952 research outputs found

    Little genomic support for Cyclophilin A-matrix metalloproteinase-9 pathway as a therapeutic target for cognitive impairment in APOE4 carriers

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    Therapeutic targets for halting the progression of Alzheimer’s disease pathology are lacking. Recent evidence suggests that APOE4, but not APOE3, activates the Cyclophilin-A matrix metalloproteinase-9 (CypA-MMP9) pathway, leading to an accelerated breakdown of the blood–brain barrier (BBB) and thereby causing neuronal and synaptic dysfunction. Furthermore, blockade of the CypA-MMP9 pathway in APOE4 knock-in mice restores BBB integrity and subsequently normalizes neuronal and synaptic function. Thus, CypA has been suggested as a potential target for treating APOE4 mediated neurovascular injury and the resulting neuronal dysfunction and degeneration. The odds of drug targets passing through clinical trials are greatly increased if they are supported by genomic evidence. We found little evidence to suggest that CypA or MMP9 affects the risk of Alzheimer’s disease or cognitive impairment using two-sample Mendelian randomization and polygenic risk score analysis in humans. This casts doubt on whether they are likely to represent effective drug targets for cognitive impairment in human APOE4 carriers

    CoastalImageLib: An open- source Python package for creating common coastal image products

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    CoastalImageLib is a Python library that produces common coastal image products intended for quantitative analysis of coastal environments. This library contains functions to georectify and merge multiple oblique camera views, produce statistical image products for a given set of images, and create subsampled pixel instruments for use in bathymetric inversion, surface current estimation, run-up calculations, and other quantitative analyses. This package intends to be an open-source broadly generalizable front end to future coastal imaging applications, ultimately expanding user accessibility to optical remote sensing of coastal environments. This package was developed and tested on data collected from the Argus Tower, a 43 m tall observation structure in Duck, North Carolina at the US Army Engineer Research and Development Center’s Field Research Facility that holds six stationary cameras which collect twice-hourly coastal image products. Thus, CoastalImageLib also contains functions designed to interface with the file storage and collection system implemented at the Argus Tower

    Development of the Nebraska Department of Transportation Winter Severity Index

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    Adverse weather conditions are responsible for millions of vehicular crashes, thousands of vehicular deaths and billions of dollars in economic and congestion costs. Many transportation agencies utilize a performance or mobility metric to assess how well they are maintaining road access. This research focuses on the development of a winter severity index for the State of Nebraska (NEWINS). NEWINS is an event-driven index that was derived for the Nebraska Department of Transportation (NDOT) and its districts across the state. The NEWINS framework includes a categorical storm classification framework and climatological aspect to capture atmospheric conditions more accurately across the diverse spatial regions of Nebraska. A ten-year (2006-2016) winter season database of meteorological variables for Nebraska was obtained from the National Centers for Environmental Information. Meteorological parameters were grouped into categories that subsequently provided a storm classification database. The NEWINS is based on a weighted linear combination to the collected database to measure severity statewide and across NDOT individual districts. The NEWINS results were compared to other meteorological variables, many used in other agencies’ winter severity indices. This comparison verified the NEWINS robustness for the observed events for the ten year period. For example, an assessment of the difference between days with observed snowfall versus days with accumulated snowfall revealed a 39% average reduction in days. Furthermore, the NEWINS results highlight the greater number of events during the 2009-2010 winter season, and the lack of events during the 2011-2012 drought year. The NEWINS also shows strong differences monthly and among NDOT districts across the state with a general decrease in events from the western to eastern NDOT districts. In addition, NEWINS storm classifications were compared to NDOT winter maintenance operations performance data for a sample winter season. Last, the 2016-17 winter season was computed to provide a testbed for the NEWINS procedure. It is expected that the NEWINS could help transportation personnel to efficiently allocate resources during adverse weather events, while balancing safety, mobility, and available budget. Further, the theoretical and practical contributions provided by the NEWINS can be used by other agencies to assess their weather sensitivity

    Development of the Nebraska Department of Transportation Winter Severity Index

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    Adverse weather conditions are responsible for millions of vehicular crashes, thousands of vehicular deaths and billions of dollars in economic and congestion costs. Many transportation agencies utilize a performance or mobility metric to assess how well they are maintaining road access. This research focuses on the development of a winter severity index for the State of Nebraska (NEWINS). NEWINS is an event-driven index that was derived for the Nebraska Department of Transportation (NDOT) and its districts across the state. The NEWINS framework includes a categorical storm classification framework and climatological aspect to capture atmospheric conditions more accurately across the diverse spatial regions of Nebraska. A ten-year (2006-2016) winter season database of meteorological variables for Nebraska was obtained from the National Centers for Environmental Information. Meteorological parameters were grouped into categories that subsequently provided a storm classification database. The NEWINS is based on a weighted linear combination to the collected database to measure severity statewide and across NDOT individual districts. The NEWINS results were compared to other meteorological variables, many used in other agencies’ winter severity indices. This comparison verified the NEWINS robustness for the observed events for the ten year period. For example, an assessment of the difference between days with observed snowfall versus days with accumulated snowfall revealed a 39% average reduction in days. Furthermore, the NEWINS results highlight the greater number of events during the 2009-2010 winter season, and the lack of events during the 2011-2012 drought year. The NEWINS also shows strong differences monthly and among NDOT districts across the state with a general decrease in events from the western to eastern NDOT districts. In addition, NEWINS storm classifications were compared to NDOT winter maintenance operations performance data for a sample winter season. Last, the 2016-17 winter season was computed to provide a testbed for the NEWINS procedure. It is expected that the NEWINS could help transportation personnel to efficiently allocate resources during adverse weather events, while balancing safety, mobility, and available budget. Further, the theoretical and practical contributions provided by the NEWINS can be used by other agencies to assess their weather sensitivity

    Satellite detection of dinoflagellate blooms off California by UV reflectance ratios

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    © The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Kahru, M., Anderson, C., Barton, A. D., Carter, M. L., Catlett, D., Send, U., Sosik, H. M., Weiss, E. L., & Mitchell, B. G. Satellite detection of dinoflagellate blooms off California by UV reflectance ratios. Elementa: Science of the Anthropocene, 9(1), (2021): 00157, https://doi.org/10.1525/elementa.2020.00157.As harmful algae blooms are increasing in frequency and magnitude, one goal of a new generation of higher spectral resolution satellite missions is to improve the potential of satellite optical data to monitor these events. A satellite-based algorithm proposed over two decades ago was used for the first time to monitor the extent and temporal evolution of a massive bloom of the dinoflagellate Lingulodinium polyedra off Southern California during April and May 2020. The algorithm uses ultraviolet (UV) data that have only recently become available from the single ocean color sensor on the Japanese GCOM-C satellite. Dinoflagellates contain high concentrations of mycosporine-like amino acids and release colored dissolved organic matter, both of which absorb strongly in the UV part of the spectrum. Ratios 1, consistent with historical observations showing a sharp transition from dinoflagellate- to diatom-dominated waters in these areas. UV bands are thus potentially useful in the remote sensing of phytoplankton blooms but are currently available only from a single ocean color sensor. As several new satellites such as the NASA Plankton, Aerosol, Cloud, and marine Ecosystem mission will include UV bands, new algorithms using these bands are needed to enable better monitoring of blooms, especially potentially harmful algal blooms, across large spatiotemporal scales.Part of this work was funded by National Science Foundation (NSF) grants to the CCE-LTER Program, most recently OCE-1637632. Processing of Second-Generation Global Imager satellite data was funded by Japan Aerospace Exploration Agency. Data shown in Figure 1 were collected by BGM and MK with support from the NASA SIMBIOS project. DC was supported by the NASA Biodiversity and Ecological Forecasting Program (Grant NNX14AR62A), the Bureau of Ocean and Energy Management Ecosystem Studies Program (BOEM award MC15AC00006), and the NOAA through the Santa Barbara Channel Marine Biodiversity Observation Network. HMS was supported by NSF (Grant OCE-1810927) and the Simons Foundation (Grant 561126). ELW was supported by NSF GRFP (Grant DGE-1650112). Funding for Scripps and Santa Monica Piers sampling was through the Southern California Coastal Ocean Observing Harmful Algal Bloom Monitoring Program by NOAA NA16NOS0120022

    The GBT Diffuse Ionized Gas Survey (GDIGS): Survey Overview and First Data Release

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    The Green Bank Telescope (GBT) Diffuse Ionized Gas Survey (GDIGS) traces ionized gas in the Galactic midplane by measuring 484-8GHz radio recombination line (RRL) emission. The nominal survey zone is 32.3>l>532.3^{\circ}> l >-5^{\circ}, b<0.5|b|<0.5^{\circ}, but coverage extends above and below the plane in select fields, and additionally includes the areas around W47 (l37.5l \simeq 37.5^{\circ}) and W49 (l43l \simeq 43^{\circ}). GDIGS simultaneously observes 22 Hnα\alpha (15 usable), 25 Hnβ\beta (18 usable), and 8 Hnγ\gamma RRLs (all usable), as well as multiple molecular line transitions (including of H213_2^{13}CO, H2_2CO, and CH3_3OH). Here, we describe the GDIGS survey parameters and characterize the RRL data, focusing primarily on the Hnα\alpha data. We produce sensitive data cubes by averaging the usable RRLs, after first smoothing to a common spectral resolution of 0.5km/s and a spatial resolution of 2.65' for Hnα\alpha, 2.62' for Hnβ\beta, and 2.09' for Hnγ\gamma. The average spectral noise per spaxel in the \hna\ data cubes is  ⁣10\sim\!10mK ( ⁣5\sim\!5mJy/beam). This sensitivity allows GDIGS to detect RRLs from plasma throughout the inner Galaxy. The GDIGS Hnα\alpha data are sensitive to emission measures EM1100EM \gtrsim 1100cm6^{-6}pc, which corresponds to a mean electron density ne30\langle n_e \rangle \gtrsim 30cm3^{-3} for a 1pc path length or ne1\langle n_e \rangle \gtrsim 1cm3^{-3} for a 1kpc path length.Comment: Accepted for publication by ApJS. Data may be downloaded here: http://astro.phys.wvu.edu/gdigs

    A quantitative meta-analysis and qualitative meta-synthesis of aged care residents’ experiences of autonomy, being controlled, and optimal functioning

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    Background and Objectives The poor mental health of adults living in aged care needs addressing. Improvements to nutrition and exercise are important, but mental health requires a psychological approach. Self-determination theory finds that autonomy is essential to wellbeing while experiences of being controlled undermine it. A review of existing quantitative data could underscore the importance of autonomy in aged care, and a review of the qualitative literature could inform ways to promote autonomy and avoid control. Testing these possibilities was the objective of this research. Research Design and Methods We conducted a mixed-methods systematic review of studies investigating autonomy, control, and indices of optimal functioning in aged care settings. The search identified 30 eligible reports (19 quantitative, 11 qualitative), including 141 quantitative effect sizes, 84 qualitative data items, and N = 2,668. Quantitative effects were pooled using three-level meta-analytic structural equation models, and the qualitative data were meta-synthesized using a grounded theory approach. Results As predicted, the meta-analysis showed a positive effect of aged care residents’ autonomy and their wellness, r = 0.33 [95% CI: 0.27, 0.39], and a negative effect of control, r = −0.16 [95% CI: −0.27, −0.06]. The meta-synthesis revealed seven primary and three sub-themes describing the nuanced ways autonomy, control, and help seeking are manifest in residential aged care settings. Discussion and Implications The results suggest that autonomy should be supported, and unnecessary external control should be minimized in residential aged care, and we discuss ways the sector could strive for both aims
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