216 resultados para life-cycle perspective


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Plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. Disease occurs during the blood-stage of the parasite’s life cycle, where the parasite is thought to replicate exclusively within erythrocytes. Infected individuals can also suffer relapses after several years, from Plasmodium vivax and Plasmodium ovale surviving in hepatocytes. Plasmodium falciparum and Plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood, suggesting that host cells other than erythrocytes (but not hepatocytes) may harbor these blood-stage parasites, thereby assisting their escape from host immunity. Using blood stage transgenic Plasmodium berghei-expressing GFP (PbGFP) to track parasites in host cells, we found that the parasite had a tropism for CD317+ dendritic cells. Other studies using confocal microscopy, in vitro cultures, and cell transfer studies showed that blood-stage parasites could infect, survive, and replicate within CD317+ dendritic cells, and that small numbers of these cells released parasites infectious for erythrocytes in vivo. These data have identified a unique survival strategy for blood-stage Plasmodium, which has significant implications for understanding the escape of Plasmodium spp. from immune-surveillance and for vaccine development.

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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).

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This paper focuses on information sharing with key suppliers and seeks to explore the factors that might influence its extent and depth. We also investigate how information sharing affects a company’s performance with regards to resource usage, output, and flexibility. Drawing from transaction cost- and contingency theories, several factors, namely environmental uncertainty, demand uncertainty, dependency and, the product life cycle stage are proposed to explain the level of information shared with key suppliers. We develop a model where information sharing mediates the (contingent) factors and company performance. A mail survey was used to collect data from Finnish and Swedish companies. Partial Least Squares analysis was separately performed for each country (n=119, n=102). There was consistent evidence that environmental uncertainty, demand uncertainty and supplier/buyer dependency had explanatory power, whereas no significance was found for the product life cycle stage. The results also confirm previous studies by providing support for a positive relationship between information sharing and performance, where output performance was found to be the most strongly related

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This paper focuses on information sharing with key suppliers and seeks to explore the factors that might influence its extent and depth. We also investigate how information sharing affects a company’s performance with regards to resource usage, output, and flexibility. Drawing from transaction cost- and contingency theories, several factors, namely environmental uncertainty, demand uncertainty, dependency and, the product life cycle stage are proposed to explain the level of information shared with key suppliers. We develop a model where information sharing mediates the (contingent) factors and company performance. A mail survey was used to collect data from Finnish and Swedish companies. Partial Least Squares analysis was separately performed for each country (n=119, n=102). There was consistent evidence that environmental uncertainty, demand uncertainty and supplier/buyer dependency had explanatory power, whereas no significance was found for the relationship between product life cycle stage and information sharing. The results also confirm previous studies by providing support for a positive relationship between information sharing and performance, where output performance was found to be the most strongly related.

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Purpose: Important performance objectives manufacturers sought can be achieved through adopting the appropriate manufacturing practices. This paper presents a conceptual model proposing relationship between advanced quality practices, perceived manufacturing difficulties and manufacturing performances. Design/methodology/approach: A survey-based approach was adopted to test the hypotheses proposed in this study. The selection of research instruments for inclusion in this survey was based on literature review, the pilot case studies and relevant industrial experience of the author. A sample of 1000 manufacturers across Australia was randomly selected. Quality managers were requested to complete the questionnaire, as the task of dealing with the quality and reliability issues is a quality manager’s major responsibility. Findings: Evidence indicates that product quality and reliability is the main competitive factor for manufacturers. Design and manufacturing capability and on time delivery came second. Price is considered as the least important factor for the Australian manufacturers. Results show that collectively the advanced quality practices proposed in this study neutralize the difficulties manufacturers face and contribute to the most performance objectives of the manufacturers. The companies who have put more emphasize on the advanced quality practices have less problem in manufacturing and better performance in most manufacturing performance indices. The results validate the proposed conceptual model and lend credence to hypothesis that proposed relationship between quality practices, manufacturing difficulties and manufacturing performances. Practical implications: The model shown in this paper provides a simple yet highly effective approach to achieving significant improvements in product quality and manufacturing performance. This study introduces a relationship based ‘proactive’ quality management approach and provides great potential for managers and engineers to adopt the model in a wide range of manufacturing organisations. Originality/value: Traditional ways of checking product quality are different types of testing, inspection and screening out bad products after manufacturing them. In today’s manufacturing where product life cycle is very short, it is necessary to focus on not to manufacturing them first rather than screening out the bad ones. This study introduces, for the first time, the idea of relationship based advanced quality practices (AQP) and suggests AQPs will enable manufacturers to develop reliable products and minimize the manufacturing anomalies. This paper explores some of the attributes of AQP capable of reducing manufacturing difficulties and improving manufacturing performances. The proposed conceptual model contributes to the existing knowledge base of quality practices and subsequently provides impetus and guidance towards increasing manufacturing performance.

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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.

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Building Information Modeling (BIM) is a modern approach to the design, documentation, delivery, and life cycle management of buildings through the use of project information databases coupled with object-based parametric modeling. BIM has the potential to revolutionize the Architecture, Engineering and Construction (AEC) industry in terms of the positive impact it may have on information flows, working relationships between project participants from different disciplines and the resulting benefits it may achieve through improvements to conventional methods. This chapter reviews the development of BIM, the extent to which BIM has been implemented in Australia, and the factors which have affected the up-take of BIM. More specifically, the objectives of this chapter are to investigate the adoption of BIM in the Australian AEC industry and factors that contribute towards the uptake (or non uptake) of BIM. These objectives are met by a review of the related literature in the first instance, followed by the presentation of the results of a 2007 postal questionnaire survey and telephone interviews of a random sample of professionals in the Australian AEC industry. The responses suggest that less than 25 percent of the sample had been involved in BIM – rather less than might be expected from reading the literature. Also, of those who have been involved with BIM, there has been very little interdisciplinary collaboration. The main barriers impeding the implementation of BIM widely across the Australian AEC industry are also identified. These were found to be primarily a lack of BIM expertise, lack of awareness and resistance to change. The benefits experienced as a result of using BIM are also discussed. These include improved design consistency, better coordination, cost savings, higher quality work, greater productivity and increased speed of delivery. In terms of conclusion, some suggestions are made concerning the underlying practical reasons for the slow up-take of BIM and the successes for those early adopters. Prospects for future improvement are discussed and proposals are also made for a large scale worldwide comparative study covering industry-wide participants

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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.

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This paper investigates the policies and instruments adopted in Hong Kong to control the carbon emissions of construction facilities, including the whole building life cycle: production of material stage, construction stage, operation stage and demolition stage. This commences with a literature review comparing activities world-wide to those in Hong Kong to identify the main issues at stake, followed by a report on a series of local interviews to evaluate the present situation in Hong Kong, as well as future opportunities for local carbon mitigation. The interviewees included practitioners from engineering contracting firms, consulting firms, clients and energy provider, together with two university experts and a counsellor. A small case study is also provided of a building project in Hong Kong to illustrate some of the innovative design aspects being incorporated into buildings in Hong Kong as a result of the current emphasis on sustainability. The paper concludes with a summary of main findings and proposals for improvement in policy related to carbon mitigation and building sustainability in Hong Kong.

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There is an abundance of books available on the topic of motherhood and mothering; the majority of these books focus on the vulnerability of babies and young children and the motherwork such vulnerability demands. In particular they focus on what it is right to do in the interests of the child, and particularly his or her growth and development. Such a focus is consistent in Western culture with modern moral frameworks where understandings of goodness have been assimilated to dimensions of human action rather than dimensions of human being, selfhood, or specific forms of life. As Charles Taylor has observed, much modern moral philosophy has focused =on what it is right to do rather than the nature of the good life‘ (1989, 13). The master narratives of motherhood and the prevailing social discourses of intensive1 and sacrificial2 mothering exemplify this view as such narratives and discourses depict =what mothers are expected to do [and] how mothers are supposed to be‘ (Nelson 2001, 140). From such infant/child-focused accounts a canonical maternal identity can be discerned; arguably, it is a restricted one. The majority of these books fail to address questions related to what it means be a mother in particular situated, existing, living realities. For instance, ask a mother with young children what being a mother means to her and she may speak of the challenges she faces balancing paid employment and her role as a mother, or the impact of the demands being made on her time and energy. However, ask a mother with young adult-children3 what being a mother means to her and she may speak in similar tones, but she may also speak in differing tones. For example, a "mature" mother may speak of the "empty nest", the "crowded house" and/or "its revolving front door". She may speak of issues related to the vulnerability of the long term marriage, elder care, or grandparenting, or even disillusionment and disenchantment. The purpose of this research is to explore the identity challenges and prospects of some mothers with young adult-children aged between 18 and 30 years of age in twenty-first century Australia. In interpreting the identity challenges and prospects this particular cohort of mothers encounter in their ordinary, everyday living, a diverse and particular range of maternal experiences.my own included5.have been traced, along with the social and ethical meanings ascribed in them. With an understanding and appreciation of voice as the medium which connects one's inner and outer worlds, this research illuminates the plurality of voices and the multiple layers of meaning in each of these mother's particular living and existing realities. Specifically, this research addresses the narrowly constructed, canonical maternal identity through a critical exploration and reflection on stories, shared in a research context, of the living realities of a group of self-identified "mature", middle-class, Australian mothers with children aged between 18 and 30 years of age6. By appraising the broader familial, historical, social, cultural, institutional, and, importantly, moral contexts in which these mothers are situated, 'thick descriptions' (Geertz 1973, 27)7 of maternal identities, and the challenges and prospects these mothers are negotiating, are provided. In terms of its ethical orientation, the frameworks which support and frame this research reject, repudiate and contest (Nelson 2001) the reduction of ethical concerns to individual or intellectual problems or dilemmas to be solved through the application of a theory derived from reasoned thinking. In dismissing deductive and =theoretical-juridical‘8 approaches, the individualistic orientation entrenched in contemporary Western moral thinking, expressed in the notion of '"what ought I to do" when faced with a problem, issue or dilemma of practical urgency' (Isaacs & Massey 1994, 1), is simultaneously rejected, repudiated and contested (Nelson 2001). In countering such understandings, this research reorients us to the illumination and articulation of who it is good to be, for each of these mothers, in allegiance with those goods which guide and inspire her orientations towards living a good life—a life which embraces and enhances the flourishing of herself and her significant others. With an understanding and appreciation that 'mind is never free of precommitment[—t]here is no innocent eye, nor is there one that penetrates aboriginal reality' (Bruner 1987, 32), this thesis is written with the voices of other interlocutors9. These interlocutors include the voices of my research participants whom I refer to as "research interlocutors", my textual "friends" — those scholars whose work resonates strongly with my orientations—as well as the myriad other voices that speak to mothers, for mothers and about mothers, such as those found in popular and mainstream press and culture. Sometimes these voices resonate; other times dissonance may be heard. In situating this research within these complementary frameworks, this research invites readers to join with me in considering, appreciating and appraising the narrow construction of maternal identity. I seek for this engagement, like the engagements with my research interlocutors, to be 'a meeting of voices, an authentic dialogue that is inclusive of the voices of all concerned participants' (Isaacs 2001, 6). I hope that the voices in this thesis resonate with yours (although, at times, you may feel some dissonance) and that together we can draw closer to the accounting, re-counting and re-stor(y)ing of maternal identities; like concentric circles of witness, the dialogue, ...will thus be expanded rippling into corners where one might both imagine, and least expect. Possibilities, then, are vast; the future exciting (Smith 2007, 397). This research is also shaped and guided by maternal scholarship, a relatively new field of inquiry known as 'motherhood studies' (O'Reilly 2011, xvii) which has its origins within the broader terrain of feminist scholarship. As a work of maternal scholarship, this thesis draws upon and continues the tradition of examining motherhood as it is experienced 'in a social context, as embedded in a political institution: in feminist terms' (Rich 1995, ix). It values mothers, their experiences, their stories, their lives. As such, this research is oriented towards 'matricentric feminism', a particular form of feminist inquiry, politics and theory which is consistent with and receptive to feminist frameworks of care and equal rights (O‘Reilly 2011, 25). A number of complementary conceptual frameworks have been engaged in this research with the thesis presented in three parts: the pre-figurative, configurative and re-configurative. As my particular living experiences provided the initial motivation for this research, an account of the challenges I experienced as a mother with young adult-children are outlined as a Prelude to this thesis. Attention then turns to Part One – Pre-figuring Maternal Identities in which the contextual, conceptual and methodological foundations underpinning this research are explored and outlined. In Chapter One, the prevailing cultural narratives and social discourses supporting and shaping the construction of the canonical maternal identity are outlined. Next, in setting the scholarly context, the critiques — arising from feminist and maternal scholarship — of motherhood as a patriarchal institution, mothering as experience, and mothering as work, are explored. As this research engaged with participants who are embedded in particular middle-class, heterosexual, familial and cultural structures, an exploration of family life cycle theory and main stream media accounts are also incorporated. The terrain in which "mature" mothering within an Australian context is experienced is also outlined, including the notions of "empty nests" and "crowded houses", grandparenting, elder care and women's midlife transition. Chapter Two gives an account of the conceptual ontological, ethical, identity and narrative frameworks underpinning this research. In setting the context for rich interpretations, the characteristics of being human10 are outlined before attention turns to our embodiment and embeddedness in our shared human condition11. From this point, attention then turns to understanding the moral form of human living12. In appreciating the vulnerability inherent in our shared human condition, the ways in which we may experience trouble in our lives is noted. The framing of identity constitution13 as complex, multi-faceted, relationally negotiated and composed is then outlined, followed by an understanding of why narrative is a valuable interpretive tool for interpreting and understanding human experiences. This chapter concludes with an appreciation of the ethical significance of storytelling. The research methodology is then outlined in Chapter Three. The rationale underpinning the adoption of the narrative interviewing technique of in-depth interviewing is explored. In exploring these methodological frameworks, the recruitment and interview processes involved in gathering and interpreting the recorded transcripts of ten Australian mothers with young adult-children are outlined. The method of analysis known as the Listening Guide14 best complements the multi-layered, pluri-vocal nature of narrative accounting. The final section of Chapter Three outlines The Guide, with one mother's recorded transcript used to illustrate this method's step-by-step process. Having gathered an understanding and appreciation of the pluri-vocal, multi-layered nature of narrative and identity constitution, the tone of this thesis changes in Part Two . Configuring Maternal Identities. This section consists of Chapters Four and Five and seeks to find meaning in, and make sense of, the differences and commonalities across these particular accounts. Chapter Four explores the living realities of four Australian mothers with young adult-children: Poppy, Honey, Lily and Heather. In presenting a thick description of these mothers' situated realities, the frameworks.the familial, social, cultural, historical and institutional backgrounds.which have supported and shaped each mother's experiences are illuminated. Simultaneously revealed through these particular accounts are the plurality of goods focusing and moving each mother to the moral form of life, a life of meaning and purpose. The harms challenging some mothers' moral motivations are also revealed in this chapter. Specifically illustrated in Chapter Four are the unique and qualitative differences of particular maternal identity configurations. Chapter Five reveals the commonalities amongst all of the research interlocutors' accounts. This chapter contests the individualistic orientation of many contemporary accounts of motherhood which are aimed at defining or contesting what a "good" mother ought to do. By turning away from such individualistic orientations, the chapter does not seek to define 'the content of obligation' (Taylor 1989, 3) but rather seeks to illuminate and articulate a richer, deeper understanding and appreciation of maternal be-ing and be-coming - that is, who it is good to be, for each of these mothers - in allegiance with those goods that focus and inspire her moral motivations. Part Three - Re-Configuring Maternal Identities, which is comprised of Chapter Six, draws this thesis to a close. In this final chapter, the preconceptions, conditions and aspirations for this mother-centred account of the living realities of a small, local cohort of mothers are reiterated. The insights gathered from the rich, descriptive accounts are illuminated and articulated, and the chapter closes with some suggestions for future research. In a Postlude, I reflect on how this research has been a transformative learning experience in my own life.an experience in which I have been able to not only deeply understand and appreciate the challenges and disorientation I was experiencing but also to identify and reorient my stance in relation to the good. In a practical sense, by offering thick descriptions of the living realities of this cohort of "mature" mothers, this research challenges the canonical maternal identity and questions its relevance for, and effect on, "mature" mothers' identity constitution. By bringing to light the complex existing realities of these particular mothers, this research critiques the canonical maternal identity by illustrating that each mother's life and her identity constitutions are complex, relationally negotiated and composed and that motherhood is an enduring way of being. Through these illustrations, this research engages with and extends understandings of difference feminism. This research, however, not only rejects, repudiates and contests (Nelson 2001) the narrowly defined canonical maternal identity. By illuminating and articulating the goods which shape and inspire these "mature" mothers' motherwork, this research offers a matricentric account which is consistent with and respectful of the particular, situated realities—the broader familial, social, institutional, but most importantly, moral values and frameworks—in which each mother‘s life is embedded and her motherwork oriented. By understanding and appreciating the complex and multiple webs of relationships in which each mother exists, this matricentric re-stor(y)ing of maternal experiences not only understands and appreciates the unique nature of each mother‘s existing realities, it is oriented to the continuing enhancing of the shared pursuit of the good which underpins particular maternal practices and particular maternal ways of being.

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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.

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A building information model (BIM) is an electronic repository of structured, three-dimensional data that captures both the physical and dynamic functional characteristics of a facility. In addition to its more traditional function as a tool to aid design and construction, a BIM can be used throughout the life cycle of a facility, functioning as a living database that places resources contained within the building in their spatial and temporal context. Through its comprehension of spatial relationships, a BIM can meaningfully represent and integrate previously isolated control and management systems and processes, and thereby provide a more intuitive interface to users. By placing processes in a spatial context, decision-making can be improved, with positive flow-on effects for security and efficiency. In this article, we systematically analyse the authorization requirements involved in the use of BIMs. We introduce the concept of using a BIM as a graphical tool to support spatial access control configuration and management (including physical access control). We also consider authorization requirements for regulating access to the structured data that exists within a BIM as well as to external systems and data repositories that can be accessed via the BIM interface. With a view to addressing these requirements we present a survey of relevant spatiotemporal access control models, focusing on features applicable to BIMs and highlighting capability gaps. Finally, we present a conceptual authorization framework that utilizes BIMs.

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"This book explores the foundations of modern developmental thought, incorporating the latest in international research set within a cultural and historical context. Richly illustrated and enhanced by a range of practical teaching resources, this clear and engaging text is intended to reach students across a range of teaching, psychology, social science and health science disciplines. By employing a thematic approach within the chronologically ordered chapters, this text offers a systematic and intuitive structure for both learning and teaching. This new edition features a set of fully updated case studies that consider current trends and issues in developmental theory and practice, as well as end-of-chapter sections that address important stages in the family life cycle."--publisher website

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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.