836 resultados para BIM, LCA, Building Information Modelling, Life Cycle Assessment
Resumo:
Business processes have emerged as a well-respected variable in the design of successful corporations. However, unlike other key managerial variables, such as products and services, customers and employees, physical or digital assets, the conceptualization and management of business processes are in many respects in their infancy. In this book, Jan Recker investigates the notion of quality of business process modeling grammars. His evaluation is based on an ontological-, qualitative-, and quantitative analysis, applied to BPMN, a widely-used business process modeling grammar. His results reveal the ontological shortcomings of BPMN and how these manifest themselves in actual process modeling practice, as well as how they influence the usage behavior of modeling practitioners. More generally, his book constitutes a landmark for empirical technology assessment, analyzing the way in which design flaws in technology influence usage behavior.
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The concept of constructability is to use construction knowledge and experience during all phases of a project, particularly in the earliest phases of planning and design. It facilitates project objectives before delivery stage, and decreases unnecessary costs during construction phase. Despite the extensive use, constructability concept fails to address many issues related to Operation and Maintenance (O&M) of construction projects. Extending constructability concept, to include the O&M issues, could lead to the projects that are not fitted for construction purposes only, but also fitted for use. This study reviews the literature of constructability implementation, its benefits and shortcomings during the infrastructure life cycle, as well as the delivery success factors of infrastructure projects. This contributes to the propose need of a model to improve the effectiveness and efficiency of infrastructure project by extending the concept of constructability to include O&M. Development of such a model can facilitate post-occupancy stakeholders’ participation in a constructability program. It will help infrastructure owners eliminate project reworks, and improve O&M effectiveness and efficiency.
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As the world’s rural populations continue to migrate from farmland to sprawling cities, transport networks form an impenetrable maze within which monocultures of urban form erupt from the spaces in‐between. These urban monocultures are as problematic to human activity in cities as cropping monocultures are to ecosystems in regional landscapes. In China, the speed of urbanisation is exacerbating the production of mono‐functional private and public spaces. Edges are tightly controlled. Barriers and management practices at these boundaries are discouraging the formation of new synergistic relationships, critical in the long‐term stability of ecosystems that host urban habitats. Some urban planners, engineers, urban designers, architects and landscape architects have recognised these shortcomings in contemporary Chinese cities. The ideology of sustainability, while critically debated, is bringing together thinking people in these and other professions under the umbrella of an ecological ethic. This essay aims to apply landscape ecology theory, a conceptual framework used by many professionals involved in land development processes, to a concept being developed by BAU International called Networks Cities: a city with its various land uses arranged in nets of continuity, adjacency, and superposition. It will consider six lesser‐known concepts in relation to creating enhanced human activity along (un)structured edges between proposed nets and suggest new frontiers that might be challenged in an eco‐city. Ecological theory suggests that sustaining biodiversity in regions and landscapes depends on habitat distribution patterns. Flora and fauna biologists have long studied edge habitats and have been confounded by the paradox that maximising the breadth of edges is detrimental to specialist species but favourable to generalist species. Generalist species of plants and animals tolerate frequent change in the landscape, frequenting two or more habitats for their survival. Specialist species are less tolerant of change, having specific habitat requirements during their life cycle. Protecting species richness then may be at odds with increasing mixed habitats or mixed‐use zones that are dynamic places where diverse activities occur. Forman (1995) in his book Land Mosaics however argues that these two objectives of land use management are entirely compatible. He postulates that an edge may be comprised of many small patches, corridors or convoluting boundaries of large patches. Many ecocentrists now consider humans to be just another species inhabiting the ecological environments of our cities. Hence habitat distribution theory may be useful in planning and designing better human habitats in a rapidly urbanising context like China. In less‐constructed environments, boundaries and edges provide important opportunities for the movement of multi‐habitat species into, along and from adjacent land use areas. For instance, invasive plants may escape into a national park from domestic gardens while wildlife may forage on garden plants in adjoining residential areas. It is at these interfaces that human interactions too flow backward and forward between land types. Spray applications of substances by farmers on cropland may disturb neighbouring homeowners while suburban residents may help themselves to farm produce on neighbouring orchards. Edge environments are some of the most dynamic and contested spaces in the landscape. Since most of us require access to at least two or three habitats diurnally, weekly, monthly or seasonally, their proximity to each other becomes critical in our attempts to improve the sustainability of our cities.
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Construction 2020 is a national initiative undertaken by CRC for Construction Innovation to focus its ongoing leadership of the Australian property and construction industry in applied research and best contribute to the industry's national and international growth and competitiveness. It is the first major report on the long-term outlook for the industry since the late 1990s. The report identifies nine key themes for the future of the property and construction industry. These visions describe the major concerns of the industry and the improved future working environment favoured by its stakeholders. The first and clearest vision, agreed across the industry, is that environmentally sustainable construction the creation of buildings and infrastructure that minimise their impact on the natural environment is an area of huge potential. Here technologies like Construction Innovation's LCADesign can make a big difference. This is a calculator that works out automatically from 3D computer-aided design the environmental costs of materials in a building all at the push of a button. By working with industry, we'd expect to have a comprehensive set of eco-design tools for all stages of the construction life cycle, to minimise energy use, greenhouse and other forms of waste or pollution. Other significant areas of focus in the report include the development of nationally uniform codes of practice, new tools to evaluate design and product performance, comparisons with overseas industries, and a worldwide research network to ensure that Australian technology is at the cutting edge.
Resumo:
The concept of constructability uses integration art of individual functions through a valuable and timely construction inputs into planning and design development stages. It results in significant savings in cost and time needed to finalize infrastructure projects. However, available constructability principles, developed by CII Australia (1993), do not cover Operation and Maintenance (O&M) phases of projects, whilst major cost and time in multifaceted infrastructure projects are spent in post-occupancy stages. This paper discusses the need to extend the constructability concept by examining current O&M issues in the provision of multifaceted building projects. It highlights available O&M problems and shortcomings of building projects, as well as their causes and reasons in different categories. This initial categorization is an efficient start point for testing probable present O&M issues in various cases of complex infrastructure building projects. This preliminary categorization serve as a benchmark to develop an extended constructability model that considers the whole project life cycle phases rather than a specific phase. It anticipates that the development of an extended constructability model can reduce significant number of reworks, mistakes, extra costs and time wasted during delivery stages of multifaceted building projects.
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Research found that today’s organisations are increasingly aware of the potential barriers and perceived challenges associated with the successful delivery of change — including cultural and sub-cultural indifferences; financial constraints; restricted timelines; insufficient senior management support; fragmented key stakeholder commitment; and inadequate training. The delivery and application of Innovative Change (see glossary) within a construction industry organisation tends to require a certain level of ‘readiness’. This readiness is the combination of an organisation’s ability to part from undertakings that may be old, traditional, or inefficient; and then being able to readily adopt a procedure or initiative which is new, improved, or more efficient. Despite the construction industry’s awareness of the various threats and opportunities associated with the delivery of change, research found little attention is currently given to develop a ‘decision-making framework’ that comprises measurable elements (dynamics) that may assist in more accurately determining an organisation’s level of readiness or ability to deliver innovative change. To resolve this, an initial Background Literature Review in 2004 identified six such dynamics, those of Change, Innovation, Implementation, Culture, Leadership, and Training and Education, which were then hypothesised to be key components of a ‘Conceptual Decision-making Framework’ (CDF) for delivering innovative change within an organisation. To support this hypothesis, a second (more extensive) Literature Review was undertaken from late 2007 to mid 2009. A Delphi study was embarked on in June 2008, inviting fifteen building and construction industry members to form a panel and take part in a Delphi study. The selection criterion required panel members to have senior positions (manager and above) within a recognised field or occupation, and to have experience, understanding and / or knowledge in the process of delivering change within organisations. The final panel comprised nine representatives from private and public industry organisations and tertiary / research and development (R&D) universities. The Delphi study developed, distributed and collated two rounds of survey questionnaires over a four-month period, comprising open-ended and closed questions (referred to as factors). The first round of Delphi survey questionnaires were distributed to the panel in August 2008, asking them to rate the relevancy of the six hypothesised dynamics. In early September 2008, round-one responses were returned, analysed and documented. From this, an additional three dynamics were identified and confirmed by the panel as being highly relevant during the decision-making process when delivering innovative change within an organisation. The additional dynamics (‘Knowledge-sharing and Management’; ‘Business Process Requirements’; and ‘Life-cycle Costs’) were then added to the first six dynamics and used to populate the second (final) Delphi survey questionnaire. This was distributed to the same nine panel members in October 2008, this time asking them to rate the relevancy of all nine dynamics. In November 2008, round-two responses were returned, analysed, summarised and documented. Final results confirmed stability in responses and met Delphi study guidelines. The final contribution is twofold. Firstly, findings confirm all nine dynamics as key components of the proposed CDF for delivering innovative change within an organisation. Secondly, the future development and testing of an ‘Innovative Change Delivery Process’ (ICDP) is proposed, one that is underpinned by an ‘Innovative Change Decision-making Framework’ (ICDF), an ‘Innovative Change Delivery Analysis’ (ICDA) program, and an ‘Innovative Change Delivery Guide’ (ICDG).
Resumo:
Measuring the business value that Internet technologies deliver for organisations has proven to be a difficult and elusive task, given their complexity and increased embeddedness within the value chain. Yet, despite the lack of empirical evidence that links the adoption of Information Technology (IT) with increased financial performance, many organisations continue to adopt new technologies at a rapid rate. This is evident in the widespread adoption of Web 2.0 online Social Networking Services (SNSs) such as Facebook, Twitter and YouTube. These new Internet based technologies, widely used for social purposes, are being employed by organisations to enhance their business communication processes. However, their use is yet to be correlated with an increase in business performance. Owing to the conflicting empirical evidence that links prior IT applications with increased business performance, IT, Information Systems (IS), and E-Business Model (EBM) research has increasingly looked to broader social and environmental factors as a means for examining and understanding the broader influences shaping IT, IS and E-Business (EB) adoption behaviour. Findings from these studies suggest that organisations adopt new technologies as a result of strong external pressures, rather than a clear measure of enhanced business value. In order to ascertain if this is the case with the adoption of SNSs, this study explores how organisations are creating value (and measuring that value) with the use of SNSs for business purposes, and the external pressures influencing their adoption. In doing so, it seeks to address two research questions: 1. What are the external pressures influencing organisations to adopt SNSs for business communication purposes? 2. Are SNSs providing increased business value for organisations, and if so, how is that value being captured and measured? Informed by the background literature fields of IT, IS, EBM, and Web 2.0, a three-tiered theoretical framework is developed that combines macro-societal, social and technological perspectives as possible causal mechanisms influencing the SNS adoption event. The macro societal view draws on the concept of Castells. (1996) network society and the behaviour of crowds, herds and swarms, to formulate a new explanatory concept of the network vortex. The social perspective draws on key components of institutional theory (DiMaggio & Powell, 1983, 1991), and the technical view draws from the organising vision concept developed by Swanson and Ramiller (1997). The study takes a critical realist approach, and conducts four stages of data collection and one stage of data coding and analysis. Stage 1 consisted of content analysis of websites and SNSs of many organisations, to identify the types of business purposes SNSs are being used for. Stage 2 also involved content analysis of organisational websites, in order to identify suitable sample organisations in which to conduct telephone interviews. Stage 3 consisted of conducting 18 in-depth, semi-structured telephone interviews within eight Australian organisations from the Media/Publishing and Galleries, Libraries, Archives and Museum (GLAM) industries. These sample organisations were considered leaders in the use of SNSs technologies. Stage 4 involved an SNS activity count of the organisations interviewed in Stage 3, in order to rate them as either Advanced Innovator (AI) organisations, or Learning Focussed (LF) organisations. A fifth stage of data coding and analysis of all four data collection stages was conducted, based on the theoretical framework developed for the study, and using QSR NVivo 8 software. The findings from this study reveal that SNSs have been adopted by organisations for the purpose of increasing business value, and as a result of strong social and macro-societal pressures. SNSs offer organisations a wide range of value enhancing opportunities that have broader benefits for customers and society. However, measuring the increased business value is difficult with traditional Return On Investment (ROI) mechanisms, ascertaining the need for new value capture and measurement rationales, to support the accountability of SNS adoption practices. The study also identified the presence of technical, social and macro-societal pressures, all of which influenced SNS adoption by organisations. These findings contribute important theoretical insight into the increased complexity of pressures influencing technology adoption rationales by organisations, and have important practical implications for practice, by reflecting the expanded global online networks in which organisations now operate. The limitations of the study include the small number of sample organisations in which interviews were conducted, its limited generalisability, and the small range of SNSs selected for the study. However, these were compensated in part by the expertise of the interviewees, and the global significance of the SNSs that were chosen. Future research could replicate the study to a larger sample from different industries, sectors and countries. It could also explore the life cycle of SNSs in a longitudinal study, and map how the technical, social and macro-societal pressures are emphasised through stages of the life cycle. The theoretical framework could also be applied to other social fad technology adoption studies.
Resumo:
Mandatory data breach notification laws are a novel and potentially important legal instrument regarding organisational protection of personal information. These laws require organisations that have suffered a data breach involving personal information to notify those persons that may be affected, and potentially government authorities, about the breach. The Australian Law Reform Commission (ALRC) has proposed the creation of a mandatory data breach notification scheme, implemented via amendments to the Privacy Act 1988 (Cth). However, the conceptual differences between data breach notification law and information privacy law are such that it is questionable whether a data breach notification scheme can be solely implemented via an information privacy law. Accordingly, this thesis by publications investigated, through six journal articles, the extent to which data breach notification law was conceptually and operationally compatible with information privacy law. The assessment of compatibility began with the identification of key issues related to data breach notification law. The first article, Stakeholder Perspectives Regarding the Mandatory Notification of Australian Data Breaches started this stage of the research which concluded in the second article, The Mandatory Notification of Data Breaches: Issues Arising for Australian and EU Legal Developments (‘Mandatory Notification‘). A key issue that emerged was whether data breach notification was itself an information privacy issue. This notion guided the remaining research and focused attention towards the next stage of research, an examination of the conceptual and operational foundations of both laws. The second article, Mandatory Notification and the third article, Encryption Safe Harbours and Data Breach Notification Laws did so from the perspective of data breach notification law. The fourth article, The Conceptual Basis of Personal Information in Australian Privacy Law and the fifth article, Privacy Invasive Geo-Mashups: Privacy 2.0 and the Limits of First Generation Information Privacy Laws did so for information privacy law. The final article, Contextualizing the Tensions and Weaknesses of Information Privacy and Data Breach Notification Laws synthesised previous research findings within the framework of contextualisation, principally developed by Nissenbaum. The examination of conceptual and operational foundations revealed tensions between both laws and shared weaknesses within both laws. First, the distinction between sectoral and comprehensive information privacy legal regimes was important as it shaped the development of US data breach notification laws and their subsequent implementable scope in other jurisdictions. Second, the sectoral versus comprehensive distinction produced different emphases in relation to data breach notification thus leading to different forms of remedy. The prime example is the distinction between market-based initiatives found in US data breach notification laws compared to rights-based protections found in the EU and Australia. Third, both laws are predicated on the regulation of personal information exchange processes even though both laws regulate this process from different perspectives, namely, a context independent or context dependent approach. Fourth, both laws have limited notions of harm that is further constrained by restrictive accountability frameworks. The findings of the research suggest that data breach notification is more compatible with information privacy law in some respects than others. Apparent compatibilities clearly exist as both laws have an interest in the protection of personal information. However, this thesis revealed that ostensible similarities are founded on some significant differences. Data breach notification law is either a comprehensive facet to a sectoral approach or a sectoral adjunct to a comprehensive regime. However, whilst there are fundamental differences between both laws they are not so great to make them incompatible with each other. The similarities between both laws are sufficient to forge compatibilities but it is likely that the distinctions between them will produce anomalies particularly if both laws are applied from a perspective that negates contextualisation.
Resumo:
Highway construction works have significant bearings on all aspects of sustainability. As they typically involve huge capital funds, stakeholders tend to place all interests on the financial justifications of the project, especially when embedding sustainability principles and practices may demand significant initial investment. Increasing public awareness and government policies demand that infrastructure projects respond to environmental challenges and people start to realise the negative consequences of not to pursue sustainability. Stakeholders are now keen to identify sustainable alternatives and financial implications of including them on a whole lifecycle basis. Therefore tools that aid the evaluation of investment options, such as provision of environmentally sustainable features in roads and highways, are highly desirable. Life-cycle cost analysis (LCCA) is generally recognised as a valuable approach for investment decision making for construction works. However to date it has limited application because the current LCCA models tend to focus on economic issues alone and are not able to deal with sustainability factors. This paper reports a research on identifying sustainability related factors in highway construction projects, in quantitative and qualitative forms of a multi-criteria analysis. These factors are then incorporated into existing LCCA models to produce a new sustainability based LCCA model with cost elements specific to sustainability measures. This presents highway project stakeholders a practical tool to evaluate investment decisions and reach an optimum balance between financial viability and sustainability deliverables.
Resumo:
The development of highway infrastructure typically requires major capital input over a long period. This often causes serious financial constraints for investors. The push for sustainability has added new dimensions to the complexity in the evaluation of highway projects, particularly on the cost front. This makes the determination of long-term viability even more a precarious exercise. Life-cycle costing analysis (LCCA) is generally recognised as a valuable tool for the assessment of financial decisions on construction works. However to date, existing LCCA models are deficient in dealing with sustainability factors, particularly for infrastructure projects due to their inherent focus on the economic issues alone. This research probed into the major challenges of implementing sustainability in highway infrastructure development in terms of financial concerns and obligations. Using results of research through literature review, questionnaire survey of industry stakeholders and semi-structured interview of senior practitioners involved in highway infrastructure development, the research identified the relative importance of cost components relating to sustainability measures and on such basis, developed ways of improving existing LCCA models to incorporate sustainability commitments into long-term financial management. On such a platform, a decision support model incorporated Fuzzy Analytical Hierarchy Process and LCCA for the evaluation of the specific cost components most concerned by infrastructure stakeholders. Two real highway infrastructure projects in Australia were then used for testing, application and validation, before the decision support model was finalised. Improved industry understanding and tools such as the developed model will lead to positive sustainability deliverables while ensuring financial viability over the lifecycle of highway infrastructure projects.
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Purpose With an increasingly ageing population and widespread acceptance of the need for sustainable development in Australia, the demand for green retirement villages is increasing. This paper aims to identify the critical issues to be considered by developers and practitioners when embarking on their first green residential retirement project in Australia. Design/methodology/approach In view of the lack of adequate historical data for quantitative analysis, a case study approach is employed to examine the successful delivery of green retirement villages. Face-to-face interviews and document analysis were conducted for data collection. Findings The findings of the study indicate that one of the major obstacles to the provision of affordable green retirement villages is the higher initial costs involved. However, positive aspects were identified, the most significant of which relate to: the innovative design of site and floor plans; adoption of thermally efficient building materials; orientation of windows; installation of water harvesting and recycling systems, water conservation fittings and appliances; and waste management during the construction stage. With the adoption of these measures, it is believed that sustainable retirement development can be achieved without significant additional capital costs. Practical implications The research findings serve as a guide for developers in decision making throughout the project life-cycle when introducing green features into the provision of affordable retirement accommodation. Originality/value This paper provides insights into the means by which affordable green residential retirement projects for aged people can be successfully completed.
Resumo:
Among the Australian general public, there are increasing concerns about environmental issues. Accordingly, sustainability in the housing industry is also becoming a priority on the development agenda. However, putting the principles of ecological sustainability into practice within social and economic development requires intensive involvement of major stakeholders such as governments, developers, builders, consumers and a range of other professionals. Establishing a sustainable value entails asymmetric life-cycle returns, making it important for major stakeholders to appreciate the benefits of this new agenda not only for the individual businesses but also for other supply chain partners. This context warrants the study to promote collective benefits for key stakeholders by establishing a mutual-benefit framework for sustainable housing implementation. A research was carried out in the hope to establish a mutual-benefit framework by investigating challenges of achieving benefits (CABs) from sustainable housing development in a multi-stakeholder context. In the research work reported in this article, a comparative questionnaire study was first conducted among seven stakeholder groups in the Australian housing industry, to examine the importance and inter-relationships of CABs. In-depth interviews then furthered the survey findings with a focus on stakeholder diversity. The synthesized findings of the survey and interview study lead to the identification of 12 critical mutual-benefit factors and their mutual influence. Based on such a platform, a systematic framework is developed with the aid of Interpretive Structural Modelling (ISM), to identify the patterns of stakeholder benefit materialisation, suggest the priority of critical factors and provide related stakeholder-specific action guide for sustainable housing implementation.
Resumo:
Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.
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The growing awareness of sustainability issues around the world has put extensive pressure on the construction industry to improve its sustainable practice. Sustainability principles need to be applied to not just during design and construction phase but the entire life cycle of a construction project. Compared to sustainability endeavours on earlier development phases, the pace to implement sustainability agenda during the operation and maintenance phase has not been as fast during past practices of facilities management (FM). Literature study suggests that sustainable practices in FM activities can bring substantial benefits such as reducing energy consumptions and waste, while increasing productivity, financial return and standing in the community. It also suggests several barriers which inhibit the implementation of sustainability in FM practices, including the lack of knowledge, discrepancy between capability and skills, and unwillingness of the FM personnel and organizations to adapt to new routines in order to implement sustainability in their business. The capabilities of FM personnel and organizations were regarded as the key enablers in managing sustainability knowledge. In a sustainable development context, capabilities are vital to the fostering of competency in an organization to innovate in a more sustainable way and support the agenda in an organization. Additionally, research which focused on people’s capabilities and skills is still lagging behind the efforts to develop guidelines, technical manuals and knowledge portals. Therefore, it is beneficial to explore the issues of capabilities in dealing with the implementation of sustainable practices in FM. This paper introduces a research project which is aimed at establishing a knowledge capabilities framework for promoting sustainability measures in FM practices. It will explore and highlight challenges to integrate sustainability as well as the personnel and organizational capabilities that are vital in dealing with knowledge issues in implementing sustainability agenda in FM practices. The expected outcome of this research has the potential to further sustainability endeavours in FM practices, while providing a useful source of knowledge to the FM personnel and organizations.
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The construction industry has been under pressure for many years to produce economical buildings which offer value for money, not only during the construction phase, but more importantly, during the full life of the building. Whole Life Cycle Costing (WLCC) is a relatively new concept for the construction industry especially on residential development and particularly for Malaysia. Discussing the speculation in using WLCC for the Malaysian residential constructions is the aim for this paper and it is one of the research questions on my research. This paper also wants to gather more speculation that may involve through others experienced. Basically, this paper is written to facilitate the current or future individual which will involve in residential property development sector with a new sensible approach to what at times seems impressively confusing especially in simplifying the operations and maintenance services and rehabilitation as well.