The Potential Uses of Operational Earthquake Forecasting

This article reports on a workshop held to explore the potential uses of operational earthquake forecasting (OEF). We discuss the current status of OEF in the United States and elsewhere, the types of products that could be generated, the various potential users and uses of OEF, and the need for carefully crafted communication protocols. Although operationalization challenges remain, there was clear consensus among the stakeholders at the workshop that OEF could be useful

A physics-based earthquake simulator replicates seismic hazard statistics across California

Seismic hazard models are important for society, feeding into building codes and hazard mitigation efforts. These models, however, rest on many uncertain assumptions and are difficult to test observationally because of the long recurrence times of large earthquakes. Physics-based earthquake simulators offer a potentially helpful tool, but they face a vast range of fundamental scientific uncertainties. We compare a physics-based earthquake simulator against the latest seismic hazard model for California. Using only uniform parameters in the simulator, we find strikingly good agreement of the long-term shaking hazard compared with the California model. This ability to replicate statistically based seismic hazard estimates by a physics-based model cross-validates standard methods and provides a new alternative approach needing fewer inputs and assumptions for estimating hazard

Pseudo-prospective Evaluation of UCERF3-ETAS Forecasts During the 2019 Ridgecrest Sequence

The 2019 Ridgecrest sequence provides the first opportunity to evaluate Uniform California Earthquake Rupture Forecast v.3 with epidemic‐type aftershock sequences (UCERF3‐ETAS) in a pseudoprospective sense. For comparison, we include a version of the model without explicit faults more closely mimicking traditional ETAS models (UCERF3‐NoFaults). We evaluate the forecasts with new metrics developed within the Collaboratory for the Study of Earthquake Predictability (CSEP). The metrics consider synthetic catalogs simulated by the models rather than synoptic probability maps, thereby relaxing the Poisson assumption of previous CSEP tests. Our approach compares statistics from the synthetic catalogs directly against observations, providing a flexible approach that can account for dependencies and uncertainties encoded in the models. We find that, to the first order, both UCERF3‐ETAS and UCERF3‐NoFaults approximately capture the spatiotemporal evolution of the Ridgecrest sequence, adding to the growing body of evidence that ETAS models can be informative forecasting tools. However, we also find that both models mildly overpredict the seismicity rate, on average, aggregated over the evaluation period. More severe testing indicates the overpredictions occur too often for observations to be statistically indistinguishable from the model. Magnitude tests indicate that the models do not include enough variability in forecasted magnitude‐number distributions to match the data. Spatial tests highlight discrepancies between the forecasts and observations, but the greatest differences between the two models appear when aftershocks occur on modeled UCERF3‐ETAS faults. Therefore, any predictability associated with embedding earthquake triggering on the (modeled) fault network may only crystalize during the presumably rare sequences with aftershocks on these faults. Accounting for uncertainty in the model parameters could improve test results during future experiments.Maximilian J. Werner and Warner Marzocchi received funding from the European Union's Horizon 2020 research and innovation program (Number 821115, RISE: Real‐Time Earthquake Risk Reduction for a Resilient Europe). This research was supported by the Southern California Earthquake Center (SCEC; Contribution Number 10082). SCEC is funded by National Science Foundation (NSF) Cooperative Agreement EAR‐1600087 and the U.S. Geological Survey (USGS) Cooperative Agreement G17AC00047

Absence of cardiomyocyte differentiation following transplantation of adult cardiac-resident Sca-1+ cells into infarcted mouse hearts

Although several lines of evidence suggest that the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 marks cardiac-resident stem cells, a critical analysis of the literature raises some concerns regarding their cardiomyogenic potential.1 Here, isolated adult cardiac-resident Sca-1+ cells were engrafted into infarcted hearts and monitored for cardiomyogenic differentiation. Donor cells were prepared from ACT-EGFP; MHC-nLAC double-transgenic mice ([C57/Bl6J x DBA/2J]F1 genetic background; all procedures followed were in accordance with Institutional Guidelines). The ACT-EGFP transgene targets ubiquitous expression of an enhanced green fluorescent protein reporter, and the MHC-nLAC transgene targets cardiomyocyte-restricted expression of a nuclear-localized β-galactosidase reporter. Donor cell survival was monitored via EGFP fluorescence, while cardiomyogenic differentiation was monitored by reacting with the chromogenic β-galactosidase substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-GAL), which gives rise to a blue product.2 Double-transgenic hearts were dispersed with Blendzyme and the resulting cells reacted with an APC-conjugated anti-Sca-1 antibody and a PE-conjugated cocktail of antibodies recognizing hematopoietic lineage markers.3 Sca-1+, EGFP+, lineage- cells were then isolated via fluorescence-activated cell sorting (FACS; characterization of the donor cells is provided in Figure 1A), and 100,000 cells were injected into the infarct border zone of non-transgenic [C57/Bl6J x DBA/2J]F1 mice immediately following permanent coronary artery occlusion

Adult Bone Marrow–derived Cells Do Not Acquire Functional Attributes of Cardiomyocytes When Transplanted into Peri-infarct Myocardium

(BM) cells after being directly transplanted into the ischemically injured heart remains a controversial issue. In this study, we investigated the ability of transplanted BM cells to develop intracellular calcium ([Ca2+] i ) transients in response to membrane depolarization in situ. Low-density mononuclear (LDM) BM cells, c-kit-enriched (c-kitenr) BM cells, and highly enriched lin– c-kit+ BM cells were obtained from adult transgenic mice ubiquitously expressing enhanced green fluorescent protein (EGFP), and injected into peri-infarct myocardiums of nontransgenic mice. After 9–10 days the mice were killed, and the hearts were removed, perfused in Langendorff mode, loaded with the calcium-sensitive fluorophore rhod-2, and subjected to two-photon laser scanning fluorescence microscopy (TPLSM) to monitor action potential–induced [Ca2+] i transients in EGFP-expressing donor-derived cells and non-expressing host cardiomyocytes. Whereas spontaneous and electrically evoked [Ca2+] i transients were found to occur synchronously in host cardiomyocytes along the graft–host border and in areas remote from the infarct, they were absent in all of the >3,000 imaged BM-derived cells that were located in clusters throughout the infarct scar or peri-infarct zone. We conclude that engrafted BM-derived cells lack attributes of functioning cardiomyocytes, calling into question the concept that adult BM cells can give rise to substantive cardiomyocyte regeneration within the infarcted heart

Large-scale comparative genomic ranking of taxonomically restricted genes (TRGs) in bacterial and archaeal genomes

BACKGROUND: Lineage-specific, or taxonomically restricted genes (TRGs), especially those that are species and strain-specific, are of special interest because they are expected to play a role in defining exclusive ecological adaptations to particular niches. Despite this, they are relatively poorly studied and little understood, in large part because many are still orphans or only have homologues in very closely related isolates. This lack of homology confounds attempts to establish the likelihood that a hypothetical gene is expressed and, if so, to determine the putative function of the protein. METHODOLOGY/PRINCIPAL FINDINGS: We have developed "QIPP" ("Quality Index for Predicted Proteins"), an index that scores the "quality" of a protein based on non-homology-based criteria. QIPP can be used to assign a value between zero and one to any protein based on comparing its features to other proteins in a given genome. We have used QIPP to rank the predicted proteins in the proteomes of Bacteria and Archaea. This ranking reveals that there is a large amount of variation in QIPP scores, and identifies many high-scoring orphans as potentially "authentic" (expressed) orphans. There are significant differences in the distributions of QIPP scores between orphan and non-orphan genes for many genomes and a trend for less well-conserved genes to have lower QIPP scores. CONCLUSIONS: The implication of this work is that QIPP scores can be used to further annotate predicted proteins with information that is independent of homology. Such information can be used to prioritize candidates for further analysis. Data generated for this study can be found in the OrphanMine at http://www.genomics.ceh.ac.uk/orphan_mine

Toward Identifying the Next Generation of Superfund and Hazardous Waste Site Contaminants

Reproduced with permission from Environmental Health Perspectives."This commentary evolved from a workshop sponsored by the National Institute of Environmental Health Sciences titled "Superfund Contaminants: The Next Generation" held in Tucson, Arizona, in August 2009. All the authors were workshop participants." doi:10.1289/ehp.1002497Our aim was to initiate a dynamic, adaptable process for identifying contaminants of emerging concern (CECs) that are likely to be found in future hazardous waste sites, and to identify the gaps in primary research that cause uncertainty in determining future hazardous waste site contaminants. Superfund-relevant CECs can be characterized by specific attributes: they are persistent, bioaccumulative, toxic, occur in large quantities, and have localized accumulation with a likelihood of exposure. Although still under development and incompletely applied, methods to quantify these attributes can assist in winnowing down the list of candidates from the universe of potential CECs. Unfortunately, significant research gaps exist in detection and quantification, environmental fate and transport, health and risk assessment, and site exploration and remediation for CECs. Addressing these gaps is prerequisite to a preventive approach to generating and managing hazardous waste sites.Support for the workshop, from which this article evolved, was provided by the National Institute of Environmental Health Sciences Superfund Research Program (P42-ES04940)