113 research outputs found

    1,2,6-thiadiazinones as novel narrow spectrum calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) inhibitors

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    We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors

    Altitude of the Potentiometric Surface in the Mississippi River Valley Alluvial Aquifer, Spring 2018

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    The Mississippi River Valley alluvial (MRVA) aquifer is an important surficial aquifer in the Mississippi Alluvial Plain (MAP) area. The aquifer is generally considered to be an unconfined aquifer (fig. 1; Clark and others, 2011), and withdrawals are primarily used for irrigation (Maupin and Barber, 2005). These groundwater withdrawals have resulted in substantial areas of water-level decline in parts of the aquifer. Concerns about water-level declines and the sustainability of the MRVA aquifer have prompted the U.S. Geological Survey (USGS), as part of the USGS Water Availability and Use Science Program and with assistance from other Federal, State, and local agencies, to undertake a regional water-availability study to assess the characteristics of the MRVA aquifer, including the potentiometric-surface altitude of the MRVA aquifer for spring 2018, and to provide information to water managers to inform their decisions about resource allocations and aquifer sustainability. The purpose of this report was to present a potentiometric-surface map for the MRVA aquifer using manually measured groundwater-altitude data and daily mean or maximum groundwater-altitude data from wells measured generally in spring 2018, which is after water levels have substantially recovered from pumping in the previous irrigation season and before pumping begins for the next irrigation season, and using the altitude of the top of the water surface in rivers in the area, hereinafter referred to as “surface-water altitude,” generally on April 10, 2018, from streamgages in the area. The term “potentiometric surface” is used in this report because it is applicable for maps of the groundwater-altitude surface in unconfined, semiconfined, and confined aquifers (Lohman, 1972). In this report, the maps of the MRVA aquifer’s groundwater surface are termed potentiometric-surface maps as opposed to water-table maps because, although the MRVA aquifer generally exhibits characteristics of unconfined conditions, where surface-water features may or may not be hydraulically connected, it also exhibits characteristics of confined or semiconfined conditions in some areas at least during part of the year. The location of these areas, where the aquifer is confined or semiconfined, is not well understood or defined (Arthur, 1994; Kleiss and others, 2000). Datasets used attache

    Altitude of the Potentiometric Surface in the Mississippi River Valley Alluvial Aquifer, Spring 2018

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    The Mississippi River Valley alluvial (MRVA) aquifer is an important surficial aquifer in the Mississippi Alluvial Plain (MAP) area. The aquifer is generally considered to be an unconfined aquifer (fig. 1; Clark and others, 2011), and withdrawals are primarily used for irrigation (Maupin and Barber, 2005). These groundwater withdrawals have resulted in substantial areas of water-level decline in parts of the aquifer. Concerns about water-level declines and the sustainability of the MRVA aquifer have prompted the U.S. Geological Survey (USGS), as part of the USGS Water Availability and Use Science Program and with assistance from other Federal, State, and local agencies, to undertake a regional water-availability study to assess the characteristics of the MRVA aquifer, including the potentiometric-surface altitude of the MRVA aquifer for spring 2018, and to provide information to water managers to inform their decisions about resource allocations and aquifer sustainability. The purpose of this report was to present a potentiometric-surface map for the MRVA aquifer using manually measured groundwater-altitude data and daily mean or maximum groundwater-altitude data from wells measured generally in spring 2018, which is after water levels have substantially recovered from pumping in the previous irrigation season and before pumping begins for the next irrigation season, and using the altitude of the top of the water surface in rivers in the area, hereinafter referred to as “surface-water altitude,” generally on April 10, 2018, from streamgages in the area. The term “potentiometric surface” is used in this report because it is applicable for maps of the groundwater-altitude surface in unconfined, semiconfined, and confined aquifers (Lohman, 1972). In this report, the maps of the MRVA aquifer’s groundwater surface are termed potentiometric-surface maps as opposed to water-table maps because, although the MRVA aquifer generally exhibits characteristics of unconfined conditions, where surface-water features may or may not be hydraulically connected, it also exhibits characteristics of confined or semiconfined conditions in some areas at least during part of the year. The location of these areas, where the aquifer is confined or semiconfined, is not well understood or defined (Arthur, 1994; Kleiss and others, 2000). Datasets used attache

    The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2

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    The design and performance of the inner detector trigger for the high level trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-18 data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector recorded 35.6 fb1^{-1}, 46.9 fb1^{-1}, and 60.6 fb1^{-1} respectively of proton-proton collision data at a centre-of-mass energy of 13 TeV. In order to deal with the very high interaction multiplicities per bunch crossing expected with the 13 TeV collisions the inner detector trigger was redesigned during the long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of these developments is provided and the performance of the tracking in the trigger for the muon, electron, tau and bb-jet signatures is discussed. The high performance of the inner detector trigger with these extreme interaction multiplicities demonstrates how the inner detector tracking continues to lie at the heart of the trigger performance and is essential in enabling the ATLAS physics programme

    Measurement of the charge asymmetry in top-quark pair production in the lepton-plus-jets final state in pp collision data at s=8TeV\sqrt{s}=8\,\mathrm TeV{} with the ATLAS detector

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    Search for single production of vector-like quarks decaying into Wb in pp collisions at s=8\sqrt{s} = 8 TeV with the ATLAS detector

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    Search for dark matter in association with a Higgs boson decaying to bb-quarks in pppp collisions at s=13\sqrt s=13 TeV with the ATLAS detector

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