1,318 research outputs found

    Global search algorithm for optimal control

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    Random-search algorithm employs local and global properties to solve two-point boundary value problem in Pontryagin maximum principle for either fixed or variable end-time problems. Mixed boundary value problem is transformed to an initial value problem. Mapping between initial and terminal values utilizes hybrid computer

    Interactions of alkali cations with glutamate transporters

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    The transport of glutamate is coupled to the co-transport of three Na+ ions and the countertransport of one K+ ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure of the Pyrococcus horikoshii transporter GltPh and in its human glutamate transporter homologue EAAT3. Two predicted Na+-binding sites were found to overlap precisely with the Tl+ densities observed in the aspartate-bound complex. A novel third site predicted to favourably bind Na+ (but not Tl+) is formed by interaction with the substrate and the occluding HP2 loop. A fourth predicted site in the apo state exhibits selectivity for K+ over both Na+ and Tl+. Notably, this K+ site partially overlaps the glutamate-binding site, and their binding is mutually exclusive. These results are consistent with kinetic and structural data and suggest a plausible mechanism for the flux coupling of glutamate with Na+ and K+ ions

    Shuttle-launch triangular space station

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    A triangular space station deployable in orbit is described. The framework is comprized of three trusses, formed of a pair of generally planar faces consistine of foldable struts. The struts expand and lock into rigid structural engagement forming a repetition of equilater triangles and nonfolding diagonal struts interconnecting the two faces. The struts are joined together by node fittings. The framework can be packaged into a size and configuration transportable by a space shuttle. When deployed, the framework provides a large work/construction area and ample planar surface area for solar panels and thermal radiators. A plurity of modules are secured to the framework and then joined by tunnels to make an interconnected modular display. Thruster units for the space station orientation and altitude maintenance are provided

    Interactions of alkali cations with glutamate transporters

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    The transport of glutamate is coupled to the co-transport of three Na+ ions and the countertransport of one K+ ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure of the Pyrococcus horikoshii transporter GltPh and in its human glutamate transporter homologue EAAT3. Two predicted Na+-binding sites were found to overlap precisely with the Tl+ densities observed in the aspartate-bound complex. A novel third site predicted to favourably bind Na+ (but not Tl+) is formed by interaction with the substrate and the occluding HP2 loop. A fourth predicted site in the apo state exhibits selectivity for K+ over both Na+ and Tl+. Notably, this K+ site partially overlaps the glutamate-binding site, and their binding is mutually exclusive. These results are consistent with kinetic and structural data and suggest a plausible mechanism for the flux coupling of glutamate with Na+ and K+ ions

    Implications of future northwest Atlantic bottom temperatures on the American lobster (Homarus americanus) fishery

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    © The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 9387–9398, doi:10.1002/2017JC012949.Sea surface temperatures of the northwest Atlantic have warmed dramatically over the last several decades, while benthic temperatures have increased at a slower pace. Here we analyze a subset of the CMIP5 global Earth system model ensemble using a statistical downscaling approach to determine potential future changes in benthic temperatures on the northwest Atlantic continental shelf and slope (<500 m). We put future changes in the context of possible impacts of ocean warming on the high-value, wild-caught American Lobster (Homarus americanus) fishery. Future bottom temperatures of the northwest Atlantic under a business-as-usual (RCP8.5) and a climate-policy (RCP4.5) scenario are projected to increase by 0–1.5°C and 1.2–2.4°C by 2050 and 0–1.9°C and 2.3–4.3°C by the end of the century for RCP4.5 and RCP8.5, respectively. H. americanus experiences thermal stress at temperatures above 20°C, and projected increases in temperature is likely to result in changes in the distribution of optimal thermal egg hatching and settlement indicators. Inshore regions of southern New England, where H. americanus biomass and catch have been declining historically, will likely become inhospitable under either future scenario, while thermal egg hatching and settlement indicators will expand offshore and in the Gulf of Maine. These changes imply that members of the fishery based in southern New England may need to recapitalize to larger vessels to prepare for potential changes brought on by future climate warming. Results from the downscaling presented here can be useful in preparing for potential changes to other fisheries or in future climate vulnerability analyses.John D. and Catherine T. MacArthur Foundation Grant Number: 14-106159-000-CFP; NASA Grant Number: NNX14AP62A; “National Marine Sanctuaries as Sentinel Sites for a Demonstration Marine Biodiversity Observation Network (MBON)”; National Ocean Partnership Program Grant Number: NOPP RFP NOAA-NOS IOOS-2014-2003803; NOAA Integrated Ocean Observing System (IOOS) Program Offic

    Variability in the mechanisms controlling Southern Ocean phytoplankton bloom phenology in an ocean model and satellite observations

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    Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 31 (2017): 922–940, doi:10.1002/2016GB005615.A coupled global numerical simulation (conducted with the Community Earth System Model) is used in conjunction with satellite remote sensing observations to examine the role of top-down (grazing pressure) and bottom-up (light, nutrients) controls on marine phytoplankton bloom dynamics in the Southern Ocean. Phytoplankton seasonal phenology is evaluated in the context of the recently proposed “disturbance-recovery” hypothesis relative to more traditional, exclusively “bottom-up” frameworks. All blooms occur when phytoplankton division rates exceed loss rates to permit sustained net population growth; however, the nature of this decoupling period varies regionally in Community Earth System Model. Regional case studies illustrate how unique pathways allow blooms to emerge despite very poor division rates or very strong grazing rates. In the Subantarctic, southeast Pacific small spring blooms initiate early cooccurring with deep mixing and low division rates, consistent with the disturbance-recovery hypothesis. Similar systematics are present in the Subantarctic, southwest Atlantic during the spring but are eclipsed by a subsequent, larger summer bloom that is coincident with shallow mixing and the annual maximum in division rates, consistent with a bottom-up, light limited framework. In the model simulation, increased iron stress prevents a similar summer bloom in the southeast Pacific. In the simulated Antarctic zone (70°S–65°S) seasonal sea ice acts as a dominant phytoplankton-zooplankton decoupling agent, triggering a delayed but substantial bloom as ice recedes. Satellite ocean color remote sensing and ocean physical reanalysis products do not precisely match model-predicted phenology, but observed patterns do indicate regional variability in mechanism across the Atlantic and Pacific.NDSEG Graduate Fellowship; National Aeronautics and Space Administration Ocean Biology and Biogeochemistry Program Grant Number: NNX14L86G; NSF Poloar Programs Award Grant Number: 1440435; National Aeronautics and Space Administration Grant Number: NNX14AL86G; NDSEG; National Science Foundation Grant Number: 14404352017-11-3

    Federalism: Deference Meets Delegation: Which Is the Most Dangerous Branch

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    The following is a transcript of a 2016 Federalist Society panel entitled Federalism: Deference Meets Delegation: Which is the Most Dangerous Branch? The panel originally occurred on November 12, 2015, during the National Lawyers Convention in Washington, D.C. The panelists were: C. Boyden Gray, Attorney at Boyden, Gray and Associates and former U.S. Ambassador to the European Union; David B. Rivkin Jr., Partner at BakerHostetler; Neal K. Katyal, Attorney at Hogan Lovells and former acting U.S. Solicitor General; and John C. Eastman, Henry Salvatori Professor of Law & Community Service at Chapman University School of Law. The moderator was the Honorable Judge Brett Kavanaugh of the U.S. Court of Appeals, D.C. Circuit

    Specificity and Actions of an Arylaspartate Inhibitor of Glutamate Transport at the Schaffer Collateral-CA1 Pyramidal Cell Synapse

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    In this study we characterized the pharmacological selectivity and physiological actions of a new arylaspartate glutamate transporter blocker, L-threo-ß-benzylaspartate (L-TBA). At concentrations up to 100 µM, L-TBA did not act as an AMPA receptor (AMPAR) or NMDA receptor (NMDAR) agonist or antagonist when applied to outside-out patches from mouse hippocampal CA1 pyramidal neurons. L-TBA had no effect on the amplitude of field excitatory postsynaptic potentials (fEPSPs) recorded at the Schaffer collateral-CA1 pyramidal cell synapse. Excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons were unaffected by L-TBA in the presence of physiological extracellular Mg2+ concentrations, but in Mg2+-free solution, EPSCs were significantly prolonged as a consequence of increased NMDAR activity. Although L-TBA exhibited approximately four-fold selectivity for neuronal EAAT3 over glial EAAT1/EAAT2 transporter subtypes expressed in Xenopus oocytes, the L-TBA concentration-dependence of the EPSC charge transfer increase in the absence of Mg2+ was the same in hippocampal slices from EAAT3 +/+ and EAAT3 −/− mice, suggesting that TBA effects were primarily due to block of glial transporters. Consistent with this, L-TBA blocked synaptically evoked transporter currents in CA1 astrocytes with a potency in accord with its block of heterologously expressed glial transporters. Extracellular recording in the presence of physiological Mg2+ revealed that L-TBA prolonged fEPSPs in a frequency-dependent manner by selectively increasing the NMDAR-mediated component of the fEPSP during short bursts of activity. The data indicate that glial glutamate transporters play a dominant role in limiting extrasynaptic transmitter diffusion and binding to NMDARs. Furthermore, NMDAR signaling is primarily limited by voltage-dependent Mg2+ block during low-frequency activity, while the relative contribution of transport increases during short bursts of higher frequency signaling

    Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

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    Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs
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