302 research outputs found

    Poisson approximation of Rademacher functionals by the Chen-Stein method and Malliavin calculus

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    New bounds on the total variation distance between the law of integer valued functionals of possibly non-symmetric and non-homogeneous infinite Rademacher sequences and the Poisson distribution are established. They are based on a combination of the Chen-Stein method and a discrete version of Malliavin calculus. We give some applications to shifted discrete multiple stochastic integrals.Comment: Comments on version 2: An error in the bound of Theorem 3.4 was corrected. Corollary 3.9, Remark 3.10 and Remark 3.14 were added to discuss some concrete applications to Theorem 3.7 and Theorem 3.13 (formerly Theorem 3.11

    A decade of monitoring and management of freshwater algae, in particular Cyanobacteria, in England and Wales

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    Although the toxicity of cyanobacteria has been known for many years, cyanobacteria-related problems in the UK were generally limited in frequency. However, this all changed and became of national concern following the exceptional environmental conditions in the autumn of 1989, when widespread cyanobacterial blooms and scums developed in fresh waters. This paper summarises the Environment Agency's monitoring programme for freshwater algae since 1991 and describes the actions the Environment Agency has taken as a result of the monitoring data

    The use of Shigella flexneri to study bacterial cell biology during infection of host cells

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    Shigella flexneri is a facultative intracellular bacterium and a paradigm to address key issues in cell biology and cell-autonomous immunity. Cell-autonomous immunity is a system of host defence that senses invading pathogens and mobilises anti-pathogen mechanisms, including autophagy. Recently, it has become clear that the cytoskeleton is directly linked to cell-autonomous immunity. During my PhD, I used S. flexneri to investigate bacterial factors that mediate interactions with the cytoskeleton and cell-autonomous immunity. Bacteria have counterparts to the host cytoskeleton components actin (e.g. MreB), microtubules (e.g. FtsZ), intermediate filaments (e.g. CreS) and septins (MinCD). However, rearrangements of the bacterial cytoskeleton have never been followed in pathogenic bacteria during infection of host cells. In Chapter 1, I generate new tools to follow the Shigella MreB, FtsZ and MinC cytoskeleton during infection of host cells using fluorescence microscopy. S. flexneri can exploit the host actin cytoskeleton to form ‘actin tails’ for its own motility. Actin-based motility enables bacterial cell-to-cell spread and evasion of the immune system. Polar localisation of the autotransporter IcsA is required for efficient actin tail formation, yet how IcsA is targeted to the bacterial cell pole was not fully known. In Chapter 2, I use Shigella MreB-msfGFPsw to reveal that MreB targets IcsA to the bacterial cell pole to promote actin tail formation and autophagy escape. To entrap Shigella for autophagy, the host septin cytoskeleton forms cage-like structures around actin polymerising bacteria. How septins recognise bacteria is poorly understood. In Chapter 3, I report that septins sense micron-scale curvature, cardiolipin and cell growth of dividing bacterial cells to inhibit Shigella cell division via autophagy and lysosome fusion. Therefore, the host septin cytoskeleton offers great potential to boost the recognition and restriction of dividing bacterial cells. Overall, the findings in this thesis have discovered that by controlling bacterial cell polarity, morphology and division, the bacterial cytoskeleton shapes host-pathogen interactions. Moreover, they highlight that investigation of the bacterial cytoskeleton during infection can inspire the development of new therapeutic regimes for infection control.Open Acces

    Bacterial cell division is recognized by the septin cytoskeleton for restriction by autophagy.

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    Septins are cytoskeletal proteins widely recognized for their role in eukaryotic cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella flexneri targeted to macroautophagy/autophagy. Although the Shigella septin cage was discovered ~10 y ago, how septins recognize Shigella was poorly understood. We found that septins are recruited to regions of micrometer-scale curvature presented by dividing bacterial cells, and cardiolipin (a curvature-specific phospholipid) promotes septin recruitment to these regions. Chemical manipulation of bacteria revealed that following recruitment, septins assemble into cages around growing bacterial cells. Once assembled, septin cages inhibit Shigella cell division by autophagy and fusion with lysosomes. Thus, recognition of dividing bacterial cells by the septin cytoskeleton targets intracellular pathogens to antibacterial autophagy

    Interactions between Shigella flexneri and the Autophagy Machinery.

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    Autophagy, an intracellular degradation process, is increasingly recognized as having important roles in host defense. Interactions between Shigella flexneri and the autophagy machinery were first discovered in 2005. Since then, work has shown that multiple autophagy pathways are triggered by S. flexneri, and autophagic responses can have different roles during Shigella infection. Here, we review the interactions between S. flexneri and the autophagy machinery, highlighting that studies using Shigella can reveal the breadth of autophagic responses available to the host

    Promises and Myths of Artificial Intelligence

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    The development dynamics of any new technology are usually associated with promises of its special performance and completely new application possibilities. This is especially true for artificial intelligence (AI), prompting this contribution to inquire into which particular special features the technology promises. However, the imprecise rhetoric of that promise becomes apparent. Although it appears simple, clear, and convincing, it is fundamentally difficult to dispute and introduces multitudes of ambiguity, relying on fuzzy conceptual metaphors, very unspecific assessments, implicit misconceptions, technological determinism, and exaggerations of the future opportunities AI offers for economic and social progress. Ultimately, the promises of AI nourish their lasting persuasive power with notions from the old myth of the intelligent machine
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