Pseudo plastic zone analysis of steel frame structures comprising non-compact sections

Application of `advanced analysis' methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A concentrated plasticity method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in this paper. The pseudo plastic zone method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established by comparison with a comprehensive range of analytical benchmark frame solutions. The pseudo plastic zone method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

Safety at railway level crossings : driver acceptance of potential ITS interventions

There is a continuing need to improve safety at Railway Level Crossings (RLX) particularly those that do not have gates and lights regulating traffic flow. A number of Intelligent Transport System (ITS) interventions have been proposed to improve drivers’ awareness and reduce errors in detecting and responding appropriately at level crossings. However, as with other technologies, successful implementation and ultimately effectiveness rests with the acceptance of the technology by the end user. In the current research, four focus groups were held (n=38) with drivers in metropolitan and regional locations in Queensland to examine their perceptions of potential in-vehicle and road-based ITS interventions to improve safety at RLX. The findings imply that further development of the ITS interventions, in particular the design and related promotion of the final product, must consider ease of use, usefulness and relative cost.

The potential of Circles of Support and Accountability (COSA) to reduce child sexual abuse in Australia

This report addresses a number of issues relating to Circles of Support and Accountability, and their compatibility with the Australian criminal justice context, including: - What are Circles of Support and Accountability? - When and how did Circles of Support and Accountability emerge? - What forms do Circles of Support and Accountability take? - What is the purpose of Circles of Support and Accountability? - Where do Circles of Support and Accountability currently operate? - Why is it important for Australia to understand Circles of Support and Accountability? - What is the scope of the problem of child sexual abuse in Australia? - What is the research evidence about the effectiveness of Circles of Support and Accountability? - Some key issues for consideration. - Some limitations and potential “dangers” of Circles of Support and Accountability. - Recommendations for Australia. The report concludes that given the research evidence about Circles of Support and Accountability, Australia should build on its existing interest to more fully implement Circles of Support and Accountability, while taking the limitations of this criminal justice measure into consideration.

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.

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.

The innovation potential of living-labs to strengthen small and medium enterprises in regional Australia

The small and medium enterprise (SME) sector has been the major source of well-being and employment opportunities in regional Australia. Consequently, fostering the innovative capacity of SMEs in regions that are struggling to grow their economies and distribute the growth fairly while not degrading the environment has never been more important. While SMEs generally face more uncertainties in relation to resources (e.g. financial, human and social capital) when compared to larger businesses, collaborative, cuttingedge mechanisms to enhance innovation capabilities of regional SMEs are lacking. This paper responds to this gap and proposes a Living Laboratory – an open, multi-disciplinary and multi-stakeholder action research platform where innovations can be co-created, tested and evaluated in the every-day environment of SMEs – as a way to strengthen the SME sector in regional Australia.

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.

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.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Delineating breast cancer cell interactions with engineered bone microenvironments

The mechanisms leading to colonization of metastatic breast cancer cells (BCa) in the skeleton are still not fully understood. Here, we demonstrate that mineralized extracellular matrices secreted by primary human osteoblasts (hOBM) modulate cellular processes associated with BCa colonization of bone. A panel of four BCa cell lines of different bone-metastatic potential (T47D, SUM1315, MDA-MB-231, and the bone-seeking subline MDA-MB-231BO) was cultured on hOBM. After 3 days, the metastatic BCa cells had undergone morphological changes on hOBM and were aligned along the hOBM's collagen type I fibrils that were decorated with bone-specific proteins. In contrast, nonmetastatic BCa cells showed a random orientation on hOBM. Atomic force microscopy-based single-cell force spectroscopy revealed that the metastatic cell lines adhered more strongly to hOBM compared with nonmetastatic cells. Function-blocking experiments indicated that β1-integrins mediated cell adhesion to hOBM. In addition, metastatic BCa cells migrated directionally and invaded hOBM, which was accompanied by enhanced MMP-2 and -9 secretion. Furthermore, we observed gene expression changes associated with osteomimickry in BCa cultured on hOBM. As such, osteopontin mRNA levels were significantly increased in SUM1315 and MDA-MB-231BO cells in a β1-integrin-dependent manner after growing for 3 days on hOBM compared with tissue culture plastic. In conclusion, our results show that extracellular matrices derived from human osteoblasts represent a powerful experimental platform to dissect mechanisms underlying critical steps in the development of bone metastases.

‘Teachers flipping out’ beyond the online lecture : maximising the educational potential of video

While video is recognised as an important medium for teaching and learning in the digital age, many video resources are not as effective as they might be, because they do not adequately exploit the strengths of the medium. Presented here are some case studies of video learning resources produced for various courses in a university environment. This ongoing project attempts to identify pedagogic strategies for the use of video; learning situations in which video has the most efficacy; and what production techniques can be employed to make effective video learning resources.

Sex hormone regulation of innate immunity in the female reproductive tract : the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens

The immune system in the female reproductive tract (FRT) does not mount an attack against HIV or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the female reproductive tract. Working together, these antimicrobials along with mucosal antibodies attack many different viral, bacterial and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus have evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells and other immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate immune response is under hormonal control, varies with the stage of the menstrual cycle, and as such is suppressed at mid-cycle to optimize conditions for successful fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets.

Development of hospital disaster resilience : conceptual framework and potential measurement

Objective Despite ‘hospital resilience’ gaining prominence in recent years, it remains poorly defined. This article aims to define hospital resilience, build a preliminary conceptual framework and highlight possible approaches to measurement. Methods Searches were conducted of the commonly used health databases to identify relevant literature and reports. Search terms included ‘resilience and framework or model’ or ‘evaluation or assess or measure and hospital and disaster or emergency or mass casualty and resilience or capacity or preparedness or response or safety’. Articles were retrieved that focussed on disaster resilience frameworks and the evaluation of various hospital capacities. Result A total of 1480 potentially eligible publications were retrieved initially but the final analysis was conducted on 47 articles, which appeared to contribute to the study objectives. Four disaster resilience frameworks and 11 evaluation instruments of hospital disaster capacity were included. Discussion and conclusion Hospital resilience is a comprehensive concept derived from existing disaster resilience frameworks. It has four key domains: hospital safety; disaster preparedness and resources; continuity of essential medical services; recovery and adaptation. These domains were categorised according to four criteria, namely, robustness, redundancy, resourcefulness and rapidity. A conceptual understanding of hospital resilience is essential for an intellectual basis for an integrated approach to system development. This article (1) defines hospital resilience; (2) constructs conceptual framework (including key domains); (3) proposes comprehensive measures for possible inclusion in an evaluation instrument, and; (4) develops a matrix of critical issues to enhance hospital resilience to cope with future disasters.

Second-order inelastic analysis of composite framed structures based on the refined plastic hinge method

Composite steel-concrete structures experience non-linear effects which arise from both instability-related geometric non-linearity and from material non-linearity in all of their component members. Because of this, conventional design procedures cannot capture the true behaviour of a composite frame throughout its full loading range, and so a procedure to account for those non-linearities is much needed. This paper therefore presents a numerical procedure capable of addressing geometric and material non-linearities at the strength limit state based on the refined plastic hinge method. Different material non-linearity for different composite structural components such as T-beams, concrete-filled tubular (CFT) and steel-encased reinforced concrete (SRC) sections can be treated using a routine numerical procedure for their section properties in this plastic hinge approach. Simple and conservative initial and full yield surfaces for general composite sections are proposed in this paper. The refined plastic hinge approach models springs at the ends of the element which are activated when the surface defining the interaction of bending and axial force at first yield is reached; a transition from the first yield interaction surface to the fully plastic interaction surface is postulated based on a proposed refined spring stiffness, which formulates the load-displacement relation for material non-linearity under the interaction of bending and axial actions. This produces a benign method for a beam-column composite element under general loading cases. Another main feature of this paper is that, for members containing a point of contraflexure, its location is determined with a simple application of the method herein and a node is then located at this position to reproduce the real flexural behaviour and associated material non-linearity of the member. Recourse is made to an updated Lagrangian formulation to consider geometric non-linear behaviour and to develop a non-linear solution strategy. The formulation with the refined plastic hinge approach is efficacious and robust, and so a full frame analysis incorporating geometric and material non-linearity is tractable. By way of contrast, the plastic zone approach possesses the drawback of strain-based procedures which rely on determining plastic zones within a cross-section and which require lengthwise integration. Following development of the theory, its application is illustrated with a number of varied examples.