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The replication accuracy of DNA polymerase gamma (Pol γ) is essential for mitochondrial genome integrity. Mutation of human Pol γ arginine-853 has been linked to neurological diseases. Although not a catalytic residue, Pol γ arginine-853 mutants are void of polymerase activity. To identify the structural basis for the disease, we determined a crystal structure of the Pol γ mutant ternary complex with correct incoming nucleotide 2′-deoxycytidine 5′-triphosphate (dCTP). Opposite to the wild type that undergoes open-to-closed conformational changes when bound to a correct nucleotide that is essential for forming a catalytically competent active site, the mutant complex failed to undergo the conformational change, and the dCTP did not base pair with its Watson-Crick complementary templating residue. Our studies revealed that arginine-853 coordinates an interaction network that aligns the 3′-end of primer and dCTP with the catalytic residues. Disruption of the network precludes the formation of Watson-Crick base pairing and closing of the active site, resulting in an inactive polymerase.more » « less
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Abstract Extreme climate events are becoming more frequent, with poorly understood implications for carbon sequestration by terrestrial ecosystems. A better understanding will critically depend on accurate and precise quantification of ecosystems responses to these events. Taking the 2019 US Midwest floods as a case study, we investigate current capabilities for tracking regional flux anomalies with “top‐down” inversion analyses that assimilate atmospheric CO2observations. For this analysis, we develop a regionally nested version of the NASA Carbon Monitoring System‐Flux system for North America (CMS‐Flux‐NA) that allows high resolution atmospheric transport (0.5° × 0.625°). Relative to a 2018 baseline, we find the 2019 US Midwest growing season net carbon uptake is reduced by 11–57 TgC (3%–16%, range across assimilated CO2data sets). These estimates are found to be consistent with independent “bottom‐up” estimates of carbon uptake based on vegetation remote sensing (15–78 TgC). We then investigate current limitations in tracking regional carbon budgets using “top‐down” methods. In a set of observing system simulation experiments, we show that the ability of atmospheric CO2inversions to capture regional carbon flux anomalies is still limited by observational coverage gaps for both in situ and satellite observations. Future space‐based missions that allow for daily observational coverage across North America would largely mitigate these observational gaps, allowing for improved top‐down estimates of ecosystem responses to extreme climate events.more » « less
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Abstract We select 48 multiflare gamma-ray bursts (GRBs) (including 137 flares) from the Swift/XRT database and estimate the spectral lag with the discrete correlation function. It is found that 89.8% of the flares have positive lags and only 9.5% of the flares show negative lags when fluctuations are taken into account. The median lag of the multiflares (2.75 s) is much greater than that of GRB pulses (0.18 s), which can be explained by the fact that we confirm that multiflare GRBs and multipulse GRBs have similar positive lag–duration correlations. We investigate the origin of the lags by checking the E peak evolution with the two brightest bursts and find the leading models cannot explain all of the multiflare lags and there may be other physical mechanisms. All of the results above reveal that X-ray flares have the same properties as GRB pulses, which further supports the observation that X-ray flares and GRB prompt-emission pulses have the same physical origin.more » « less
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High-quality temperature data at a finer spatio-temporal scale is critical for analyzing the risk of heat exposure and hazards in urban environments. The variability of urban landscapes makes cities a challenging environment for quantifying heat exposure. Most of the existing heat hazard studies have inherent limitations on two fronts; first, the spatio-temporal granularities are too coarse, and second, the inability to track the ambient air temperature (AAT) instead of land surface temperature (LST). Overcoming these limitations requires developing models for mapping the variability in heat exposure in urban environments. We investigated an integrated approach for mapping urban heat hazards by harnessing a diverse set of high-resolution measurements, including both ground-based and satellite-based temperature data. We mounted vehicle-borne mobile sensors on city buses to collect high-frequency temperature data throughout 2018 and 2019. Our research also incorporated key biophysical parameters and Landsat 8 LST data into Random Forest regression modeling to map the hyperlocal variability of heat hazard over areas not covered by the buses. The vehicle-borne temperature sensor data showed large temperature differences within the city, with the largest variations of up to 10 °C and morning-afternoon diurnal changes at a magnitude around 20 °C. Random Forest modeling on noontime (11:30 am – 12:30 pm) data to predict AAT produced accurate results with a mean absolute error of 0.29 °C and successfully showcased the enhanced granularity in urban heat hazard mapping. These maps revealed well-defined hyperlocal variabilities in AAT, which were not evident with other research approaches. Urban core and dense residential areas revealed larger than 5 °C AAT differences from their nearby green spaces. The sensing framework developed in this study can be easily implemented in other urban areas, and findings from this study will be beneficial in understanding the heat vulnerabilities of individual communities. It can be used by the local government to devise targeted hazard mitigation efforts such as increasing green space, developing better heatsafety policies, and exposure warning for workers.more » « less
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