During 2017-2018, the National Seismic Hazard Model for the conterminous United States was updated as follows: (1) an updated seismicity catalog was incorporated, which includes new earthquakes that ...occurred from 2013 to 2017; (2) in the central and eastern United States (CEUS), new ground motion models were updated that incorporate updated median estimates, modified assessments of the associated epistemic uncertainties and aleatory variabilities, and new soil amplification factors; (3) in the western United States (WUS), amplified shaking estimates of long-period ground motions at sites overlying deep sedimentary basins in the Los Angeles, San Francisco, Seattle, and Salt Lake City areas were incorporated; and (4) in the conterminous United States, seismic hazard is calculated for 22 periods (from 0.01 to 10 s) and 8 uniform VS30 maps (ranging from 1500 to 150 m/s). We also include a description of updated computer codes and modeling details. Results show increased ground shaking in many (but not all) locations across the CEUS (up to ∼30%), as well as near the four urban areas overlying deep sedimentary basins in the WUS (up to ∼50%). Due to population growth and these increased hazard estimates, more people live or work in areas of high or moderate seismic hazard than ever before, leading to higher risk of undesirable consequences from forecasted future ground shaking.
New seismic hazard maps have been developed for the conterminous United States using the latest data, models, and methods available for assessing earthquake hazard. The hazard models incorporate new ...information on earthquake rupture behavior observed in recent earthquakes; fault studies that use both geologic and geodetic strain rate data; earthquake catalogs through 2012 that include new assessments of locations and magnitudes; earthquake adaptive smoothing models that more fully accountforthe spatial clustering of earthquakes; and 22 ground motion models, some of which consider more than double the shaking data applied previously. Alternative input models account for larger earthquakes, more complicated ruptures, and more varied ground shaking estimates than assumed in earlier models. The ground motions, for levels applied in building codes, differ from the previous version by less than + or -10% over 60% of the country, but can differ by + or -50% in localized areas. The models are incorporated in insurance rates, risk assessments, and as input into the U.S. building code provisions for earthquake ground shaking.
The distribution of seismicity about strike‐slip faults provides measurements of fault roughness and damage zone width. In California, seismicity decays with distance from strike‐slip faults ...according to a power law ∼(1 + x2/d2)−γ/2. This scaling relation holds out to a fault‐normal distance x of 3–6 km and is compatible with a “rough fault loading” model in which the inner scale d measures the half width of a volumetric damage zone and the roll‐off rate γ is governed by stress variations due to fault roughness. According to Dieterich and Smith's 2‐D simulations, γ approximates the fractal dimension of along‐strike roughness. Near‐fault seismicity is more localized on faults in northern California (NoCal, d = 60 ± 20 m, γ = 1.65 ± .05) than in southern California (SoCal, d = 220 ± 40 m, γ = 1.16 ± .05). The Parkfield region has a damage zone half width (d = 120 ± 30 m) consistent with the SAFOD drilling estimate; its high roll‐off rate (γ = 2.30 ± .25) indicates a relatively flat roughness spectrum: ∼k−1 versus k−2 for NoCal, k−3 for SoCal. Our damage zone widths (the first direct estimates averaged over the seismogenic layer) can be interpreted in terms of an across‐strike “fault core multiplicity” that is ∼1 in NoCal, ∼2 at Parkfield, and ∼3 in SoCal. The localization of seismicity near individual faults correlates with cumulative offset, seismic productivity, and aseismic slip, consistent with a model in which faults originate as branched networks with broad, multicore damage zones and evolve toward more localized, lineated features with low fault core multiplicity, thinner damage zones, and less seismic coupling. Our results suggest how earthquake triggering statistics might be modified by the presence of faults.
Cells rely on autophagy to clear misfolded proteins and damaged organelles to maintain cellular homeostasis. In this study we use the new autophagy inhibitor PIK-III to screen for autophagy ...substrates. PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI(3)Kα. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates. By performing ubiquitin-affinity proteomics on PIK-III-treated cells we identified substrates including NCOA4, which accumulates in ATG7-deficient cells and co-localizes with autolysosomes. NCOA4 directly binds ferritin heavy chain-1 (FTH1) to target the iron-binding ferritin complex with a relative molecular mass of 450,000 to autolysosomes following starvation or iron depletion. Interestingly, Ncoa4(-/-) mice exhibit a profound accumulation of iron in splenic macrophages, which are critical for the reutilization of iron from engulfed red blood cells. Taken together, the results of this study provide a new mechanism for selective autophagy of ferritin and reveal a previously unappreciated role for autophagy and NCOA4 in the control of iron homeostasis in vivo.
The US Geological Survey National Seismic Hazard Models (NSHMs) are used to calculate earthquake ground-shaking intensities for design and rehabilitation of structures in the United States. The most ...recent 2014 and 2018 versions of the NSHM for the conterminous United States included major updates to ground-motion models (GMMs) for active and stable crustal tectonic settings; however, the subduction zone GMMs were largely unchanged. With the recent development of the next generation attenuation-subduction (NGA-Sub) GMMs, and recent progress in the utilization of “M9” Cascadia earthquake simulations, we now have access to improved models of ground shaking in the US subduction zones and the Seattle basin. The new NGA-Sub GMMs support multi-period response spectra calculations. They provide global models and regional terms specific to Cascadia and terms that account for deep-basin effects. This article focuses on the updates to subduction GMMs for implementation in the 2023 NSHM and compares them to the GMMs of previous NSHMs. Individual subduction GMMs, their weighted averages, and their impact on the estimated mean hazard relative to the 2018 NSHM are discussed. The updated logic trees include three of the new NGA-Sub GMMs and retain two older models to represent epistemic uncertainty in both the median and standard deviation of ground-shaking intensities at all periods of interest. Epistemic uncertainty is further represented by a three-point logic tree for the NGA-Sub median models. Finally, in the Seattle region, basin amplification factors are adjusted at long periods based on the state-of-the-art M9 Cascadia earthquake simulations. The new models increase the estimated mean hazard values at short periods and short source-to-site distances for interface earthquakes, but decrease them otherwise, relative to the 2018 NSHM. On softer soils, the new models cause decreases to the estimated mean hazard for long periods in the Puget Lowlands basin but increases within the deep Seattle portion of this basin for short periods relative to the 2018 NSHM.
Downstream purification of therapeutic antibodies requires candidates to be stable under various stress conditions, such as low pH. Current approaches to assess the conformational or colloidal ...stability of biologics may require significant amounts of material, and the testing may occur over an extended period of time. Furthermore, typical methodologies for early stability testing often do not directly address low pH stability, but focus more on conditions suitable for long-term drug product storage. Here we report a high-throughput method that measures protonation-induced unfolding of ligand binding sites for stability evaluation by surface plasmon resonance or PULSE SPR. This method, which requires only several micrograms of sample, is highly sensitive to the structural integrity of ligand binding sites and correlates well with thermal and chemical conformational stability. Combined with ligands targeting different regions of antibodies, this method allows a comprehensive assessment of antibody domain stability. By applying PULSE SPR, we found that antibodies with different complementarity-determining regions (CDRs), frameworks, formats, and interchain disulfide bonds showed different stabilities under acidic conditions. Additionally, biologics that aggregated in solution also had poor low pH stability. Taken together, PULSE SPR is a high-throughput and low sample consumption method that can be adopted to evaluate antibody domain stability and aggregation at low pH, which are two important aspects of therapeutic biologics.
We update the ground-motion characterization for the 2023 National Seismic Hazard Model (NSHM) for the conterminous United States. The update includes the use of new ground-motion models (GMMs) in ...the Cascadia subduction zone; an adjustment to the central and eastern United States (CEUS) GMMs to reduce misfits with observed data; an updated boundary for the application of GMMs for shallow, crustal earthquakes in active tectonic regions (i.e. western United States (WUS)) and stable continental regions (i.e. CEUS); and the use of improved models for the site response of deep sedimentary basins in the WUS and CEUS. Site response updates include basin models for the California Great Valley and for the Portland and Tualatin basins, Oregon, as well as long-period basin effects from three-dimensional simulations in the Greater Los Angeles region and in the Seattle basin; in the CEUS, we introduce a broadband (0.01- to 10-s period) amplification model for the effects of the passive-margin basins of the Atlantic and Gulf Coastal Plains. In addition, we summarize progress on implementing rupture directivity models into seismic hazard models, although they are not incorporated in the 2023 NSHM. We implement the ground-motion characterization for the 2023 NSHM in the US Geological Survey’s code for probabilistic seismic hazard analysis, nshmp-haz-v2, and present the sensitivity of hazard to these changes. Hazard calculations indicate widespread effects from adjustments to the CEUS GMMs, from the incorporation of Coastal Plain amplification effects, and from the treatment of shallow-basin and out-of-basin sites in the San Francisco Bay Area and Los Angeles region, as well as locally important changes from subduction-zone GMMs, and from updated and new WUS basins.
As part of the update of the 2018 National Seismic Hazard Model (NSHM) for the conterminous United States (CONUS), new ground motion and site effect models for the central and eastern United States ...were incorporated, as well as basin depths from local seismic velocity models in four western US (WUS) urban areas. These additions allow us, for the first time, to calculate probabilistic seismic hazard curves for an expanded set of spectral periods (0.01 to 10 s) and site classes (VS30 = 150 to 1500 m/s) for the CONUS, as well as account for amplification of long-period ground motions in deep sedimentary basins in the Los Angeles, San Francisco Bay, Seattle, and Salt Lake City areas. Two sets of 2018 NSHM hazard data (hazard curves and uniform-hazard ground motions) are available: (1) 0.05°-latitude-by-0.05°-longitude gridded data for the CONUS and (2) higher resolution 0.01°-latitude-by-0.01°-longitude gridded data for the four WUS basins. Both sets of data contain basin effects in the WUS deep sedimentary basins. Uniform-hazard ground motion data are interpolated for 2, 5, and 10% probability of exceedance in 50 years from the hazard curves. The gridded data for the hazard curves and uniform-hazard ground motions, for all periods and site classes, are available for download at the U.S. Geological Survey ScienceBase Catalog (https://doi.org/10.5066/P9RQMREV). The design ground motions derived from the hazard curves have been accepted by the Building Seismic Safety Council for adoption in the 2020 National Earthquake Hazard Reduction Program Recommended Seismic Provisions.
The U.S. Geological Survey (USGS) National Seismic Hazard Model (NSHM) is the scientific foundation of seismic design regulations in the United States and is regularly updated to consider the best ...available science and data. The 2018 update of the conterminous U.S. NSHM includes significant changes to the underlying ground motion models (GMMs), most of which are necessary to enable the new multi-period response spectra (MPRS) requirements of seismic design regulations that use hazard results for 22 spectral periods and eight site classes. This article focuses on the GMMs used in the western United States (WUS) and is a companion to a recent article on the GMMs used in the central and eastern United States (CEUS). In the WUS, for crustal and subduction earthquakes, two models used in previous versions of the NSHM are excluded to provide consistency over all considered periods and site classes. To more accurately estimate ground motions at long periods in the vicinity of Los Angeles, San Francisco, Salt Lake City, and Seattle, the 2018 NSHM incorporates deep sedimentary basin depth from local seismic velocity models. The subduction GMMs considered lack basin depth terms and are modified to include an additional scale factor to account for this. This article documents the WUS GMMs used in the 2018 NSHM update and provides detail on the changes to GMM medians, aleatory variability, epistemic uncertainty, and site-effect models. It compares each of these components with those considered in prior NSHMs and discusses their total effect on hazard.
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