Assessment of tumor prevention in Type 1 Neurofibromatosis using a nitroxide compound

Background Type 1 Neurofibromatosis (NF1) is a genetic disorder linked to mutations of the NF1 gene. Clinical symptoms are varied, but hallmark features of the disease include skin pigmentation anomalies (café au lait macules, skinfold freckling) and dermal neurofibromas. Method These dermal manifestations of NF1 have previously been reported in a mouse model where Nf1+/− mice are topically treated with dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). We adopted this mouse model to test the protective effects of a nitroxide antioxidant, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Antioxidants have previously been shown to increase longevity in nf1-deficient fruitflies. Doses of 4 μM and 40 μM CTMIO provided ad libitum in drinking water were given to Nf1-deficient mice. Results Consistent with previous reports, Nf1-deficient mice showed a 4.7-fold increase in papilloma formation (P < 0.036). However, neither dose of CTMIO had any significant affect on papilloma formation. A non-significant decrease in skin pigmentation abnormalities was seen with 4 μM but not 40 μM CTMIO. Subsequent analysis of genomic DNA isolated from papillomas indicated that DMBA/TPA induced tumors did not exhibit a local loss of heterozygosity (LOH) at the Nf1 locus. Conclusion These data reveal that oral antioxidant therapy with CTMIO does not reduce tumor formation in a multistage cancer model, but also that this model does not feature LOH for Nf1.

Handbook of service description

With the growth in number and sophistication of services widely available, there is a new urgency for comprehensive service descriptions that take into account both technical and business aspects. The last years have seen a number of efforts for best-of-breed service description focusing on specific aspects of services. The Handbook of Service Description provides the most advanced state of the art insights into these. The main parts of the book provide the most detailed documentation of the Unified Service Description Language (USDL) to date. USDL has been developed across several research institutes and publicly funded projects across Europe and Australia, currently extending to the Americas as part of a standardization push through W3C. The scope of services extends across IT and business, i.e., the socio-technical sense of services scaled to business networks. In this respect, purely human, purely automated and mixed human/automated services were considered, that have a boundary of cognizance that is available through the tasks of service provisioning, discovery, access and delivery. Taken together, the Handbook of Service Description provides a comprehensive reference suitable for a wide-reaching audience including researchers, practitioners, managers, and students who aspire to learn about or to create a deeper scientific foundation for service description and its methodological aspects.

Enabling USDL by tools

Fundamental tooling is required in order to apply USDL in practical settings. This chapter discusses three fundamental types of tools for USDL. First, USDL editors have been developed for expert and casual users, respectively. Second, several USDL repositories have been built to allow editors accessing and storing USDL descriptions. Third, our generic USDL marketplace allows providers to describe their services once and potentially trade them anywhere. In addition, the iosyncrasies of service trading as opposed to the simpler case of product trading. The chapter also presents several deployment scenarios of such tools to foster individual value chains and support new business models across organizational boundaries. We close the chapter with an application of USDL in the context of service engineering.

SOA approaches

As the service-oriented architecture paradigm has become ever more popular, different standardization efforts have been proposed by various consortia to enable interaction among heterongeneous environments through this paradigm. This chapter will overview the most prevalent of these SOA approaches. It will first show how technical services can be described, how they can interact with each other and be discovered by users. Next, the chapter will present different standards to facilitate service composition and to design service-oriented environments in light of a universal understanding of service orientation. The chapter will conclude with a summary and a discussion on the limitations of the reviewed standards along their ability to describe service properties. This paves the way to the next chapters where the USDL standard will be presented, which aims to lift such limitations.

Design overview of USDL

Enabling web-based service networks and ecosystems requires a way of describing services by a "commercial envelope" as discussed in Chapter 1. A uniform conception of services across all walks of life (including technical services) is required capturing business, operational and technical aspects. Therefore, our proposed Unified Service Description Language (USDL) particularly draws from and generalizes the best-of-breed approaches presented in Part I. The following chapter presents the design rationale of USDL where the different aspects are put in a framework of descriptions requirements. This is followed by the subsequent chapters of this part that provide details on specific aspects such as pricing or legal issues.

A tissue engineering solution for segmental defect regeneration in load-bearing long bones

The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep - a model closely resembling human bone formation and structure - were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

Towards local cultures of sustainability : facilitating community created environment education centres through design

Ecological sustainability has been proposed to address the problem of human impacts increasingly degrading planetary resources and ecosystems, threatening biodiversity, eco-services and human survival. Ecological sustainability is an imperative, with Australia having one of the highest eco-footprints per person worldwide. While significant progress has been made via implementation of ecologically sustainable design in urban communities, relatively little has been undertaken in small, disparate regional communities in Australia. Regional communities are disadvantaged by rural economic decline associated with structural change and inequities of resource transfer. The ecologically sustainable solution is holistic, so all settlements need to be globally wise, richly biodiverse yet locally specific. As a regional solution to this global problem, this research offers the practical means by which a small regional community can contribute. It focuses on the design and implementation of a community centre and the fostering of transformative community learning through an integrated ‘learning community’ awareness of ecologically sustainable best practice. Lessons learned are documented by the participant researcher who as a designer, facilitator, local resident and social narrator has been deeply connected with the Tweed-Caldera region over a period since 1980. The collective action of the local community of Chillingham has been diligently recorded over a decade of design and development. Over this period, several positive elements emerged in terms of improvements to the natural and built environment, greater social cohesion and co-operative learning along with a shift towards a greener local economy. Behavioural changes in the community were noted as residents strived to embrace ecological ideals and reduce fossil fuel dependency. They found attractive local solutions to sourcing of food and using local employment opportunities to up skill their residents via transformative learning as a community in transition. Finally, the catalytic impact of external partnering has also been documented. How well the region as a whole has achieved its ecologically sustainable objectives is measured in terms of the delivered success of private and public partnering with the community, the creation of a community centre cum environment education centre, the restoration of local heritage buildings, the repair of riparian forests and improved water conditions in local river systems, better roads and road safety, local skills and knowledge transfer, support of local food and local/regional growers markets to attract tourists via the integrated trails network. In aggregate, each and every element contributes to a measure of eco-positive development for the built environment, its social organisation and its economy that has guided the local community to find its own pathway to sustainability. Within the Tweed-Caldera bioregion in northern New South Wales, there has been a lack of strategic planning, ecologically sustainable knowledge and facilities in isolated communities that could support the development of a local sustained green economy, provide a hub for socio-cultural activities and ecology based education. The first challenge in this research was to model a whole systems approach to eco-positive development in Chillingham, NSW, a small community where Nature and humanity know no specific boundary. The net result was the creation of a community environment education centre featuring best-affordable ecological practice and regionally distinctive, educational building form from a disused heritage building (cow bale). This development, implemented over a decade, resonated with the later regional wide programs that were linked in the Caldera region by the common purpose of extending the reach of local and state government assistance to regional NSW in economic transition coupled with sustainability. The lessons learned from these linked projects reveal that subsequent programs have been significantly easier to initiate, manage, develop and deliver results. In particular, pursuing collaborative networks with all levels of government and external private partners has been economically effective. Each community’s uniqueness has been celebrated and through drawing out these distinctions, has highlighted local vision, strategic planning, sense of belonging and connection of people with place. This step has significantly reduced the level of friction between communities that comes from natural competition for the finite pool of funds. Following the pilot Tweed-Caldera study, several other NSW regional communities are now undertaking a Community Economic Transition Program based on the processes, trials and positive experiences witnessed in the Tweed-Caldera region where it has been demonstrated that regional community transition programs can provide an opportunity to plan and implement effective long term strategies for sustainability, empowering communities to participate in eco-governance. This thesis includes the design and development of a framework for community created environment education centres to provide an equal access place for community to participate to meet their essential needs locally. An environment centre that facilitates community transition based on easily accessible environmental education, skills and infrastructure is necessary to develop local cultures of sustainability. This research draws upon the literatures of ecologically sustainable development, environmental education and community development in the context of regional community transition towards ‘strong sustainability’. The research approach adapted is best described as a four stage collaborative action research cycle where the participant researcher (me) has a significant involvement in the process to foster local cultures of sustainability by empowering its citizens to act locally and in doing so, become more self reliant and socially resilient. This research also draws upon the many fine working exemplars, such as the resilience of the Cuban people, the transition town initiative in Totnes, U.K. and the models of Australian Community Gardens, such as CERES (Melbourne) and Northey Street (Brisbane). The objectives of this study are to research and evaluate exemplars of ecologically sustainable environment education centres, to facilitate the design and development of an environment education centre created by a small regional community as an ecologically sustainable learning environment; to facilitate a framework for community transition based on environmental education, skills and infrastructure necessary to develop local cultures of sustainability. The research was undertaken as action research in the Tweed Caldera in Northern NSW. This involved the author as participant researcher, designer and volunteer in two interconnected initiatives: the Chillingham Community Centre development and the Caldera Economic Transition Program (CETP). Both initiatives involved a series of design-led participatory community workshops that were externally facilitated with the support of government agency partnerships, steering committees and local volunteers. Together the Caldera research programs involved communities participating in developing their own strategic planning process and outcomes. The Chillingham Community Centre was developed as a sustainable community centre/hub using a participatory design process. The Caldera Economic Transition Program (CETP) prioritised Caldera region projects: the Caldera farmer’s market; community gardens and community kitchens; community renewable energy systems and an integrated trails network. The significant findings were: the CETP projects were capable of moving towards an eco-positive design benchmark through transformative learning. Community transition to sustainability programs need to be underpinned by sustainability and environmental education based frameworks and practical on ground experience in local needs based projects through transformative learning. The actioned projects were successfully undertaken through community participation and teamwork. Ecological footprint surveys were undertaken to guide and assess the ongoing community transition process, however the paucity of responses needs to be revisited. The concept of ecologically sustainable development has been adopted internationally, however existing design and planning strategies do not assure future generations continued access to healthy natural life support systems. Sustainable design research has usually been urban focussed, with little attention paid to regional communities. This study seeks to redress this paucity through the design of ecologically sustainable (deep green) learning environments for small regional communities. Through a design-led process of environmental education, this study investigates how regional communities can be facilitated to model the principles of eco-positive development to support transition to local cultures of sustainability. This research shows how community transition processes and projects can incorporate sustainable community development as transformative learning through design. Regional community transition programs can provide an opportunity to plan long term strategies for sustainability, empowering people to participate in eco-governance. A framework is developed for a community created environment education centre to provide an equal access place for the local community to participate in implementing ways to meet their essential needs locally. A community environment education centre that facilitates community transition based on holistic environmental education, skills and infrastructure is necessary to develop local cultures of sustainability.

Shear tests of hollow flange channel beams with stiffened web openings

LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. The LSBs are commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Shear tests of LSBs with web openings have shown that there is up to a 60% reduction in the shear capacity due to the inclusion of web openings. Hence there is a need to improve the shear capacity of LSBs with web openings. A cost effective way to eliminate the shear capacity reduction is to attach suitable stiffeners around the web openings. Hence experimental studies were undertaken to investigate the shear behaviour and strength of LSBs with stiffened web openings. In this research, various stiffening methods using plate and LSB stiffeners attached to LSBs using both welding and screw-fastening were attempted. Our test results showed that the stiffening arrangements recommended by past research for cold-formed steel channel beams are not adequate to restore the shear strengths of LSBs with web openings. Therefore new stiffener arrangements were proposed for LSBs with web openings. This paper presents the details of this experimental study and the results including the details of the optimum stiffener details for LiteSteel beams.