Phosphatidylserine-containing liposomes:modulators of rhinovirus induced inflammatory responses

Background: Human rhinoviral infections are major contributors to the healthcare burden associated with acute exacerbations of asthma. We, and others have recently demonstrated that rhinovirus (RV)-induced inflammatory responses are mediated by multiple signalling mechanisms, such as IL-1/MyD88 (1) and TLR3/RIGI (2). We have also previously published work showing that TLR signalling is effectively inhibited by phosphatidylserine-containing liposomes (SAPS), through the disruption of membrane microdomains (3). Evidence has also suggested that membrane microdomains may influence infections with RV. In this study, we explored the ability of SAPS to modulate responses to the natural viral pathogens, RV-1B and RV-16. Method: The immortalized bronchial epithelial cell line, BEAS-2B or primary bronchial epithelial cells were infected with RV-1B or RV-16 at a TCID50/ml of 19107 for 1 h. Immediately following infection, various concentrations of SAPS were added and changes in cytokine release were measured at 24 h. SAPS remained present throughout. Type I and III interferon (IFN) expression and rates of viral replication were measured by quantitative PCR. Virus quantification was also performed using a viral CPE assay, and IFN signalling was measured by western blot. Liposome stability was characterised and intracellular trafficking of fluorescently labelled SAPS in BEAS-2B cells was investigated using confocal microscopy. For in vivo studies, female wt Balb/c mice were pre-treated with SAPS for 2 h prior to infection with RV as previously described and changes in BAL cell number, BAL cytokine production and viral replication were quantified (4). Results: Characterisation of SAPS liposomes by mass spectrometry showed no obvious signs of oxidation over the time period tested, and liposome size remained constant. Preliminary confocal studies revealed that SAPS was rapidly internalised within the cell and was found to associate with intracellular compartments such as the early endosome and golgi. Viral infected BEAS-2B cells co-incubated with SAPS, showed notably impaired responses to RV as assessed by release of CXCL8 and CCL5. SAPS also reduced RV-induced IFNb production and STAT-1 phosphorylation, without significantly influencing viral replication rates. Modest increases in viral particle production were only observed at 48 and 72 h time points. Suppression of viral-induced cytokine production was also observed in primary bronchial epithelial cells and pilot in vivo studies showed that SAPS results in reduced KC production at 24 h post viral infection, and this was associated with reduced neutrophil numbers within the BAL fluid. Conclusion: Our data demonstrates a potential means of modulating inflammatory responses induced by human rhinovirus.

An ex ante evaluation framework for the regional benefits of publicly supported R&D projects

This paper draws on the knowledge-base implicit in ex post evaluations of publicly funded R&D and other related conceptual and empirical studies to suggest a framework for the ex ante evaluation of the regional benefits from R&D projects. The framework developed comprises two main elements: an inventory of the global private and social benefits which might result from any R&D project; and, an assessment of the share of these global benefits which might accrue to a host region, taking into account the characteristics of the R&D project and the region's innovation system. The inventory of global benefits separately identifies private and social benefits and distinguishes between increments to public and private knowledge stocks, benefits to R&D productivity and benefits from commercialisation. Potential market and 'pure' knowledge spillovers are also considered separately. The paper concludes with the application of the framework to two illustrative case studies. © 2003 Elsevier B.V. All rights reserved.

External linkages, R&D and innovation performance in US business services

This paper examines the innovation performance of 206 US business services firms. Results suggest that external linkages, particularly with customers, suppliers and strategic alliances, significantly enhance innovation performance in terms of the introduction of new services. A highly qualified workforce increases the probability of service and organizational innovation, and increases the extent of a firm's innovation, but unqualified employees also play an important role. Contrasting with some earlier research on services, the presence of formal and informal R&D significantly increases the extent of new-to-market and new-to-firm innovation.

Internal versus external R&D:a study of R&D choice with sample selection

This paper extends previous analyses of the choice between internal and external R&D to consider the costs of internal R&D. The Heckman two-stage estimator is used to estimate the determinants of internal R&D unit cost (i.e. cost per product innovation) allowing for sample selection effects. Theory indicates that R&D unit cost will be influenced by scale issues and by the technological opportunities faced by the firm. Transaction costs encountered in research activities are allowed for and, in addition, consideration is given to issues of market structure which influence the choice of R&D mode without affecting the unit cost of internal or external R&D. The model is tested on data from a sample of over 500 UK manufacturing plants which have engaged in product innovation. The key determinants of R&D mode are the scale of plant and R&D input, and market structure conditions. In terms of the R&D cost equation, scale factors are again important and have a non-linear relationship with R&D unit cost. Specificities in physical and human capital also affect unit cost, but have no clear impact on the choice of R&D mode. There is no evidence of technological opportunity affecting either R&D cost or the internal/external decision.

R&D, innovation and exporting:evidence from UK new technology based firms

We examine the relationship between R&D, innovation and exporting for a sample of new technology based firms (NTBFs) in the UK. Allowance is made for selection bias and for endogeneity between innovation and exporting. Innovators are more likely to export, but conditional on entering export markets successful innovation does not increases subsequent export intensity. Lagged productivity is strongly associated with exporting, supporting the view that efficient firms are better able to overcome the barriers to entering export markets. We also find strong evidence of the importance of internal R&D and of supply-chain collaborations in fostering innovation, and that formal commercial collaborations can be important in overcoming the (information) sunk costs of entering export markets. The use of e-commerce does nothing to boost entry into export markets, but the intensity of its use is associated with increased export intensity.

R&D, product innovation, and exporting:evidence from UK new technology based firms

We examine the relationship between R&D, product innovation, and exporting for a sample of new technology based firms (NTBFs) in the UK. Allowance is made for selection bias and for endogeneity between innovation and exporting. Product innovators are more likely to export, but conditional on entering export markets successful innovation does not increase subsequent export intensity. Lagged productivity is strongly associated with exporting, supporting the view that efficient firms are better able to overcome the barriers to entering export markets. We also find strong evidence of the importance of internal R&D and of supply-chain collaborations in fostering innovation, and that formal commercial collaborations can be important in overcoming the (information) sunk costs of entering export markets. The use of e-commerce does nothing to boost entry into export markets, but the intensity of its use is associated with increased export intensity.