A comparative study of mesoporous-glass/silk and non-mesoporous-glass/silk scaffolds : physiochemistry and in vivo osteogenesis

Mesoporous bioactive glass (MBG) is a new class of biomaterials with a well-ordered nanochannel structure, whose in vitro bioactivity is far superior than that of non-mesoporous bioactive glass (BG); the material's in vivo osteogenic properties are, however, yet to be assessed. Porous silk scaffolds have been used for bone tissue engineering, but this material's osteoconductivity is far from optimal. The aims of this study were to incorporate MBG into silk scaffolds in order to improve their osteoconductivity and then to compare the effect of MBG and BG on the in vivo osteogenesis of silk scaffolds. MBG/silk and BG/silk scaffolds with a highly porous structure were prepared by a freeze-drying method. The mechanical strength, in vitro apatite mineralization, silicon ion release and pH stability of the composite scaffolds were assessed. The scaffolds were implanted into calvarial defects in SCID mice and the degree of in vivo osteogenesis was evaluated by microcomputed tomography (μCT), hematoxylin and eosin (H&E) and immunohistochemistry (type I collagen) analyses. The results showed that MBG/silk scaffolds have better physiochemical properties (mechanical strength, in vitro apatite mineralization, Si ion release and pH stability) compared to BG/silk scaffolds. MBG and BG both improved the in vivo osteogenesis of silk scaffolds. μCT and H&E analyses showed that MBG/silk scaffolds induced a slightly higher rate of new bone formation in the defects than did BG/silk scaffolds and immunohistochemical analysis showed greater synthesis of type I collagen in MBG/silk scaffolds compared to BG/silk scaffolds.

In vitro and in vivo evaluation of adenovirus combined silk fibroin scaffolds for BMP-7 gene delivery

Introduction and aims: For a scaffold material to be considered effective and efficient for tissue engineering it must be biocompatible as well as bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication; however, silk is tissue-conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue-inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteo-inductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Materials and methods: Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50) and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. Results: In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3 week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting significantly enhanced new bone formation. Conclusions: Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.

Investigation of the effect of organics on the water uptake of marine aerosols

Water uptake refers to the ability of atmospheric particles to take up water vapour from the surrounding atmosphere. This is an important property that affects particle size and phase and therefore influences many characteristics of aerosols relevant to air quality and climate. However, the water uptake properties of many important atmospheric aerosol systems, including those related to the oceans, are still not fully understood. Therefore, the primary aim of this PhD research program was to investigate the water uptake properties of marine aerosols. In particular, the effect of organics on marine aerosol water uptake was investigated. Field campaigns were conducted at remote coastal sites on the east coast of Australia (Agnes Water; March-April 2007) and west coast of Ireland (Mace Head; June 2007), and laboratory measurements were performed on bubble-generated sea spray aerosols. A combined Volatility-Hygroscopicity-Tandem Differential Mobility Analyser (VH-TDMA) was employed in all experiments. This system probes the changes in the hygroscopic properties of nanoparticles as volatile organic components are progressively evaporated. It also allows particle composition to be inferred from combined volatility-hygroscopicity measurements. Frequent new particle formation and growth events were observed during the Agnes Water campaign. The VH-TDMA was used to investigate freshly nucleated particles (17-22.5 nm) and it was found that the condensation of sulphate and/or organic vapours was responsible for driving particle growth during the events. Aitken mode particles (~40 nm) were also measured with the VH-TDMA. In 3 out of 18 VH-TDMA scans evaporation of a volatile, organic component caused a very large increase in hygroscopicity that could only be explained by an increase in the absolute water uptake of the particle residuals, and not merely an increase in their relative hygroscopicity. This indicated the presence of organic components that were suppressing the hygroscopic growth of mixed particles on the timescale of humidification in the VH-TDMA (6.5 secs). It was suggested that the suppression of water uptake was caused by either a reduced rate of hygroscopic growth due to the presence of organic films, or organic-inorganic interactions in solution droplets that had a negative effect on hygroscopicity. Mixed organic-inorganic particles were rarely observed by the VH-TDMA during the summer campaign conducted at Mace Head. The majority of particles below 100 nm in clean, marine air appeared to be sulphates neutralised to varying degrees by ammonia. On one unique day, 26 June 2007, particularly large concentrations of sulphate aerosol were observed and identified as volcanic emissions from Iceland. The degree of neutralisation of the sulphate aerosol by ammonia was calculated by the VH-TDMA and found to compare well with the same quantity measured by an aerosol mass spectrometer. This was an important verification of the VH-TMDA‘s ability to identify ammoniated sulphate aerosols based on the simultaneous measurement of aerosol volatility and hygroscopicity. A series of measurements were also conducted on sea spray aerosols generated from Moreton Bay seawater samples in a laboratory-based bubble chamber. Accumulation mode sea spray particles (38-173 nm) were found to contain only a minor organic fraction (< 10%) that had little effect on particle hygroscopicity. These results are important because previous studies have observed that accumulation mode sea spray particles are predominantly organic (~80% organic mass fraction). The work presented here suggests that this is not always the case, and that there may be currently unknown factors that are controlling the transfer of organics to the aerosol phase during the bubble bursting process. Taken together, the results of this research program have significantly improved our understanding of organic-containing marine aerosols and the way they interact with water vapour in the atmosphere.

Introduction

In this volume we compile and comment on a collection of some of the most important works on nascent entrepreneurship that have appeared in the last two decades. We do not go further back than that because up until1992 hardly any systematic research on the pre-operational stage of business creation was undertaken. In that year, the terms 'nascent entrepreneur' and 'nascent venture' appear for the first time in the research literature (Reynolds and Miller, Chapter l, 1992; Reynolds and White, 1992). This signals the emergence of a new research paradigm designed to study• business creation processes empirically at very early stages, before an operational firm has come into existence. The most central feature of this type of research is that it identifies a statistically representative sample of nascent entrepreneurs (NEs)- people engaged in ongoing but not yet operational business start-ups- via screening interviews with a very large random sample of adults. The overarching research questions pursued in this emerging research tradition are the following: 1. What proportion of individuals (in various population subgroups) are trying to start a new business at any given time? 2. What led them to engage in the creation of a new business? 3. What characteristics and behaviors associated with the founder(s), the venture, the environment and the process are associated with persistence, progress and success in trying to start a new business?

'Kaikaku’ project management : investigating the Japanese answer to the 90s depression

The purpose of this paper is to investigate the Japanese answer to the 90s depression, both as a case study of what framework has been developed to address new business challenges and value creation in complex, ambiguous and uncertain environment; and in order to expose what are, in our view, the underlying theoretical bases supporting this framework. This theoretical approach, and the resulting lessons learned, is assumed to be helpful to transpose the Japanese experience to other analogical contexts and situations.

Costco and the Aussie shopper : a case study of the market entry of an international retailer

Retailing is a globalized industry yet retailers must respond to local shopping habits if they are to be perceived as legitimate by the host country customers. However, some retailers may be unable or unwilling to respond to all customer requirements. Costco, the membership warehouse club retailer, has been successful in its international expansion efforts, establishing its first Australian store in Melbourne in 2009. In the first twelve months of operation, the store became one of Costco’s top five stores in the world. We investigate this success focussing on the customer, and use institutional theory to analyze what concessions were made by the customer and the company. Data were collected from consumer interviews, site visits and secondary media and industry sources. Analysis revealed negotiations based on the rejection, acceptance or adaptation of the regulative, normative and cultural cognitive aspects of the Australian shopper and the Costco business model. Customers made concessions to accommodate the new business model, and Costco responded to entrenched Australian shopping habits. This case is the first to explore the outcome of retail internationalization from the customers’ perspective, revealing the concept of mutual concessions. The interaction and subsequent adaptation by both customer and retailer have resulted in the institutionalization of new shopping norms in the host country and success for the international retailer.

Refund of imputation credits

The purpose of this paper is to explain the features of the new provisions for the refund of imputation credits, which are contained in the New Business Tax System (Miscellaneous) Act (No1) 2000.1 The provisions have been introduced to ensure that:  certain eligible resident taxpayers are taxed on their dividend income at their personal marginal rate of tax; and  certain eligible resident nonprofit organisations can apply their tax exemption on their dividend income. The provisions are contained in Division 67 of the Income Tax Assessment Act 1997 for refunds to resident individuals and superannuation entities and Division 7AA of Part IIIA of the Income Tax Assessment Act 1936 for refunds to endorsed income tax exempt charities and certain deductible gift recipients.

Influence of medium range transport of particles from nucleation burst on particle number concentration within the urban airshed

An elevated particle number concentration (PNC) observed during nucleation events could play a significant contribution to the total particle load and therefore to the air pollution in the urban environments. Therefore, a field measurement study of PNC was commenced to investigate the temporal and spatial variations of PNC within the urban airshed of Brisbane, Australia. PNC was monitored at urban (QUT), roadside (WOO) and semi-urban (ROC) areas around the Brisbane region during 2009. During the morning traffic peak period, the highest relative fraction of PNC reached about 5% at QUT and WOO on weekdays. PNC peaks were observed around noon, which correlated with the highest solar radiation levels at all three stations, thus suggesting that high PNC levels were likely to be associated with new particle formation caused by photochemical reactions. Wind rose plots showed relatively higher PNC for the NE direction, which was associated with industrial pollution, accounting for 12%, 9% and 14% of overall PNC at QUT, WOO and ROC, respectively. Although there was no significant correlation between PNC at each station, the variation of PNC was well correlated among three stations during regional nucleation events. In addition, PNC at ROC was significantly influenced by upwind urban pollution during the nucleation burst events, with the average enrichment factor of 15.4. This study provides an insight into the influence of regional nucleation events on PNC in the Brisbane region and it the first study to quantify the effect of urban pollution on semi-urban PNC through the nucleation events. © 2012 Author(s).

Vertical particle concentration profiles around urban office buildings

Despite its role in determining both indoor and outdoor human exposure to anthropogenic particles, there is limited information describing vertical profiles of particle concentrations in urban environments, especially for ultrafine particles. Furthermore, the results of the few studies performed have been inconsistent. As such, this study aimed to assess the influence of vehicle emissions and nucleation formation on particle characteristics (particle number size distribution-PNSD and PM 2.5 concentration) at different heights around three urban office buildings located next to busy roads in Brisbane, Australia, and place these results in the broader context of the existing literature. Two sets of instruments were used to simultaneously measure PNSD, particle number (PN) and PM 2.5 concentrations, respectively, for up to three weeks at each building. The results showed that both PNSD and PM 2.5 concentration around building envelopes were influenced by vehicle emissions and new particle formation, and that they exhibited variability across the three different office buildings. During nucleation events, PN concentration in size range of <30 nm and total PN concentration increased (7-65% and 5-46%, respectively), while PM 2.5 concentration decreased (36-52%) with height. This study has shown an under acknowledged role for nucleation in producing particles that can affect large numbers of people, due to the high density and occupancy of urban office buildings and the fact that the vast majority of people's time is spent indoors. These findings highlight important new information related to the previously overlooked role of particle formation in the urban atmosphere and its potential effects on selection of air intake locations and appropriate filter types when designing or upgrading mechanical ventilation systems in urban office buildings. The results also serve to better define particle behaviour and variability around building envelopes, which has implications for studies of both human exposure and particle dynamics. © 2012 Author(s).

Enabling USDL by tools

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

ACE research briefing paper 005: Global Entrepreneurship Monitor (GEM) - Australia 2011 National Report

This report maps the current state of entrepreneurship in Australia using data from the Global Entrepreneurship Monitor (GEM) for the year 2011. Entrepreneurship is regarded as a crucial driver for economic well-being. Entrepreneurial activity in new and established firms drives innovation and creates jobs. Entrepreneurs also fuel competition thereby contributing indirectly to market and productivity growth along with improving competitiveness of the national economy. Given the economic landscape that exists as a result of the global financial crisis (GFC), it is probably more important than ever for us to understand the effects and drivers of entrepreneurial activity and attitudes in Australia. The central finding of this report is that entrepreneurship is certainly alive and well in Australia. With 10.5 per cent of the adult population involved in setting up a new business or owning a newly founded business as measured by the total entrepreneurial activity rate (TEA) in 2011, Australia ranks second only to the United States among the innovation-driven (developed) economies. Compared with 2010 the TEA rate has increased by 2.7 percentage points. Furthermore, in regard to employee entrepreneurial activity (EEA) rate in established firms, Australia ranks above average. According to GEM data, 5 per cent of the adult population is engaged in developing or launching new products, a new business unit or subsidiary for their employer. Further analysis of the GEM data also clearly shows that Australia compares well with other major economies in terms of the ‘quality’ of entrepreneurial activities being pursued. Indeed, it is not only the quantity of entrepreneurs but also the level of their aspirations and business goals that are important drivers for economic growth. On average, for each business started in Australia driven by the lack of alternatives for the founder to generate income from any other source, there are five other businesses started where the founders specifically want to take advantage of a business opportunity that they believe will increase their personal income or independence. With respect to innovativeness, 31 per cent of Australian new businesses offer products or services which they consider to be new to customers or where very few, or in some cases no, other businesses offer the same product or service. Both these indicators are higher than the average for innovation-driven economies. Somewhat below average is the international orientation of Australian entrepreneurs whereby only 12 per cent aim at having a substantial share of customers from international markets. So what drives this high quantity and quality of entrepreneurship in Australia? The analysis of the data suggests it is a combination of both business opportunities and entrepreneurial skills. It seems that around 50 per cent of the Australian population identify opportunities for a start-up venture and believe that they have the necessary skills to start a business. Furthermore, a large majority of the Australian population report that high media attention for entrepreneurship provides successful role models for prospective entrepreneurs. As a result, 12 per cent of our respondents have expressed the intention to start a business within the next three years. These numbers are all well above average when compared to the other major economies. With regard to gender, the GEM survey shows a high proportion of female entrepreneurs. Approximately 8.4 per cent of adult females are actually involved in setting up a business or have recently done so. Although this female TEA rate is slightly down from 2010, Australia ranks second among the innovation-driven economies. This paints a healthy picture of access to entrepreneurial opportunities for Australian women.

Preparation, characterisation and in vivo osteogenesis of mesoporous bioactive glasses

Bone defects, especially large bone defects, remain a major challenge in orthopaedic surgery. Autologous bone transplantation is considered the most effective treatment, but insufficient donor tissue, coupled with concerns about donor site morbidity, has hindered this approach in large-scale applications. Alternative approaches include implanting biomaterials such as bioactive glass (BG), which has been widely used for bone defect healing, due to having generally good biocompatibility, and can be gradually biodegraded during the process of new bone formation. Mesoporous bioactive glass (MBG) is a newly developed bioactive glass which has been proven to have enhanced in-vitro bioactivity; however the in-vivo osteogenesis has not been studied. A critical problem in using the bone tissue engineering approach to restore large bone defects is that the nutrient supply and cell viability at the centre of the scaffold is severely hampered since the diffusion distance of nutrients and oxygen for cell survival is limited to 150-200µm. Cobalt ions has been shown to mimic hypoxia, which plays a pivotal role in coupling angiogenesis with osteogenesis in-vivo by activating hypoxia inducing factor-1α (HIF-1α) transcription factor, subsequently initiating the expression of genes associated with tissue regeneration. Therefore, one aim of this study is to investigate the in-vivo osteogenesis of MBG by comparison with BG and β-TCP, which are widely used clinically. The other aim is to explore hypoxia-mimicking biomaterials by incorporating Cobalt into MBG and β-TCP. MBG and β-TCP incorporated with 5% cobalt (5Co-MBG and 5CCP) have also been studied in-vivo to determine whether the hypoxic effect has a beneficial effect on the bone formation. The composition and microstructure of synthesised materials (BG, MBG, 5Co-MBG, 5CCP) were characterised, along with the mesopore properties of the MBG materials. Dissolution and cytotoxicity of the Co-containing materials were also investigated. Femoral samples with defects harvested at 4 and 8 weeks were scanned using micro-CT followed by processing for histology (H&E staining) to determine bone formation. Histology of MBG showed a slower rate of bone formation at 4 weeks than BG, however at 8 weeks it could be clearly seen that MBG had more bone formation. The in-vivo results show that the osteogenesis of MBG reciprocates the enhanced performance shown in-vitro compared to BG. Dissolution study showed that Co ions can be efficiently released from MBG and β-TCP in a controllable way. Low amounts of Co incorporated into the MBG and β-TCP showed no significant cytotoxicity and the Co-MBG powders maintained a mesopore structure although not as highly ordered as pure MBG. Preliminary study has shown that Co incorporated samples showed little to no bone formation, instead incurring high lymphocyte activity. Further studies need to be done on Co incorporated materials to determine the cause for high lymphocyte activity in-vivo, which appear to hinder bone formation. In conclusion, this study demonstrated the osteogenic activity of MBG and provided some valuable information of tissue reaction to Co-incorporated MBG and TCP materials.

Implantation of osteogenic differentiated donor mesenchymal stem cells causes recruitment of host cells

The interaction between host and donor cells is believed to play an important role in osteogenesis. However, it is still unclear how donor osteogenic cells behave and interact with host cells in vivo. The purpose of this study was to track the interactions between transplanted osteogenic cells and host cells during osteogenesis. In vitro migration assay was carried out to investigate the ability of osteogenic differentiated humanmesenchymal stemcells (O-hMSCs) to recruit MSCs. At the in vivo level, O-hMSCs were implanted subcutaneously or into skull defects in severe combined immunodeficient (SCID) mice. New bone formation was observed bymicro-CT and histological procedures. In situ hybridization (ISH) against human Alu sequences was performed to distinguish donor osteogenic cells from host cells. In vitro migration assay revealed an increased migration potential of MSCs by co-culturing with O-hMSCs. In agreement with the results of in vitro studies, ISH against human Alu sequences showed that host mouse MSCs migrated in large numbers into the transplantation site in response to O-hMSCs. Interestingly, host cells recruited by O-hMSCs were the major cell populations in newly formed bone tissues, indicating that O-hMSCs can trigger and initiate osteogenesis when transplanted in orthotopic sites. The observations fromthis study demonstrated that in vitro induced O-hMSCs were able to attract hostMSCs in vivo andwere involved inosteogenesis togetherwith host cells,whichmay be of importance for bone tissue-engineering applications.

The entrepreneurial process

This chapter revolves around research-based insights into the entrepreneurial process. By is meant the process of setting up a new business activity resulting in a new market offer. This new offer may be made by a new or an existing firm, although the main focus here is on the start-up of new, independent firms. Further, the new offer may be innovative, bringing to the market something that was not offered before or imita­tive i.e., a new competitor enters the market with products or services very similar to what other firms are already offering. Although the lsatter type of process may be less complex and also have less market impact, it still entails most of the steps that typically have to be taken in order to get a business up and running. If successful, it also shares, at least to some degree, the consequences that signify entrepreneurial processes: - it gives consumers new choice alternatives - it gives incumbent firms reason to shape up - it attracts additional followers to enter the market, further reinforcing the first two effects (Davidsson, 2004). Besides, imitatlve starr-ups outnumber by far innovative ones (Reynolds et al., 2003; Samuelsson and Davidsson, 2009).

Identification of bone morphogenetic proteins 2 and 4 in commercial demineralized freeze-dried bone allograft preparations : pilot study

BACKGROUND: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. METHODS: A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA samples were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. RESULTS: Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. CONCLUSIONS: These results indicate that all of the DFDBA samples tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.