Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Queensland Government’s people’s question time : the challenges and opportunities of population growth in Queensland

As AITPM National President, I was invited by Queensland’s Premier, Hon. Anna Bligh MP, as an audience guest to People’s Question Time on Wednesday 24 March 2010, which focused on ‘The Challenges and Opportunities of Population Growth in Queensland’. On the panel were: Premier and Minister for the Arts, Anna Bligh; Minister for Climate Change and Sustainability, Kate Jones; Minister for Infrastructure and Planning, Stirling Hinchliffe; Michael Rayner – Growth Management Summit Advisory Panel, Principal Director, Cox Rayner Architects; and Greg Hallam – Executive Director, Local Government Association of Queensland. The moderator for this session was Law Academic Erin O’Brien, of Queensland University of Technology.

Summary report : the high road or the low road? Alternatives for Australia's future

This document is a summary of the findings of the inaugural study commissioned by the Australian Business Foundation Limited. It was conducted by Professor Jane Marceau, Pro-Vice Chancellor (Research) at the University of Western Sydney Macarthur, Dr Karen Manley, Visiting Research Fellow at the University of Western Sydney Macarthur and Mr Derek Sicklen, Managing Director of Australian Economic Analysis Pty Limited. The full report is available from the Australian Business Foundation. The Australian Business Foundation Limited is a recently formed independent economic and industry policy think-tank. It has been established and sponsored by Australian Business Limited, a pre-eminent and long-standing industry association and business services network. The report is in three parts. The first reviews the key findings of contemporary international economic and innovation-oriented analyses of the characteristics of high growth economies. The second assesses the shape, structure and dynamics of Australian industry as these compare with the characteristics for successful economic development suggested in the literature. Finally, the report indicates the nature of urgently required policy directions.

The effects of pore architecture in silk fibroin scaffolds on the growth and differentiation of BMP7-expressing mesenchymal stem cells

Pore architecture of scaffolds is known to play a critical role in tissue engineering as it provides the vital framework for the seeded cells to organize into a functioning tissue. In this report, we investigated the effects of different concentration on silk fibroin protein 3D scaffold pore microstructure. Four pore size ranges of silk fibroin scaffolds were made by freeze-dry technique, with the pore sizes ranging from 50 to 300 µm. The pore size of the scaffold decreases as the concentration increases. Human mesenchymal stem cells were in vitro cultured in these scaffolds. After BMP7 gene transferred, DNA assay, ALP assay, hematoxylin–eosin staining, alizarin red staining and reverse transcription-polymerase chain reaction were performed to analyze the effect of the pore size on cell growth, differentiation and the secretion of extracellular matrix (ECM). Cell morphology in these 3D scaffolds was investigated by confocal microscopy. This study indicates mesenchymal stem cells prefer the group of scaffolds with pore size between 100 and 300 µm for better proliferation and ECM production

The ratio of VEGF/PEDF expression in bone marrow mesenchymal stem cells regulates neovascularization

Angiogenesis, or neovascularization, is a finely balanced process controlled by pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a major pro-angiogenic factor, whereas pigment epithelial-derived factor (PEDF) is the most potent natural angiogenesis inhibitor. In this study, the regulatory role of bone marrow stromal cells (BMSCs) during angiogenesis was assessed by the endothelial differentiation potential, VEGF/PEDF production and responses to pro-angiogenic and hypoxic conditions. The in vivo regulation of blood vessel formation by BMSCs was also explored in a SCID mouse model. Results showed that PEDF was expressed more prominently in BMSCs compared to VEGF. This contrasted with human umbilical vein endothelial cells (HUVECs) where the expression of VEGF was higher than that of PEDF. The ratio of VEGF/PEDF gene expression in BMSCs increased when VEGF concentration reached 40 ng/ml in the culture medium, but decreased at 80 ng/ml. Under CoCl2- induced hypoxic conditions, the VEGF/PEDF ratio of BMSCs increased significantly in both normal and angiogenic culture media. There was no expression of endothelial cell markers in BMSCs cultured in either pro-angiogenic or hypoxia culture conditions when compared with HUVECs. The in vivo study showed that VEGF/PEDF expression closely correlated with the degree of neovascularization, and that hypoxia significantly induced pro-angiogenic activity in BMSCs. These results indicate that, rather than being progenitors of endothelial cells, BMSCs play an important role in regulating the neovascularization process, and that the ratio of VEGF and PEDF may, in effect, be an indicator of the pro- or antiangiogenic activities of BMSCs.

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.

Managing Trust in Online Social Networks

In recent years, there is a dramatic growth in number and popularity of online social networks. There are many networks available with more than 100 million registered users such as Facebook, MySpace, QZone, Windows Live Spaces etc. People may connect, discover and share by using these online social networks. The exponential growth of online communities in the area of social networks attracts the attention of the researchers about the importance of managing trust in online environment. Users of the online social networks may share their experiences and opinions within the networks about an item which may be a product or service. The user faces the problem of evaluating trust in a service or service provider before making a choice. Recommendations may be received through a chain of friends network, so the problem for the user is to be able to evaluate various types of trust opinions and recommendations. This opinion or recommendation has a great influence to choose to use or enjoy the item by the other user of the community. Collaborative filtering system is the most popular method in recommender system. The task in collaborative filtering is to predict the utility of items to a particular user based on a database of user rates from a sample or population of other users. Because of the different taste of different people, they rate differently according to their subjective taste. If two people rate a set of items similarly, they share similar tastes. In the recommender system, this information is used to recommend items that one participant likes, to other persons in the same cluster. But the collaborative filtering system performs poor when there is insufficient previous common rating available between users; commonly known as cost start problem. To overcome the cold start problem and with the dramatic growth of online social networks, trust based approach to recommendation has emerged. This approach assumes a trust network among users and makes recommendations based on the ratings of the users that are directly or indirectly trusted by the target user.

Strategic management practices in the construction industry : a study of Indonesian enterprises

Since the establishment of the first national strategic development plan in the early 1970s, the construction industry has played an important role in terms of the economic, social and cultural development of Indonesia. The industry’s contribution to Indonesia’s gross domestic product (GDP) increased from 3.9% in 1973 to 7.7% in 2007. Business Monitoring International (2009) forecasts that Indonesia is home to one of the fastest-growing construction industries in Asia despite the average construction growth rate being expected to remain under 10% over the period 2006 – 2010. Similarly, Howlett and Powell (2006) place Indonesia as one of the 20 largest construction markets in 2010. Although the prospects for the Indonesian construction industry are now very promising, many local construction firms still face serious difficulties, such as poor performance and low competitiveness. There are two main reasons behind this problem: the environment that they face is not favourable; the other is the lack of strategic direction to improve competitiveness and performance. Furthermore, although strategic management has now become more widely used by many large construction firms in developed countries, practical examples and empirical studies related to the Indonesian construction industry remain scarce. In addition, research endeavours related to these topics in developing countries appear to be limited. This has potentially become one of the factors hampering efforts to guide Indonesian construction enterprises. This research aims to construct a conceptual model to enable Indonesian construction enterprises to develop a sound long-term corporate strategy that generates competitive advantage and superior performance. The conceptual model seeks to address the main prescription of a dynamic capabilities framework (Teece, Pisano & Shuen, 1997; Teece, 2007) within the context of the Indonesian construction industry. It is hypothesised that in a rapidly changing and varied environment, competitive success arises from the continuous development and reconfiguration of firm’s specific assets achieving competitive advantage is not only dependent on the exploitation of specific assets/capabilities, but on the exploitation of all of the assets and capabilities combinations in the dynamic capabilities framework. Thus, the model is refined through sequential statistical regression analyses of survey results with a sample size of 120 valid responses. The results of this study provide empirical evidence in support of the notion that a competitive advantage is achieved via the implementation of a dynamic capability framework as an important way for a construction enterprise to improve its organisational performance. The characteristics of asset-capability combinations were found to be significant determinants of the competitive advantage of the Indonesian construction enterprises, and that such advantage sequentially contributes to organisational performance. If a dynamic capabilities framework can work in the context of Indonesia, it suggests that the framework has potential applicability in other emerging and developing countries. This study also demonstrates the importance of the multi-stage nature of the model which provides a rich understanding of the dynamic process by which asset-capability should be exploited in combination by the construction firms operating in varying levels of hostility. Such findings are believed to be useful to both academics and practitioners, however, as this research represents a dynamic capabilities framework at the enterprise level, future studies should continue to explore and examine the framework in other levels of strategic management in construction as well as in other countries where different cultures or similar conditions prevails.

Vatkst, profit og strategisk orienteering i gazellevirksomheder (Growth, profitability and strategic orientation among gazelle firms)

Growth and profitability are often essential parts of the overall managerial goals of firms. High growth can be seen as an indicator of success and as a mean for achieving competitive advantage and higher profitability. But high growth can also lead to a number of managerial and organisational challenges, that may affect the profitability negatively. The aim of this article is to analyse the relationship between growth and profitability for Danish gazelle firms, and furthermore to investigate how the strategic orientation of the firm affects this relationship. Our study finds a clear positive relationship between growth and profitability among gazelle firms pursuing a broad market strategy. A managerial implication of this is that the growth strategy should be clearly integrated with the general strategic orientation of the firm.

The molecular mechanisms utilised by mesenchymal stem cells in migration to acute myocardial infarction

Heart damage caused by acute myocardial infarction (AMI) is a leading cause of death and disability in Australia. Novel therapies are still required for the treatment of this condition due to the poor reparative ability of the heart. As such, cellular therapies that assist in the recovery of heart muscle are of great current interest. Culture expanded mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical studies of AMI. For MSC-based therapies in the clinic, an intravenous route of administration would ideally be used due to the low cost, ease of delivery and relative safety. The study of MSC migration is therefore clinically relevant for a minimally invasive cell therapy to promote regeneration of damaged tissue. C57BL/6, UBI-GFP-BL/6 and CD44-/-/GFP+/+ mice were utilised to investigate mMSC migration. To assist in murine models of MSC migration, a novel method was used for the isolation of murine MSC (mMSC). These mMSC were then expanded in culture and putative mMSC were positive for Sca-1, CD90.2, and CD44 and were negative for CD45 and CD11b. Furthermore, mMSC from C57BL/6 and UBI-GFP-BL/6 mice were shown to differentiate into cells of the mesodermal lineage. Cells from CD44-/-/GFP+/+ mice were positive for Sca-1 and CD90.2, and negative for CD44, CD45 and CD11b however, these cells were unable to differentiate into adipocytes and chondrocytes and express lineage specific genes, PLIN and ACAN. Analysis of mMSC chemokine receptor (CR) expression showed that although mMSC do express chemokine receptors, (including those specific for chemokines released after AMI), these were low or undetectable by mRNA. However, protein expression could be detected, which was predominantly cytoplasmic. It was further shown that in both healthy (unperturbed) and inflamed tissues, mMSC had very little specific migration and engraftment after intravenous injection. To determine if poor mMSC migration was due to the inability of mMSC to respond to chemotactic stimuli, chemokine expression in bone marrow, skin injury and hearts (healthy and after AMI) was analysed at various time points by quantitative real-time PCR (qRT PCR). Many chemokines were up-regulated after skin biopsy and AMI, but the highest acute levels were found for CXCL12 and CCL7. Due to their high expression in infarcted hearts, the chemokines CXCL12 and CCL7 were tested for their effect on mMSC migration. Despite CR expression at both protein and mRNA levels, migration in response to CXCL12 and CCL7 was low in mMSC cultured on Nunclon plastic. A novel tissue culture plastic technology (UpCellTM) was then used that allowed gentle non-enzymatic dissociation of mMSC, thus preserving surface expression of the CRs. Despite this the in vitro data indicated that CXCL12 fails to induce significant migration ability of mMSC, while CCL7 induces significant, but low-level migration. We speculated this may be because of low levels of surface expression of chemokine receptors. In a strategy to increase cell surface expression of mMSC chemokine receptors and enhance their in vitro and in vivo migration capacity, mMSC were pre-treated with pro-inflammatory cytokines. Increased levels of both mRNA and surface protein expression were found for CRs by pre-treating mMSC with pro-inflammatory cytokines including TNF-á, IFN-ã, IL-1á and IL-6. Furthermore, the chemotactic response of mMSC to CXCL12 and CCL7 was significantly higher with these pretreated cells. Finally, the effectiveness of this type of cell manipulation was demonstrated in vivo, where mMSC pre-treated with TNF-á and IFN-ã showed significantly increased migration in skin injury and AMI models. Therefore this thesis has demonstrated, using in vitro and in vivo models, the potential for prior manipulation of MSC as a possible means for increasing the utility of intravenously delivery for MSC-based cellular therapies.

A dynamic approach to forecast rental growth

Numerous econometric models have been proposed for forecasting property market performance, but limited success has been achieved in finding a reliable and consistent model to predict property market movements over a five to ten year timeframe. This research focuses on office rental growth forecasts and overviews many of the office rent models that have evolved over the past 20 years. A model by DiPasquale and Wheaton is selected for testing in the Brisbane, Australia office market. The adaptation of this study did not provide explanatory variables that could assist in developing a reliable, predictive model of office rental growth. In light of this result, the paper suggests a system dynamics framework that includes an econometric model based on historical data as well as user input guidance for the primary variables. The rent forecast outputs would be assessed having regard to market expectations and probability profiling undertaken for use in simulation exercises. The paper concludes with ideas for ongoing research.

Crystal growth from undercooling melts under strong gradients of temperatures generating in short-duration microgravity

Crystal growth of bulk CdTe in short-duration microgravity is performed by the unidirectional cooling method. The largest growth grains in microgravity samples are 4X2mm. The cooling profiles indicate undercooling melts in microgravity. Cooling melt samples in microgravity generate strong gradient of temperature due to stop thermal convections. Temperature distribution in the melt is calculated by the one-dimensional equation of heat conduction, and about 100 K-undercooling is considered to occur at the cooling surface.