1,526 research outputs found

    Second Time Round : Fugal Memory in Ciaran Carsonā€™s For All We Know

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    Willa Muir, Imagined Corners (1931)

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    Recommends Muir\u27s novel (which came in 30th in the BBC poll), set in a small Scottish town and concerned with \u27the ideology of Scotland,\u27 and questions of class, religion, sexuality, politics, and education, as indisputably a great novel, perhaps equalled in British fiction only by To the Lighthouse, and utterly unique in the Scottish canon

    Writing Scotland\u27s Future: Speculative Fiction and the National Imagination

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    Explores the fictional treatment of future Scotlands in the wake of the 2014 Referendum, through discussion of varied speculative novels or stories by Graham Dunstan, Paul Johnston, Ken Macleod, Matthew Fitt, Julie Bertagna, Momus, Andrew Crumey, A.L.Kennedy, Michael Faber, and Sarah Hall, arguing that the relation between Scottish literature and Scottish politics is more complex than is often thought, that rather than simply commenting on current political situations, much contemporary Scottish fiction offers a rethinking of politics entirely, and that Scotlandā€™s future is not, and cannot be, confined to a single narrative

    Fear and Pity, Pity and Fear : Rereading Muriel Sparkā€™s The Driverā€™s Seat in the Age of #MeToo

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    I am indebted to my students for their seminar contributions, and particularly Caitlin Beveridge, Anita Markoff, and Darryl Peers for subsequent reflections and comments. I am also grateful to Katherine Furman for first introducing me to Manneā€™s work.Peer reviewedPublisher PD

    Variable-free exploration of stochastic models: a gene regulatory network example

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    Finding coarse-grained, low-dimensional descriptions is an important task in the analysis of complex, stochastic models of gene regulatory networks. This task involves (a) identifying observables that best describe the state of these complex systems and (b) characterizing the dynamics of the observables. In a previous paper [13], we assumed that good observables were known a priori, and presented an equation-free approach to approximate coarse-grained quantities (i.e, effective drift and diffusion coefficients) that characterize the long-time behavior of the observables. Here we use diffusion maps [9] to extract appropriate observables ("reduction coordinates") in an automated fashion; these involve the leading eigenvectors of a weighted Laplacian on a graph constructed from network simulation data. We present lifting and restriction procedures for translating between physical variables and these data-based observables. These procedures allow us to perform equation-free coarse-grained, computations characterizing the long-term dynamics through the design and processing of short bursts of stochastic simulation initialized at appropriate values of the data-based observables.Comment: 26 pages, 9 figure

    Knowledge and Use of Integrated Pest Management by Underserved Producers in Missouri and the Role of Extension

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    In Missouri, Plain producers (groups of conservative Anabaptist faith, including the Amish and Mennonites) are one type of underserved audience that has found a niche in vegetable production. The study reported here investigated the level of knowledge and use of Integrated Pest Management (IPM) gained over a 3-year period following implementation of Extension activities by the University of Missouri and Lincoln University, the two Missouri land-grant universities. Results indicate that Extension plays an important role in the observed increased use of IPM by the target audience and highlight the need to continue using traditional methods (e.g., printed documents, one-on-one interactions)

    Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis

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    Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon in vitro and are attenuated in mice, further highlighting the importance of the macrodomain-PLP2 interplay in viral pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging human and veterinary pathogens with pandemic potential. Despite the established and predicted threat these viruses pose to human health, there are currently no approved countermeasures to control infections with these viruses in humans. Viral macrodomains, enzymes that remove posttranslational ADP-ribosylation of proteins, and viral multifunctional papain-like proteases, enzymes that cleave polyproteins and remove polyubiquitin chains via deubiquitinating activity, are two important virulence factors. Here, we reveal an unanticipated interplay between the macrodomain and the PLP2 domain that is important for replication and antagonizing the host innate immune response. Targeting the interaction of these enzymes may provide new therapeutic opportunities to treat CoV disease
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