994 resultados para Nuclear arsenal project


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The literature abounds with descriptions of failures in high-profile projects and a range of initiatives has been generated to enhance project management practice (e.g., Morris, 2006). Estimating from our own research, there are scores of other project failures that are unrecorded. Many of these failures can be explained using existing project management theory; poor risk management, inaccurate estimating, cultures of optimism dominating decision making, stakeholder mismanagement, inadequate timeframes, and so on. Nevertheless, in spite of extensive discussion and analysis of failures and attention to the presumed causes of failure, projects continue to fail in unexpected ways. In the 1990s, three U.S. state departments of motor vehicles (DMV) cancelled major projects due to time and cost overruns and inability to meet project goals (IT-Cortex, 2010). The California DMV failed to revitalize their drivers’ license and registration application process after spending $45 million. The Oregon DMV cancelled their five year, $50 million project to automate their manual, paper-based operation after three years when the estimates grew to $123 million; its duration stretched to eight years or more and the prototype was a complete failure. In 1997, the Washington state DMV cancelled their license application mitigation project because it would have been too big and obsolete by the time it was estimated to be finished. There are countless similar examples of projects that have been abandoned or that have not delivered the requirements.

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Georgia’s ‘National Integrity Systems’ are the institutions, laws, procedures, practices and attitudes that encourage and support integrity in the exercise of power in modern Georgian society. Integrity systems function to ensure that power is exercised in a manner that is true to the values, purposes and duties for which that power is entrusted to, or held by, institutions and individual office-holders. This report presents the results of the Open Society Institute / Open Society – Georgia Foundation funded project Georgian National Integrity Systems Assessment (GNISA), conducted in 2005–2006 by Caucasus Institute for Peace, Democracy and Development, Transparency International Georgia, Georgian Young Lawyers Association, in close cooperation with Griffith University Institute for Ethics, Governance and Law (Australia), and Tiri Group (UK), into how different elements of integrity systems interact, which combinations of institutions and reforms make for a strong integrity system, and how Georgia’s integrity systems should evolve to ensure coherence, not chaos in the way public integrity is maintained. Nevertheless all participants of the research may not share some conclusions given in the GNISA report.

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Cell based therapies require cells capable of self renewal and differentiation, and a prerequisite is the ability to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies is therefore an integral part of tissue engineering. Bone marrow is the most easily accessible source of mesenchymal stem cells (MSCs), and harbours two distinct populations of adult stem cells; namely hematopoietic stem cells (HSCs) and bone mesenchymal stem cells (BMSCs). Unlike HSCs, there are yet no rigorous criteria for characterizing BMSCs. Changing understanding about the pluripotency of BMSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to BMSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their in vitro study. Also, when BMSCs are cultured in vitro there is a loss of the in vivo microenvironment which results in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage number, characterized by the onset of senescence related changes. Accordingly, establishing protocols for generating large numbers of BMSCs without affecting their differentiation potential is necessary. The principal aims of this thesis were to identify potential molecular factors for characterizing BMSCs from osteoarthritic patients, and also to attempt to establish culture protocols favourable for generating large number of BMSCs, while at the same time retaining their proliferation and differentiation potential. Previously published studies concerning clonal cells have demonstrated that BMSCs are heterogeneous populations of cells at various stages of growth. Some cells are higher in the hierarchy and represent the progenitors, while other cells occupy a lower position in the hierarchy and are therefore more committed to a particular lineage. This feature of BMSCs was made evident by the work of Mareddy et al., which involved generating clonal populations of BMSCs from bone marrow of osteoarthritic patients, by a single cell clonal culture method. Proliferation potential and differentiation capabilities were used to group cells into fast growing and slow growing clones. The study presented here is a continuation of the work of Mareddy et al. and employed immunological and array based techniques to identify the primary molecular factors involved in regulating phenotypic characteristics exhibited by contrasting clonal populations. The subtractive immunization (SI) was used to generate novel antibodies against favourably expressed proteins in the fast growing clonal cell population. The difference between the clonal populations at the transcriptional level was determined using a Stem Cell RT2 Profiler TM PCR Array which focuses on stem cell pathway gene expression. Monoclonal antibodies (mAb) generated by SI were able to effectively highlight differentially expressed antigenic determinants, as was evident by Western blot analysis and confocal microscopy. Co-immunoprecipitation, followed by mass spectroscopy analysis, identified a favourably expressed protein as the cytoskeletal protein vimentin. The stem cell gene array highlighted genes that were highly upregulated in the fast growing clonal cell population. Based on their functions these genes were grouped into growth factors, cell fate determination and maintenance of embryonic and neural stem cell renewal. Furthermore, on a closer analysis it was established that the cytoskeletal protein vimentin and nine out of ten genes identified by gene array were associated with chondrogenesis or cartilage repair, consistent with the potential role played by BMSCs in defect repair and maintaining tissue homeostasis, by modulating the gene expression pattern to compensate for degenerated cartilage in osteoarthritic tissues. The gene array also presented transcripts for embryonic lineage markers such as FOXA2 and Sox2, both of which were significantly over expressed in fast growing clonal populations. A recent groundbreaking study by Yamanaka et al imparted embryonic stem cell (ESCs) -like characteristic to somatic cells in a process termed nuclear reprogramming, by the ectopic expression of the genes Sox2, cMyc and Oct4. The expression of embryonic lineage markers in adult stem cells may be a mechanism by which the favourable behaviour of fast growing clonal cells is determined and suggests a possible active phenomenon of spontaneous reprogramming in fast growing clonal cells. The expression pattern of these critical molecular markers could be indicative of the competence of BMSCs. For this reason, the expression pattern of Sox2, Oct4 and cMyc, at various passages in heterogeneous BMSCs population and tissue derived cells (osteoblasts and chondrocytes), was investigated by a real-time PCR and immunoflourescence staining. A strong nuclear staining was observed for Sox2, Oct4 and cMyc, which gradually weakened accompanied with cytoplasmic translocation after several passage. The mRNA and protein expression of Sox2, Oct4 and cMyc peaked at the third passage for osteoblasts, chondrocytes and third passage for BMSCs, and declined with each subsequent passage, indicating towards a possible mechanism of spontaneous reprogramming. This study proposes that the progressive decline in proliferation potential and multipotentiality associated with increased passaging of BMSCs in vitro might be a consequence of loss of these propluripotency factors. We therefore hypothesise that the expression of these master genes is not an intrinsic cell function, but rather an outcome of interaction of the cells with their microenvironment; this was evident by the fact that when removed from their in vivo microenvironment, BMSCs undergo a rapid loss of stemness after only a few passages. One of the most interesting aspects of this study was the integration of factors in the culture conditions, which to some extent, mimicked the in vivo microenvironmental niche of the BMSCs. A number of studies have successfully established that the cellular niche is not an inert tissue component but is of prime importance. The total sum of stimuli from the microenvironment underpins the complex interplay of regulatory mechanisms which control multiple functions in stem cells most importantly stem cell renewal. Therefore, well characterised factors which affect BMSCs characteristics, such as fibronectin (FN) coating, and morphogens such as FGF2 and BMP4, were incorporated into the cell culture conditions. The experimental set up was designed to provide insight into the expression pattern of the stem cell related transcription factors Sox2, cMyc and Oct4, in BMSCs with respect to passaging and changes in culture conditions. Induction of these pluripotency markers in somatic cells by retroviral transfection has been shown to confer pluripotency and an ESCs like state. Our study demonstrated that all treatments could transiently induce the expression of Sox2, cMyc and Oct4, and favourably affect the proliferation potential of BMSCs. The combined effect of these treatments was able to induce and retain the endogenous nuclear expression of stem cell transcription factors in BMSCs over an extended number of in vitro passages. Our results therefore suggest that the transient induction and manipulation of endogenous expression of transcription factors critical for stemness can be achieved by modulating the culture conditions; the benefit of which is to circumvent the need for genetic manipulations. In summary, this study has explored the role of BMSCs in the diseased state of osteoarthritis, by employing transcriptional profiling along with SI. In particular this study pioneered the use of primary cells for generating novel antibodies by SI. We established that somatic cells and BMSCs have a basal level of expression of pluripotency markers. Furthermore, our study indicates that intrinsic signalling mechanisms of BMSCs are intimately linked with extrinsic cues from the microenvironment and that these signals appear to be critical for retaining the expression of genes to maintain cell stemness in long term in vitro culture. This project provides a basis for developing an “artificial niche” required for reversion of commitment and maintenance of BMSC in their uncommitted homeostatic state.

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The Australian construction industry is characterized as being a competitive and risky business environment due to lack of cooperation, insufficient trust, ineffective communication and adversarial relationships which are likely lead to poor project performance. Relational contracting (RC) is advocated by literature as an innovative approach to improve the procurement process in the construction industry. Various studies have collectively added to the current knowledge of known RC norms, but there seem to be little effort on investigating the determinants of RC and its efficacy on project outcomes. In such circumstances, there is a lack of evidence and explanation on the manner on how these issues lead to different performance. Simultaneously, the New Engineering Contract (NEC) that embraced the concept of RC is seen as a modern way of contracting and also considered as one of the best approaches to the perennial problem of improving adversarial relationships within the industry. The reality of practice of RC in Australia is investigated through the lens of the NEC. A synthesis of literature views on the concept, processes and tools of RC is first conducted to develop the framework of RC.

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Sing & Grow is an early intervention music therapy project presented to families with additional needs, or those at risk of experiencing disadvantage due to social and/or economic circumstances that may impact on their parenting experiences. The aim of the project is to provide short term music therapy programs to families in communities where access to such services may be limited. The program is strengths-based and focuses on building upon a parent’s capacity to relate to and respond to their child’s emotional and developmental needs.

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Sing & Grow is a short term early intervention music therapy program for at risk families. Sing & Grow uses music to strengthen parent-child relationships by increasing positive parent-child interactions, assisting parents to bond with their children, and extending the repertoire of parents’ skills in relating to their child through interactive . Both the Australian and New Zealand governments are looking for evidence based research to highlight the effectiveness of funded programs in early childhood. As a government funded program, independent evaluation is a requirement of the delivery of the service. This paper explains the process involved in setting up and managing this large scale evaluation from engaging the evaluators and designing the project, to the data gathering stage. It describes the various challenges encountered and concludes that a highly collaborative and communicative partnership bet en researchers and clinicians is essential to ensure data can be gathered with minimal disturbance to clinical music therapy practice.

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There has recently been noted a rapid increase in research attention to projects that involve outside partners. Our knowledge of such inter-organizational projects, however, is limited. This paper reports large scale data from a repeated trend survey amongst 2000 SMEs in 2006 and 2009 that focused on inter-organizational project ventures. Our major findings indicate that the overall prevalence of inter-organizational project ventures remained significant and stable over time, even despite the economic crisis. Moreover, we find that these ventures predominantly solve repetitive rather than unique tasks and are embedded in prior relations between the partnering organizations. These findings provide empirical support for the recent claims that project management should pay more attention to inter-organizational forms of project organization, and suggest that the archetypical view of projects as being unique in every respect should be reconsidered. Both have important implications for project management, especially in the area of project-based learning.

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Managing project-based learning is becoming an increasingly important part of project management. This article presents a comparative case study of 12 cases of knowledge transfer between temporary inter-organizational projects and permanent parent organizations. Our set-theoretic analysis of these data yields two major findings. First, a high level of absorptive capacity of the project owner is a necessary condition for successful project knowledge transfer, which implies that the responsibility for knowledge transfer seems to in the first place lie with the project parent organization, not with the project manager. Second, none of the factors are sufficient by themselves. This implies that successful project knowledge transfer is a complex process always involving configurations of multiple factors. We link these implications with the view of projects as complex temporary organizational forms in which successful project managers need to cope with complexity by simultaneously paying attention to both relational and organizational processes.

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Design-Build (DB) project delivery systems have increasingly been adopted by many private and public sector organizations worldwide due to its many advantages. However, many Indonesian road infrastructure projects are still delivered using the traditional design-bid-build (DBB) project delivery system. This paper reviews the existing literature to explore factors that can influence the successful implementation of DB project delivery system in Indonesian road infrastructure projects. It founds the lack of clarification in existing legislations as well as the lack of experiences, knowledge and skill as the main obstacles in implementing DB systems in Indonesia. To overcome these obstacles, this paper proposes (1) A relook at existing legislation in term of providing more guidance on determining projects appropriate for the DB, procedures for implementing DB, and the structure of builder entity; (2) To develop the skills and knowledge of DB to all stakeholders through communications, knowledge sharing and training. The outcome of this review can serve as a guide to development a framework for the implementation of the design-build project delivery system in Indonesian road infrastructure projects.