912 resultados para Critical current
Resumo:
Clusterin is a stress-activated, cytoprotective chaperone that confers broad-spectrum treatment resistance in cancer. However, the molecular mechanisms mediating CLU transcription following anticancer treatment stress remain incompletely defined. We report that Y-box binding protein-1 (YB-1) directly binds to CLU promoter regions to transcriptionally regulate clusterin expression. In response to endoplasmic reticulum stress inducers, including paclitaxel, YB-1 is translocated to the nucleus to transactivate clusterin. Furthermore, higher levels of activated YB-1 and clusterin are seen in taxane-resistant, compared with parental, prostate cancer cells. Knockdown of either YB-1 or clusterin sensitized prostate cancer cells to paclitaxel, whereas their overexpression increased resistance to taxane. Clusterin overexpression rescued cells from increased paclitaxel-induced apoptosis following YB-1 knockdown; in contrast, however, YB-1 overexpression did not rescue cells from increased paclitaxel-induced apoptosis following clusterin knockdown. Collectively, these data indicate that YB-1 transactivation of clusterin in response to stress is a critical mediator of paclitaxel resistance in prostate cancer. Mol Cancer Res; 9(12); 1755–66.
Resumo:
In November 1999, the Queensland Health (QH) Transition to Practice Nurse Education Program - Intensive Care (TPNEP-IC) was initiated in QH Intensive Care Units (ICUs) across Queensland. This 12-month, state-wide, workplace based education program has set minimum standards for intensive care nursing education and therefore minimum standards for intensive care nursing practice in QH. In the 12 years of operation, 824 nurses have completed TPNEP-IC, 761 achieving academic credit status and 453 utilising this academic credit status to undertake postgraduate study in critical/intensive care nursing at three Queensland universities. These outcomes were achieved through the appointment of nurse educators within ICUs who, through a united and strong commitment to this state-wide approach formed collaborative professional networks, which resulted in the development, implementation and maintenance of the program. Furthermore, these networks enabled a framework of support for discussion and dissemination of evidence based practice, to endorse quality processes for TPNEP-IC and to nurture leadership potential among educators. Challenges to overcome included obtaining adequate resources to support all aspects of the program, gaining local management and administrative support, and embedding TPNEP-IC within ICU culture. The 12 years of operation of the program have demonstrated its long term sustainability. The program is being launched through a new blended learning approach utilising e-learning strategies. To capitalise on the current success, a strong commitment by all stakeholders will be required to ensure the ongoing sustainability of the program.
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This study examines the participation of a group of high school students in designing a Heritage Journey as part of an urban redevelopment project in their community. School-community engagement offers young people an opportunity to engage in community life and influence decisions that affect them. Forging links between community and school is becoming more important for teachers as they attempt to create new authentic learning opportunities for young people within a changing world. Increasingly, researchers and urban planners are including children and young people as active decision makers and participants in community engagement projects. However, models of participation tend to be adult-focussed, conceive participation in terms of low to high graduated levels and lack a clearly articulated theoretical basis. The research problem in this study focuses on investigating whether the inclusion of young people in school-community engagement results in value adding to urban planning and is an example of genuine participation. The aim of the study is to provide a theoretically informed, empirically rich understanding of the inclusion of young people in a community engagement strategy for an urban planning project. Theories of space developed by Henri Lefebvre and Edward Soja are drawn upon for understanding how space is understood, used, and redeveloped by the students and other stakeholders. The study also draws on David Harvey’s notion of utopia and space to consider the imaginative possibilities of the students’ designs and ideas. The study uses a participatory research approach and documents the opportunities and challenges of this methodology. The thesis argues that school-community engagement within a "Thirdspace" offers many new opportunities for the emergence of authentic learning situations. Key findings from the study show young people’s participation in an urban planning project can achieve successful results when young people are given opportunities for full participation in decision-making processes; multiple pathways for active engagement are incorporated into the research design; opportunities for mentoring are provided; realistic timelines are communicated to all stakeholders and the needs and social practices of the local community are acknowledged. A new spatial model of community engagement is proposed as an outcome of the study. Unlike previous models of participation, this model demonstrates how exclusion and inclusion can be conceived visually, and may prove effective for conceptualising future community engagement projects that involve young people.
Resumo:
The ubiquity of multimodality in hypermedia environments is undeniable. Bezemer and Kress (2008) have argued that writing has been displaced by image as the central mode for representation. Given the current technical affordances of digital technology and user-friendly interfaces that enable the ease of multimodal design, the conspicuous absence of images in certain domains of cyberspace is deserving of critical analysis. In this presentation, I examine the politics of discourses implicit within hypertextual spaces, drawing textual examples from a higher education website. I critically examine the role of writing and other modes of production used in what Fairclough (1993) refers to as discourses of marketisation in higher education, tracing four pervasive discourses of teaching and learning in the current economy: i) materialization, ii) personalization, iii) technologisation, and iv) commodification (Fairclough, 1999). Each of these arguments is supported by the critical analysis of multimodal texts. The first is a podcast highlighting the new architectonic features of a university learning space. The second is a podcast and transcript of a university Open Day interview with prospective students. The third is a time-lapse video showing the construction of a new science and engineering precinct. These three multimodal texts contrast a final web-based text that exhibits a predominance of writing and the powerful absence or silencing of the image. I connect the weightiness of words and the function of monomodality in the commodification of discourses, and its resistance to the multimodal affordances of web-based technologies, and how this is used to establish particular sets of subject positions and ideologies through which readers are constrained to occupy. Applying principles of critical language study by theorists that include Fairclough, Kress, Lemke, and others whose semiotic analysis of texts focuses on the connections between language, power, and ideology, I demonstrate how the denial of image and the privileging of written words in the multimodality of cyberspace is an ideological effect to accentuate the dominance of the institution.
Resumo:
Governments increasingly rely on forms of privatisation to provide critical public infrastructure yet when those infrastructures fail to meet community expectations government bears the political and economic risks, being held accountable by the public as steward for those infrastructures. Reconfiguration of the contractual relationships may achieve better stewardship. Many of the forms of privatization rely on Agency theory prescriptions, conceptualizing organisations and individuals as motivated solely by self-interest. Stewardship theory (Van Slyke 2007) has developed as a complement to Agency theory offering the possibility of contractual relationships which maximize stewardship outcome. Stewardship theory asserts that pro-stewardship factors cause the agent/steward to act in the interests of the principal. This research has interrogated the literature finding that of the pro-stewardship factors, sense of responsibility is pre-eminent and has a significant link to the agent acting as a steward. The research has explored how important it is that the steward feel sense of responsibility and the actions that sense of responsibility. Case studies of privatized core elements of urban water systems infrastructure were explored. Data has been gathered primarily from archival sources and individual interviews of government and private sector executives key to those systems. This paper reports the findings as to the extent of stewardship, how important it is that the steward acts in the interests of the principal, even to the steward’s detriment and the importance of the steward feeling a sense of responsibility. The actions which increase that sense of responsibility will be assembled to position the research to better proceed with the analysis of the data as to these actions.
Resumo:
This paper describes part of an action research study that was designed to explore the outcomes of an ongoing program in which the participants, a group of domestic and international pre-service teachers and lecturers, worked together in reflective writing workshops. While the primary long-term goal of the program was to develop the intercultural competence and understanding of all of the participants through social activities, the development of social relationships was initiated and supported by involving the participants in weekly writing workshops that focused on shared salient skills of critical reflective thinking and writing. The focus of this paper is upon the outcomes for the international students, a cohort of second year pre-service teachers from Malaysia. Findings indicated that the program was successful in developing the Malaysian pre-service teachers’ self-confidence in perceiving themselves as writers and future teachers of writing, in shifting their focus from writing product to writing process and content, and in increasing the depth of their critical reflective thinking and writing
Resumo:
Strong regulatory pressure on environmental issues and the improved public awareness will continue to influence the market demand for sustainable housing in the coming years. Despite this potential, the voluntary up-take rate of sustainable practices is not as high as expected within the new built housing industry. This is in contrast to the influx of emerging building technologies, new materials and innovative designs as seen in office buildings and exemplar homes built worldwide. One possible reason for this is that key stakeholders such as developers, builders and consumers do not fully understand and appreciate the tangible and mutual benefits of sustainability in their professional and business activities. This situation warrants the study of a multifaceted strategy that integrates the needs of multiple stakeholders. This research investigates multiple factors that affect key stakeholder’s benefits in sustainable housing implementation. Drawing insights from a quantitative study on a questionnaire survey and a qualitative study of in-depth interviews with key stakeholders in the Australian housing industry, 11 critical factors of driving market demand for sustainable housing were unearthed. Their inter-relationships were identified with the aid of Interpretive Structural Modelling. The study concludes with a hierarchical model that amalgamates the strategies for the decision making of key stakeholders.
Resumo:
Purpose – This paper presents findings of a research study aimed at identifying critical sustainability factors for improved implementation of Industrialised Building Systems (IBS). It also highlights the importance of decision support, through the establishment of decision making guidelines, for sustainability deliverables in IBS development. Design/methodology/approach – A broad range of sustainability factors, as perceived by researchers and practitioners, are identified through a comprehensive literature study. A study of the survey and statistical data analysis is conducted to examine the criticality of these sustainability factors in IBS implementation. Findings – 18 sustainability factors are identified as critical to IBS implementation. Their interrelationships and driving forces are explored, which leads to the development of a conceptual model to map these factors for actions or potential solutions. The work provides a sound basis towards a set of decision making guidelines for sustainable IBS implementation. Originality/value – Compared with previous studies that focus on technical or economical aspects, this study extends existing knowledge on construction prefabrication by linking all aspects of sustainability issues with the design process. It also covers industry characteristics of developing countries, as represented by Malaysia’s scenarios.
Bone tissue engineering : reconstruction of critical sized segmental bone defects in the ovine tibia
Resumo:
Well-established therapies for bone defects are restricted to bone grafts which face significant disadvantages (limited availability, donor site morbidity, insufficient integration). Therefore, the objective was to develop an alternative approach investigating the regenerative potential of medical grade polycaprolactone-tricalcium phosphate (mPCL-TCP) and silk-hydroxyapatite (silk-HA) scaffolds. Critical sized ovine tibial defects were created and stabilized. Defects were left untreated, reconstructed with autologous bone grafts (ABG) and mPCL-TCP or silk-HA scaffolds. Animals were observed for 12 weeks. X-ray analysis, torsion testing and quantitative computed tomography (CT) analyses were performed. Radiological analysis confirmed the critical nature of the defects. Full defect bridging occurred in the autograft and partial bridging in the mPCL-TCP group. Only little bone formation was observed with silk-HA scaffolds. Biomechanical testing revealed a higher torsional moment/stiffness (p < 0.05) and CT analysis a significantly higher amount of bone formation for the ABG group when compared to the silk-HA group. No significant difference was determined between the ABG and mPCL-TCP groups. The results of this study suggest that mPCL-TCP scaffolds combined can serve as an alternative to autologous bone grafting in long bone defect regeneration. The combination of mPCL-TCP with osteogenic cells or growth factors represents an attractive means to further enhance bone formation.
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Traffic safety studies demand more than what current micro-simulation models can provide as they presume that all drivers exhibit safe behaviors. All the microscopic traffic simulation models include a car following model. This paper highlights the limitations of the Gipps car following model ability to emulate driver behavior for safety study purposes. A safety adapted car following model based on the Gipps car following model is proposed to simulate unsafe vehicle movements, with safety indicators below critical thresholds. The modifications are based on the observations of driver behavior in real data and also psychophysical notions. NGSIM vehicle trajectory data is used to evaluate the new model and short following headways and Time To Collision are employed to assess critical safety events within traffic flow. Risky events are extracted from available NGSIM data to evaluate the modified model against them. The results from simulation tests illustrate that the proposed model can predict the safety metrics better than the generic Gipps model. The outcome of this paper can potentially facilitate assessing and predicting traffic safety using microscopic simulation.
Resumo:
The 12 to 13 July 2003 andesite lava dome collapse at the Soufrière Hills volcano, Montserrat, provides the first opportunity to document comprehensively both the sub-aerial and submarine sequence of events for an eruption. Numerous pyroclastic flows entered the ocean during the collapse, depositing approximately 90% of the total material into the submarine environment. During peak collapse conditions, as the main flow penetrated the air–ocean interface, phreatic explosions were observed and a surge cloud decoupled from the main flow body to travel 2 to 3 km over the ocean surface before settling. The bulk of the flow was submerged and rapidly mixed with sea water forming a water-saturated mass flow. Efficient sorting and physical differentiation occurred within the flow before initial deposition at 500 m water depth. The coarsest components (∼60% of the total volume) were deposited proximally from a dense granular flow, while the finer components (∼40%) were efficiently elutriated into the overlying part of the flow, which evolved into a far-reaching turbidity current.
Resumo:
A strongly progressive surveying and mapping industry depends on a shared understanding of the industry as it exists, some shared vision or imagination of what the industry might become, and some shared action plan capable of bringing about a realisation of that vision. The emphasis on sharing implies a need for consensus reached through widespread discussion and mutual understanding. Unless this occurs, concerted action is unlikely. A more likely outcome is that industry representatives will negate each other's efforts in their separate bids for progress. The process of bringing about consensual viewpoints is essentially one of establishing an industry identity. Establishing the industry's identity and purpose is a prerequisite for rational development of the industry's education and training, its promotion and marketing, and operational research that can deal .with industry potential and efficiency. This paper interprets evolutionary developments occurring within Queensland's surveying and mapping industry within a framework that sets out logical requirements for a viable industry.
Numerical and experimental studies of cold-formed steel floor systems under standard fire conditions
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Light gauge cold-formed steel frame (LSF) structures are increasingly used in industrial, commercial and residential buildings because of their non-combustibility, dimensional stability, and ease of installation. A floor-ceiling system is an example of its applications. LSF floor-ceiling systems must be designed to serve as fire compartment boundaries and provide adequate fire resistance. Fire rated floor-ceiling assemblies formed with new materials and construction methodologies have been increasingly used in buildings. However, limited research has been undertaken in the past and hence a thorough understanding of their fire resistance behaviour is not available. Recently a new composite panel in which an external insulation layer is used between two plasterboards has been developed at QUT to provide a higher fire rating to LSF floors under standard fire conditions. But its increased fire rating could not be determined using the currently available design methods. Research on LSF floor systems under fire conditions is relatively recent and the behaviour of floor joists and other components in the systems is not fully understood. The present design methods thus require the use of expensive fire protection materials to protect them from excessive heat increase during a fire. This leads to uneconomical and conservative designs. Fire rating of these floor systems is provided simply by adding more plasterboard sheets to the steel joists and such an approach is totally inefficient. Hence a detailed fire research study was undertaken into the structural and thermal performance of LSF floor systems including those protected by the new composite panel system using full scale fire tests and extensive numerical studies. Experimental study included both the conventional and the new steel floor-ceiling systems under structural and fire loads using a gas furnace designed to deliver heat in accordance with the standard time- temperature curve in AS 1530.4 (SA, 2005). Fire tests included the behavioural and deflection characteristics of LSF floor joists until failure as well as related time-temperature measurements across the section and along the length of all the specimens. Full scale fire tests have shown that the structural and thermal performance of externally insulated LSF floor system was superior than traditional LSF floors with or without cavity insulation. Therefore this research recommends the use of the new composite panel system for cold-formed LSF floor-ceiling systems. The numerical analyses of LSF floor joists were undertaken using the finite element program ABAQUS based on the measured time-temperature profiles obtained from fire tests under both steady state and transient state conditions. Mechanical properties at elevated temperatures were considered based on the equations proposed by Dolamune Kankanamge and Mahendran (2011). Finite element models were calibrated using the full scale test results and used to further provide a detailed understanding of the structural fire behaviour of the LSF floor-ceiling systems. The models also confirmed the superior performance of the new composite panel system. The validated model was then used in a detailed parametric study. Fire tests and the numerical studies showed that plasterboards provided sufficient lateral restraint to LSF floor joists until their failure. Hence only the section moment capacity of LSF floor joists subjected to local buckling effects was considered in this research. To predict the section moment capacity at elevated temperatures, the effective section modulus of joists at ambient temperature is generally considered adequate. However, this research has shown that it leads to considerable over- estimation of the local buckling capacity of joist subject to non-uniform temperature distributions under fire conditions. Therefore new simplified fire design rules were proposed for LSF floor joist to determine the section moment capacity at elevated temperature based on AS/NZS 4600 (SA, 2005), NAS (AISI, 2007) and Eurocode 3 Part 1.3 (ECS, 2006). The accuracy of the proposed fire design rules was verified with finite element analysis results. A spread sheet based design tool was also developed based on these design rules to predict the failure load ratio versus time, moment capacity versus time and temperature for various LSF floor configurations. Idealised time-temperature profiles of LSF floor joists were developed based on fire test measurements. They were used in the detailed parametric study to fully understand the structural and fire behaviour of LSF floor panels. Simple design rules were also proposed to predict both critical average joist temperatures and failure times (fire rating) of LSF floor systems with various floor configurations and structural parameters under any given load ratio. Findings from this research have led to a comprehensive understanding of the structural and fire behaviour of LSF floor systems including those protected by the new composite panel, and simple design methods. These design rules were proposed within the guidelines of the Australian/New Zealand, American and European cold- formed steel structures standard codes of practice. These may also lead to further improvements to fire resistance through suitable modifications to the current composite panel system.