The effect of R-plasmid RP1 on the properties of Proteus mirabilis

A clinical isolate of Proteus mirabilis containing R-plasmid RP1 (R+ cells), grown in both iron- and carbon- limited chemically defined media in mixed culture with plasmid-free (R- cells), did not disappear as expected, due to adherence of R+ cells to the wall of the chemostat vessel. Plasmid RP1 promoted adherence to glass and to medical prostheses. The hydrophobicity and surface charge of R+ cells were different from those of R- cells and both factors may contribute to the adherence of R+ cells to surfaces. The mode of cultivation of the cells, whether batch or continuous culture, were also found to affect the result. Antibodies raised against homologous cells increased the surface hydrophobicity of both R+ and R- cells and eliminated the differences between them. Results for surface hydrophobicity varied with the method used for measuring it. R+ cells were more sensitive than R- cells to tbe bacteridical action of normal serum and whole blood and to phagocytosis as measured by chemiluminescence. No clear differences were revealed in the protein antigens of R+ and R- cells by both SDS PAGE gels and immunoblots reacted with homologous antibodies. However, lectins revealed differences in the sugars exposed on the cell surfaces. Chemical analysis of R&43 and R- cells also revealed differences in the content of 2-keto-3-deoxy-D-manno-2-octulosonate, lipopolysaccharide and total fatty acids, when cells were grown in media containing added iron; however, no qualitative differences in the lipopolysaccharide were found. Removal of iron from the medium was found to have considerable effects on the chemical structure of R+ cells but not of R- ones. Adhesion to prostheses and to leucocytes is discussed in the light of the results and the clinical relevance outlined with respect to the initiation of infection and the association of virulence with antibiotic resistance.

Regression with input-dependent noise: A Gaussian process treatment

Gaussian processes provide natural non-parametric prior distributions over regression functions. In this paper we consider regression problems where there is noise on the output, and the variance of the noise depends on the inputs. If we assume that the noise is a smooth function of the inputs, then it is natural to model the noise variance using a second Gaussian process, in addition to the Gaussian process governing the noise-free output value. We show that prior uncertainty about the parameters controlling both processes can be handled and that the posterior distribution of the noise rate can be sampled from using Markov chain Monte Carlo methods. Our results on a synthetic data set give a posterior noise variance that well-approximates the true variance.

The mechanical properties and formability of dual-phase steel

In recent years dual phase steels comprising of 5-20% martensite in a ferrite matrix have come into the limelight of high strength cold formable steels because of their potential for vehicle weight saving. They show the following features: no yield point; relatively low initial flow stress; high initial workhardening rate; well sustained work hardening. As a consequence of these characteristics, dual phase steels exhibit a better combination of strength and elongation than other HSLA steels. In this thesis, a broad view of the factors which influence their properties is presented. Mechanical properties and forming ability of a commercially available dual phase steel and an AL-Si killed steel processed to dual phase form are investigated to ascertain the effect of their microstructure on their properties. It is found that the yield phenomena are masked by the transformation induced stresses present during processing and so yield point could be recovered under suitable ageing treatment; that apart from giving the above properties dual phasing gives rise to very low strain-rate sensitivity and a low R value ~ 1; that the mechanical response under rolling conditions is not different from those under tension; that there is a danger of damage to tooling during forming operations of these steels if fracture should precede instability as a result of grain size dependent strength found for these steels. It is also found that very little deformation of the martensite islands took place during deformation except at high strains. The work-hardening and the strength levels can be controlled by either decreasing the grain size or increasing the martensite volume fraction, but it is found that increasing martensite has a detrimental effect on ductility and the ductility and fracture strength can be controlled better by refining the grain size. A remarkable effect found in the dual phase steel tested is that the compressive strength is higher than the tensile strength. The reason for this observation is not yet clear but it is suggested that it might be due to the introduction of emissary type dislocations into the ferrite lattice as a result of twins formed in the martensite during transformation from austenite. The twins are envisaged to be {111} <112> in character.

The value of innovation:the interaction of competition, R&D and IP

This paper analyses market valuations of UK companies using a new data set of their R&D and IP activities (1989–2002). In contrast to previous studies, the analysis is conducted at the sectoral-level, where the sectors are based on the technological classification originating from Pavitt [Pavitt, K., 1984. Sectoral patterns of technical change. Research Policy 13, 343–373]. The first main result is that the valuation of R&D varies substantially across these sectors. Another important result is that, on average, firms that receive only UK patents tend to have no significant market premium. In direct contrast, patenting through the European Patent Office does raise market value, as does the registration of trade marks in the UK for most sectors. To explore these variations the paper links competitive conditions with the market valuation of innovation. Using profit persistence as a measure of competitive pressure, we find that the sectors that are the most competitive have the lowest market valuation of R&D. Furthermore, within the most competitive sector (‘science based’ manufacturing), firms with larger market shares (an inverse indicator of competitive pressure) also have higher R&D valuations, as well as some positive return to UK patents. We conclude that this evidence supports Schumpeter by finding higher returns to innovation in less than fully competitive markets and contradicts Arrow [Arrow, K., 1962. Economic welfare and the allocation of resources for invention. In: Nelson, R. (Ed.), The Rate and Direction of Inventive Activity. Princeton University Press, Princeton], who argued that, with the existence of IP rights, competitive market structure provides higher incentives to innovate.

Market value, R&D and intellectual property:an empirical analysis of large Australian firms

This paper considers the value of innovation to large Australian firms. Specifically, we investigate how R&D and intellectual property activity influences the market value of firms, using a Tobin’s q approach. R&D data are available for the period 1994–96 and data on patent, trade mark and design applications for 1996. The findings suggest that R&D and patent activity are positively and significantly associated with market value. The results also suggest that private returns to R&D in Australia are low by international standards.

To what extent and in what manner do Chinese and Indian contract research organisation learn and upgrade with the unbundling the global pharmaceutical R&D value chain?

The paper applies the GVC framework to analyse the organisational and geographical reconfiguration of the global R&D function of leading US and European pharmaceutical MNCs. Though pharmaceutical MNCs have been outsourcing clinical trial activities since the mid-1990s, the outsourcing of discovery research tasks is a phenomenon of the 2000s (Ramirez 2013). Moreover, in the context of a crisis of R&D productivity and increasing pressure from shareholders, a number of US and European pharmaceutical MNCs are breaking up their R&D function in an attempt to increase flexibility and reduce risk as well as costs and are thereby restructuring the global architecture of their R&D function. This break-up, or unbundling (Sako 2006), of the R&D function is particularly interesting given the prevalence of market failure in innovation (Howells et al 2008), the non-modular nature of the R&D process in this industry (Pisano 2006) and the strategic important of this activity to the core competence and long-term competitive advantage of firms in this sector. The focus of this paper is on the outsourcing of R&D activities to Chinese and Indian independently-owned contract research organisations (CROs) and the way these firms are becoming integrated as service providers into the global R&D function (or R&D value chain) of pharmaceutical MNCs. Above all the paper is concerned with the development of capabilities of CROs from these two countries and the dynamics of upgrading in GVCs in knowledge-intensive functions. The paper therefore discusses the role of both knowledge flows within global pharmaceutical R&D value chains as well as national innovation systems on the development of capabilities of Chinese and Indian CROs. Our analysis is based on data from semi-structured interviews collected from senior R&D managers from a sample of ten US and European pharmaceutical MNCs and owners and senior R&D managers from five Chinese and five Indian CROs who are providing research services to MNCs in this industry. We discuss the emergence of R&D outsourcing in this industry and the nature and mechanisms of knowledge flows within R&D value chains. The embeddedness of CROS in the national innovation systems of their home countries is also discussed.