1,676 research outputs found

    Smooth stable and unstable manifolds for stochastic partial differential equations

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    Invariant manifolds are fundamental tools for describing and understanding nonlinear dynamics. In this paper, we present a theory of stable and unstable manifolds for infinite dimensional random dynamical systems generated by a class of stochastic partial differential equations. We first show the existence of Lipschitz continuous stable and unstable manifolds by the Lyapunov-Perron's method. Then, we prove the smoothness of these invariant manifolds

    The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease – A systematic literature review by a European panel of experts

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    BACKGROUND: Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. METHODS: A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. RESULTS: Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. CONCLUSIONS: Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage

    Stable Word-Clouds for Visualising Text-Changes Over Time

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    Word-clouds are a useful tool for providing overviews over texts, visualising relevant words. Multiple word-clouds can also be used to visualise changes over time in a text. This requires that the words in the individual word-clouds have stable positions, as otherwise it is very difficult so see what changed between two consecutive word-clouds. Existing approaches have used coordinated positioning algorithms, which do not allow for their use in an online, dynamic context. In this paper we present a fast word-cloud algorithm that uses word orthogonality to determine which words can share the same space in the word-clouds combined with a simple, but fast spiral-based layout algorithm. The evaluation shows that the algorithm achieves its goal of creating series of word-clouds fast enough to enable use in an online, dynamic context

    Single mutation to a sex pheromone receptor provides adaptive specificity between closely related moth species

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    Sex pheromone communication, acting as a prezygotic barrier to mating, is believed to have contributed to the speciation of moths and butterflies in the order Lepidoptera. Five decades after the discovery of the first moth sex pheromone, little is known about the molecular mechanisms that underlie the evolution of pheromone communication between closely related species. Although Asian and European corn borers (ACB and ECB) can be interbred in the laboratory, they are behaviorally isolated from mating naturally by their responses to subtly different sex pheromone isomers, (E)-12- and (Z)-12-tetradecenyl acetate and (E)-11- and (Z)-11-tetradecenyl acetate (ACB: E12, Z12; ECB; E11, Z11). Male moth olfactory systems respond specifically to the pheromone blend produced by their conspecific females. In vitro, ECB(Z) odorant receptor 3 (OR3), a sex pheromone receptor expressed in male antennae, responds strongly to E11 but also generally to the Z11, E12, and Z12 pheromones. In contrast, we show that ACB OR3, a gene that has been subjected to positive selection (ω = 2.9), responds preferentially to the ACB E12 and Z12 pheromones. In Ostrinia species the amino acid residue corresponding to position 148 in transmembrane domain 3 of OR3 is alanine (A), except for ACB OR3 that has a threonine (T) in this position. Mutation of this residue from A to T alters the pheromone recognition pattern by selectively reducing the E11 response ∼14-fold. These results suggest that discrete mutations that narrow the specificity of more broadly responsive sex pheromone receptors may provide a mechanism that contributes to speciation

    Novel approach to observing system simulation experiments improves information gain of surface-atmosphere field measurements

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    The observing system design of multidisciplinary field measurements involves a variety of considerations on logistics, safety, and science objectives. Typically, this is done based on investigator intuition and designs of prior field measurements. However, there is potential for considerable increases in efficiency, safety, and scientific success by integrating numerical simulations in the design process. Here, we present a novel numerical simulation–environmental response function (NS–ERF) approach to observing system simulation experiments that aids surface–atmosphere synthesis at the interface of mesoscale and microscale meteorology. In a case study we demonstrate application of the NS–ERF approach to optimize the Chequamegon Heterogeneous Ecosystem Energy-balance Study Enabled by a High-density Extensive Array of Detectors 2019 (CHEESEHEAD19). During CHEESEHEAD19 pre-field simulation experiments, we considered the placement of 20 eddy covariance flux towers, operations for 72 h of low-altitude flux aircraft measurements, and integration of various remote sensing data products. A 2 h high-resolution large eddy simulation created a cloud-free virtual atmosphere for surface and meteorological conditions characteristic of the field campaign domain and period. To explore two specific design hypotheses we super-sampled this virtual atmosphere as observed by 13 different yet simultaneous observing system designs consisting of virtual ground, airborne, and satellite observations. We then analyzed these virtual observations through ERFs to yield an optimal aircraft flight strategy for augmenting a stratified random flux tower network in combination with satellite retrievals. We demonstrate how the novel NS–ERF approach doubled CHEESEHEAD19's potential to explore energy balance closure and spatial patterning science objectives while substantially simplifying logistics. Owing to its modular extensibility, NS–ERF lends itself to optimizing observing system designs also for natural climate solutions, emission inventory validation, urban air quality, industry leak detection, and multi-species applications, among other use cases.</p

    Towards a multimedia knowledge-based agent with social competence and human interaction capabilities

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    We present work in progress on an intelligent embodied conversation agent in the basic care and healthcare domain. In contrast to most of the existing agents, the presented agent is aimed to have linguistic cultural, social and emotional competence needed to interact with elderly and migrants. It is composed of an ontology-based and reasoning-driven dialogue manager, multimodal communication analysis and generation modules and a search engine for the retrieval of multimedia background content from the web needed for conducting a conversation on a given topic.The presented work is funded by the European Commission under the contract number H2020-645012-RIA

    LISA Pathfinder: First steps to observing gravitational waves from space

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    LISA Pathfinder, the European Space Agency's technology demonstrator mission for future spaceborne gravitational wave observatories, was launched on 3 December 2015, from the European space port of Kourou, French Guiana. After a short duration transfer to the final science orbit, the mission has been gathering science data since. This data has allowed the science community to validate the critical technologies and measurement principle for low frequency gravitational wave detection and thereby confirming the readiness to start the next generation gravitational wave observatories, such as LISA. This paper will briefly describe the mission, followed by a description of the science operations highlighting the performance achieved. Details of the various experiments performed during the nominal science operations phase can be found in accompanying papers in this volume

    The importance of language for language development: Linguistic determinism in the 1980s

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    The semantic and syntactic functions of verbs are the major aspects of linguistic complexity that contribute to the cognitive requirements for learning language between two and three years of age. Several contrastive categories of verbs emerged from our studies with action/state as the largest and most general. Contrastive subcategories of action verbs were locative/nonlocative action, durative/nondurative action, and completive/noncompletive action. The subcategories of state verbs were volitional/epistemic/notice/communication states. The psychological and linguistic validity of these semantic categories rests on their being coextensive with major grammatical developments and/or their sequential development

    LISA Pathfinder closed-loop analysis: a model breakdown of the in-loop observables

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    This paper describes a methodology to analyze, in the frequency domain, the steady-state control performances of the LISA Pathfinder mission. In particular, it provides a technical framework to give a comprehensive understanding of the spectra of all the degrees of freedom by breaking them down into their various physical origins, hence bringing out the major contributions of the control residuals. A reconstruction of the measured in-loop output, extracted from a model of the closed-loop system, is shown as an instance to illustrate the potential of such a model breakdown of the data

    Beyond the required LISA free-fall performance: new LISA pathfinder results down to 20  μHz

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    In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency
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