443 research outputs found

    The importance of investing in physics:The fundamental value of knowledge

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    Spatial and temporal variability of groundwater recharge in a sandstone aquifer in a semiarid region

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    With the aim to understand the spatial and temporal variability of groundwater recharge, a high-resolution, spatially distributed numerical model (MIKE SHE) representing surface water and groundwater was used to simulate responses to precipitation in a 2.16&thinsp;km2 upland catchment on fractured sandstone near Los Angeles, California. Exceptionally high temporal and spatial resolution was used for this catchment modeling: hourly climate data, a 20 m×20 m grid in the horizontal plane, and 240 numerical layers distributed vertically within the thick vadose zone and in the upper part of the groundwater zone. The finest practical spatial and temporal resolutions were selected to accommodate the large degree of surface and subsurface variability of catchment features. Physical property values for the different lithologies were assigned based on previous on-site investigations, whereas the parameters controlling streamflow and evapotranspiration were derived from calibration to continuous streamflow at the outfall and to average hydraulic heads from 17 wells. Confidence in the calibrated model was enhanced by validation through (i) comparison of simulated average recharge to estimates based on the applications of the chloride mass-balance method to data from the groundwater and vadose zones within and beyond the catchment, (ii) comparison of the water isotope signature (18O and 2H) in shallow groundwater to the variability of isotope signatures for precipitation events over an annual cycle, and (iii) comparison of simulated recharge time series and observed fluctuation of water levels. The average simulated recharge across the catchment for the period 1995–2014 is 16&thinsp;mm&thinsp;yr−1 (4&thinsp;% of the average annual precipitation), which is consistent with previous estimates obtained by using the chloride mass balance method (4.2&thinsp;% of the average precipitation). However, one of the most unexpected results was that local recharge was simulated to vary from 0 to &gt;1000&thinsp;mm&thinsp;yr−1 due to episodic precipitation and overland runoff effects. This recharge occurs episodically with the major flux events at the bottom of the evapotranspiration zone, as simulated by MIKE SHE and confirmed by the isotope signatures, occurring only at the end of the rainy season. This is the first study that combines MIKE SHE simulations with the analysis of water isotopes in groundwater and rainfall to determine the timing of recharge in a sedimentary bedrock aquifer in a semiarid region. The study advances the understanding of recharge and unsaturated flow processes and enhances our ability to predict the effects of surface and subsurface features on recharge rates. This is crucial in highly heterogeneous contaminated sites because different contaminant source areas have widely varying recharge and, hence, groundwater fluxes impacting their mobility.</p

    Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells

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    Immune cells regulate tumor growth by mirroring their function as tissue repair organizers in normal tissues. To understand the different facets of immune-tumor collaboration through genetics, spatial transcriptomics, and immunologic manipulation with noninvasive, longitudinal imaging, we generated a penetrant double oncogene-driven autochthonous model of neuroblastoma. Spatial transcriptomic analysis showed that CD4(+) and myeloid populations colocalized within the tumor parenchyma, while CD8(+) T cells and B cells were peripherally dispersed. Depletion of CD4(+) T cells or CCR2(+) macrophages, but not B cells, CD8(+) T cells, or natural killer (NK) cells, prevented tumor formation. Tumor CD4(+) T cells displayed unconventional phenotypes and were clonotypically diverse and antigen independent. Within the myeloid fraction, tumor growth required myeloid cells expressing arginase-1. Overall, these results demonstrate how arginine-metabolizing myeloid cells conspire with pathogenic CD4(+) T cells to create permissive conditions for tumor formation, suggesting that these protumorigenic pathways could be disabled by targeting myeloid arginine metabolism. Significance: A new model of human neuroblastoma provides ways to track tumor formation and expansion in living animals, allowing identification of CD4(+) T-cell and macrophage functions required for oncogenesis. [GRAPHICS

    Fluent Speech Via Visual Choral Speech

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    A novel phenomenon of fluency enhancement via visual gestures of speech in the absence of traditional auditory feedback is reported herein. The effect on visual choral speech on stuttering frequency was investigated. Ten participants who stuttered recited memorized text aloud under two conditions. In a Visual Choral Speech (VCS) condition participants were instructed to focus their gaze on the face, lips and jaw of a research assistant who "silently mouthed" the text in unison. In a control condition, participants recited memorized text to the research assistant who sat motionless. A statistically significant (p= .0025) reduction of approximately 80% in stuttering frequency was observed in the VCS condition. As visual linguistic cues are sufficient to activate the auditory cortex, one may speculate that VCS induces fluency in a similar yet undetermined manner as altered auditory feedback does

    Global Analysis of RNA Secondary Structure in Two Metazoans

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    The secondary structure of RNA is necessary for its maturation, regulation, processing, and function. However, the global influence of RNA folding in eukaryotes is still unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach to identify the paired (double-stranded RNA [dsRNA]) and unpaired (single-stranded RNA [ssRNA]) components of the Drosophila melanogaster and Caenorhabditis elegans transcriptomes, which allows us to identify conserved features of RNA secondary structure in metazoans. From this analysis, we find that ssRNAs and dsRNAs are significantly correlated with specific epigenetic modifications. Additionally, we find key structural patterns across protein-coding transcripts that indicate that RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in animals. Finally, we identify and characterize 546 mRNAs whose folding pattern is significantly correlated between these metazoans, suggesting that their structure has some function. Overall, our findings provide a global assessment of RNA folding in animals

    Confocal microscopy of colloidal particles: towards reliable, optimum coordinates

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    Over the last decade, the light microscope has become increasingly useful as a quantitative tool for studying colloidal systems. The ability to obtain particle coordinates in bulk samples from micrographs is particularly appealing. In this paper we review and extend methods for optimal image formation of colloidal samples, which is vital for particle coordinates of the highest accuracy, and for extracting the most reliable coordinates from these images. We discuss in depth the accuracy of the coordinates, which is sensitive to the details of the colloidal system and the imaging system. Moreover, this accuracy can vary between particles, particularly in dense systems. We introduce a previously unreported error estimate and use it to develop an iterative method for finding particle coordinates. This individual-particle accuracy assessment also allows comparison between particle locations obtained from different experiments. Though aimed primarily at confocal microscopy studies of colloidal systems, the methods outlined here should transfer readily to many other feature extraction problems, especially where features may overlap one another.Comment: Accepted by Advances in Colloid and Interface Scienc

    Hackable Instruments: Supporting Appropriation and Modification in Digital Musical Interaction

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    This paper investigates the appropriation of digital musical instruments, wherein the performer develops a personal working relationship with an instrument that may differ from the designer's intent. Two studies are presented which explore different facets of appropriation. First, a highly restrictive instrument was designed to assess the effects of constraint on unexpected creative use. Second, a digital instrument was created which initially shared several constraints and interaction modalities with the first instrument, but which could be rewired by the performer to discover sounds not directly anticipated by the designers. Each instrument was studied with 10 musicians working individually to prepare public performances on the instrument. The results suggest that constrained musical interactions can promote the discovery of unusual and idiosyncratic playing techniques, and that tighter constraints may paradoxically lead to a richer performer experience. The diversity of ways in which the rewirable instrument was modified and used indicates that its design is open to interpretation by the performer, who may discover interaction modalities that were not anticipated by the designers

    Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

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    Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers
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