311 resultados para Fibroblast viability


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Structural reform through forced mergers has been a dominant feature of Australian local government for decades. Advocates of compulsory consolidation contend that larger municipalities perform better across a wide range of attributes, including financial sustainability. While empirical scholars of local government have invested considerable effort into investigating these claims, no-one has yet examined the performance of Brisbane City Council against other local authorities, despite the fact that it is by far the largest council in Australia. This paper seeks to remedy this neglect by comparing Brisbane with Sydney City Council, an average of six south east Queensland councils and an average of ten metropolitan New South Wales councils against four measures of financial performance over the period 2008 to 2011.

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Atmospheric pressure gas plasma (AGP) generates reactive oxygen species (ROS) that induce apoptosis in cultured cancer cells. The majority of cancer cells develop a ROS-scavenging anti-oxidant system regulated by Nrf2, which confers resistance to ROS-mediated cancer cell death. Generation of ROS is involved in the AGP-induced cancer cell death of several colorectal cancer cells (Caco2, HCT116 and SW480) by activation of ASK1-mediated apoptosis signaling pathway without affecting control cells (human colonic sub-epithelial myofibroblasts; CO18, human fetal lung fibroblast; MRC5 and fetal human colon; FHC). However, the identity of an oxidase participating in AGP-induced cancer cell death is unknown. Here, we report that AGP up-regulates the expression of Nox2 (NADPH oxidase) to produce ROS. RNA interference designed to target Nox2 effectively inhibits the AGP-induced ROS production and cancer cell death. In some cases both colorectal cancer HT29 and control cells showed resistance to AGP treatment. Compared to AGP-sensitive Caco2 cells, HT29 cells show a higher basal level of the anti-oxidant system transcriptional regulator Nrf2 and its target protein sulfiredoxin (Srx) which are involved in cellular redox homeostasis. Silencing of both Nrf2 and Srx sensitized HT29 cells, leads to ROS overproduction and decreased cell viability. This indicates that in HT29 cells, Nrf2/Srx axis is a protective factor against AGP-induced oxidative stress. The inhibition of Nrf2/Srx signaling should be considered as a central target in drug-resistant colorectal cancer treatments.

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The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

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The nanometer scale surface topography of a solid substrate is known to influence the extent of bacterial attachment and their subsequent proliferation to form biofilms. As an extension of our previous work on the development of a novel organic polymer coating for the prevention of growth of medically significant bacteria on three-dimensional solid surfaces, this study examines the effect of surface coating on the adhesion and proliferation tendencies of Staphylococcus aureus and compares to those previously investigated tendencies of Pseudomonas aeruginosa on similar coatings. Radio frequency plasma enhanced chemical vapor deposition was used to coat the surface of the substrate with thin film of terpinen-4-ol, a constituent of tea-tree oil known to inhibit the growth of a broad range of bacteria. The presence of the coating decreased the substrate surface roughness from approximately 2.1 nm to 0.4 nm. Similar to P. aeruginosa, S. aureus presented notably different patterns of attachment in response to the presence of the surface film, where the amount of attachment, extracellular polymeric substance production, and cell proliferation on the coated surface was found to be greatly reduced compared to that obtained on the unmodified surface. This work suggests that the antimicrobial and antifouling coating used in this study could be effectively integrated into medical and other clinically relevant devices to prevent bacterial growth and to minimize bacteria-associated adverse host responses.

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Fibroblast growth factors (FGFs) regulate a plethora of biological functions, in both the embryonic and adult stages of development, binding their cognate receptors and thus activating a variety of downstream signalling pathways. Deregulation of the FGF/FGFR signalling axis, observed in multifarious tumor types including squamous non-small cell lung cancer, occurs through genomic FGFR alterations that drive ligand-independent receptor signalling or alterations that support ligand-dependent activation. Mutations are not restricted to the tyrosine kinase domain and aberrations appear to be tumor type dependent. As well as its complementarity and synergy with VEGF of particular interest is the interplay between FGFR and EGFR and the ability of these pathways to offer a compensatory signalling escape mechanism when either is inhibited. Hence there exists a rationale for a combinatorial approach to inhibition of these dysregulated pathways to reverse drug resistance. To date, several multi-target tyrosine kinase inhibitors as well as FGFR specific tyrosine kinase inhibitors (TKIs), monoclonal antibodies and FGF ligand traps have been developed. Promising preclinical data has resulted in several drugs entering clinical trials. This review explores aberrant FGFR and its potential as a therapeutic target in solid tumors.

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The history of the settlement of the province is tied to patterns of exploration and min development. In Northern British Columbia the Cariboo goldfields provided the impetus for settlement of the region and the beginning for mining to extend into the watern and northern regions in a series of minor gold rushes. The northern half of the province has a geological diverse mineral base that supports a wide variety of mining, and a gradual improvement of exploration and mining methods due to scientific knowledge and technology provided opportunities for lode gold and base metal mines to be developed. The success of mining is based on world ore prices and competitive markets that impact the economic viability of developing a mine. Mining faces increasing pressures in the northern half of the province due to other resource values, such as tourism or protected areas, that claim and compete for a similar land base.

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Habitat fragmentation can have an impact on a wide variety of biological processes including abundance, life history strategies, mating system, inbreeding and genetic diversity levels of individual species. Although fragmented populations have received much attention, ecological and genetic responses of species to fragmentation have still not been fully resolved. The current study investigated the ecological factors that may influence the demographic and genetic structure of the giant white-tailed rat (Uromys caudimaculatus) within fragmented tropical rainforests. It is the first study to examine relationships between food resources, vegetation attributes and Uromys demography in a quantitative manner. Giant white-tailed rat densities were strongly correlated with specific suites of food resources rather than forest structure or other factors linked to fragmentation (i.e. fragment size). Several demographic parameters including the density of resident adults and juvenile recruitment showed similar patterns. Although data were limited, high quality food resources appear to initiate breeding in female Uromys. Where data were sufficient, influx of juveniles was significantly related to the density of high quality food resources that had fallen in the previous three months. Thus, availability of high quality food resources appear to be more important than either vegetation structure or fragment size in influencing giant white-tailed rat demography. These results support the suggestion that a species’ response to fragmentation can be related to their specific habitat requirements and can vary in response to local ecological conditions. In contrast to demographic data, genetic data revealed a significant negative effect of habitat fragmentation on genetic diversity and effective population size in U. caudimaculatus. All three fragments showed lower levels of allelic richness, number of private alleles and expected heterozygosity compared with the unfragmented continuous rainforest site. Populations at all sites were significantly differentiated, suggesting restricted among population gene flow. The combined effects of reduced genetic diversity, lower effective population size and restricted gene flow suggest that long-term viability of small fragmented populations may be at risk, unless effective management is employed in the future. A diverse range of genetic reproductive behaviours and sex-biased dispersal patterns were evident within U. caudimaculatus populations. Genetic paternity analyses revealed that the major mating system in U. caudimaculatus appeared to be polygyny at sites P1, P3 and C1. Evidence of genetic monogamy, however, was also found in the three fragmented sites, and was the dominant mating system in the remaining low density, small fragment (P2). High variability in reproductive skew and reproductive success was also found but was less pronounced when only resident Uromys were considered. Male body condition predicted which males sired offspring, however, neither body condition nor heterozygosity levels were accurate predictors of the number of offspring assigned to individual males or females. Genetic spatial autocorrelation analyses provided evidence for increased philopatry among females at site P1, but increased philopatry among males at site P3. This suggests that male-biased dispersal occurs at site P1 and female-biased dispersal at site P3, implying that in addition to mating systems, Uromys may also be able to adjust their dispersal behaviour to suit local ecological conditions. This study highlights the importance of examining the mechanisms that underlie population-level responses to habitat fragmentation using a combined ecological and genetic approach. The ecological data suggested that habitat quality (i.e. high quality food resources) rather than habitat quantity (i.e. fragment size) was relatively more important in influencing giant white-tailed rat demographics, at least for the populations studied here . Conversely, genetic data showed strong evidence that Uromys populations were affected adversely by habitat fragmentation and that management of isolated populations may be required for long-term viability of populations within isolated rainforest fragments.

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For the last two decades heart disease has been the highest single cause of death for the human population. With an alarming number of patients requiring heart transplant, and donations not able to satisfy the demand, treatment looks to mechanical alternatives. Rotary Ventricular Assist Devices, VADs, are miniature pumps which can be implanted alongside the heart to assist its pumping function. These constant flow devices are smaller, more efficient and promise a longer operational life than more traditional pulsatile VADs. The development of rotary VADs has focused on single pumps assisting the left ventricle only to supply blood for the body. In many patients however, failure of both ventricles demands that an additional pulsatile device be used to support the failing right ventricle. This condition renders them hospital bound while they wait for an unlikely heart donation. Reported attempts to use two rotary pumps to support both ventricles concurrently have warned of inherent haemodynamic instability. Poor balancing of the pumps’ flow rates quickly leads to vascular congestion increasing the risk of oedema and ventricular ‘suckdown’ occluding the inlet to the pump. This thesis introduces a novel Bi-Ventricular Assist Device (BiVAD) configuration where the pump outputs are passively balanced by vascular pressure. The BiVAD consists of two rotary pumps straddling the mechanical passive controller. Fluctuations in vascular pressure induce small deflections within both pumps adjusting their outputs allowing them to maintain arterial pressure. To optimise the passive controller’s interaction with the circulation, the controller’s dynamic response is optimised with a spring, mass, damper arrangement. This two part study presents a comprehensive assessment of the prototype’s ‘viability’ as a support device. Its ‘viability’ was considered based on its sensitivity to pathogenic haemodynamics and the ability of the passive response to maintain healthy circulation. The first part of the study is an experimental investigation where a prototype device was designed and built, and then tested in a pulsatile mock circulation loop. The BiVAD was subjected to a range of haemodynamic imbalances as well as a dynamic analysis to assess the functionality of the mechanical damper. The second part introduces the development of a numerical program to simulate human circulation supported by the passively controlled BiVAD. Both investigations showed that the prototype was able to mimic the native baroreceptor response. Simulating hypertension, poor flow balancing and subsequent ventricular failure during BiVAD support allowed the passive controller’s response to be assessed. Triggered by the resulting pressure imbalance, the controller responded by passively adjusting the VAD outputs in order to maintain healthy arterial pressures. This baroreceptor-like response demonstrated the inherent stability of the auto regulating BiVAD prototype. Simulating pulmonary hypertension in the more observable numerical model, however, revealed a serious issue with the passive response. The subsequent decrease in venous return into the left heart went unnoticed by the passive controller. Meanwhile the coupled nature of the passive response not only decreased RVAD output to reduce pulmonary arterial pressure, but it also increased LVAD output. Consequently, the LVAD increased fluid evacuation from the left ventricle, LV, and so actually accelerated the onset of LV collapse. It was concluded that despite the inherently stable baroreceptor-like response of the passive controller, its lack of sensitivity to venous return made it unviable in its present configuration. The study revealed a number of other important findings. Perhaps the most significant was that the reduced pulse experienced during constant flow support unbalanced the ratio of effective resistances of both vascular circuits. Even during steady rotary support therefore, the resulting ventricle volume imbalance increased the likelihood of suckdown. Additionally, mechanical damping of the passive controller’s response successfully filtered out pressure fluctuations from residual ventricular function. Finally, the importance of recognising inertial contributions to blood flow in the atria and ventricles in a numerical simulation were highlighted. This thesis documents the first attempt to create a fully auto regulated rotary cardiac assist device. Initial results encourage development of an inlet configuration sensitive to low flow such as collapsible inlet cannulae. Combining this with the existing baroreceptor-like response of the passive controller will render a highly stable passively controlled BiVAD configuration. The prototype controller’s passive interaction with the vasculature is a significant step towards a highly stable new generation of artificial heart.

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The road and transport industry in Australia and overseas has come a long way to understanding the impact of road traffic noise on the urban environment. Most road authorities now have guidelines to help assess and manage the impact of road traffic noise on noise-sensitive areas and development. While several economic studies across Australia and overseas have tried to value the impact of noise on property prices, decision-makers investing in road traffic noise management strategies have relatively limited historic data and case studies to go on. The perceived success of a noise management strategy currently relies largely on community expectations at a given time, and is not necessarily based on the analysis of the costs and benefits, or the long-term viability and value to the community of the proposed treatment options. With changing trends in urban design, it is essential that the 'whole-of-life' costs and benefits of noise ameliorative treatment options and strategies be identified and made available for decisionmakers in future investment considerations. For this reason, CRC for Construction Innovation Australia funded a research project, Noise Management in Urban Environments to help decision-makers with future road traffic noise management investment decisions. RMIT University and the Queensland Department of Main Roads (QDMR) have conducted the research work, in collaboration with the Queensland Department of Public Works, ARUP Pty Ltd, and the Queensland University of Technology. The research has formed the basis for the development of a decision-support software tool, and helped collate technical and costing data for known noise amelioration treatment options. We intend that the decision support software tool (DST) should help an investment decision-maker to be better informed of suitable noise ameliorative treatment options on a project-by-project basis and identify likely costs and benefits associated with each of those options. This handbook has been prepared as a procedural guide for conducting a comparative assessment of noise ameliorative options. The handbook outlines the methodology and assumptions adopted in the decision-support framework for the investment decision-maker and user of the DST. The DST has been developed to provide an integrated user-friendly interface between road traffic noise modelling software, the relevant assessment criteria and the options analysis process. A user guide for the DST is incorporated in this handbook.

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A simple mimetic of a heparan sulfate disaccharide sequence that binds to the growth factors FGF-1 and FGF-2 was synthesized by coupling a 2-azido-2-deoxy-D-glucosyl trichloroacetimidate donor with a 1,6-anhydro-2-azido-2-deoxy--D-glucose acceptor. Both the donor and acceptor were obtained from a common intermediate readily obtained from D-glucal. Molecular docking calculations showed that the predicted locations of the disaccharide sulfo groups in the binding site of FGF-1 and FGF-2 are similar to the positions observed for co-crystallized heparin-derived oligosaccharides obtained from published crystal structures.

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Application of cell-–biomaterial systems in regenerative medicine can be facilitated by their successful low temperature preservation. Vitrification, which avoids ice crystal formation by amorphous solidification, is an emerging approach to cryopreservation. Developing vitrification strategy, effective cryopreservation of alginate–fibrin beads with porcine mesenchymal stromal cells has been achieved in this study. The cell–biomaterial constructs were pre-cultured for 20 days before cryopreservation, allowing for cell proliferation and construct stabilization. Ethylene glycol (EG) was employed as the basic cryoprotectant for two equilibration solutions. Successful cryopreservation of the constructs was achieved using vitrification solution composed of penetrating (EG MW 62 Da) and non-penetrating (sucrose MW 342 Da) cryoprotectants. Stepwise procedure of introduction to and removal of cryoprotectants was brief; direct plunging into liquid nitrogen was applied. Cell viability, evaluated by combining live/death staining and confocal laser microscopy, was similar for both control and vitrified cells in the beads. No detectable damage of microstructure of cryopreserved beads was found as shown by scanning electron microscopy. Both osteogenically induced control and vitrified cells in the constructs were equally capable of mineral production and deposition. There was no statistically significant difference in metabolic activity and proliferation between both groups during the entire culture period. Our study leads to the conclusion that the developed cryopreservation protocol allowed to maintain the integrity of the beads while preserving the ability of the pig bone marrow derived mesenchymal stromal cells to proliferate and subsequently differentiate; demonstrating that vitrification is a promising approach for cryopreser-vation of “ready-to-use” cell–biomaterial constructs.

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Since the 1980s, industries and researchers have sought to better understand the quality of services due to the rise in their importance (Brogowicz, Delene and Lyth 1990). More recent developments with online services, coupled with growing recognition of service quality (SQ) as a key contributor to national economies and as an increasingly important competitive differentiator, amplify the need to revisit our understanding of SQ and its measurement. Although ‘SQ’ can be broadly defined as “a global overarching judgment or attitude relating to the overall excellence or superiority of a service” (Parasuraman, Berry and Zeithaml 1988), the term has many interpretations. There has been considerable progress on how to measure SQ perceptions, but little consensus has been achieved on what should be measured. There is agreement that SQ is multi-dimensional, but little agreement as to the nature or content of these dimensions (Brady and Cronin 2001). For example, within the banking sector, there exist multiple SQ models, each consisting of varying dimensions. The existence of multiple conceptions and the lack of a unifying theory bring the credibility of existing conceptions into question, and beg the question of whether it is possible at some higher level to define SQ broadly such that it spans all service types and industries. This research aims to explore the viability of a universal conception of SQ, primarily through a careful re-visitation of the services and SQ literature. The study analyses the strengths and weaknesses of the highly regarded and widely used global SQ model (SERVQUAL) which reflects a single-level approach to SQ measurement. The SERVQUAL model states that customers evaluate SQ (of each service encounter) based on five dimensions namely reliability, assurance, tangibles, empathy and responsibility. SERVQUAL, however, failed to address what needs to be reliable, assured, tangible, empathetic and responsible. This research also addresses a more recent global SQ model from Brady and Cronin (2001); the B&C (2001) model, that has potential to be the successor of SERVQUAL in that it encompasses other global SQ models and addresses the ‘what’ questions that SERVQUAL didn’t. The B&C (2001) model conceives SQ as being multidimensional and multi-level; this hierarchical approach to SQ measurement better reflecting human perceptions. In-line with the initial intention of SERVQUAL, which was developed to be generalizable across industries and service types, this research aims to develop a conceptual understanding of SQ, via literature and reflection, that encompasses the content/nature of factors related to SQ; and addresses the benefits and weaknesses of various SQ measurement approaches (i.e. disconfirmation versus perceptions-only). Such understanding of SQ seeks to transcend industries and service types with the intention of extending our knowledge of SQ and assisting practitioners in understanding and evaluating SQ. The candidate’s research has been conducted within, and seeks to contribute to, the ‘IS-Impact’ research track of the IT Professional Services (ITPS) Research Program at QUT. The vision of the track is “to develop the most widely employed model for benchmarking Information Systems in organizations for the joint benefit of research and practice.” The ‘IS-Impact’ research track has developed an Information Systems (IS) success measurement model, the IS-Impact Model (Gable, Sedera and Chan 2008), which seeks to fulfill the track’s vision. Results of this study will help future researchers in the ‘IS-Impact’ research track address questions such as: • Is SQ an antecedent or consequence of the IS-Impact model or both? • Has SQ already been addressed by existing measures of the IS-Impact model? • Is SQ a separate, new dimension of the IS-Impact model? • Is SQ an alternative conception of the IS? Results from the candidate’s research suggest that SQ dimensions can be classified at a higher level which is encompassed by the B&C (2001) model’s 3 primary dimensions (interaction, physical environment and outcome). The candidate also notes that it might be viable to re-word the ‘physical environment quality’ primary dimension to ‘environment quality’ so as to better encompass both physical and virtual scenarios (E.g: web sites). The candidate does not rule out the global feasibility of the B&C (2001) model’s nine sub-dimensions, however, acknowledges that more work has to be done to better define the sub-dimensions. The candidate observes that the ‘expertise’, ‘design’ and ‘valence’ sub-dimensions are supportive representations of the ‘interaction’, physical environment’ and ‘outcome’ primary dimensions respectively. The latter statement suggests that customers evaluate each primary dimension (or each higher level of SQ classification) namely ‘interaction’, physical environment’ and ‘outcome’ based on the ‘expertise’, ‘design’ and ‘valence’ sub-dimensions respectively. The ability to classify SQ dimensions at a higher level coupled with support for the measures that make up this higher level, leads the candidate to propose the B&C (2001) model as a unifying theory that acts as a starting point to measuring SQ and the SQ of IS. The candidate also notes, in parallel with the continuing validation and generalization of the IS-Impact model, that there is value in alternatively conceptualizing the IS as a ‘service’ and ultimately triangulating measures of IS SQ with the IS-Impact model. These further efforts are beyond the scope of the candidate’s study. Results from the candidate’s research also suggest that both the disconfirmation and perceptions-only approaches have their merits and the choice of approach would depend on the objective(s) of the study. Should the objective(s) be an overall evaluation of SQ, the perceptions-only approached is more appropriate as this approach is more straightforward and reduces administrative overheads in the process. However, should the objective(s) be to identify SQ gaps (shortfalls), the (measured) disconfirmation approach is more appropriate as this approach has the ability to identify areas that need improvement.

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Development of an effective preservation strategy to fulfill off-the-shelf availability of tissue-engineered constructs (TECs) is demanded for realizing their clinical potential. In this study, the feasibility of vitrification, ice-free cryopreservation, for precultured ready-to-use TECs was evaluated. To prepare the TECs, bone marrow-derived porcine mesenchymal stromal cells (MSCs) were seeded in polycaprolactone-gelatin nanofibrous scaffolds and cultured for 3 weeks before vitrification treatment. The vitrification strategy developed, which involved exposure of the TECs to low concentrations of cryoprotectants followed by a vitrification solution and sterile packaging in a pouch with its subsequent immersion directly into liquid nitrogen, was accomplished within 11min. Stepwise removal of cryoprotectants, after warming in a 38 degrees C water bath, enabled rapid restoration of the TECs. Vitrification did not impair microstructure of the scaffold or cell viability. No significant differences were found between the vitrified and control TECs in cellular metabolic activity and proliferation on matched days and in the trends during 5 weeks of continuous culture postvitrification. Osteogenic differentiation ability in vitrified and control groups was similar. In conclusion, we have developed a time- and cost-efficient cryopreservation method that maintains integrity of the TECs while preserving MSCs viability and metabolic activity, and their ability to differentiate.

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Despite the advances that have been made in relation to the valuation of Commercial, Industrial and retail property, there has not been the same progress in relation to the valuation of rural property. Although number of rural property valuations also require the valuer to carry out a full analysis of the economic performance of the farming operations, as well as the long term environmental viability of the farm, this information is rarely used to assess the value of the property, nor is it even used for a secondary valuation method. Over the past 20 years the nature of rural valuation practice has required most rural valuers to undertake studies in both agriculture (farm management) and valuation, especially if carrying out valuation work for financial institutions. The additional farm financial and management information obtained by rural valuers exceeds that level of information required to value commercial, retail and industrial by the capitalisation of net rent/profit valuation method and is very similar to the level of information required for the valuation of commercial and retail property by the Discounted Cash Flow valuation method. On this basis the valuers specialising in rural valuation practice have the necessary skills and information to value rural properties by an income valuation method. Although the direct comparison method of valuation has been sufficient in the past to value rural properties the future use of the method as the main valuation method is limited and valuers need to adopt an income valuation method as at least a secondary valuation method to overcome the problems associated with the use of direct comparison as the only rural property valuation method, especially in view of the impact that farm technical, financial and environmental .management can have on rural property values. This paper will review the results of an extensive survey carried out by rural property valuers and agribusiness managers in NSW, in relation to the impact of farm management on rural property values and rural property valuation practice.

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Growing participation is a key challenge for the viability of sustainability initiatives, many of which require enactment at a local community level in order to be effective. This paper undertakes a review of technology assisted carpooling in order to understand the challenge of designing participation and consider how mobile social software and interface design can be brought to bear. It was found that while persuasive technology and social networking approaches have roles to play, critical factors in the design of carpooling are convenience, ease of use and fit with contingent circumstances, all of which require a use-centred approach to designing a technological system and building participation. Moreover, the reach of technology platform-based global approaches may be limited if they do not cater to local needs. An approach that focuses on iteratively designing technology to support and grow mobile social ridesharing networks in particular locales is proposed. The paper contributes an understanding of HCI approaches in the context of other designing participation approaches.