954 resultados para Fibroblast viability


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Living with substance users negatively impacts upon family members in many ways, and distress is common. Despite these deep and wide-ranging impacts, supportive interventions for family members in their own right are rarely available. Thailand has substantial and growing problems with substance use, and there is very little support or family members of drug users, especially in community setting. The Thai Family Support (TFS) program was designed for implementation in primary health care units (PCUs) in Thailand. TFS was based on two approaches with existing empirical support in Western contexts—the 5-step method and CRAFT—with adaptations to a Thai setting that included integration with Buddhist practices. Its aims were to increase well-being of family members, reduce mental distress, improve family relationships between family members, and engage substance users in behaviour change. A small-scale randomised controlled trial on TFS with a Delayed Treatment control was conducted, with assessments at 8 weeks (Post 1) and 20-24 weeks (Post 2). Structured interviews with participants and PCU staff and an examination of five case studies augmented the quantitative results. Mixed Model Analyses were applied to quantitative outcomes, and thematic analysis was used for qualitative data. Thirty-six participants (18 in each of Immediate and Delayed Conditions) were recruited. A significant difference at Baseline between the two conditions was observed on the Thai GHQ-28 and Gender, but it was not possible to statistically control for these effects. There was a significant Time by Condition interaction on the Thai GHQ-28, WHOQOL-BREF-THAI and FAS, reflecting greater improvements in the Immediate condition by Post 1, but with the Delayed condition meeting or exceeding that effect by Post 2. On FES Cohesion and Conflict, there were falls across conditions at Post 2, but only Cohesion also showed a Time by Condition interaction, and that effect was consistent with a delayed impact of treatment. Overall, TFS by PCU staff in the Delayed Condition gave similar results to TFS conducted by the researcher, supporting the viability of its dissemination to standard health services. Qualitative data also confirmed the quantitative results. Most participants reported physiological and psychological improvements even though their substance-using relative did not change their drug use behaviour. After completing TFS, participants reported increased knowledge, group support and sharing feeling, having positive patient-professional relationship, having greater knowledge of substance abuse and social support. In particular, they changed their behaviour towards the substance user, resulting in improvements to family relationships. PCU staff gave similar responses on the efficacy of TFS, and saw it as feasible for routine use, although some implementation challenges were identified. The cultural adaptation and in particular the religious activities, were recognised by participants and PCU staff as an important component of TFS to support psychological health and well-being. Findings from this study showed the impact of substance use on family members and difficulties that they experienced when living with the substance users, resulting distresses and burden that may develop severe mental health disease. Drug use policies should be modified to support family members and response to their needs effectively for early prevention. This study also gave preliminary support for application of the TFS program in rural primary care settings and identified some policies that will be required for it to be disseminated more broadly.

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Tourism New Zealand (TNZ) is the national tourism office responsible for coordinating international marketing of New Zealand as a tourism destination (see www.newzealand.com ). Typical of most destination marketing organisations (DMO), TNZ is funded by government to work with the private sector in an effort to improve the financial viability of the tourism industry. A competitive tourism industry can provide a number of economic and socio-cultural benefits to a community, such as increased job opportunities and lower unemployment, new amenities and attractions, and revival of indigenous culture.

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Average speed enforcement is a relatively new approach gaining popularity throughout Europe and Australia. This paper reviews the evidence regarding the impact of this approach on vehicle speeds, crashes rates and a number of additional road safety and public health outcomes. The economic and practical viability of the approach as a road safety countermeasure is also explored. A literature review, with an international scope, of both published and grey literature was conducted. There is a growing body of evidence to suggest a number of road safety benefits associated with average speed enforcement, including high rates of compliance with speed limits, reductions in average and 85th percentile speeds and reduced speed variability between vehicles. Moreover, the approach has been demonstrated to be particularly effective in reducing excessive speeding behaviour. Reductions in crash rates have also been reported in association with average speed enforcement, particularly in relation to fatal and serious injury crashes. In addition, the approach has been shown to improve traffic flow, reduce vehicle emissions and has also been associated with high levels of public acceptance. Average speed enforcement offers a greater network-wide approach to managing speeds that reduces the impact of time and distance halo effects associated with other automated speed enforcement approaches. Although comparatively expensive it represents a highly reliable approach to speed enforcement that produces considerable returns on investment through reduced social and economic costs associated with crashes.

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Academically gifted students are recognised as possessing considerable achievement potential. Yet many fail to perform at a level commensurate with their ability. Often gifted students in early adolescence are faced with a forced choice between fulfilment of potential and achieving stable positive relationships with peers. This choice can affect their achievement and may have far-reaching personal and social costs. This case study explored the viability of self-presentation theory to explain students' ways of negotiating their sense of self whilst developing public identity and the concomitant affects on achievement and the fulfilment of potential. It examined how gifted students moderate their images in their learning and extra-curricular environments. Further, the study identifies those self-presentation strategies adopted that either facilitate or hinder achievement. This study may assist parents, educators and school counsellors to provide greater support for gifted adolescents.

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Standard differential equation–based models of collective cell behaviour, such as the logistic growth model, invoke a mean–field assumption which is equivalent to assuming that individuals within the population interact with each other in proportion to the average population density. Implementing such assumptions implies that the dynamics of the system are unaffected by spatial structure, such as the formation of patches or clusters within the population. Recent theoretical developments have introduced a class of models, known as moment dynamics models, which aim to account for the dynamics of individuals, pairs of individuals, triplets of individuals and so on. Such models enable us to describe the dynamics of populations with clustering, however, little progress has been made with regard to applying moment dynamics models to experimental data. Here, we report new experimental results describing the formation of a monolayer of cells using two different cell types: 3T3 fibroblast cells and MDA MB 231 breast cancer cells. Our analysis indicates that the 3T3 fibroblast cells are relatively motile and we observe that the 3T3 fibroblast monolayer forms without clustering. Alternatively, the MDA MB 231 cells are less motile and we observe that the MDA MB 231 monolayer formation is associated with significant clustering. We calibrate a moment dynamics model and a standard mean–field model to both data sets. Our results indicate that the mean–field and moment dynamics models provide similar descriptions of the 3T3 fibroblast monolayer formation whereas these two models give very different predictions for the MDA MD 231 monolayer formation. These outcomes indicate that standard mean–field models of collective cell behaviour are not always appropriate and that care ought to be exercised when implementing such a model.

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Unlike most genera in the early-divergent angiosperm family Annonaceae, Pseuduvaria exhibits a diversity of floral sex expression. Most species are structurally andromonoecious (or possibly androdioecious), although the hermaphroditic flowers have been inferred to be functionally pistillate, with sterile staminodes. Pseuduvaria presents an ideal model for investigating the evolution of floral sex in early-divergent angiosperms, although detailed empirical studies are currently lacking. The phenology and pollination ecology of the Australian endemic species Pseuduvaria mulgraveana are studied in detail, including evaluations of floral scent chemistry, pollen viability, and floral visitors. Results showed that the flowers are pollinated by small diurnal nitidulid beetles and are protogynous. Pollen from both hermaphroditic and staminate flowers are shown to be equally viable. The structurally hermaphroditic flowers are nevertheless functionally pistillate as anther dehiscence is delayed until after petal abscission and hence after the departure of pollinators. This mechanism to achieve functional unisexuality of flowers has not previously been reported in angiosperms. It is known that protogyny is widespread amongst early-divergent angiosperms, including the Annonaceae, and is effective in preventing autogamy. Delayed anther dehiscence represents a further elaboration of this, and is effective in preventing geitonogamy since very few sexually mature flowers occur simultaneously in an individual. We highlight the necessity for field-based empirical interpretations of functional floral sex expression prior to evaluations of evolutionary processes.

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Pricing greenhouse gas emissions is a burgeoning and possibly lucrative financial means for climate change mitigation. Emissions pricing is being used to fund emissions-abatement technologies and to modify land management to improve carbon sequestration and retention. Here we discuss the principal land-management options under existing and realistic future emissions-price legislation in Australia, and examine them with respect to their anticipated direct and indirect effects on biodiversity. The main ways in which emissions price-driven changes to land management can affect biodiversity are through policies and practices for (1) environmental plantings for carbon sequestration, (2) native regrowth, (3) fire management, (4) forestry, (5) agricultural practices (including cropping and grazing), and (6) feral animal control. While most land-management options available to reduce net greenhouse gas emissions offer clear advantages to increase the viability of native biodiversity, we describe several caveats regarding potentially negative outcomes, and outline components that need to be considered if biodiversity is also to benefit from the new carbon economy. Carbon plantings will only have real biodiversity value if they comprise appropriate native tree species and provide suitable habitats and resources for valued fauna. Such plantings also risk severely altering local hydrology and reducing water availability. Management of regrowth post-agricultural abandonment requires setting appropriate baselines and allowing for thinning in certain circumstances, and improvements to forestry rotation lengths would likely increase carbon-retention capacity and biodiversity value. Prescribed burning to reduce the frequency of high-intensity wildfires in northern Australia is being used as a tool to increase carbon retention. Fire management in southern Australia is not readily amenable for maximising carbon storage potential, but will become increasingly important for biodiversity conservation as the climate warms. Carbon price-based modifications to agriculture that would benefit biodiversity include reductions in tillage frequency and livestock densities, reductions in fertiliser use, and retention and regeneration of native shrubs; however, anticipated shifts to exotic perennial grass species such as buffel grass and kikuyu could have net negative implications for native biodiversity. Finally, it is unlikely that major reductions in greenhouse gas emissions arising from feral animal control are possible, even though reduced densities of feral herbivores will benefit Australian biodiversity greatly.

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Vision-based SLAM is mostly a solved problem providing clear, sharp images can be obtained. However, in outdoor environments a number of factors such as rough terrain, high speeds and hardware limitations can result in these conditions not being met. High speed transit on rough terrain can lead to image blur and under/over exposure, problems that cannot easily be dealt with using low cost hardware. Furthermore, recently there has been a growth in interest in lifelong autonomy for robots, which brings with it the challenge in outdoor environments of dealing with a moving sun and lack of constant artificial lighting. In this paper, we present a lightweight approach to visual localization and visual odometry that addresses the challenges posed by perceptual change and low cost cameras. The approach combines low resolution imagery with the SLAM algorithm, RatSLAM. We test the system using a cheap consumer camera mounted on a small vehicle in a mixed urban and vegetated environment, at times ranging from dawn to dusk and in conditions ranging from sunny weather to rain. We first show that the system is able to provide reliable mapping and recall over the course of the day and incrementally incorporate new visual scenes from different times into an existing map. We then restrict the system to only learning visual scenes at one time of day, and show that the system is still able to localize and map at other times of day. The results demonstrate the viability of the approach in situations where image quality is poor and environmental or hardware factors preclude the use of visual features.

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Quantitative imaging methods to analyze cell migration assays are not standardized. Here we present a suite of two–dimensional barrier assays describing the collective spreading of an initially–confined population of 3T3 fibroblast cells. To quantify the motility rate we apply two different automatic image detection methods to locate the position of the leading edge of the spreading population after 24, 48 and 72 hours. These results are compared with a manual edge detection method where we systematically vary the detection threshold. Our results indicate that the observed spreading rates are very sensitive to the choice of image analysis tools and we show that a standard measure of cell migration can vary by as much as 25% for the same experimental images depending on the details of the image analysis tools. Our results imply that it is very difficult, if not impossible, to meaningfully compare previously published measures of cell migration since previous results have been obtained using different image analysis techniques and the details of these techniques are not always reported. Using a mathematical model, we provide a physical interpretation of our edge detection results. The physical interpretation is important since edge detection algorithms alone do not specify any physical measure, or physical definition, of the leading edge of the spreading population. Our modeling indicates that variations in the image threshold parameter correspond to a consistent variation in the local cell density. This means that varying the threshold parameter is equivalent to varying the location of the leading edge in the range of approximately 1–5% of the maximum cell density.

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The double-stranded conformation of cellular DNA is a central aspect of DNA stabilisation and protection. The helix preserves the genetic code against chemical and enzymatic degradation, metabolic activation, and formation of secondary structures. However, there are various instances where single-stranded DNA is exposed, such as during replication or transcription, in the synthesis of chromosome ends, and following DNA damage. In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. We discuss the central roles of single-stranded DNA binding proteins from the OB-fold domain family in DNA replication, the restart of stalled replication forks, DNA damage repair, cell cycle-checkpoint activation, and telomere maintenance.

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Genetically distinct checkpoints, activated as a consequence of either DNA replication arrest or ionizing radiation-induced DNA damage, integrate DNA repair responses into the cell cycle programme. The ataxia-telangiectasia mutated (ATM) protein kinase blocks cell cycle progression in response to DNA double strand breaks, whereas the related ATR is important in maintaining the integrity of the DNA replication apparatus. Here, we show that thymidine, which slows the progression of replication forks by depleting cellular pools of dCTP, induces a novel DNA damage response that, uniquely, depends on both ATM and ATR. Thymidine induces ATM-mediated phosphorylation of Chk2 and NBS1 and an ATM-independent phosphorylation of Chk1 and SMC1. AT cells exposed to thymidine showed decreased viability and failed to induce homologous recombination repair (HRR). Taken together, our results implicate ATM in the HRR-mediated rescue of replication forks impaired by thymidine treatment.

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We sought to identify fibroblast growth factor receptor 2 (FGFR2) kinase domain mutations that confer resistance to the pan-FGFR inhibitor, dovitinib, and explore the mechanism of action of the drug-resistant mutations. We cultured BaF3 cells overexpressing FGFR2 in high concentrations of dovitinib and identified fourteen dovitinib-resistant mutations, including the N550K mutation observed in 25% of FGFR2mutant endometrial cancers (EC). Structural and biochemical in vitro kinase analyses, together with BaF3 proliferation assays, showed that the resistance mutations elevate the intrinsic kinase activity of FGFR2. BaF3 lines were used to assess the ability of each mutation to confer cross-resistance to PD173074 and ponatinib. Unlike PD173074, ponatinib effectively inhibited all the dovitinib-resistant FGFR2 mutants except the V565I gatekeeper mutation, suggesting ponatinib but not dovitinib targets the active conformation of FGFR2 kinase. EC cell lines expressing wild-type FGFR2 were relatively resistant to all inhibitors. Whereas EC cell lines expressing mutated FGFR2 showed differential sensitivity. Within the FGFR2mutant cell lines, 3/7 showed marked resistance to PD173074 and relative resistance to dovitinib and ponatinib. This suggests that alternative mechanisms distinct from kinase domain mutations are responsible for intrinsic resistance in these three EC lines. Finally, overexpression of FGFR2N550K in JHUEM-2 cells (FGFR2C383R) conferred resistance (~5 fold) to PD173074, providing independent data that FGFR2N550K can be associated with drug resistance. Biochemical in vitro kinase analyses also shows ponatinib is more effective than dovitinib at inhibiting FGFR2N550K. We propose tumors harboring mutationally activated FGFRs should be treated with FGFR inhibitors that specifically bind the active kinase.

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Background WSUD implementation in the Gold Coast City Council area commenced more than a decade ago. As a result, Council is expected to be in possession of WSUD assets valued at over tens of million dollars. The Gold Coast City Council is responsible for the maintenance and long-term management of these WSUD assets. Any shortcoming in implementation of best WSUD practices can potentially result in substantial liabilities and ineffective expenditure for the Council in addition to reduced efficiencies and outcomes. This highlights the importance of periodic auditing of WSUD implementation. Project scope The overall study entailed the following tasks: * A state-of-the-art literature review of the conceptual hydraulic and water quality treatment principles, current state of knowledge in relation to industry standards, best practice and identification of knowledge gaps in relation to maintenance and management practices and potential barriers to the implementation of WSUD. * Council stakeholder interviews to understand current practical issues in relation to the implementation of WSUD and the process of WSUD application from development application approval to asset management. * Field auditing of selected WSUD systems for condition assessment and identification of possible strengths and weaknesses in implementation. * Review of the Land Development Guidelines in order to identify any gaps and to propose recommendations for improvement. Conclusions Given below is a consolidated summary of the findings of the study undertaken. State-of-the-art literature review Though the conceptual framework for WSUD implementation is well established, the underlying theoretical knowledge underpinning the treatment processes and maintenance regimes and life cycle costing are still not well understood. Essentially, these are the recurring themes in the literature, namely, the inadequate understanding of treatment processes and lack of guidance to ensure specificity of maintenance regimes and life cycle costing of WSUDs. The fundamental barriers to successful WSUD implementation are: * Lack of knowledge transfer – This essentially relates to the lack of appropriate dissemination of research outcomes and the common absence of protocols for knowledge transfer within the same organisation. * Cultural barriers – These relate to social and institutional factors, including institutional inertia and the lack of clear understanding of the benefits. * Fragmented responsibilities – This results from poor administrative integration within local councils in relation to WSUDs. * Technical barriers – These relate to lack of knowledge on operational and maintenance practices which is compounded by model limitations and the lack of long-term quantitative performance evaluation data. * Lack of engineering standards – Despite the availability of numerous guidelines which are non-enforceable and can sometimes be confusing, there is a need for stringent engineering standards. The knowledge gaps in relation to WSUDs are only closing very slowly. Some of the common knowledge gaps identified in recent publications have been recognised almost a decade ago. The key knowledge gaps identified in the published literature are: * lack of knowledge on operational and maintenance practices; * lack of reliable methodology for identifying life cycle issues including costs; * lack of technical knowledge on system performance; * lack of guidance on retrofitting in existing developments. Based on the review of barriers to WSUD implementation and current knowledge gaps, the following were identified as core areas for further investigation: * performance evaluation of WSUD devices to enhance model development and to assess their viability in the context of environmental, economic and social drivers; establishing realistic life cycle costs to strengthen maintenance and asset management practices; * development of guidelines specific to retrofitting in view of the unique challenges posed by existing urban precincts together with guidance to ensure site specificity; establishment of a process for knowledge translation for enhancing currently available best practice guidelines; * identification of drivers and overcoming of barriers in the areas of institutional fragmentation, knowledge gaps and awareness of WSUD practices. GCCC stakeholder interviews Fourteen staff members involved in WSUD systems management in the Gold Coast City Council, representing four Directorates were interviewed using a standard questionnaire. The primary issues identified by the stakeholders were: * standardisation of WSUD terminology; * clear protocols for safeguarding devices during the construction phase; * engagement of all council stakeholders in the WSUD process from the initial phase; * limitations in the Land Development Guidelines; * ensuring public safety through design; * system siting to avoid conflicts with environmental and public use of open space; * provision of adequate access for maintenance; * integration of social and ecosystem issues to ensure long-term viability of systems in relation to both, vandalism and visual recreation; * lack of performance monitoring and inadequacy of the maintenance budget; * lack of technical training for staff involved in WSUD design approvals and maintenance; incentives for developers for acting responsibly in stormwater management. Field auditing of WSUD systems A representative cross section of WSUD systems in the Gold Coast were audited in the field. The following strengths and weaknesses in WSUD implementation were noted: * The implementation of WSUD systems in the field is not consistent. * The concerns raised by the stakeholders during the interviews in relation to WSUD implementation was validated from the observations from the field auditing, particularly in relation to the following: * safeguarding of devices during the construction phase * public safety * accessibility for maintenance * lack of performance monitoring by Council to assess system performance * inadequate maintenance of existing systems to suit site specific requirements. * A treatment train approach is not being consistently adopted. * Most of the systems audited have satisfactorily catered for public safety. Accessibility for maintenance has been satisfactorily catered for in most of the systems that were audited. * Systems are being commissioned prior to construction activities being substantially completed. * The hydraulic design of most systems appears to be satisfactory. * The design intent of the systems is not always clear. Review of Land Development Guidelines The Land Development Guidelines (TDG) was extensively reviewed and the following primary issues were noted in relation to WSUD implementation: * the LDG appears to have been prepared primarily to provide guidance to developers. It is not clear to what extent the guidelines are applicable to Council staff involved in WSUD maintenance and management; * Section 13 is very voluminous and appears to be a compilation of a series of individual documents resulting in difficulties in locating specific information, a lack of integration and duplication of information; * the LDG has been developed with a primary focus on new urban precinct development and the retrofitting of systems in existing developments has not been specifically discussed; * WSUDs are discussed in two different sections in the LDG and it is not clear which section takes precedence as there are inconsistencies between the two sections; there is inconsistent terminology being used; * there is a need for consolidation of information provided in different sections in the LDG; * there are inconsistencies in the design criteria provided; * there is a need for regular updating of the LDG to ensure that the information provided encompasses the state-of-the-art; * there is limited guidance provided for the preparation of maintenance plans and life cycle costing to assist developers in asset handover and to assist Council staff in assessment. * Based on these observations, eleven recommendations have been provided which are discussed below. Additionally, the stakeholder provided the following specific comments during the interviews in relation to the LDG: * lack of flexibility to cover the different stages of the life cycle of the systems; * no differentiation in projects undertaken by developers and Council; * inadequate information with regards to safety issues such as maximum standing water depth, fencing and safety barriers and public access; * lack of detailed design criteria in relation to Crime Prevention through Environmental Design, safety, amenity, environment, surrounding uses and impacts on surroundings; * inadequate information regarding maintenance requirements specific to the assessment and compliance phases; * recommendations for plantings are based primarily on landscape requirements rather than pollutant uptake capability. Recommendations With regards to the Land Development Guidelines, the following specific recommendations are provided: 1. the relevant sections and their extent of applicability to Council should be clearly identified; 2. integration of the different subsections within Section 13 and re-formatting the document for easy reference; 3. the maintenance guidelines provided in Section 13 should be translated to a maintenance manual for guidance of Council staff; 4. should consider extending the Guidelines to specifically encompass retrofitting of WSUD systems to existing urban precincts; 5. Section 3 needs to be revised to be made consistent with Section 13, to ensure priority for WSUD practices in urban precincts and to move away from conventional stormwater drainage design such as kerb and channelling; 6. it would also be good to specify as to which Section takes predominance in relation to stormwater drainage. It is expected that Section 13 would take predominance over the other sections in the LDG; 7. terminology needs to be made consistent to avoid confusion among developers and Council staff. Water Sensitive Urban Design is the term commonly used in Australia for stormwater quality treatment, rather than Stormwater Quality Improvement Devices. This once again underlines the need for ensuring consistency between Section 3 and Section 13; 8. it would also be good if there is a glossary of commonly used terms in relation to WSUD for use by all stakeholders and which should also be reflected in the LDG; 9. consolidation of all WSUD information into one section should be considered together with appropriate indicators in other LDG Sections regarding the availability of WSUD information. Ensuring consistency in the information provided is implied; 10. Section 13 should be updated at regular intervals to ensure the incorporation of the latest in research outcomes and incorporating criteria and guidance based on the state-of-the-art knowledge. The updating could be undertaken, say, in five year cycles. This would help to overcome the current lack of knowledge transfer; 11. the Council should consider commissioning specialised studies to extend the current knowledge base in relation to WSUD maintenance and life cycle costing. Additionally, Recommendation 10 is also applicable in this instance. The following additional recommendations are made based on the state-of-the-art literature review, stakeholder interviews and field auditing of WSUD systems: 1. Performance monitoring of existing systems to assess improvements to water quality, identify modifications and enhancements to improve performance; 2. Appropriate and monitored maintenance during different phases of development of built assets over time is needed to investigate the most appropriate time/phase of development to commission the final WSUD asset. 3. Undertake focussed investigations in the areas of WSUD maintenance and asset management in order to establish more realistic life cycle costs of systems and maintenance schedules; 4. the engagement of all relevant Council stakeholders from the initial stage of concept planning through to asset handover, and ongoing monitoring. This close engagement of internal stakeholders will assist in building a greater understanding of responsibilities and contribute to overcoming constraints imposed by fragmented responsibilities; 5. the undertaking of a public education program to inform the community of the benefits and ecosystem functions of WSUD systems; 6. technical training to impart state-of-the-art knowledge to staff involved in the approval of designs and maintenance and management of WSUD projects; 7. during the construction phase, it is important to ensure that appropriate measures to safeguard WSUD devices are implemented; 8. risks associated with potential public access to open water zones should be minimised with the application of appropriate safety measures; 9. system siting should ensure that potential conflicts are avoided with respect to public and ecosystem needs; 10. integration of social and ecosystem issues to ensure long-term viability of systems; provide incentives to developers who are proactive and responsible in the area of stormwater management.

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Development of hypoxia-mimicking bone tissue engineering scaffolds is of great importance in stimulating angiogenesis for bone regeneration. Dimethyloxallyl glycine (DMOG) is a cell-permeable, competitive inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression. The aim of this study was to develop hypoxia-mimicking scaffolds by delivering DMOG in mesoporous bioactive glass (MBG) scaffolds and to investigate whether the delivery of DMOG could induce a hypoxic microenvironment for human bone marrow stromal cells (hBMSC). MBG scaffolds with varied mesoporous structures (e.g. surface area and mesopore volume) were prepared by controlling the contents of mesopore-template agent. The composition, large-pore microstructure and mesoporous properties of MBG scaffolds were characterized. The effect of mesoporous properties on the loading and release of DMOG in MBG scaffolds was investigated. The effects of DMOG delivery on the cell morphology, cell viability, HIF-1α stabilization, vascular endothelial growth factor (VEGF) secretion and bone-related gene expression (alkaline phosphatase, ALP; osteocalcin, OCN; and osteopontin, OPN) of hBMSC in MBG scaffolds were systematically investigated. The results showed that the loading and release of DMOG in MBG scaffolds can be efficiently controlled by regulating their mesoporous properties via the addition of different contents of mesopore-template agent. DMOG delivery in MBG scaffolds had no cytotoxic effect on the viability of hBMSC. DMOG delivery significantly induced HIF-1α stabilization, VEGF secretion and bone-related gene expression of hBMSC in MBG scaffolds in which DMOG counteracted the effect of HIF-PH and stabilized HIF-1α expression under normoxic condition. Furthermore, it was found that MBG scaffolds with slow DMOG release significantly enhanced the expression of bone-related genes more than those with instant DMOG release. The results suggest that the controllable delivery of DMOG in MBG scaffolds can mimic a hypoxic microenvironment, which not only improves the angiogenic capacity of hBMSC, but also enhances their osteogenic differentiation.

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The success or effectiveness for any aircraft design is a function of many trade-offs. Over the last 100 years of aircraft design these trade-offs have been optimized and dominant aircraft design philosophies have emerged. Pilotless aircraft (or uninhabited airborne systems, UAS) present new challenges in the optimization of their configuration. Recent developments in battery and motor technology have seen an upsurge in the utility and performance of electric powered aircraft. Thus, the opportunity to explore hybrid-electric aircraft powerplant configurations is compelling. This thesis considers the design of such a configuration from an overall propulsive, and energy efficiency perspective. A prototype system was constructed using a representative small UAS internal combustion engine (10cc methanol two-stroke) and a 600W brushless Direct current (BLDC) motor. These components were chosen to be representative of those that would be found on typical small UAS. The system was tested on a dynamometer in a wind-tunnel and the results show an improvement in overall propulsive efficiency of 17% when compared to a non-hybrid powerplant. In this case, the improvement results from the utilization of a larger propeller that the hybrid solution allows, which shows that general efficiency improvements are possible using hybrid configurations for aircraft propulsion. Additionally this approach provides new improvements in operational and mission flexibility (such as the provision of self-starting) which are outlined in the thesis. Specifically, the opportunity to use the windmilling propeller for energy regeneration was explored. It was found (in the prototype configuration) that significant power (60W) is recoverable in a steep dive, and although the efficiency of regeneration is low, the capability can allow several options for improved mission viability. The thesis concludes with the general statement that a hybrid powerplant improves the overall mission effectiveness and propulsive efficiency of small UAS.