945 research outputs found

    Tripping into the Light Fantastic: Seeing (through) MacDonald

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    Review of From Spare Oom to War Drobe: Travels in Narnia with my Nine-Year-Old Self

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    Sarah Waters: Review of Katherine Langrish, From Spare Oom to War Drobe: Travels in Narnia with my Nine-Year-Old Self (London: Darton, Longman and Todd, 2021). 286 pages. $26.00. ISBN 9781913657079

    Review of The Lion, the Witch and the Wardrobe (play)

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    Review of The Lion, the Witch and the Wardrobe, based on the book by C. S. Lewis, directed by Mike Fentiman (based on the original production by Sally Cookson). Produced by Elliott and Harper Productions, and Catherine Schreiber. London, UK: Gillian Lynne Theatre, 30 October, 2022

    Review of The Faithful Imagination: Papers from the 2018 Frances White Ewbank Colloquium on C. S. Lewis & Friends

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    Review of Joe Ricke and Ashley Chu, eds., The Faithful Imagination: Papers from the 2018 Frances White Ewbank Colloquium on C. S. Lewis & Friends (Hamden, CT: Winged Lion Press, 2019). 440 pages. $32.95. ISBN 9781935688303

    Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside

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    Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches. We discuss how in silico approaches, alongside complementary experimental approaches, can enhance our understanding of the mechanisms underlying successful cell delivery and engraftment. Furthermore, such combined theoretical-experimental approaches can be exploited to develop novel therapies, address safety and efficacy challenges, bridge the gap between in vitro and in vivo model systems, and compensate for the inherent differences between animal model systems and humans. We also highlight how in silico model development can result in fewer and more targeted in vivo experiments, thereby reducing preclinical costs and experimental animal numbers and potentially accelerating translation to the clinic. The development of biologically-accurate in silico models that capture the mechanisms underpinning the behaviour of these complex systems must be reinforced by quantitative methods to assess cell survival post-transplant, and we argue that non-invasive in vivo imaging strategies should be routinely integrated into transplant studies

    Horizontal transfer of OC1 transposons in the Tasmanian devil

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    BACKGROUND There is growing recognition that horizontal DNA transfer, a process known to be common in prokaryotes, is also a significant source of genomic variation in eukaryotes. Horizontal transfer of transposable elements (HTT) may be especially prevalent in eukaryotes given the inherent mobility, widespread occurrence, and prolific abundance of these elements in many eukaryotic genomes. RESULTS Here, we provide evidence for a new case of HTT of the transposon family OposCharlie1 (OC1) in the Tasmanian devil, Sarcophilus harrisii. Bioinformatic analyses of OC1 sequences in the Tasmanian devil genome suggest that this transposon infiltrated the common ancestor of the Dasyuridae family ~17 million years ago. This estimate is corroborated by a PCR-based screen for the presence/absence of this family in Tasmanian devils and closely-related species. CONCLUSIONS This case of HTT is the first to be reported in dasyurids. It brings the number of animal lineages independently invaded by OC1 to 12, and adds a fourth continent to the pandemic-like pattern of invasion of this transposon. In the context of these data, we discuss the evolutionary history of this transposon family and its potential impact on the diversification of marsupials.The authors would like to acknowledge the following organizations for funding portions of this work: NIH-R01 GM077582 (CF), M.J. Murdock Charitable Trust (SS) and NSF-MCB-1150213 (SS

    Local and global instabilities of flow in a flexible-walled channel

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    We consider laminar high-Reynolds-number flow through a long finite-length planar channel, where a segment of one wall is replaced by a massless membrane held under longitudinal tension. The flow is driven by a fixed pressure difference across the channel and is described using an integral form of the unsteady boundary-layer equations. The basic flow state, for which the channel has uniform width, exhibits static and oscillatory global instabilities, having distinct modal forms. In contrast, the corresponding local problem (neglecting boundary conditions associated with the rigid parts of the system) is found to be convectively, but not absolutely, unstable to small-amplitude disturbances in the absence of wall damping. We show how amplification of the primary global oscillatory instability can arise entirely from wave reflections with the rigid parts of the system, involving interacting travelling wave flutter and static-divergence modes that are convectively stable; alteration of the mean flow by oscillations makes the onset of this primary instability subcritical. We also show how distinct mechanisms of energy transfer differentiate the primary global mode from other modes of oscillatory instability

    Hamlet in Narnia: The Prince and the Poem in Lewis’s Chronicles of Narnia

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    C.S. Lewis is little-known for his Shakespeare scholarship except perhaps for his lecture “Hamlet: The Prince or the Poem” for the British Academy (1942). This essay begins by discussing Lewis’s approach to the play and his desire to reenchant his audience with the play he had loved as a child, before character-criticism got in the way. It then explores how Lewis takes the Prince and the aspects he found most affective in Hamlet out of the play and explores them, imaginatively, in another world: recasting them “for children” in Narnia. The essay considers Hamlet in The Silver Chair in which Rilian is literally compared to the Prince, the Hamlet-like trajectory of Prince Caspian, and finally, in The Last Battle, the recreation of another world characterized by its pervasive atmosphere of death in which characters and readers alike are called to consider “being dead”

    Bifurcations and dynamics emergent from lattice and continuum models of bioactive porous media

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    We study dynamics emergent from a two-dimensional reaction--diffusion process modelled via a finite lattice dynamical system, as well as an analogous PDE system, involving spatially nonlocal interactions. These models govern the evolution of cells in a bioactive porous medium, with evolution of the local cell density depending on a coupled quasi--static fluid flow problem. We demonstrate differences emergent from the choice of a discrete lattice or a continuum for the spatial domain of such a process. We find long--time oscillations and steady states in cell density in both lattice and continuum models, but that the continuum model only exhibits solutions with vertical symmetry, independent of initial data, whereas the finite lattice admits asymmetric oscillations and steady states arising from symmetry-breaking bifurcations. We conjecture that it is the structure of the finite lattice which allows for more complicated asymmetric dynamics. Our analysis suggests that the origin of both types of oscillations is a nonlocal reaction-diffusion mechanism mediated by quasi-static fluid flow.Comment: 30 pages, 21 figure

    Lattice and Continuum Modelling of a Bioactive Porous Tissue Scaffold

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    A contemporary procedure to grow artificial tissue is to seed cells onto a porous biomaterial scaffold and culture it within a perfusion bioreactor to facilitate the transport of nutrients to growing cells. Typical models of cell growth for tissue engineering applications make use of spatially homogeneous or spatially continuous equations to model cell growth, flow of culture medium, nutrient transport, and their interactions. The network structure of the physical porous scaffold is often incorporated through parameters in these models, either phenomenologically or through techniques like mathematical homogenization. We derive a model on a square grid lattice to demonstrate the importance of explicitly modelling the network structure of the porous scaffold, and compare results from this model with those from a modified continuum model from the literature. We capture two-way coupling between cell growth and fluid flow by allowing cells to block pores, and by allowing the shear stress of the fluid to affect cell growth and death. We explore a range of parameters for both models, and demonstrate quantitative and qualitative differences between predictions from each of these approaches, including spatial pattern formation and local oscillations in cell density present only in the lattice model. These differences suggest that for some parameter regimes, corresponding to specific cell types and scaffold geometries, the lattice model gives qualitatively different model predictions than typical continuum models. Our results inform model selection for bioactive porous tissue scaffolds, aiding in the development of successful tissue engineering experiments and eventually clinically successful technologies.Comment: 38 pages, 16 figures. This version includes a much-expanded introduction, and a new section on nonlinear diffusion in addition to polish throughou
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