3,193 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

    Developing Intensity-Duration-Frequency (IDF) Curves From Satellite-Based Precipitation: Methodology and Evaluation

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    Given the continuous advancement in the retrieval of precipitation from satellites, it is important to develop methods that incorporate satellite-based precipitation data sets in the design and planning of infrastructure. This is because in many regions around the world, in situ rainfall observations are sparse and have insufficient record length. A handful of studies examined the use of satellite-based precipitation to develop intensity-duration-frequency (IDF) curves; however, they have mostly focused on small spatial domains and relied on combining satellite-based with ground-based precipitation data sets. In this study, we explore this issue by providing a methodological framework with the potential to be applied in ungauged regions. This framework is based on accounting for the characteristics of satellite-based precipitation products, namely, adjustment of bias and transformation of areal to point rainfall. The latter method is based on previous studies on the reverse transformation (point to areal) commonly used to obtain catchment-scale IDF curves. The paper proceeds by applying this framework to develop IDF curves over the contiguous United States (CONUS); the data set used is Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks – Climate Data Record (PERSIANN-CDR). IDFs are then evaluated against National Oceanic and Atmospheric Administration (NOAA) Atlas 14 to provide a quantitative estimate of their accuracy. Results show that median errors are in the range of (17–22%), (6–12%), and (3–8%) for one-day, two-day and three-day IDFs, respectively, and return periods in the range (2–100) years. Furthermore, a considerable percentage of satellite-based IDFs lie within the confidence interval of NOAA Atlas 14

    A Policy Maker’s Guide to Designing Payments for Ecosystem Services

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    Over the past five years, there has been increasing interest around the globe in payment schemes for the provision of ecosystem services, such as water purification, carbon sequestration, flood control, etc. Written for an Asian Development Bank project in China, this report provides a user-friendly guide to designing payments for the provision of ecosystem services. Part I explains the different types of ecosystem services, different ways of assessing their value, and why they are traditionally under-protected by law and policy. This is followed by an analysis of when payments for services are a preferable approach to other policy instruments. Part II explains the design issues underlying payments for services. These include identification of the service as well as potential buyers and sellers, the level of service needed, payment timing, payment type, and risk allocation. Part II contains a detailed analysis of the different types of payment mechanisms, ranging from general subsidy and certification to mitigation and offset payments. Part III explores the challenges to designing a payment scheme. These include the ability to monitor service provision, secure property rights, perverse incentives, supporting institutions, and poverty alleviation

    W(h)ither the academy? An exploration of the role of university social work in shaping the future of social work in Europe

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    A controversial proposal to pilot the training of child protection social workers through an intensive work-based route in England is being supported and funded by the UK Government. Frontline, the brainchild of a former teacher, locates social work training within local authorities (‘the agency’) rather than university social work departments (‘the academy’) and has stimulated debate amongst social work academics about their role in shaping the direction of the profession. As a contribution to this debate, this paper explores the duality of social work education, which derives its knowledge from both the academic social sciences and the experience of practice within social work agencies. While social work education has traditionally been delivered by the academy, this paper also explores whether the delivery of training in the allied professions of probation and nursing by ‘the agency’ is equally effective. Finally, this paper explores the Helsinki model which achieves a synergy of ‘academy’ and ‘agency’. It suggests that there are alternative models of social work education, practice and research which avoid dichotomies between the ‘academy’ and the ‘agency’ and enable the profession to be shaped by both social work academics and practitioners

    Dynamics and stability of the Godel universe

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    We use covariant techniques to describe the properties of the Godel universe and then consider its linear response to a variety of perturbations. Against matter aggregations, we find that the stability of the Godel model depends primarily upon the presence of gradients in the centrifugal energy, and secondarily on the equation of state of the fluid. The latter dictates the behaviour of the model when dealing with homogeneous perturbations. The vorticity of the perturbed Godel model is found to evolve as in almost-FRW spacetimes, with some additional directional effects due to shape distortions. We also consider gravitational-wave perturbations by investigating the evolution of the magnetic Weyl component. This tensor obeys a simple plane-wave equation, which argues for the neutral stability of the Godel model against linear gravity-wave distortions. The implications of the background rotation for scalar-field Godel cosmologies are also discussed.Comment: Revised version, to match paper published in Class. Quantum Gra

    Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

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    The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

    Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

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    Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

    Standalone vertex finding in the ATLAS muon spectrometer

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    A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

    Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

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    Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson
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