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The Global Carbon Budget 2018 (GCB2018) estimated by the atmospheric CO 2 growth rate, fossil fuel emissions, and modeled (bottom‐up) land and ocean fluxes cannot be fully closed, leading to a "budget imbalance," highlighting uncertainties in GCB components. However, no systematic analysis has been performed on which regions or processes contribute to this term. To obtain deeper insight on the sources of uncertainty in global and regional carbon budgets, we analyzed differences in Net Biome Productivity (NBP) for all possible combinations of bottom‐up and top‐down data sets in GCB2018: (i) 16 dynamic global vegetation models (DGVMs), and (ii) 5 atmospheric inversions that match the atmospheric CO 2 growth rate. We find that the global mismatch between the two ensembles matches well the GCB2018 budget imbalance, with Brazil, Southeast Asia, and Oceania as the largest contributors. Differences between DGVMs dominate global mismatches, while at regional scale differences between inversions contribute the most to uncertainty. At both global and regional scales, disagreement on NBP interannual variability between the two approaches explains a large fraction of differences. We attribute this mismatch to distinct responses to El Niño–Southern Oscillation variability between DGVMs and inversions and to uncertainties in land use change emissions, especially in South America and Southeast Asia. We identify key needs to reduce uncertainty in carbon budgets: reducing uncertainty in atmospheric inversions (e.g., through more observations in the tropics) and in land use change fluxes, including more land use processes and evaluating land use transitions (e.g., using high‐resolution remote‐sensing), and, finally, improving tropical hydroecological processes and fire representation within DGVMs. Key Points: Top‐down and bottom‐up estimates of net land‐atmosphere CO 2 fluxes agree well globally but show important mismatches at regional scalesRegional mismatches are dominated by differences between inversions and interannual variability in CO 2 fluxesMismatches between top‐down and bottom‐up data sets are explained by sensitivity to climate and by uncertainty in land use change forcing [ABSTRACT FROM AUTHOR]

Abstract: Carbon exchange over croplands plays an important role in the European carbon cycle over daily to seasonal time scales. A better description of this exchange in terrestrial biosphere models—most of which currently treat crops as unmanaged grasslands—is needed to improve atmospheric CO2 simulations. In the framework we present here, we model gross European cropland CO2 fluxes with a crop growth model constrained by grain yield observations. Our approach follows a two‐step procedure. In the first step, we calculate day‐to‐day crop carbon fluxes and pools with the WOrld FOod STudies (WOFOST) model. A scaling factor of crop growth is optimized regionally by minimizing the final grain carbon pool difference to crop yield observations from the Statistical Office of the European Union. In a second step, we re‐run our WOFOST model for the full European 25 × 25 km gridded domain using the optimized scaling factors. We combine our optimized crop CO2 fluxes with a simple soil respiration model to obtain the net cropland CO2 exchange. We assess our model's ability to represent cropland CO2 exchange using 40 years of observations at seven European FluxNet sites and compare it with carbon fluxes produced by a typical terrestrial biosphere model. We conclude that our new model framework provides a more realistic and strongly observation‐driven estimate of carbon exchange over European croplands. Its products will be made available to the scientific community through the ICOS Carbon Portal and serve as a new cropland component in the CarbonTracker Europe inverse model. [ABSTRACT FROM AUTHOR]

Two major droughts in the past decade had large impacts on carbon exchange in the Amazon. Recent analysis of vertical profile measurements of atmospheric CO2 and CO by Gatti et al. (2014) suggests that the 2010 drought turned the normally close-to-neutral annual Amazon carbon balance into a substantial source of nearly 0.5 PgC/yr, revealing a strong drought response. In this study, we revisit this hypothesis and interpret not only the same CO2/CO vertical profile measurements but also additional constraints on carbon exchange such as satellite observations of CO, burned area, and fire hot spots. The results from our CarbonTracker South America data assimilation system suggest that carbon uptake by vegetation was indeed reduced in 2010 but that the magnitude of the decrease strongly depends on the estimated 2010 and 2011 biomass burning emissions. We have used fire products based on burned area (Global Fire Emissions Database version 4), satellite-observed CO columns (Infrared Atmospheric Sounding Interferometer), fire radiative power (Global Fire Assimilation System version 1), and fire hot spots (Fire Inventory from NCAR version 1), and found an increase in biomass burning emissions in 2010 compared to 2011 of 0.16 to 0.24 PgC/yr. We derived a decrease of biospheric uptake ranging from 0.08 to 0.26 PgC/yr, with the range determined from a set of alternative inversions using different biomass burning estimates. Our numerical analysis of the 2010 Amazon drought results in a total reduction of carbon uptake of 0.24 to 0.50 PgC/yr and turns the balance from carbon sink to source. Our findings support the suggestion that the hydrological cycle will be an important driver of future changes in Amazonian carbon exchange. [ABSTRACT FROM AUTHOR]

Previous studies suggest that a large part of the variability in the atmospheric ratio of 13CO2/12CO2originates from carbon exchange with the terrestrial biosphere rather than with the oceans. Since this variability is used to quantitatively partition the total carbon sink, we here investigate the contribution of interannual variability (IAV) in biospheric exchange to the observed atmospheric 13C variations. We use the Simple Biosphere - Carnegie-Ames-Stanford Approach biogeochemical model, including a detailed isotopic fractionation scheme, separate 12C and 13C biogeochemical pools, and satellite-observed fire disturbances. This model of 12CO2 and 13CO2 thus also produces return fluxes of 13CO2from its differently aged pools, contributing to the so-called disequilibrium flux. Our simulated terrestrial 13C budget closely resembles previously published model results for plant discrimination and disequilibrium fluxes and similarly suggests that variations in C3 discrimination and year-to-year variations in C3and C4 productivity are the main drivers of their IAV. But the year-to-year variability in the isotopic disequilibrium flux is much lower (1 σ=±1.5 PgC ‰ yr−1) than required (±12.5 PgC ‰ yr−1) to match atmospheric observations, under the common assumption of low variability in net ocean CO2 fluxes. This contrasts with earlier published results. It is currently unclear how to increase IAV in these drivers suggesting that SiBCASA still misses processes that enhance variability in plant discrimination and relative C3/C4productivity. Alternatively, 13C budget terms other than terrestrial disequilibrium fluxes, including possibly the atmospheric growth rate, must have significantly different IAV in order to close the atmospheric 13C budget on a year-to-year basis. [ABSTRACT FROM AUTHOR]

The 14C/C abundance in CO2(Δ14CO2) promises to provide useful constraints on regional fossil fuel emissions and atmospheric transport through the large gradients introduced by anthropogenic activity. The currently sparse atmospheric Δ14CO2 monitoring network can potentially be augmented by using plant biomass as an integrated sample of the atmospheric Δ14CO2. But the interpretation of such an integrated sample requires knowledge about the day-to-day CO2 uptake of the sampled plants. We investigate here the required detail in daily plant growth variations needed to accurately interpret regional fossil fuel emissions from annual plant samples. We use a crop growth model driven by daily meteorology to reproduce daily fixation of Δ14CO2 in maize and wheat plants in the Netherlands in 2008. When comparing the integrated Δ14CO2 simulated with this detailed model to the values obtained when using simpler proxies for daily plant growth (such as radiation and temperature), we find differences that can exceed the reported measurement precision of Δ14CO2(∼2‰). Furthermore, we show that even in the absence of any spatial differences in fossil fuel emissions, differences in regional weather can induce plant growth variations that result in spatial gradients of up to 3.5‰ in plant samples. These gradients are even larger when interpreting separate plant organs (leaves, stems, roots, or fruits), as they each develop during different time periods. Not accounting for these growth-induced differences in Δ14CO2 in plant samples would introduce a substantial bias (1.5-2 ppm) when estimating the fraction of atmospheric CO2 variations resulting from nearby fossil fuel emissions. [ABSTRACT FROM AUTHOR]

We present an estimate of net ecosystem exchange (NEE) of CO2 in Europe for the years 2001–2007. It is derived with a data assimilation that uses a large set of atmospheric CO2 mole fraction observations (∼70 000) to guide relatively simple descriptions of terrestrial and oceanic net exchange, while fossil fuel and fire emissions are prescribed. Weekly terrestrial sources and sinks are optimized (i.e., a flux inversion) for a set of 18 large ecosystems across Europe in which prescribed climate, weather, and surface characteristics introduce finer scale gradients. We find that the terrestrial biosphere in Europe absorbed a net average of −165 Tg C yr−1 over the period considered. This uptake is predominantly in non-EU countries, and is found in the northern coniferous (−94 Tg C yr−1) and mixed forests (−30 Tg C yr−1) as well as the forest/field complexes of eastern Europe (−85 Tg C yr−1). An optimistic uncertainty estimate derived using three biosphere models suggests the uptake to be in a range of −122 to −258 Tg C yr−1, while a more conservative estimate derived from the a-posteriori covariance estimates is −165±437 Tg C yr−1. Note, however, that uncertainties are hard to estimate given the nature of the system and are likely to be significantly larger than this. Interannual variability in NEE includes a reduction in uptake due to the 2003 drought followed by 3 years of more than average uptake. The largest anomaly of NEE occurred in 2005 concurrent with increased seasonal cycles of observed CO2. We speculate these changes to result from the strong negative phase of the North Atlantic Oscillation in 2005 that lead to favorable summer growth conditions, and altered horizontal and vertical mixing in the atmosphere. All our results are available through [ABSTRACT FROM AUTHOR]

The ability to reliably estimate CO2 fluxes from current in situ atmospheric CO2 measurements and future satellite CO2 measurements is dependent on transport model performance at synoptic and shorter timescales. The TransCom continuous experiment was designed to evaluate the performance of forward transport model simulations at hourly, daily, and synoptic timescales, and we focus on the latter two in this paper. Twenty-five transport models or model variants submitted hourly time series of nine predetermined tracers (seven for CO2) at 280 locations. We extracted synoptic-scale variability from daily averaged CO2 time series using a digital filter and analyzed the results by comparing them to atmospheric measurements at 35 locations. The correlations between modeled and observed synoptic CO2 variabilities were almost always largest with zero time lag and statistically significant for most models and most locations. Generally, the model results using diurnally varying land fluxes were closer to the observations compared to those obtained using monthly mean or daily average fluxes, and winter was often better simulated than summer. Model results at higher spatial resolution compared better with observations, mostly because these models were able to sample closer to the measurement site location. The amplitude and correlation of model-data variability is strongly model and season dependent. Overall similarity in modeled synoptic CO2 variability suggests that the first-order transport mechanisms are fairly well parameterized in the models, and no clear distinction was found between the meteorological analyses in capturing the synoptic-scale dynamics. [ABSTRACT FROM AUTHOR]

A forward atmospheric transport modeling experiment has been coordinated by the TransCom group to investigate synoptic and diurnal variations in CO[sub2]. Model simulations were run for biospheric, fossil, and air-sea exchange of CO[sub2] and for SF6 and radon for 2000-2003. Twenty-five models or model variants participated in the comparison. Hourly concentration time series were submitted for 280 sites along with vertical profiles, fluxes, and meteorological variables at 100 sites. The submitted results have been analyzed for diurnal variations and are compared with observed CO[sub2] in 2002. Mean summer diurnal cycles vary widely in amplitude across models. The choice of sampling location and model level account for part of the spread suggesting that representation errors in these types of models are potentially large. Despite the model spread, most models simulate the relative variation in diurnal amplitude between sites reasonably well. The modeled diurnal amplitude only shows a weak relationship with vertical resolution across models; differences in near-surface transport simulation appear to play a major role. Examples are also presented where there is evidence that the models show useful skill in simulating seasonal and synoptic changes in diurnal amplitude. [ABSTRACT FROM AUTHOR]

Background Colon carcinogenesis is a multifactorial process influenced by hereditary as well as environmental factors. The glutathione/glutathione S-transferase detoxification system in the colon is important for protection against carcinogens. We investigated the levels of glutathione/glutathione S-transferase in normal colon mucosa of patients with colorectal cancer and in patients at high risk for colorectal cancer compared with those in healthy controls. Materials and methods Glutathione content was analyzed by high-performance liquid chromatography, and glutathione S-transferase enzyme activity by spectrophotometric determination with 1-chloro 2,4-dinitrobenzene. Normal colon tissue of patients with colon adenoma ( n = 64), colorectal cancer ( n = 37), familial adenomatous polyposis (FAP; n = 19), hereditary non-polyposis colorectal cancer families with (HNPCC+Ad; n = 34) or without (HNPCC-Ad; n = 33) adenoma was investigated. Results Glutathione levels were significantly lower in the normal colon mucosa of patients with cancer, FAP, HNPCC-Ad or HNPCC+Ad compared with adenoma patients or healthy controls. Glutathione S-transferase enzyme activity in the distal colon was significantly lower in patients with cancer or FAP compared with the adenoma patients or healthy controls, whereas values in carcinoma patients were significantly lower compared with both the HNPCC-Ad and HNPCC+Ad groups. Conclusions An association of low colonic glutathione/glutathione S-transferase activity levels and high clinical risk for the development of colorectal cancer was observed. This low glutathione detoxification capacity might contribute to the colon cancer risk. [ABSTRACT FROM AUTHOR]

Measurements of nitrous oxide in air samples from 48 sites in the Cooperative Global Air Sampling Network made by NOAA/ESRL GMD CCGG (the Carbon Cycle Greenhouse Gases group in the Global Monitoring Division at the NOAA Earth System Research Laboratory in Boulder, Colorado) and the three-dimensional chemical transport model TM3 were used to infer global nitrous oxide fluxes and their uncertainties from 1998–2001. Results are presented for four semihemispherical regions (90°S–30°S, 30°S to equator, equator to 30°N, 30°N–90°N) and six broad ‘super regions’ (Southern Land, Southern Oceans, Tropical Land, Tropical Oceans, Northern Land, and Northern Oceans). We found that compared to our a priori estimate (from the International Geosphere-Biosphere Programme's Global Emissions Inventory Activity), the a posteriori flux was much lower from 90°S–30°S and substantially higher from equator to 30°N. Consistent with these results, the a posteriori flux from the Southern Oceans region was lower than the a priori estimate, while Tropical Land and Tropical Ocean estimates were higher. The ratio of Northern Hemisphere to Southern Hemisphere fluxes was found to range from 1.9 to 5.2 (depending on the model setup), which is higher than the a priori ratio (1.5) and at the high end of previous estimates. Globally, ocean emissions contributed 26–36% of the total flux (again depending on the model setup), consistent with the a priori estimate (29%), though somewhat higher than some other previous estimates. [ABSTRACT FROM AUTHOR]

Background Small intestinal malignancies in humans are rare; however, patients with coeliac disease have a relatively high risk for such tumours. Intestinal UDP-glucuronosyltransferases are phase II drug metabolism enzymes also involved in the detoxification of ingested toxins and carcinogens. As many toxins and carcinogens are ingested via food, the human gastrointestinal tract not only has an important role in the uptake of essential nutrients, but also acts as a first barrier against such harmful constituents of the food. Therefore, the gastrointestinal mucosa contains high levels of detoxification enzymes such as cytochromes-P450, glutathione S-transferases and UDP-glucuronosyltransferases. Aim To compare the UDP-glucuronosyltransferase detoxification capacity in small intestinal mucosa of patients with coeliac disease vs. that in normal controls. Methods We assessed UDP-glucuronosyltransferase enzyme activities towards 4-methylumbelliferone in small intestinal biopsies of patients with coeliac disease ( n = 22) and age- and sex-matched controls ( n = 27). Results Small intestinal UDP-glucuronosyltransferase enzyme activity in controls was significantly higher than in patients with coeliac disease: 0.55 ± 0.27 vs. 0.35 ± 0.16 nmol/min mg protein, respectively (mean ± s.d., P = 0.005). Discussion The low small intestinal UDP-glucuronosyltransferase detoxification activity in patients with coeliac disease may result in a deficient detoxification of potential carcinogens, and thus could explain in part the relatively high small intestinal cancer risk in these patients. [ABSTRACT FROM AUTHOR]

Abstract The protein tyrosine phosphatases PTP-SL and PTPBR7 differ only in the length of their N-terminal domain. We show here that PTP-SL and PTPBR7 are isoforms derived from a single gene (Ptprr) through developmentally regulated use of alternative promoters. Isoform-specific reverse transcriptase-polymer chain reaction (RT-PCR) and RNA in situ hybridization experiments reveal that PTPBR7 is expressed during early embryogenesis in spinal ganglia cells as well as in developing Purkinje cells. Post-natally, PTPBR7 is expressed in various regions of the adult mouse brain, but expression in Purkinje cells has ceased and is replaced by the PTP-SL-specific transcript. In transient transfection experiments it is confirmed that PTPBR7 is a type I transmembrane protein tyrosine phosphatase (PTPase). PTP-SL, however, appears to be a cytosolic membrane-associated PTPase that is located at perinuclear vesicular structures that partly belong to the endosomal compartment. Thus, during maturation of Purkinje cells, a gene-promoter switch results in the replacement of a receptor-type PTPase by a cytosolic vesicle-associated isoform. [ABSTRACT FROM AUTHOR]

Introduction: Single lead VDD pacing has offered an alternative to DDD .systems in patients with isolated AV block. Up to now, however, the relative performance of these pacemaker systems was not systematically compared. Methods and Results: Three hundred sixty patients who received either a VDD pacemaker (n = 180) or a DDD device (n = 180) with a hipolar atrial lead were investigated prospectively for a mean period of 30 ± 13 months. Pacemaker function was analyzed by telemetry. Holter monitoring, and exercise ECG. Time of implantation and fluoroscopy was significantly lower with VDD devices (44.3 ± 5.1 min vs 74.4 ± 13.5 min and 4.6 ± 2.5 min vs 10.3 ± 5.6 min in DDD pacemakers, respectively). Intermittent atrial undersensing occurred in 23.3% of patients with a VDD pacemaker and in 9.4% with DDD devices (NS). The incidence of atrial tachyarrhythmias did not differ between the VDD (6.7%) and the DDD group (6.1%). Sinus node dysfunction developed in 1.9% of patients, but the vast majority (85.7%) of patients were asymptomatic. There was a tendency for a higher rate of operative revisions in the DDD group (6.1% vs 3.3% in VDD pacemakers, P = 0.15). Cumulative maintenance of AV-.synchronized pacing mode was 94.9% in patients with VDD pacemakers and 92.1% with DDD devices (NS). Conclusion: With the benefit of a simpler implant procedure, long-term outcome of single lead VDD pacing is equivalent to DDD pacing in patients with AV block and preoperative normal sinus node function. [ABSTRACT FROM AUTHOR]