18 resultados para Systemic thinking

em Cambridge University Engineering Department Publications Database


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Growth of Salmonella enterica in mammalian tissues results from continuous spread of bacteria to new host cells. Our previous work indicated that infective S. enterica are liberated from host cells via stochastic necrotic burst independently of intracellular bacterial numbers. Here we report that liver phagocytes can undergo apoptotic caspase-3-mediated cell death in vivo, with apoptosis being a rare event, more prevalent in heavily infected cells. The density-dependent apoptotic cell death is likely to constitute an alternative mechanism of bacterial spread as part of a bet-hedging strategy, ensuring an ongoing protective intracellular environment in which some bacteria can grow and persist.

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Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

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Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.

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Matching a new technology to an appropriate market is a major challenge for new technology-based firms (NTBF). Such firms are often advised to target niche-markets where the firms and their technologies can establish themselves relatively free of incumbent competition. However, technologies are diverse in nature and do not benefit from identical strategies. In contrast to many Information and Communication Technology (ICT) innovations which build on an established knowledge base for fairly specific applications, technologies based on emerging science are often generic and so have a number of markets and applications open to them, each carrying considerable technological and market uncertainty. Each of these potential markets is part of a complex and evolving ecosystem from which the venture may have to access significant complementary assets in order to create and sustain commercial value. Based on dataset and case study research on UK advanced material university spin-outs (USO), we find that, contrary to conventional wisdom, the more commercially successful ventures were targeting mainstream markets by working closely with large, established competitors during early development. While niche markets promise protection from incumbent firms, science-based innovations, such as new materials, often require the presence, and participation, of established companies in order to create value. © 2012 IEEE.