Potential role of bcl-2 as a suppressor of tumour angiogenesis in non- small-cell lung cancer

It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship between bcl-2, p53 and tumour vascularization and epidermal-growth-factor- receptor(EGFR) and c-erbB-2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p53, EGFR and c-erbB-2 expression. bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03). A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005). All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found between c-erbB-2 expression and vascular grade. However, in bcl-2-negative cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade. The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization. The results suggest that the anti-apoptotic gene bcl- 2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed.

Double strap joint tests to determine the bond characteristics between CFRP and steel plates

Advanced composite materials offer remarkable potential in the upgrade of civil engineering structures. The evolution of CFRP (carbon fibre reinforced polymer) technologies and their versatility for applications in civil constructions require comprehensive and reliable codes of practice. Guidelines are available on the rehabilitation and retrofit of concrete structures with advanced composite materials. However, there is a need to develop appropriate design guidelines for CFRP strengthened steel structures. It is important to understand the bond characteristics between CFRP and steel plates. This paper describes a series of double strap shear tests loaded in tension to investigate the bond between CFRP sheets and steel plates. Both normal modulus (240 GPa) and high modulus (640 GPa) CFRPs were used in the test program. Strain gauges were mounted to capture the strain distribution along the CFRP length. Different failure modes were observed for joints with normal modulus CFRP and those with high modulus CFRP. The strain distribution along the CFRP length is similar for the two cases. A shorter effective bond length was obtained for joints with high modulus CFRP whereas larger ultimate load carrying capacity can be achieved for joints with normal modulus CFRP when the bond length is long enough.

Much ado about nothing? Tracing the progress of innovations borne on enterprise social network sites

Enterprise social networks are organizationally bounded online platforms for users to interact with another and maintain interpersonal relationships. The allure of these technologies is often seen in intra-organizational communication, collaboration and innovation. How these technologies actually support organizational innovation efforts remains unclear. A specific challenge is whether digital content on these platforms converts to actual innovation development efforts. In this study we set out to examine innovation-centric content flows on enterprise social networking platforms, and advance a conceptual model that seeks to explain which innovation conveyed in the digital content will traverse from the digital platform into regular processes. We describe important constructs of our model and offer strategies for the operationalization of the constructs. We conclude with an outlook to our ongoing empirical study that will explore and validate the key propositions of our model, and we sketch some potential implications for industry and academia.

Thorough assessment of DNA preservation from fossil bone and sediments excavated from a late Pleistocene–Holocene cave deposit on Kangaroo Island, South Australia

Fossils and sediments preserved in caves are an excellent source of information for investigating impacts of past environmental changes on biodiversity. Until recently studies have relied on morphology-based palaeontological approaches, but recent advances in molecular analytical methods offer excellent potential for extracting a greater array of biological information from these sites. This study presents a thorough assessment of DNA preservation from late Pleistocene–Holocene vertebrate fossils and sediments from Kelly Hill Cave Kangaroo Island, South Australia. Using a combination of extraction techniques and sequencing technologies, ancient DNA was characterised from over 70 bones and 20 sediment samples from 15 stratigraphic layers ranging in age from >20 ka to ∼6.8 ka. A combination of primers targeting marsupial and placental mammals, reptiles and two universal plant primers were used to reveal genetic biodiversity for comparison with the mainland and with the morphological fossil record for Kelly Hill Cave. We demonstrate that Kelly Hill Cave has excellent long-term DNA preservation, back to at least 20 ka. This contrasts with the majority of Australian cave sites thus far explored for ancient DNA preservation, and highlights the great promise Kangaroo Island caves hold for yielding the hitherto-elusive DNA of extinct Australian Pleistocene species.

Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer : potential targets for chemoprevention and systemic therapy

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Effective technologies for noninvasive remote monitoring in heart failure

Background Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of non-invasive remote monitoring for heart failure management is unknown. Objective To examine the effect of specific technology used for non-invasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalisations. Methods A sub-analysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used and separate meta-analyses were performed. Four different types of non-invasive remote monitoring technologies were identified including structured telephone calls, videophone, interactive voice response devices and telemonitoring. Results Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (RR 0.87; 95% CI=0.75-1.01; p=0.06 and 0.62; 95% CI=0.50-0.77; p<0.0001) and heart failure-related hospitalisations (RR 0.77; 95% CI=0.68-0.87; p<0.001) and 0.75; 95% CI=0.63-0.91; p=0.003). More research data is required for videophone and interactive voice response technologies. Conclusions This sub-analysis identified that only two of the four specific technologies used for non-invasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomised controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.

Nondiscretionary residential water use : the impact of habits and water-efficient technologies

Several studies published in the last few decades have demonstrated a low price-elasticity for residential water use. In particular, it has been shown that there is a quantity of water demanded that remains constant regardless of prices and other economic factors. In this research, we characterise residential water demand based on a Stone-Geary utility function. This specification is not only theory-compatible but can also explicitly model a minimum level of consumption not dependent on prices or income. This is described as minimum threshold or nondiscretionary water use. Additionally, the Stone-Geary framework is used to model the subsistence level of water consumption that is dependent on the temporal evolution of consumer habits and stock of physical capital. The main aim of this study is to analyse the impact of water-saving habits and water-efficient technologies on residential water demand, while additionally focusing attention on nondiscretionary uses. This is informed by an empirical application using data from a survey conducted among residents of Brisbane City Council, Australia. The results will be especially useful in the design of water tariffs and other water-saving policies.

A rural health education, training and research network

The purpose of the Rural Health Education, Training and Research Network is to support the education and training of rural health practitioners and research in rural health through the optimum use of appropriate information and communication technologies to link and inform all individuals and organisation involved in the teaching, planning and delivery of health care in rural and remote Queensland. The health care of people in rural areas has the potential to be enhanced, through providing the rural and remote health professionals in Queensland with the same access to educational and training opportunities as their metropolitan colleagues. This consultative, coordinated approach should be cost-effective through both increasing awareness and utilisation of existing and developing networks, and through more efficient and rational use of both the basic and sophisticated technologies which support them. Technological hardware, expertise and infrastructure are already in place in Queensland to support a Rural Health Education, Training and Research Network, but are not being used to their potential, more often due to a lack of awareness of their existence and utility than to their perceived costs. Development of the network has commenced through seeding funds provided by Queensland Health. Future expansion will ensure access by health professionals to existing networks within Queensland. This paper explores the issues and implications of a network for rural health professionals in Queensland and potentially throughout Australia, with a specific focus on the implications for rural and isolated health professional.

Talk in activity during young children’s use of digital technologies at home

Internet-connected tablets and smart phones are being used increasingly by young children. Little is known, however, about their social interactions with family members when engaged with these technologies. This article examines video-recorded interactions between a father and his two young children, one aged 18 months using an iPhone and one aged three years accessing an iPad. Drawing on Ethnomethodology and Conversation Analysis, analysis establishes ways the family members engage and disengage in talk so as to manage their individual activity with mobile devices and accomplish interaction with each other. Findings are relevant for understanding children’s everyday practices with mobile technologies.

Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

Perdido ties together Shell digital oilfield technologies

Located in the Gulf of Mexico in nearly 8,000 ft of water, the Perdido project is the deepest spar application to date in the world and Shell’s first fully integrated application of its inhouse digital oilfield technology— called “Smart Field”—in the Western hemisphere. Developed by Shell on behalf of partners BP and Chevron, the spar and the subsea equipment connected to it will eventually capture about an order of magnitude more data than is collected from any other Shelldesigned and -managed development operating in the Gulf of Mexico. This article describes Shell’s digital oilfield design philosophy, briefly explains the five design elements that underpin “smartness” in Shell’s North and South American operations and sheds light on the process by which a highly customized digital oilfield development and management plan was put together for Perdido. Although Perdido is the first instance in North and South America in which these design elements and processes were applied in an integrated way, all of Shell’s future new developments in the Western hemisphere are expected to follow the same overarching design principles. Accordingly, this article uses Perdido as a real-world example to outline the high-level details of Shell’s digital oilfield design philosophy and processes.

The potential of combining phenomenography, variation theory and threshold concepts to inform curriculum design in higher education

This chapter describes an innovative method of curriculum design that is based on combining phenomenographic research, and the associated variation theory of learning, with the notion of disciplinary threshold concepts to focus specialised design attention on the most significant and difficult parts of the curriculum. The method involves three primary stages: (i) identification of disciplinary concepts worthy of intensive curriculum design attention, using the criteria for threshold concepts; (ii) action research into variation in students’ understandings/misunderstandings of those concepts, using phenomenography as the research approach; (iii) design of learning activities to address the poorer understandings identified in the second stage, using variation theory as a guiding framework. The curriculum design method is inherently theory and evidence based. It was developed and trialed during a two-year project funded by the Australian Learning and Teaching Council, using physics and law disciplines as case studies. Disciplinary teachers’ perceptions of the impact of the method on their teaching and understanding of student learning were profound. Attempts to measure the impact on student learning were less conclusive; teachers often unintentionally deviated from the design when putting it into practice for the first time. Suggestions for improved implementation of the method are discussed.

Children and information communication technologies in the media : a study using moral panic theory

This thesis is an investigation of the media's representation of children and ICT. The study draws on moral panic theory and Queensland newspaper media, to identify the impact of newspaper reporting on the public's perceptions of young people and ICT.

RNA silencing platforms in plants

Since the discovery of RNAi, its mechanism in plants and animals has been intensively studied, widely exploited as a research tool, and used for a number of potential commercial applications. In this article, we discuss the platforms for delivering RNAi in plants. We provide a brief background to these platforms and concentrate on discussing the more recent advances, comparing the RNAi technologies used in plants with those used in animals, and trying to predict the ways in which RNAi technologies may further develop. © 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The local library across the digital and physical city : opportunities for economic development

This paper considers the role of the public library as a community hub, engagement space, and entrepreneurial incubator in the context of the city, city governance, and local government planning. It considers this role from the perspective of library experts and their future visions for libraries in a networked knowledge economy. Public libraries (often operated by or on behalf of local governments) potentially play a pivotal role for local governments in positioning communities within the global digital network. Fourteen qualitative interviews with library experts informed the study which investigates how the relationship between digital technology and the physical library space can potentially support the community to develop innovative, collaborative environments for transitioning to a digital future. The study found that libraries can capitalise on their position as community hubs for two purposes: first, to build vibrant community networks and forge economic links across urban localities; and second, to cross the digital divide and act as places of innovation and lifelong learning. Libraries provide a specific combination of community and technology spaces and have significant tangible connection points in the digital age. The paper further discusses the potential benefits for libraries in using ICT networks and infrastructure, such as the National Broadband Network in Australia. These networks could facilitate greater use of library assets and community knowledge, which, in turn, could assist knowledge economies and regional prosperity.