradation models play a significant role in reliability analysis, there are few review papers on that. This paper presents a review of the existing literature on commonly used degradation models in reliability analysis. The current research and developments in degradation models are reviewed and summarised in this paper. This study synthesises these models and classifies them in certain groups. Additionally, it attempts to identify the merits, limitations, and applications of each model. It provides potential applications of these degradation models in asset health and reliability prediction.

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Technology platforms originally developed for tissue engineering applications produce valuable models that mimic three-dimensional (3D) tissue organization and function to enhance the understanding of cell/tissue function under normal and pathological situations. These models show that when replicating physiological and pathological conditions as closely as possible investigators are allowed to probe the basic mechanisms of morphogenesis, differentiation and cancer. Significant efforts investigating angiogenetic processes and factors in tumorigenesis are currently undertaken to establish ways of targeting angiogenesis in tumours. Anti-angiogenic agents have been accepted for clinical application as attractive targeted therapeutics for the treatment of cancer. Combining the areas of tumour angiogenesis, combination therapies and drug delivery systems is therefore closely related to the understanding of the basic principles that are applied in tissue engineering models. Studies with 3D model systems have repeatedly identified complex interacting roles of matrix stiffness and composition, integrins, growth factor receptors and signalling in development and cancer. These insights suggest that plasticity, regulation and suppression of these processes can provide strategies and therapeutic targets for future cancer therapies. The historical perspective of the fields of tissue engineering and controlled release of therapeutics, including inhibitors of angiogenesis in tumours is becoming clearly evident as a major future advance in merging these fields. New delivery systems are expected to greatly enhance the ability to deliver drugs locally and in therapeutic concentrations to relevant sites in living organisms. Investigating the phenomena of angiogenesis and anti-angiogenesis in 3D in vivo models such as the Arterio-Venous (AV) loop mode in a separated and isolated chamber within a living organism adds another significant horizon to this perspective and opens new modalities for translational research in this field.

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

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Objective - We report the first randomised controlled trial (RCT) using a combination of St. John’s wort (SJW) and Kava for the treatment of major depressive disorder (MDD) with comorbid anxiety. Methods - Twenty-eight adults with MDD and co-occurring anxiety were recruited for a double-blind RCT. After a placebo run-in of 2 weeks, the trial had a crossover design testing SJW and Kava against placebo over two controlled phases, each of 4 weeks. The primary analyses used intention-to-treat and completer analyses. Results - On both intention-to-treat ( p¼0.047) and completer analyses ( p¼0.003), SJW and Kava gave a significantly greater reduction in self-reported depression on the Beck Depression Inventory (BDI-II) over placebo in the first controlled phase. However, in the crossover phase, a replication of those effects in the delayed medication group did not occur. Nor were there significant effects on anxiety or quality of life. Conclusion - There was some evidence of antidepressant effects using SJW and Kava in a small sample with comorbid anxiety. Possible explanations for the absence of anxiolysis may include a potential interaction with SJW, the presence of depression, or an inadequate dose of Kava.

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This chapter elucidates key ideas behind neurocomputational and ecological dynamics and perspectives of understanding the organisation of action in complex neurobiological systems. The need to study the close link between neurobiological systems and their environments (particularly their sensory and movement subsystems and the surrounding energy sources) is advocated. It is proposed how degeneracy in complex neurobiological systems provides the basis for functional variability in organisation of action. In such systems processes of cognition and action facilitate the specific interactions of each performer with particular task and environmental constraints.

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Traditionally, the aquisition of skills and sport movement has been characterised by numerous repetitions of presumed model movement pattern to be acquired by learners. This approach has been questioned by research identifying the presence of individualised movement patterns and the low probability of occurrence of two identical movements within and between individuals. In contrast, the differential learning approach claims advantage for incurring variability in the learning process by adding stochastic perturbations during practice. These ideas are exemplified by data from a high jump experiment which compared the effectiveness of classical and a differential training approach with pre-post test design. Results showed clear advantages for the group with additional stochastic perturbation during the aquisition phase in comparison to classically trained athletes. Analogies to similar phenomenological effects in the neurobiological literature are discussed.

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There is consensus among community and road safety agencies that driver fatigue is a major road safety issue and it is well known that excessive fatigue is linked with an increased risk of a motor vehicle crash. Previous research has implicated a wide variety of factors involved in fatigue-related crashes and the effects of these various factors in regard to crash risk can be interpreted as causal (i.e. alcohol and/or drugs may induce fatigue states) or additive (e.g. where a lack of sleep is combined with alcohol). As such, the purpose of this investigation was to examine self-report data to determine whether there are any differences in the prevalence, crash characteristics, and travel patterns of males and females involved in a fatigue-related crash or close call event. Such research is important to understand how fatigue related incidents occur within the typical driving patterns of men and women and it provides a starting point in order to explore if males and females experience and understand the risk of diving when tired in the same way. A representative sample of (N = 1,600) residents living in the Australian Capital Territory (ACT) and New South Wales (NSW), Australia, were surveyed regarding their experience of fatigue and their involvement in fatigue-related crashes and close call incidents. Results revealed that over 35% of participants reported having had a close call or crash due to driving when tired in the five years prior to the study being conducted. In addition, the results obtained revealed a number of interesting characteristics that provide preliminary evidence that gender differences do exist when examining the prevalence, crash characteristics, and travel patterns of males and females involved in a fatigue-related crash or close call event. It is argued that the results obtained can provide particularly useful information for the refinement and further development of appropriate countermeasures that better target this complex issue.