Vitronectin modulates human mesenchymal stem cell response to insulin-like growth factor-I and transforming growth factor beta 1 in a serum-free environment

The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.

The creative sector in New Zealand : mapping and economic role : report to New Zealand Trade and Enterprise

The New Zealand creative sector was responsible for almost 121,000 jobs at the time of the 2006 Census (6.3% of total employment). These are divided between • 35,751 creative specialists – persons employed doing creative work in creative industries • 42,300 support workers - persons providing management and support services in creative industries • 42,792 embedded creative workers – persons engaged in creative work in other types of enterprise The most striking feature of this breakdown is the fact that the largest group of creative workers are employed outside the creative industries, i.e. in other types of businesses. Even within the creative industries, there are fewer people directly engaged in creative work than in providing management and support. Creative sector employees earned incomes of approximately $52,000 per annum at the time of the 2006 Census. This is relatively uniform across all three types of creative worker, and is significantly above the average for all employed persons (of approximately $40,700). Creative employment and incomes were growing strongly over both five year periods between the 1996, 2001 and 2006 Censuses. However, when we compare creative and general trends, we see two distinct phases in the development of the creative sector: • rapid structural growth over the five years to 2001 (especially led by developments in ICT), with creative employment and incomes increasing rapidly at a time when they were growing modestly across the whole economy; • subsequent consolidation, with growth driven by more by national economic expansion than structural change, and creative employment and incomes moving in parallel with strong economy-wide growth. Other important trends revealed by the data are that • the strongest growth during the decade was in embedded creative workers, especially over the first five years. The weakest growth was in creative specialists, with support workers in creative industries in the middle rank, • by far the strongest growth in creative industries’ employment was in Software & digital content, which trebled in size over the decade Comparing New Zealand with the United Kingdom and Australia, the two southern hemisphere nations have significantly lower proportions of total employment in the creative sector (both in creative industries and embedded employment). New Zealand’s and Australia’s creative shares in 2001 were similar (5.4% each), but in the following five years, our share has expanded (to 5.7%) whereas Australia’s fell slightly (to 5.2%) – in both cases, through changes in creative industries’ employment. The creative industries generated $10.5 billion in total gross output in the March 2006 year. Resulting from this was value added totalling $5.1b, representing 3.3% of New Zealand’s total GDP. Overall, value added in the creative industries represents 49% of industry gross output, which is higher than the average across the whole economy, 45%. This is a reflection of the relatively high labour intensity and high earnings of the creative industries. Industries which have an above-average ratio of value added to gross output are usually labour-intensive, especially when wages and salaries are above average. This is true for Software & Digital Content and Architecture, Design & Visual Arts, with ratios of 60.4% and 55.2% respectively. However there is significant variation in this ratio between different parts of the creative industries, with some parts (e.g. Software & Digital Content and Architecture, Design & Visual Arts) generating even higher value added relative to output, and others (e.g. TV & Radio, Publishing and Music & Performing Arts) less, because of high capital intensity and import content. When we take into account the impact of the creative industries’ demand for goods and services from its suppliers and consumption spending from incomes earned, we estimate that there is an addition to economic activity of: • $30.9 billion in gross output, $41.4b in total • $15.1b in value added, $20.3b in total • 158,100 people employed, 234,600 in total The total economic impact of the creative industries is approximately four times their direct output and value added, and three times their direct employment. Their effect on output and value added is roughly in line with the average over all industries, although the effect on employment is significantly lower. This is because of the relatively high labour intensity (and high earnings) of the creative industries, which generate below-average demand from suppliers, but normal levels of demand though expenditure from incomes. Drawing on these numbers and conclusions, we suggest some (slightly speculative) directions for future research. The goal is to better understand the contribution the creative sector makes to productivity growth; in particular, the distinctive contributions from creative firms and embedded creative workers. The ideas for future research can be organised into the several categories: • Understanding the categories of the creative sector– who is doing the business? In other words, examine via more fine grained research (at a firm level perhaps) just what is the creative contribution from the different aspects of the creative sector industries. It may be possible to categorise these in terms of more or less striking innovations. • Investigate the relationship between the characteristics and the performance of the various creative industries/ sectors; • Look more closely at innovation at an industry level e.g. using an index of relative growth of exports, and see if this can be related to intensity of use of creative inputs; • Undertake case studies of the creative sector; • Undertake case studies of the embedded contribution to growth in the firms and industries that employ them, by examining taking several high performing noncreative industries (in the same way as proposed for the creative sector). • Look at the aggregates – drawing on the broad picture of the extent of the numbers of creative workers embedded within the different industries, consider the extent to which these might explain aspects of the industries’ varied performance in terms of exports, growth and so on. • This might be able to extended to examine issues like the type of creative workers that are most effective when embedded, or test the hypothesis that each industry has its own particular requirements for embedded creative workers that overwhelms any generic contributions from say design, or IT.

Posttraumatic growth in Australian populations

It is easy to assume that because Australia and the United States are both predominantly English speaking countries that are relatively young and share many similarities in terms of their historical beginnings, they elicit the same results when investigating psychological constructs. In recent years this has been questioned across a number of domains (e.g., personality and stereotyping) and research has demonstrated that although many constructs are universal, there are differences between these nations; some subtle and others quite stark (McCrae et al., 2005; Terraciano et al., 2005). In this chapter we discuss research that has investigated Posttraumatic Growth (PTG) in various populations in Australia and highlight the similarities and differences that have been found between Australian samples and those published in other countries, especially the US. Data are drawn from quantitative and qualitative investigations conducted with groups who have experienced diverse traumatic events as either direct survivors (e.g., rape, armed hold-up, bereavement) or vicarious survivors (e.g., paramedics). A description of the Australian context sets the scene for the ensuing discussion about PTG in Australian populations.

Porous polyurethane coatings bonded onto surface-modified titanium substrates for the growth of an endothelial cell layer

Cardiovascular diseases refer to the class of diseases that involve the heart or blood vessels (arteries and veins). Examples of medical devices for treating the cardiovascular diseases include ventricular assist devices (VADs), artificial heart valves and stents. Metallic biomaterials such as titanium and its alloy are commonly used for ventricular assist devices. However, titanium and its alloy show unacceptable thrombosis, which represents a major obstacle to be overcome. Polyurethane (PU) polymer has better blood compatibility and has been used widely in cardiovascular devices. Thus one aim of the project was to coat a PU polymer onto a titanium substrate by increasing the surface roughness, and surface functionality. Since the endothelium of a blood vessel has the most ideal non-thrombogenic properties, it was the target of this research project to grow an endothelial cell layer as a biological coating based on the tissue engineering strategy. However, seeding endothelial cells on the smooth PU coating surfaces is problematic due to the quick loss of seeded cells which do not adhere to the PU surface. Thus it was another aim of the project to create a porous PU top layer on the dense PU pre-layer-coated titanium substrate. The method of preparing the porous PU layer was based on the solvent casting/particulate leaching (SCPL) modified with centrifugation. Without the step of centrifugation, the distribution of the salt particles was not uniform within the polymer solution, and the degree of interconnection between the salt particles was not well controlled. Using the centrifugal treatment, the pore distribution became uniform and the pore interconnectivity was improved even at a high polymer solution concentration (20%) as the maximal salt weight was added in the polymer solution. The titanium surfaces were modified by alkli and heat treatment, followed by functionlisation using hydrogen peroxide. A silane coupling agent was coated before the application of the dense PU pre-layer and the porous PU top layer. The ability of the porous top layer to grow and retain the endothelial cells was also assessed through cell culture techniques. The bonding strengths of the PU coatings to the modified titanium substrates were measured and related to the surface morphologies. The outcome of the project is that it has laid a foundation to achieve the strategy of endothelialisation for the blood compatibility of medical devices. This thesis is divided into seven chapters. Chapter 2 describes the current state of the art in the field of surface modification in cardiovascular devices such as ventricular assist devices (VADs). It also analyses the pros and cons of the existing coatings, particularly in the context of this research. The surface coatings for VADs have evolved from early organic/ inorganic (passive) coatings, to bioactive coatings (e.g. biomolecules), and to cell-based coatings. Based on the commercial applications and the potential of the coatings, the relevant review is focused on the following six types of coatings: (1) titanium nitride (TiN) coatings, (2) diamond-like carbon (DLC) coatings, (3) 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer coatings, (4) heparin coatings, (5) textured surfaces, and (6) endothelial cell lining. Chapter 3 reviews the polymer scaffolds and one relevant fabrication method. In tissue engineering, the function of a polymeric material is to provide a 3-dimensional architecture (scaffold) which is typically used to accommodate transplanted cells and to guide their growth and the regeneration of tissue. The success of these systems is dependent on the design of the tissue engineering scaffolds. Chapter 4 describes chemical surface treatments for titanium and titanium alloys to increase the bond strength to polymer by altering the substrate surface, for example, by increasing surface roughness or changing surface chemistry. The nature of the surface treatment prior to bonding is found to be a major factor controlling the bonding strength. By increasing surface roughness, an increase in surface area occurs, which allows the adhesive to flow in and around the irregularities on the surface to form a mechanical bond. Changing surface chemistry also results in the formation of a chemical bond. Chapter 5 shows that bond strengths between titanium and polyurethane could be significantly improved by surface treating the titanium prior to bonding. Alkaline heat treatment and H2O2 treatment were applied to change the surface roughness and the surface chemistry of titanium. Surface treatment increases the bond strength by altering the substrate surface in a number of ways, including increasing the surface roughness and changing the surface chemistry. Chapter 6 deals with the characterization of the polyurethane scaffolds, which were fabricated using an enhanced solvent casting/particulate (salt) leaching (SCPL) method developed for preparing three-dimensional porous scaffolds for cardiac tissue engineering. The enhanced method involves the combination of a conventional SCPL method and a step of centrifugation, with the centrifugation being employed to improve the pore uniformity and interconnectivity of the scaffolds. It is shown that the enhanced SCPL method and a collagen coating resulted in a spatially uniform distribution of cells throughout the collagen-coated PU scaffolds.In Chapter 7, the enhanced SCPL method is used to form porous features on the polyurethane-coated titanium substrate. The cavities anchored the endothelial cells to remain on the blood contacting surfaces. It is shown that the surface porosities created by the enhanced SCPL may be useful in forming a stable endothelial layer upon the blood contacting surface. Chapter 8 finally summarises the entire work performed on the fabrication and analysis of the polymer-Ti bonding, the enhanced SCPL method and the PU microporous surface on the metallic substrate. It then outlines the possibilities for future work and research in this area.

The growth-profitability relationship : strategic orientations as moderator

Principal Topic: In this study we investigate how strategic orientation moderates the impact of growth on profitability for a sample of Danish high growth (Gazelle) firms. ---------- Firm growth has been an essential part of both management research and entrepreneurship research for decades (e.g. Penrose 1959, Birch 1987, Storey 1994). From a societal point of view, firm growth has been perceived as economic generator and job creator. In entrepreneurship research, growth has been an important part of the field (Davidsson, Delmar and Wiklund 2006), and many have used growth as a measure of success. In strategic management, growth has been seen as an approach to achieve competitive advantages and a way of becoming increasing profitable (e.g. Russo and Fouts 1997, Cho and Pucic 2005). However, although firm growth used to be perceived as a natural pathway to profitability recently more skepticism has emerged due to both new theoretical development and new empirical insights. Empirically, studies show inconsistent and inconclusive empirical evidence regarding the impact of growth on profitability. Our review reveals that some studies find a substantial positive relationship, some find a weak positive relationship, some find no relationship and further some find a negative relationship. Overall, two dominant yet divergent theoretical positions can be identified. The first position, mainly focusing on the environmental fit, argues that firms are likely to become more profitable if they enter a market quickly and on a larger scale due to first mover advantages and economic of scale. The second position, mainly focusing the internal fit, argues that growth may lead to a range of internal challenges and difficulties, including rapid change in structure, reward systems, decision making, communication and management style. The inconsistent empirical results together with two divergent theoretical positions call for further investigations into the circumstances by which growth generate profitability and into the circumstances by which growth do not generate profitability. In this project, we investigate how strategic orientations influence the impact of growth on profitability by asking the following research question: How is the impact of growth on profitability moderated by strategic orientation? Based on a literature review of how growth impacts profitability in areas such as entrepreneurship, strategic management and strategic entrepreneurship we develop three hypotheses regarding the growth-profitability relationship and strategic orientation as a potential moderator. ---------- Methodology/Key Propositions: The three hypotheses are tested on data collected in 2008. All firms in Denmark, including all listed and non-listed (VAT-registered) firms who experienced a 100 % growth and had a positive sales or gross profit over a four years period (2004-2007) were surveyed. In total 2,475 fulfilled the requirements. Among those 1,107 firms returned usable questionnaires satisfactory giving us a response rate on 45 %. The financial data together with data on number of employees were obtained from D&B (previously Dun & Bradstreet). The remaining data were obtained through the survey. Hierarchical regression models with ROA (return on assets) as the dependent variable were used to test the hypotheses. In the first model control variables including region, industry, firm age, CEO age, CEO gender, CEO education and number of employees were entered. In the second model, growth measured as growth in employees was entered. Then strategic orientation (differentiation, cost leadership, focus differentiation and focus cost leadership) and then interaction effects of strategic orientation and growth were entered in the model. ---------- Results and Implications: The results show a positive impact of firm growth on profitability and further that this impact is moderated by strategic orientation. Specifically, it was found that growth has a larger impact on profitability when firms do not pursue a focus strategy including both focus differentiation and focus cost leadership. Our preliminary interpretation of the results suggests that the value of growth depends on the circumstances and more specifically 'how much is left to fight for'. It seems like those firms who target towards a narrow segment are less likely to gain value of growth. The remaining market shares to fight for to these firms are not large enough to compensate for the cost of growing. Based on our findings, it therefore seems like growth has a more positive relationship with profitability for those who approach a broad market segment. Furthermore we argue that firms pursuing af Focus strategy will have more specialized assets that decreases the possibilities of further profitable expansion. For firms, CEOs, board of directors etc., the study shows that high growth is not necessarily something worth aiming for. It is a trade-off between the cost of growing and the value of growing. For many firms, there might be better ways of generating profitability in the long run. It depends on the strategic orientation of the firm. For advisors and consultants, the conditional value of growth implies that in-depth knowledge on their clients' situation is necessary before any advice can be given. And finally, for policy makers, it means they have to be careful when initiating new policies to promote firm growth. They need to take into consideration firm strategy and industry conditions.

Can book-to-market and size be risk factors that predict economic growth in Asia's emerging economies?

We investigate whether the two 2 zero cost portfolios, SMB and HML, have the ability to predict economic growth for markets investigated in this paper. Our findings show that there are only a limited number of cases when the coefficients are positive and significance is achieved in an even more limited number of cases. Our results are in stark contrast to Liew and Vassalou (2000) who find coefficients to be generally positive and of a similar magnitude. We go a step further and also employ the methodology of Lakonishok, Shleifer and Vishny (1994) and once again fail to support the risk-based hypothesis of Liew and Vassalou (2000). In sum, we argue that search for a robust economic explanation for firm size and book-to-market equity effects needs sustained effort as these two zero cost portfolios do not represent economically relevant risk.

Selective growth of carbon nanotubes on bare silicon : MWNT sinthesys on patterned substrates without predeposition of metal catalyst

Carbon nanotubes (CNTs) are expected to become the ideal constituent of many technologes, in particular for future generation electronics. This considerable interest is due to their unique electrical and mechanical properties. They show indeed super-high current-carrying capacity, ballistic electron transport and good field-emission properties. Then, these superior features make CNTs the most promising building blocks for electronic devices, as organic solar cells and organic light emitting devices (OLED). By using Focused Ion Beam (FIB) patterning it is possible to a obtain a high control on position, relative distances and diameter of CNTs. The present work shows how to grow three-dimensional architecture made of vertical-aligned CNTs directly on silicon. Thanks to the higher activity of a pre-patterned surface the synthesis process results very quick, cheap and simple. Such large area growths of CNTs could be used in preliminary test for application as electrodes for organic solar cells.

Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells

Multipotent mesenchymal stem cells (MSCs), first identified in the bone marrow, have subsequently been found in many other tissues, including fat, cartilage, muscle, and bone. Adipose tissue has been identified as an alternative to bone marrow as a source for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of bone marrow-derived mesenchymal stem cells (BMSCs) with that of adipose-derived mesenchymal stem cells (AMSCs) from 12 age- and sex-matched donors. Phenotypically, the cells are very similar, with only three surface markers, CD106, CD146, and HLA-ABC, differentially expressed in the BMSCs. Although colony-forming units-fibroblastic numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, like that of fibroblast growth factor 2 (FGF2), the Wnt pathway effectors FRAT1 and frizzled 1, and other self-renewal markers, was greater in AMSCs. Furthermore, AMSCs displayed enhanced osteogenic and adipogenic potential, whereas BMSCs formed chondrocytes more readily than AMSCs. However, by removing the effects of proliferation from the experiment, AMSCs no longer out-performed BMSCs in their ability to undergo osteogenic and adipogenic differentiation. Inhibition of the FGF2/fibroblast growth factor receptor 1 signaling pathway demonstrated that FGF2 is required for the proliferation of both AMSCs and BMSCs, yet blocking FGF2 signaling had no direct effect on osteogenic differentiation. Disclosure of potential conflicts of interest is found at the end of this article.

Small firm growth

We review and discuss the literature on small firm growth with an intention to provide a useful vantage point for new research studies regarding this important phenomenon. We first discuss conceptual and methodological issues that represent critical choices for those who research growth and which make it challenging to compare results from previous studies. The substantial review of past research is organized into four sections representing two smaller and two larger literatures. The first of the latter focuses on internal and external drivers of small firm growth. Here we find that much has been learnt and that many valuable generalizations can be made. However, we also conclude that more research of the same kind is unlikely to yield much. While interactive and non-linear effects may be worth pursuing it is unlikely that any new and important growth drivers or strong, linear main effects would be found. The second large literature deals with organizational life-cycles or stages of development. While deservedly criticized for unwarranted determinism and weak empirics this type of approach addresses problems of high practical and also theoretical relevance, and should not be shunned by researchers. We argue that with a change in the fundamental assumptions and improved empirical design, research on the organizational and managerial consequences of growth is an important line of inquiry. With this, we overlap with one of the smaller literatures, namely studies focusing on the effects of growth. We argue that studies too often assume that growth equals success. We advocate instead the use of growth as an intermediary variable that influences more fundamental goals in ways that should be carefully examined rather than assumed. The second small literature distinguishes between different modes or forms of growth, including, e.g., organic vs. acquisition-based growth, and international expansion. We note that modes of growth is an important topic that has been under studied in the growth literature, whereas in other branches of research aspects of it may have been studied intensely, but not primarily from a growth perspective. In the final section we elaborate on ways forward for research on small firm growth. We point at rich opportunities for researchers who look beyond drivers of growth, where growth is viewed as a homogenous phenomenon assumed to unambiguously reflect success, and instead focus on growth as a process and a multi-dimensional phenomenon, as well as on how growth relates to more fundamental outcomes.

The contribution of physical activity and sedentary behaviours to the growth and development of children and adolescents : implications for overweight and obesity

The obesity epidemic is a global trend and is of particular concern in children. Recent reports have highlighted the severity of obesity in children by suggesting: “today's generation of children will be the first for over a century for whom life expectancy falls.” This review assesses the evidence that identifies the important role of physical activity in the growth, development and physical health of young people, owing to its numerous physical and psychological health benefits. Key issues, such as “does a sedentary lifestyle automatically lead to obesity” and “are levels of physical activity in today's children less than physical activity levels in children from previous generations?”, are also discussed. Today's environment enforces an inactive lifestyle that is likely to contribute to a positive energy balance and childhood obesity. Whether a child or adolescent, the evidence is conclusive that physical activity is conducive to a healthy lifestyle and prevention of disease. Habitual physical activity established during the early years may provide the greatest likelihood of impact on mortality and longevity. It is evident that environmental factors need to change if physical activity strategies are to have a significant impact on increasing habitual physical activity levels in children and adolescents. There is also a need for more evidence-based physical activity guidelines for children of all ages. Efforts should be concentrated on facilitating an active lifestyle for children in an attempt to put a stop to the increasing prevalence of obese children

A new future for growth factor complexes as wound therapies?

Background: Topical administration of growth factors (GFs) has displayed some potential in wound healing, but variable efficacy, high doses and costs have hampered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple GFs and extracellular matrix (ECM) proteins. The Problem: Deep dermal partial thickness burn (DDPTB) injuries are the most common burn presentation to pediatric hospitals and also represent the most difficult burn injury to manage clinically. DDPTB often repair with a hypertrophic scar. Wounds that close rapidly exhibit reduced scarring. Thus treatments that shorten the time taken to close DDTPB’s may coincidently reduce scarring. Basic/Clinical Science Advances: We have observed that multi-protein complexes comprised of IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes. These responses require activation of both the IGF-1R and the VN-binding αv integrins. We have recently evaluated the wound healing potential of these GF:VN complexes in a porcine model of DDTPB injury. Clinical Care Relevance: This pilot study demonstrates that GF:VN complexes hold promise as a wound healing therapy. Enhanced healing responses were observed after treatment with nanogram doses of the GF:VN complexes in vitro and in vivo. Critically healing was achieved using substantially less GF than studies in which GFs alone have been used. Conclusion: These data suggest that coupling GFs to ECM proteins, such as VN, may ultimately prove to be an improved technique for the delivery of novel GF-based wound therapies.

Effect of poly(acrylic acid) end-group functionality on inhibition of calcium oxalate crystal growth

A number of series of poly(acrylic acids) (PAA) of differing end-groups and molecular weights prepared using atom transfer radical polymerization were used as inhibitors for the crystallization of calcium oxalate at 23 and 80°C. As measured by turbidimetry and conductivity and as expected from previous reports, all PAA series were most effective for inhibition of crystallization at molecular weights of 1500–4000. However, the extent of inhibition was in general strongly dependent on the hydrophobicity and molecular weight of the end-group. These results may be explicable in terms of adsorption/desorption of PAA to growth sites on crystallites. The overall effectiveness of the series didn't follow a simple trend with end-group hydrophobicity, suggesting self-assembly behavior or a balance between adsorption and desorption rates to crystallite surfaces may be critical in the mechanism of inhibition of calcium oxalate crystallization.

Effect of poly(acrylic acid) molecular mass and end-group functionality on calcium oxalate crystal morphology and growth

A number of series of poly(acrylic acids) (PAA) of differing end-groups and molecular mass were used to study the inhibition of calcium oxalate crystallization. The effects of the end-group on crystal speciation and morphology were significant and dramatic, with hexyl-isobutyrate end groups giving preferential formation of calcium oxalate dihydrate (COD) rather than the more stable calcium oxalate monohydrate (COM), while both more hydrophobic end-groups and less-hydrophobic end groups led predominantly to formation of the least thermodynamically stable form of calcium oxalate, calcium oxalate trihydrate. Conversely, molecular mass had little impact on calcium oxalate speciation or crystal morphology. It is probable that the observed effects are related to the rate of desorption of the PAA moiety from the crystal (lite) surfaces and that the results point to a major role for end-group as well as molecular mass in controlling desorption rate.