Combining tower mixing ratio and community model data to estimate regional-scale net ecosystem carbon exchange by boundary layer inversion over 4 flux towers in the U.S.A.

We evaluated an idealized boundary layer (BL) model with simple parameterizations using vertical transport information from community model outputs (NCAR/NCEP Reanalysis and ECMWF Interim Analysis) to estimate regional-scale net CO2 fluxes from 2002 to 2007 at three forest and one grassland flux sites in the United States. The BL modeling approach builds on a mixed-layer model to infer monthly average net CO2 fluxes using high-precision mixing ratio measurements taken on flux towers. We compared BL model net ecosystem exchange (NEE) with estimates from two independent approaches. First, we compared modeled NEE with tower eddy covariance measurements. The second approach (EC-MOD) was a data-driven method that upscaled EC fluxes from towers to regions using MODIS data streams. Comparisons between modeled CO2 and tower NEE fluxes showed that modeled regional CO2 fluxes displayed interannual and intra-annual variations similar to the tower NEE fluxes at the Rannells Prairie and Wind River Forest sites, but model predictions were frequently different from NEE observations at the Harvard Forest and Howland Forest sites. At the Howland Forest site, modeled CO2 fluxes showed a lag in the onset of growing season uptake by 2 months behind that of tower measurements. At the Harvard Forest site, modeled CO2 fluxes agreed with the timing of growing season uptake but underestimated the magnitude of observed NEE seasonal fluctuation. This modeling inconsistency among sites can be partially attributed to the likely misrepresentation of atmospheric transport and/or CO2gradients between ABL and the free troposphere in the idealized BL model. EC-MOD fluxes showed that spatial heterogeneity in land use and cover very likely explained the majority of the data-model inconsistency. We show a site-dependent atmospheric rectifier effect that appears to have had the largest impact on ABL CO2 inversion in the North American Great Plains. We conclude that a systematic BL modeling approach provided new insights when employed in multiyear, cross-site synthesis studies. These results can be used to develop diagnostic upscaling tools, improving our understanding of the seasonal and interannual variability of surface CO2 fluxes

Effects of postdepositional processing on nitrogen isotopes of nitrate in the Greenland Ice Sheet Project 2 ice core

Records of ice core nitrate and its isotopes hold the potential to assess past atmospheric conditions regarding NOx and oxidant levels. However, relating such records to past atmospheric conditions requires a site-specific understanding of the postdepositional processing of snow nitrate. We report δ15N(NO3−) records from the Greenland Ice Sheet Project 2 (GISP2) ice core over major climate transitions. Model calculations and comparison with records of parameters influencing UV-driven postdepositional processing of snow nitrate suggest that the observed variability in GISP2 δ15N(NO3−) over major climate transitions is primarily driven by changes in the degree of postdepositional loss of snow nitrate. Estimates of the fractional loss of snow nitrate is (16–23)% in the Holocene and (45–53)% in the glacial period, suggesting a (41 ± 32)% lower nitrate depositional flux to Greenland during the glacial period relative to the Holocene

Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives

Naturally occurring 2,7-anhydro-alpha-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac) is a transglycosylation product of bacterial intramolecular trans-sialidases (IT-sialidases). A facile one-pot two-enzyme approach has been established for the synthesis of 2,7-anhydro-sialic acid derivatives including those containing different sialic acid forms such as Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The approach is based on the use of Ruminoccocus gnavus IT-sialidase for the release of 2,7-anhydro-sialic acid from glycoproteins, and the conversion of free sialic acid by a sialic acid aldolase. This synthetic method, which is based on a membrane-enclosed enzymatic synthesis, can be performed on a preparative scale. Using fetuin as a substrate, high-yield and cost-effective production of 2,7-anhydro-Neu5Ac was obtained to high-purity. This method was also applied to the synthesis of 2,7-anhydro-Neu5Gc. The membrane-enclosed multienzyme (MEME) strategy reported here provides an efficient approach to produce a variety of sialic acid derivatives

Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multisubstrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structureguided development of XL177A, which irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of similar to 500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO