1,821 research outputs found

    Putting things in places: Developmental consequences of linguistic typology

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    This study explores how adults and children describe placement events (e.g., putting a book on a table) in a range of different languages (Finnish, English, German, Russian, Hindi, Tzeltal Maya, Spanish, and Turkish). Results show that the eight languages grammatically encode placement events in two main ways (Talmy, 1985, 1991), but further investigation reveals fine-grained crosslinguistic variation within each of the two groups. Children are sensitive to these finer-grained characteristics of the input language at an early age, but only when such features are perceptually salient. Our study demonstrates that a unitary notion of 'event' does not suffice to characterize complex but systematic patterns of event encoding crosslinguistically, and that children are sensitive to multiple influences, including the distributional properties of the target language, in constructing these patterns in their own speech

    Fasudil improves survival and promotes skeletal muscle development in a mouse model of spinal muscular atrophy

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    <p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. It is caused by mutations/deletions of the survival motor neuron 1 (<it>SMN1</it>) gene and is typified by the loss of spinal cord motor neurons, muscular atrophy, and in severe cases, death. The SMN protein is ubiquitously expressed and various cellular- and tissue-specific functions have been investigated to explain the specific motor neuron loss in SMA. We have previously shown that the RhoA/Rho kinase (ROCK) pathway is misregulated in cellular and animal SMA models, and that inhibition of ROCK with the chemical Y-27632 significantly increased the lifespan of a mouse model of SMA. In the present study, we evaluated the therapeutic potential of the clinically approved ROCK inhibitor fasudil.</p> <p>Methods</p> <p>Fasudil was administered by oral gavage from post-natal day 3 to 21 at a concentration of 30 mg/kg twice daily. The effects of fasudil on lifespan and SMA pathological hallmarks of the SMA mice were assessed and compared to vehicle-treated mice. For the Kaplan-Meier survival analysis, the log-rank test was used and survival curves were considered significantly different at <it>P </it>< 0.05. For the remaining analyses, the Student's two-tail <it>t </it>test for paired variables and one-way analysis of variance (ANOVA) were used to test for differences between samples and data were considered significantly different at <it>P </it>< 0.05.</p> <p>Results</p> <p>Fasudil significantly improves survival of SMA mice. This dramatic phenotypic improvement is not mediated by an up-regulation of Smn protein or via preservation of motor neurons. However, fasudil administration results in a significant increase in muscle fiber and postsynaptic endplate size, and restores normal expression of markers of skeletal muscle development, suggesting that the beneficial effects of fasudil could be muscle-specific.</p> <p>Conclusions</p> <p>Our work underscores the importance of muscle as a therapeutic target in SMA and highlights the beneficial potential of ROCK inhibitors as a therapeutic strategy for SMA and for other degenerative diseases characterized by muscular atrophy and postsynaptic immaturity.</p

    A Human Development Framework for CO2 Reductions

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    Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

    HIF-1 and SKN-1 Coordinate the Transcriptional Response to Hydrogen Sulfide in Caenorhabditis elegans

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    Hydrogen sulfide (H2S) has dramatic physiological effects on animals that are associated with improved survival. C. elegans grown in H2S are long-lived and thermotolerant. To identify mechanisms by which adaptation to H2S effects physiological functions, we have measured transcriptional responses to H2S exposure. Using microarray analysis we observe rapid changes in the abundance of specific mRNAs. The number and magnitude of transcriptional changes increased with the duration of H2S exposure. Functional annotation suggests that genes associated with protein homeostasis are upregulated upon prolonged exposure to H2S. Previous work has shown that the hypoxia-inducible transcription factor, HIF-1, is required for survival in H2S. In fact, we show that hif-1 is required for most, if not all, early transcriptional changes in H2S. Moreover, our data demonstrate that SKN-1, the C. elegans homologue of NRF2, also contributes to H2S-dependent changes in transcription. We show that these results are functionally important, as skn-1 is essential to survive exposure to H2S. Our results suggest a model in which HIF-1 and SKN-1 coordinate a broad transcriptional response to H2S that culminates in a global reorganization of protein homeostasis networks

    A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

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    We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 fb−1{\rm fb}^{-1} recorded at the ΄(4S)\Upsilon(4S) resonance and 3.9 fb−1{\rm fb}^{-1} off-resonance. One of the neutral B mesons, which are produced in pairs at the ΄(4S)\Upsilon(4S), is fully reconstructed in the CP decay modes J/ψKS0J/\psi K^0_S, ψ(2S)KS0\psi(2S) K^0_S, χc1KS0\chi_{c1} K^0_S, J/ψK∗0J/\psi K^{*0} (K∗0→KS0π0K^{*0}\to K^0_S\pi^0) and J/ψKL0J/\psi K^0_L, or in flavor-eigenstate modes involving D(∗)π/ρ/a1D^{(*)}\pi/\rho/a_1 and J/ψK∗0J/\psi K^{*0} (K∗0→K+π−K^{*0}\to K^+\pi^-). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds Δmd=0.516±0.016(stat)±0.010(syst)ps−1\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}. The value of the asymmetry amplitude sin⁥2ÎČ\sin2\beta is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged B0B^0 decays in the CP-eigenstate modes. We find sin⁥2ÎČ=0.59±0.14(stat)±0.05(syst)\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

    Regional Variations in Emergency Service Performance: Does Social Capital Matter?

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    Regional variations in emergency service performance: does social capital matter?, Regional Studies. The relationship between social capital and the performance of public organizations is currently at the top of the UK policy agenda and elsewhere. This paper examines whether social capital is associated with improved regional emergency service performance by exploring its relationship with the achievements of ambulance trusts in England. Drawing on a six-year panel dataset, ambulance response times are modelled using an index of social capital, incorporating measures of community organizational life, political efficacy and social trust, in the regions served by National Health Service (NHS) ambulance trusts. Theoretical and practical implications are discussed

    Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

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    The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table
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