380 research outputs found

    Reuse of Software Assets for the NASA Earth Science Decadal Survey Missions

    Get PDF
    Software assets from existing Earth science missions can be reused for the new decadal survey missions that are being planned by NASA in response to the 2007 Earth Science National Research Council (NRC) Study. The new missions will require the development of software to curate, process, and disseminate the data to science users of interest and to the broader NASA mission community. In this paper, we discuss new tools and a blossoming community that are being developed by the Earth Science Data System (ESDS) Software Reuse Working Group (SRWG) to improve capabilities for reusing NASA software assets

    Software support for environmental evidence synthesis

    Get PDF
    Ecological research is central to efforts to ensure the provision of critical societal needs such as clean water, carbon abatement, and to avert the loss of biodiversity. The amount of research published on these subjects has increased enormously in recent ears, yet this research is not always used to improve environmental management or policy4. This ‘research-implementation gap’ is sustained by many factors including low access to scientific research outside of academia, a lack of flexible decision-making structures to incorporate new information, and mismatches between management and scientific priorities. A key step towards bridging the research-implementation gap, however, is to gather insights from the entire body of available evidence to ensure that scientific advice is as consistent and accurate as possible. This requires evidence synthesis; work by individuals or teams that take scientific outputs (articles and reports) and use them to understand the effectiveness of an intervention in a range of contexts. Consequently, applied synthesis has become indispensable to the application of scientific information to socio-ecological problems

    The microvascular endothelial glycocalyx:An additional piece of the puzzle in veterinary medicine

    Get PDF
    The endothelial glycocalyx (eGlx) is a critically important structure lining the luminal surface of endothelial cells. There is increasing evidence, in human patients and animal models, for its crucial role in the maintenance of health. Moreover, its damage is associated with the pathogenesis of multiple disease states. This review provides readers with an overview of the eGlx; summarising its structure, essential functions, and evidence for its role in disease. We highlight the lack of studies regarding the eGlx in cats and dogs, particularly in naturally occurring diseases. Importantly, we discuss techniques to aid its study, which can be applied to veterinary species. Finally, we present targeted therapies aimed at preserving, and in some cases, restoring damaged eGlx

    A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function

    Get PDF
    Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum (ER), which is an essential process in eukaryotic cells. In vertebrates, the MIA3 gene encodes two major forms of transport and Golgi organization protein 1 (TANGO1S and TANGO1L), which have previously been implicated in selective trafficking of procollagen. Using genome engineering of human cells, light microscopy, secretion assays, genomics and proteomics, we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function, including having limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 (also known as LMAN1) and SURF4 to the ER–Golgi intermediate compartment and dramatic changes to the ultrastructure of the ER–Golgi interface. Disruption of TANGO1 causes significant changes in early secretory pathway gene and protein expression, and impairs secretion not only of large proteins, but of all types of secretory cargo, including small soluble proteins. Our data support a general role for MIA3/TANGO1 in maintaining secretory pathway structure and function in vertebrate cells

    Long-term Hydro-economic Analysis Tool for Evaluating Global Groundwater Cost and Supply: Superwell v1.0

    Get PDF
    Groundwater plays a key role in meeting water demands, supplying over 40 % of irrigation water globally, with this role likely to grow as water demands and surface water variability increase. A better understanding of the future role of groundwater in meeting sectoral demands requires an integrated hydro-economic evaluation of its cost and availability. Yet substantial gaps remain in our knowledge and modeling capabilities related to groundwater availability, feasible locations for extraction, extractable volumes, and associated extraction costs, which are essential for large-scale analyses of integrated human-water systems scenarios, particularly at the global scale. To address these needs, we developed Superwell, a physics-based groundwater extraction and cost accounting model that operates at 0.5° (≈50x50 km) gridded spatial resolution with global coverage. The model produces location-specific groundwater supply-cost curves that provide the levelized cost to access different quantities of available groundwater. The inputs to Superwell include recent high-resolution hydrogeologic datasets of permeability, porosity, aquifer thickness, depth to water table, and hydrogeological complexity zones. It also accounts for well capital and maintenance costs, and the energy costs required to lift water to the surface. The model employs a Theis-based scheme coupled with an amortization-based cost accounting formulation to simulate groundwater extraction and quantify the cost of groundwater pumping. The result is a spatiotemporally flexible, physically-realistic, economics-based model that produces groundwater supply-cost curves. We show examples of these supply-cost curves and the insights that can be derived from them across a set of scenarios designed to explore model outcomes. The supply-cost curves produced by the model show that most nonrenewable groundwater in storage globally is extractable at costs lower than 0.23 USD/m3, while half of the volume remains extractable at under 0.138 USD/m3. We also demonstrate and discuss examples of how these cost curves could be used by linking Superwell’s outputs with other models to explore coupled human-environmental systems challenges, such as water resources planning and management, or broader analyses of multi-sectoral feedbacks

    Measuring protein concentration with entangled photons

    Get PDF
    Optical interferometry is amongst the most sensitive techniques for precision measurement. By increasing the light intensity a more precise measurement can usually be made. However, in some applications the sample is light sensitive. By using entangled states of light the same precision can be achieved with less exposure of the sample. This concept has been demonstrated in measurements of fixed, known optical components. Here we use two-photon entangled states to measure the concentration of the blood protein bovine serum albumin (BSA) in an aqueous buffer solution. We use an opto-fluidic device that couples a waveguide interferometer with a microfluidic channel. These results point the way to practical applications of quantum metrology to light sensitive samples

    Permeability changes and effect of chemotherapy in brain adjacent to tumor in an experimental model of metastatic brain tumor from breast cancer

    Get PDF
    Abstract Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of female NuNu mice. Metastases were allowed to grow for 28 days, after which animals were injected fluorescent tracers Texas Red (625 Da) or Texas Red dextran (3 kDa) or a chemotherapeutic agent 14C-paclitaxel. The accumulation of tracers and 14C-paclitaxel in BAT were determined by using quantitative fluorescent microscopy and autoradiography respectively. The effect of chemotherapy in BAT was determined by staining for activated astrocytes. Results: The mean permeability of texas Red (625 Da) within BAT region increased 1.0 to 2.5-fold when compared to normal brain, whereas, Texas Red dextran (3 kDa) demonstrated mean permeability increase ranging from 1.0 to 1.8-fold compared to normal brain. The Kin values in the BAT for both Texas Red (625 Da) and Texas Red dextran (3 kDa) were found to be 4.32 ± 0.2 × 105 mL/s/g and 1.6 ± 1.4 × 105 mL/s/g respectively and found to be significantly higher than the normal brain. We also found that there is significant increase in accumulation of 14C-Paclitaxel in BAT compared to the normal brain. We also observed animals treated with chemotherapy (paclitaxel (10 mg/kg), erubilin (1.5 mg/kg) and docetaxel (10 mg/kg)) showed activated astrocytes in BAT. Conclusions: Our data showed increased permeation of fluorescent tracers and 14C-paclitaxel in the BAT. This increased permeation lead to elevated levels of activated astrocytes in BAT region in the animals treated with chemotherapy

    Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors

    Get PDF
    It remains unresolved how retinal pigment epithelial cell metabolism is regulated following immune activation to maintain retinal homeostasis and retinal function. We exposed retinal pigment epithelium (RPE) to several stress signals, particularly Toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-33) as a key metabolic checkpoint that antagonizes the Warburg effect to ensure the functional stability of the RPE. The identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its extracellular “alarmin” activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declined and resultant bioenergetic switching was aligned with altered mitochondrial morphology. Our data not only shed new light on the molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors but also uncover a potentially novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator
    corecore