6,199 research outputs found

    Multivariate emulation of computer simulators: model selection and diagnostics with application to a humanitarian relief model

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    We present a common framework for Bayesian emulation methodologies for multivariate-output simulators, or computer models, that employ either parametric linear models or nonparametric Gaussian processes. Novel diagnostics suitable for multivariate covariance-separable emulators are developed and techniques to improve the adequacy of an emulator are discussed and implemented. A variety of emulators are compared for a humanitarian relief simulator, modelling aid missions to Sicily after a volcanic eruption and earthquake, and a sensitivity analysis is conducted to determine the sensitivity of the simulator output to changes in the input variables. The results from parametric and nonparametric emulators are compared in terms of prediction accuracy, uncertainty quantification and scientific interpretability

    Evidence for potential underestimation of clinical folate deficiency in resource-limited countries using blood tests

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    Although a low serum folate concentration is a useful biomarker of pure folate deficiency, the presence of vitamin B12 deficiency or hemolysis or both in individuals with low folate status predictably raises serum folate levels. Therefore, in resource-limited settings where dietary folate deficiency can coexist with vitamin B12 deficiency or malaria or both, the serum folate concentration can range from normal to high, leading to serious underestimation of tissue folate status. This review traces the genesis of an inappropriate overreliance on the serum folate concentration to rule out folate deficiency in vulnerable populations of women and children. Of significance, without due consideration of a chronically inadequate dietary folate intake, authors of influential studies have likely wrongly judged these populations to have an adequate folate status. Through repetition, this error has led to a dangerous entry into the contemporary medical literature that folate deficiency is rare in women and children. As a consequence, many millions of under-resourced women and children with mild to moderate tissue folate deficiency may have been deprived of folate replacement. This review uses historical documents to challenge earlier conclusions and re-emphasizes the need for contextual integration of clinical information in resource-limited settings

    Deletion mutants in COP9/Signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes

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    The COP9/signalosome complex is highly conserved in evolution and possesses significant structural similarity to the 19S regulatory lid complex of the proteasome. It also shares limited similarity to the translation initiation factor eIF3. The signalosome interacts with multiple cullins in mammalian cells. In the fission yeast Schizosaccharomyces pombe, the Csn1 subunit is required for the removal of covalently attached Nedd8 from Pcu1, one of three S. pombe cullins. It remains unclear whether this activity is required for all the functions ascribed to the signalosome. We previously identified Csn1 and Csn2 as signalosome subunits in S. pombe. csn1 and csn2 null mutants are DNA damage sensitive and exhibit slow DNA replication. Two further putative subunits, Csn4 and Csn5, were identified from the S. pombe genome database. Herein, we characterize null mutations of csn4 and csn5 and demonstrate that both genes are required for removal of Nedd8 from the S. pombe cullin Pcu1 and that their protein products associate with Csn1 and Csn2. However, neither csn4 nor csn5 null mutants share the csn1 and csn2 mutant phenotypes. Our data suggest that the subunits of the signalosome cannot be considered as a distinct functional unit and imply that different subunits of the signalosome mediate distinct functions

    Chromatin Structure in the Cellular Slime Mold Dictyostelium discoideum

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    The structure of Dictyostelium discoideum chromatin has been studied by the following techniques: electron microscopy, staphylococcal nuclease digestion, acrylamide gel electrophoresis, sucrose gradient centrifugation, and melting. The basic unit of chromatin is the nucleosome, which is a particle 98.6 angstrom in diameter. Approximately 50% of the chromatin is protected from nuclease digestion, but this decreases when protease activity is not inhibited. The nucleosome contains 187 base pairs of DNA, including a 137-base-pair core and a 50-base-pair linker. The monomer nucleosome has an s20,w value of 11.5 S on isokinetic sucrose gradients. When the chromatin is melted, four transitions are observed, at 54.5 degrees, 66.7 degrees, 74.9 degrees, and 79.7 degrees. The structure of Dictyostelium chromatin is very similar to that seen in higher eukaryotes

    Spaces of Appearance: Writings on Contemporary Theatre and Performance

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    This thesis, a collection of previously published materials, reflects a plural and evolving engagement with theatre and performance over the past fifteen years or so: as researcher, writer, editor, teacher, practitioner, spectator. These have rarely been discreet categories for me, but rather different modalities of exploration and enquiry, interrelated spaces encouraging dynamic connectivities, flows and further questions. Section 1 offers critical accounts of the practices of four contemporary theatre directors: Jerzy Grotowski, Robert Wilson, Peter Brook and Ariane Mnouchkine. Section 2 draws on elements of contemporary philosophy and critical thinking to explore the mutable parameters of performance. lt proposes performative mappings of certain unpredictable, energetic events 'in proximity of performance', to borrow Matthew Goulish's phrase: contact, fire, animals, alterity, place. Section 3 contains examples of documentation of performance practices, including a thick description of a mise en scene of a major international theatre production, reflections on process, training and dramaturgy, a performance text with a framing dramaturgical statement, and personal perspectives on particular collaborations. The external Appendix comprises a recently published collection of edited and translated materials concerning five core collaborative projects realised by Ariane Mnouchkine and the Theatre du Soleil at their base in the Cartoucherie de Vincennes, Paris. The core concerns of this thesis include attempts to think through: ā€¢ the working regimes, poetics and pedagogies of certain directors, usually in collaborative devising contexts within which the creative agency of performers is privileged; ā€¢ the processes and micro-politics of collaboration, devising, and dramaturgical composition; the dramaturgical implications of trainings, narrative structures, spaces, mise en scene, and of images as multi-layered, dynamic 'fields'; ā€¢ the predicament and agency of spectators in diverse performance contexts, and the ways in which spectatorial roles are posited or constructed by dramaturgies; ā€¢ the imbrication of embodiment, movement and perception in performance, and the plurality of modes of perception; ā€¢ the critical and political functions of theatre and theatre criticism as cultural/social practice and 'art of memory' (de Certeau), of dramaturgies as critical historiographies, and of theatre cultures (and identities) as plural, dynamic, and contested; ā€¢ performance as concentrated space for inter-subjectivity and the flaring into appearance of the 'face-to-face' (Levinas); the possibility of ethical, 'response-able' encounter and exchange with another; identity as relational and in-process, alterity as productive event, the inter-personal as political; ā€¢ the poetics and politics of what seems an unthinkable surplus (and constitutive 'outside') to the cognitive reach of many conventional frames and maps in theatre criticism and historiography; an exploration of acts of writing as performative propositions and provocations ('critical fictions') to think the event of meanings at/of the limits of knowledge and subjectivity. This partial listing of recurrent and evolving concerns within the thesis traces a trajectory in my evolution as a writer and thinker, a gradual displacement from the relatively 'solid ground' of theatre studies and theatre history towards more fluid and tentative articulations of the shifting 'lie of the land' in contemporary performance and philosophy. This trajectory reflects a growing fascination with present process, conditions, practices, perceptions 'in the middle', and ways of writing (about) performance as interactive and ephemeral event

    Bayesian Optimal Design for Ordinary Differential Equation Models

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    Bayesian optimal design is considered for experiments where it is hypothesised that the responses are described by the intractable solution to a system of non-linear ordinary differential equations (ODEs). Bayesian optimal design is based on the minimisation of an expected loss function where the expectation is with respect to all unknown quantities (responses and parameters). This expectation is typically intractable even for simple models before even considering the intractability of the ODE solution. New methodology is developed for this problem that involves minimising a smoothed stochastic approximation to the expected loss and using a state-of-the-art stochastic solution to the ODEs, by treating the ODE solution as an unknown quantity. The methodology is demonstrated on three illustrative examples and a real application involving estimating the properties of human placentas

    Light Dependent Morpho-Physiological Changes and Yield Response of Hybrid Napier Cultivars under Rainfed System

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    For small dairy farmers in the tropics, open land for fodder cultivation is often limited because of the predominance of tree crops and paddies. Probably because of this limitation, to offset fodder supply for the livestock, growing fodder crops under tree crops such as coconut is a widely prevalent practice in the tropics. However, successful establishment and growth of most fodder crops especially high yielding types such as hybrid napier under shade depends on the amount of light available and the consequent morpho-physiological responses of the crops
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