2,217 research outputs found

    Ex. 279-US-405

    Get PDF
    Report: The Relative Merits of the Modified Sag-Tape Method for Determining Instream Flow Requirement

    Ex. 277-US-403

    Get PDF
    Report: The Relative Merits of the Modified Sag-Tape Method for Determining Instream Flow Requirement

    Ex. 277-US-403

    Get PDF
    Report: The Relative Merits of the Modified Sag-Tape Method for Determining Instream Flow Requirement

    Ex. 281-US-403

    Get PDF
    Report: The Relative Merits of the Modified Sag-Tape Method for Determining Instream Flow Requirement

    Ex. 281-US-403

    Get PDF
    Report: The Relative Merits of the Modified Sag-Tape Method for Determining Instream Flow Requirement

    Asymmetric Cyclopropanation of Styrene Catalyzed by Chiral Macrocyclic Iron(II) Complexes

    Get PDF
    Three chiral tetraaza macrocyclic ligands (4a−c) were synthesized by the cyclization reaction of diamines with dithioaldehydes. The iron(II) complexes of ligands 4a and 4c, as well as two chiral iron(II) porphyrin complexes, FeII(D4-TpAP) and Fe(α2β2-BNP), are efficient catalysts for the cyclopropanation of styrene with diazoacetate reagents. The cyclopropyl esters were produced with high diastereoselectivities and good yields. However, the enantioselectivities were modest at best. The rationalization of the stereoselectivity in these cyclopropanation reactions is presented. The results of a single-crystal X-ray analysis of the ligand 4a are also reported

    Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia

    Get PDF
    Deletion of exon 9 from Cullin‐3 (CUL3, residues 403–459: CUL3Δ403–459) causes pseudohypoaldosteronism type IIE (PHA2E), a severe form of familial hyperkalaemia and hypertension (FHHt). CUL3 binds the RING protein RBX1 and various substrate adaptors to form Cullin‐RING‐ubiquitin‐ligase complexes. Bound to KLHL3, CUL3‐RBX1 ubiquitylates WNK kinases, promoting their ubiquitin‐mediated proteasomal degradation. Since WNK kinases activate Na/Cl co‐transporters to promote salt retention, CUL3 regulates blood pressure. Mutations in both KLHL3 and WNK kinases cause PHA2 by disrupting Cullin‐RING‐ligase formation. We report here that the PHA2E mutant, CUL3Δ403–459, is severely compromised in its ability to ubiquitylate WNKs, possibly due to altered structural flexibility. Instead, CUL3Δ403–459 auto‐ubiquitylates and loses interaction with two important Cullin regulators: the COP9‐signalosome and CAND1. A novel knock‐in mouse model of CUL3WT/Δ403–459 closely recapitulates the human PHA2E phenotype. These mice also show changes in the arterial pulse waveform, suggesting a vascular contribution to their hypertension not reported in previous FHHt models. These findings may explain the severity of the FHHt phenotype caused by CUL3 mutations compared to those reported in KLHL3 or WNK kinases

    Benefit-Cost Analysis of FEMA Hazard Mitigation Grants

    Get PDF
    Mitigation ameliorates the impact of natural hazards on communities by reducing loss of life and injury, property and environmental damage, and social and economic disruption. The potential to reduce these losses brings many benefits, but every mitigation activity has a cost that must be considered in our world of limited resources. In principle benefit-cost analysis (BCA) can be used to assess a mitigation activity’s expected net benefits (discounted future benefits less discounted costs), but in practice this often proves difficult. This paper reports on a study that refined BCA methodologies and applied them to a national statistical sample of FEMA mitigation activities over a ten-year period for earthquake, flood, and wind hazards. The results indicate that the overall benefit-cost ratio for FEMA mitigation grants is about 4 to 1, though the ratio varies according to hazard and mitigation type.

    Multi-point Assessment of the Kinematics of Shocks (MAKOS): A Heliophysics Mission Concept Study

    Full text link
    Collisionless shocks are fundamental processes that are ubiquitous in space plasma physics throughout the Heliosphere and most astrophysical environments. Earth's bow shock and interplanetary shocks at 1 AU offer the most readily accessible opportunities to advance our understanding of the nature of collisionless shocks via fully-instrumented, in situ observations. One major outstanding question pertains to the energy budget of collisionless shocks, particularly how exactly collisionless shocks convert incident kinetic bulk flow energy into thermalization (heating), suprathermal particle acceleration, and a variety of plasma waves, including nonlinear structures. Furthermore, it remains unknown how those energy conversion processes change for different shock orientations (e.g., quasi-parallel vs. quasi-perpendicular) and driving conditions (upstream Alfv\'enic and fast Mach numbers, plasma beta, etc.). Required to address these questions are multipoint observations enabling direct measurement of the necessary plasmas, energetic particles, and electric and magnetic fields and waves, all simultaneously from upstream, downstream, and at the shock transition layer with observatory separations at ion to magnetohydrodynamic (MHD) scales. Such a configuration of spacecraft with specifically-designed instruments has never been available, and this white paper describes a conceptual mission design -- MAKOS -- to address these outstanding questions and advance our knowledge of the nature of collisionless shocks.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 9 pages, 3 figures, 5 table
    corecore