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Anthropogenic emissions are the primary source of atmospheric methane (CH4) growth. However, estimates of anthropogenic CH4 emissions still show large uncertainties on global and regional scales. Differences in CH4 isotopic source signatures δ13C and δ2H can help to constrain different source contributions (e.g. fossil, waste, agriculture, etc.). The Upper Silesian Coal Basin (USCB) represents one of the largest European CH4 emission regions, with more than 500 Gg CH4 yr-1 released from more than 50 coal mine ventilation shafts and other anthropogenic sources. During the CoMet (Carbon Dioxide and Methane Mission) campaign in June 2018 methane observations were conducted from a variety of platforms including aircraft and cars to quantify these emissions. Beside the continuous sampling of atmospheric methane concentration, numerous air samples were taken from inside and around the ventilation shafts (1–2 km distance) and aboard the High Altitude and Long Range Research Aircraft (HALO) and DLR Cessna Caravan aircraft, and analyzed in the laboratory for the isotopic composition of CH4. The airborne samples downwind of the USCB contained methane from all sources in the region and thus enabled determining the mean signature of the USCB accurately. This mean isotopic signature of methane emissions was -50.9 ± 0.7 ‰ for δ13C and -226 ± 9 ‰ for δ2H. This is in the range of previous USCB studies based on samples taken within the mines for δ13C, but more depleted in δ2H than reported before. Signatures of methane enhancements sampled upwind of the mines and in the free troposphere clearly showed the influence of biogenic sources (e.g. wetlands, waste, ruminants). The ground-based samples taken during CoMet allowed determining the source signatures of individual coal mine ventilation shafts. These signatures displayed a considerable range between different shafts and also varied for individual shafts from day to day. Mean shaft signatures range from -60 ‰ to -42 ‰ for δ13C and from -200 ‰ to 160 ‰ for δ2H. A gradient in the signatures of sub-regions of the USCB is reflected both in the aircraft data as well as in the ground samples with emissions from the southwest being most depleted in δ2H and emissions from the south most depleted in δ13C. The average signature of -49.8 ± 5.7 ‰ in δ13C and -184 ± 32 ‰ in δ2H from the ventilation shafts fits with values from previous studies, but clearly differs from the USCB regional signature in δ2H. We assume that the USCB plume mainly contains fossil coal mine methane and biogenic methane from waste treatment, because the USCB is a highly industrialized region with few other possible methane sources. Assuming a biogenic methane signature between and -320 ‰ and -280 ‰ for δ2H, the biogenic methane emissions from the USCB account for 15–50 % of total emissions. The share of anthropogenic-biogenic emissions from this densely populated industrial region is underestimated in commonly used emission inventories. Generally, this study demonstrates the importance and usefulness of δ2H-CH4 observations for methane source attribution, but highlights the need of comprehensive and extensive sampling from all possible source sectors.

Since 1999, Environment and Climate Change Canada (ECCC) has been coordinating a multi-laboratory comparison of measurements of long-lived greenhouse gases in whole air samples collected at the Global Atmosphere Watch (GAW) Alert Observatory located in the Canadian high Arctic (82°28' N, 62°30' W). In this paper, we evaluate the measurement agreement of atmospheric CO2, CH4, N2O, SF6, and stable isotopes of CO2 (δ13C, δ18O) between leading laboratories from 7 independent international institutions. The measure of success is linked to target goals for network compatibility outlined by the World Meteorological Organization’s (WMO) GAW greenhouse gas measurement community. Overall, based on ~8000 discrete flask samples, we find that the co-located atmospheric CO2 and CH4 measurement records from Alert by CSIRO, MPI-BGC, SIO, UHEI-IUP, ECCC, and NOAA are generally consistent with the WMO compatibility goals of ±0.1 ppm CO2 and ±2 ppb CH4 over the 17-year period (1999 – 2016), although there are periods where differences exceed target levels and persist as systematic bias for months or years. Consistency with the WMO goals for N2O, SF6, and stable isotopes of CO2 (δ13C, δ18O) has not been demonstrated. Additional analysis of co-located comparison measurements between CSIRO, SIO, and NOAA at other geographical sites suggests that the findings at Alert for CO2, CH4, N2O and δ13C-CO2 could be extended across the CSIRO, SIO, and NOAA observing networks. Two approaches are carried out to determine the level of agreement as a collective for the 7 individual laboratories (1) pooling the differences of individual laboratories over the entire sampling records from a designated reference laboratory and determining the 95th percentile range of these data points and (2) averaging the 2 standard deviations (2-sigma) of the means for all flask samples taken in each individual sampling episode over the entire sampling record. For CO2, from 5691 samples, we derive a measurement agreement level of -0.51 to +0.53 ppm using the 95th percentile range of the differences from NOAA measurements. Similarly, we derive a corresponding value of ± 0.37 ppm using the mean of 2-sigma values from 923 individual weekly sampling episodes. For CO2 isotopes using INSTAAR measurements as a reference, we derive measurement agreement values of -0.09 to +0.07 and ± 0.06 ‰ for δ13C and -0.50 to +0.58 and ± 0.31 ‰ for δ18O, for the 95th percentile ranges and the mean of the 2-sigma values, respectively. For other gases, the corresponding values for both approaches are 4.86 to +6.16 and ± 3.62 ppb for CH4, -0.75 to +1.20 and ± 0.64 ppb for N2O, and -0.14 to +0.09 and ± 0.09 ppt for SF6. These upper and lower limits represent our best estimate of the measurement agreement at the 95 % confidence level for these individual laboratories, providing more confidence for using these datasets in various scientific applications (e.g., long-term trend analysis).

Purpose This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. Methods IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. Results Minimal significant beneficial exercise effects on self-reported CF (β=−0.09 [−0.16; −0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=−0.13 [−0.24; −0.02]), and no significant effect during cancer treatment (n=1,162, β=−0.08 [−0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=−0.14 [−0.25; −0.04]) or 24 weeks or longer (β=−0.18 [−0.32; −0.02]), whereas no effects were observed in interventions of 12–24 weeks (β=0.01 [−0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=−0.10 [−0.19; −0.02]) or after completion of treatment in patients with cognitive problems (β=−0.19 [−0.31; −0.06]). No other significant moderators were identified. Conclusions This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. Implications for Cancer Survivors This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.

Hydrogen (δ2H) and oxygen (δ18O) isotopes of water extracted from speleothem fluid inclusions are important proxies used for paleoclimate reconstruction. In our study we use a cavity ring-down laser spectroscopy system for analysis and modified the approach of Affolter et al. (2014) for sample extraction. The method is based on crushing of small sub-gram speleothem samples in a heated and continuously water-vapour purged extraction line. The following points were identified: Injection of reference water shows a precision (1σ) of 0.4-0.5 permil for δ18O values and 1.1-1.9 permil for δ2H values for water amounts of 0.1-0.5 μl, which improves with increasing water amount to 0.1-0.3 permil and 0.2-0.7 permil, respectively, above 1 μl. The accuracy of measurements of water injections and water-filled glass capillaries crushed in the system is better than 0.08 permil for δ18O and 0.3 permil for δ2H values. The reproducibility (1σ) based on replicate analysis of speleothem fluid inclusion samples with water amounts > 0.2 μl is 0.5 permil for δ18O and 1.2 permil for δ2H values, respectively. Isotopic differences between the water vapour background of the extraction system and the fluid inclusions have no significant impact on the measured fluid inclusion isotope values if they are within 10 permil for δ18O and 50 permil for δ2H values of the background. Tests of potential adsorption effects with inclusion free spar calcite confirm that the isotope values are unaffected by adsorption for water contents of about 1 μl (fluid inclusion) water per g of carbonate or above. Fluid inclusion analysis on three different modern to late Holocene speleothems from caves in northwest Germany resulted in δ18O and δ2H values that follow the relationship as defined by the meteoric water line and that correspond to the local drip water. Yet, due to potential isotope exchange reactions for oxygen atoms, hydrogen isotope measurements are preferentially to be used for temperature reconstructions. We demonstrate this in a case study with a Romanian stalagmite, for which we reconstruct the 20th century warming with an amplitude of approximately 1 °C, with a precision for each data point of better than ±0.5 °C

Recent climate change mitigation strategies rely on the reduction of methane (CH4) emissions. Carbon and hydrogen isotope ratio (δ13CCH4 and δ2HCH4) measurements can be used to distinguish sources and thus to understand the CH4 budget better. The CH4 emission estimates by models are sensitive to the isotopic signatures assigned to each source category, so it is important to provide representative estimates of the different CH4 source isotopic signatures worldwide. We present new measurements of isotope signatures of various, mainly anthropogenic, CH4 sources in Europe, which represent a substantial contribution to the global dataset of source isotopic measurements from the literature, especially for δ2HCH4. They improve the definition of δ13CCH4 from waste sources, and demonstrate the use of δ2HCH4 for fossil fuel source attribution. We combined our new measurements with the last published database of CH4 isotopic signatures and with additional literature, and present a new global database. We found that microbial sources are generally well characterised. The large variability in fossil fuel isotopic compositions requires particular care in the choice of weighting criteria for the calculation of a representative global value. The global dataset could be further improved by measurements from African, South American, and Asian countries, and more measurements from pyrogenic sources. We improved the source characterisation of CH4 emissions using stable isotopes and associated uncertainty, to be used in top-down studies. We emphasise that an appropriate use of the database requires the analysis of specific parameters in relation to source type and the region of interest. The final version of the European CH4 isotope database coupled with a global inventory of fossil and non-fossil δ13CCH4 and δ2HCH4 source signature measurements is available at https://doi.org/10.24416/UU01-YP43IN (Menoud et al., 2022a).

Mapping trace gas emission plumes using in situ measurements from unmanned aerial vehicles (UAVs) is an emerging and attractive possibility to quantify emissions from localized sources. Here, we present the results of an extensive controlled-release experiment in Dubendorf, Switzerland, which was conducted to develop an optimal quantification method and to determine the related uncertainties under various environmental and sampling conditions. Atmospheric methane mole fractions were simultaneously measured using a miniaturized fast-response quantum cascade laser absorption spectrometer (QCLAS) and an active AirCore system mounted on a commercial UAV. Emission fluxes were estimated using a mass-balance method by flying the UAV-based system through a vertical cross-section downwind of the point source perpendicular to the main wind direction at multiple altitudes. A refined kriging framework, called cluster-based kriging, was developed to spatially map individual methane measurement points into the whole measurement plane, while taking into account the different spatial scales between background and enhanced methane values in the plume. We found that the new kriging framework resulted in better quantification compared to ordinary kriging. The average bias of the estimated emissions was -1 %, and the average residual of individual errors was 54 %. A Direct comparison of QCLAS and AirCore measurements shows that AirCore measurements are smoothed by 20 s and had an average time lag of 7 s. AirCore measurements also stretch linearly with time at an average rate of 0.06 s for every second of QCLAS measurement. Applying these corrections to the AirCore measurements and successively calculating an emission estimate shows an enhancement of the accuracy by 3 % as compared to its uncorrected counterpart. Optimal plume sampling, including the downwind measurement distance, depends on wind and turbulence conditions, and it is furthermore limited by numerous parameters such as the maximum flight time and the measurement accuracy. Under favourable measurement conditions, emissions could be quantified with an uncertainty of 30 %. Uncertainties increase when wind speeds are below 2.3 m s(-1) and directional variability is above 33 degrees, and when the downwind distance is above 75 m. In addition, the flux estimates were also compared to estimates from the well-established OTM-33A method involving stationary measurements. A good agreement was found, both approaches being close to the true release and uncertainties of both methods usually capturing the true release., Atmospheric Measurement Techniques, 15 (7), ISSN:1867-1381, ISSN:1867-8548

We present speleothem fluid inclusion δ18Of and δ2Hf values from Larga Cave, Puerto Rico, that cover the interval between 46.2 and 15.3 ka on the millennial scale, including the Last Glacial Maximum (LGM) and several stadial and interstadial cycles. The data set can be divided in two main clusters of stable isotope compositions of the fluid inclusion water with respect to the global meteoric water line (GMWL), which coincide with strong variations in the water content of the stalagmite. In particular, this clustering is found to be climate related, where one cluster comprises samples from cold and dry periods, such as the Heinrich and Greenland stadials (HSs and GSs), as well as parts of the LGM, which exhibit very high δ18Of and δ2Hf values. We interpret this enrichment as being caused by evaporation inside the cave due to enhanced cave ventilation during these colder and drier times. In contrast, in most samples corresponding to warmer and wetter Greenland interstadials (GIs), but also for some from HS 2 and 3, the δ18Of and δ2Hf values plot on the meteoric water line and modification of fluid inclusion water due to “in-cave” evaporation are found to be negligible. Consequently, variations of recent glacial hydro-climate and temperatures in the western tropical Atlantic can be constrained. In general, δ18Of values from fluid inclusions are up to 3 ‰ higher than those of modern drip water, which is interpreted as a weaker atmospheric convective activity during the last glacial period. In addition, reconstructed temperatures suggest an average cooling of 2–3 ∘C during the LGM compared to modern cave temperatures. Reconstructed cave temperatures yield an average cooling of −1.4 ± 2.8 ∘C for HS 2 and −3.6 ± 2.2 ∘C for HS 3. Higher δ18Of values of these samples further suggest that the drip water was dominated by orographic rainfall and/or cold fronts, along with weak or even absent convective activity. In contrast, during interstadial phases, reconstructed temperatures reached nearly modern values, and convective activity was comparable to or only slightly weaker than today.

Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research. CA extern

Additional file 2: Appendix II. Add-on measurements.

Additional file 1: Appendix I. Organizational aspects of the trial.

We present speleothem fluid inclusion ��18Of and ��2Hf values from Larga Cave, Puerto Rico, that cover the interval between 46.2 and 15.3 ka on the millennial scale, including the Last Glacial Maximum (LGM) and several stadial and interstadial cycles. The data set can be divided in two main clusters of stable isotope compositions of the fluid inclusion water with respect to the global meteoric water line (GMWL), which coincide with strong variations in the water content of the stalagmite. In particular, this clustering is found to be climate related, where one cluster comprises samples from cold and dry periods, such as the Heinrich and Greenland stadials (HSs and GSs), as well as parts of the LGM, which exhibit very high ��18Of and ��2Hf values. We interpret this enrichment as being caused by evaporation inside the cave due to enhanced cave ventilation during these colder and drier times. In contrast, in most samples corresponding to warmer and wetter Greenland interstadials (GIs), but also for some from HS 2 and 3, the ��18Of and ��2Hf values plot on the meteoric water line and modification of fluid inclusion water due to ���in-cave��� evaporation are found to be negligible. Consequently, variations of recent glacial hydro-climate and temperatures in the western tropical Atlantic can be constrained. In general, ��18Of values from fluid inclusions are up to 3 ��� higher than those of modern drip water, which is interpreted as a weaker atmospheric convective activity during the last glacial period. In addition, reconstructed temperatures suggest an average cooling of 2���3 ���C during the LGM compared to modern cave temperatures. Reconstructed cave temperatures yield an average cooling of ���1.4 �� 2.8 ���C for HS 2 and ���3.6 �� 2.2 ���C for HS 3. Higher ��18Of values of these samples further suggest that the drip water was dominated by orographic rainfall and/or cold fronts, along with weak or even absent convective activity. In contrast, during intersta-dial phases, reconstructed temperatures reached nearly modern values, and convective activity was comparable to or only slightly weaker than today.

We present speleothem fluid inclusion δ18Of and δ2Hf values from Larga Cave, Puerto Rico, that covers the interval between 46.2 to 15.3 ka before present on millennial scale, including the Last Glacial Maximum (LGM) and several stadial and interstadial cycles. The dataset can be divided in two main clusters of stable isotope compositions of the fluid inclusion water with respect to the global meteoric water line which coincide with strong variations in the water content of the stalagmite. In particular, this clustering is found to be climate related, where the first cluster comprises samples from cold and dry periods, such as Heinrich and Greenland stadials, as well as parts of the LGM, which exhibit very high δ18Of and δ2Hf values. We interpret this enrichment as caused by evaporation inside the cave due to enhanced cave ventilation during these colder and drier times. In contrast, in most samples corresponding to warmer and wetter Greenland interstadials, but also for some from Heinrich Stadial 2 and 3, the δ18Of and δ2Hf values plot on the meteoric water line and modification of fluid inclusion water due to “in-cave” evaporation is found negligible. Consequently, variations of last glacial hydro-climate and temperature in the western tropical Atlantic can be constrained. In general, δ18Of values from fluid inclusions are up to 3 ‰ higher than those of modern drip water, which is interpreted as a weaker atmospheric convective activity during the last glacial period. In addition, reconstructed temperatures suggest an average cooling of c. 3 °C during the LGM compared to modern cave temperature. During Heinrich Stadials 2 and 3, reconstructed cave temperatures yield an additional cooling of 2.9 ± 2.6 °C and 4.4 ± 0.6 °C, respectively. Higher δ18Of values of these samples further suggest that the drip water was dominated by orographic rainfall and/or cold fronts, along with weak or even absent convective activity. In contrast, during interstadial phases, reconstructed temperatures reached nearly modern values, and convective activity was comparable or only slightly weaker than today.

A severe reduction of greenhouse gas emissions is necessary to reach the objectives of the Paris Agreement. The implementation and continuous evaluation of mitigation measures requires regular independent information on emissions of the two main anthropogenic greenhouse gases, carbon dioxide (CO2) and methane (CH4). Our aim is to employ an observation-based method to determine regional-scale greenhouse gas emission estimates with high accuracy. We use aircraft- and ground-based in situ observations of CH4, CO2, carbon monoxide (CO), and wind speed from two research flights over the Upper Silesian Coal Basin (USCB), Poland, in summer 2018. The flights were performed as a part of the Carbon Dioxide and Methane (CoMet) mission above this European CH4 emission hot-spot region. A kriging algorithm interpolates the observed concentrations between the downwind transects of the trace gas plume, and then the mass flux through this plane is calculated. Finally, statistic and systematic uncertainties are calculated from measurement uncertainties and through several sensitivity tests, respectively. For the two selected flights, the in-situ-derived annual CH4 emission estimates are 13.8±4.3 and 15.1±4.0 kg s−1, which are well within the range of emission inventories. The regional emission estimates of CO2, which were determined to be 1.21±0.75 and 1.12±0.38 t s−1, are in the lower range of emission inventories. CO mass balance emissions of 10.1±3.6 and 10.7±4.4 kg s−1 for the USCB are slightly higher than the emission inventory values. The CH4 emission estimate has a relative error of 26 %–31 %, the CO2 estimate of 37 %–62 %, and the CO estimate of 36 %–41 %. These errors mainly result from the uncertainty of atmospheric background mole fractions and the changing planetary boundary layer height during the morning flight. In the case of CO2, biospheric fluxes also add to the uncertainty and hamper the assessment of emission inventories. These emission estimates characterize the USCB and help to verify emission inventories and develop climate mitigation strategies.

The carbon isotopic signature (δ13CH4) of several methane sources in Germany (around Heidelberg and in North Rhine-Westphalia) were characterised. Mobile measurements of the plume of CH4 sources are carried out using an analyser based on cavity ring-down spectroscopy (CRDS). To achieve precise results a CRDS analyser, which measures methane (CH4), carbon dioxide (CO2) and their 13C-to-12C ratios, was characterised especially with regard to cross sensitivities of composition differences of the gas matrix in air samples or calibration tanks. The two most important gases which affect δ13CH4 are water vapour (H2O) and ethane (C2H6). To avoid the cross sensitivity with H2O, the air is dried with a Nafion dryer during mobile measurements. C2H6 is typically abundant in natural gases and thus in methane plumes or samples originating from natural gas. A C2H6 correction and calibration are essential to obtain accurate δ13CH4 results, which can deviate by up to 3 ‰ depending on whether a C2H6 correction is applied. The isotopic signature is determined with the Miller–Tans approach and the York fitting method. During 21 field campaigns the mean δ13CH4 signatures of three dairy farms (-63.9±0.9‰), a biogas plant (-62.4±1.2‰), a landfill (-58.7±3.3‰), a wastewater treatment plant (-52.5±1.4‰), an active deep coal mine (-56.0±2.3‰) and two natural gas storage and gas compressor stations (-46.1±0.8‰) were recorded. In addition, between December 2016 and November 2018 gas samples from the Heidelberg natural gas distribution network were measured with a mean δ13CH4 value of -43.3±0.8‰. Contrary to previous measurements between 1991 and 1996 by Levin et al. (1999), no strong seasonal cycle is shown.

© 2017 Springer Science+Business Media, LLC, part of Springer Nature Purpose: Exercise has been shown to reduce fatigue during cancer treatment. Hypothesized mechanisms include inflammatory pathways. Therefore, we investigated effects of exercise on markers of inflammation in breast cancer patients during adjuvant chemotherapy. Methods: We pooled data from two randomized controlled exercise intervention trials with breast cancer patients during adjuvant chemotherapy (n = 130), which had previously shown beneficial effects of exercise on fatigue. Exercise comprised a 12-week resistance training (BEATE study) or an 18-week combined resistance and aerobic training (PACT study). Serum IL-6, IL-1ra, and the IL-6/IL-1ra ratio were quantified at baseline, mid-intervention, post-intervention, and 6–9 months post-baseline. Results: Mixed effect models showed significant increases in IL-6 and IL-6/IL-1ra ratio during chemotherapy and decreases afterwards. Differences between exercise and control group were not significant at any time point. Changes in total cancer-related fatigue were significantly correlated with changes in IL-6/IL-1ra ratio (partial correlation r = 0.23) and IL-6 (r = 0.21), and changes in physical cancer-related fatigue with changes in IL-6/IL-1ra ratio (r = 0.21). Conclusions: Changes in fatigue were slightly correlated with changes in inflammatory markers, and there was a strong inflammatory response to adjuvant chemotherapy. The supervised exercise training did not counteract this increase in inflammation, suggesting that beneficial effects of exercise on fatigue during adjuvant chemotherapy for breast cancer are not essentially mediated by IL-6, IL-1ra, or the IL-6/IL-1ra ratio.

Over the last few decades, in situ measurements of atmospheric N2O mole fractions have been performed using gas chromatographs (GCs) equipped with electron capture detectors. This technique, however, becomes very challenging when trying to detect the small variations of N2O as the detectors are highly nonlinear and the GCs at remote stations require a considerable amount of maintenance by qualified technicians to maintain good short-term and long-term repeatability. With new robust optical spectrometers now available for N2O measurements, we aim to identify a robust and stable analyzer that can be integrated into atmospheric monitoring networks, such as the Integrated Carbon Observation System (ICOS). In this study, we present the most complete comparison of N2O analyzers, with seven analyzers that were developed and commercialized by five different companies. Each instrument was characterized during a time period of approximately 8 weeks. The test protocols included the characterization of the short-term and long-term repeatability, drift, temperature dependence, linearity and sensitivity to water vapor. During the test period, ambient air measurements were compared under field conditions at the Gif-sur-Yvette station. All of the analyzers showed a standard deviation better than 0.1 ppb for the 10 min averages. Some analyzers would benefit from improvements in temperature stability to reduce the instrument drift, which could then help in reducing the frequency of calibrations. For most instruments, the water vapor correction algorithms applied by companies are not sufficient for high-precision atmospheric measurements, which results in the need to dry the ambient air prior to analysis.

International audience; Most of the global fossil fuel CO2 emissions arise out of urbanized and industrialized areas. Bottom-up inventories quantify them but with large uncertainties. In 2010–2011, the first atmospheric in-situ CO2 measurement network for Paris, the capital of France, has been operated with the aim of monitoring the regional atmospheric impact of the emissions out coming from this megacity. Five stations sampled air along a northeast-southwest axis that corresponds to the direction of the dominant winds. Two stations are classified as rural (TRN and MON), two are peri-urban (GON and GIF) and one is urban (EIF, located on top of the Eiffel tower). In this study, we analyze the diurnal, synoptic and seasonal variability of the in-situ CO2 measurements over nearly one year (8 August 2010–13 July 2011). We compare these datasets with remote CO2 measurements made at Mace Head (MHD) on the Atlantic coast of Ireland, and support our analysis with atmospheric boundary layer height (ABLH) observations made in the centre of Paris and with both modeled and observed meteorological fields. The average hourly CO2 diurnal cycles observed at the regional stations are mostly driven by the CO2 biospheric cycle, the ABLH cycle, and the proximity to urban CO2 emissions. Differences of several μmol mol−1 (ppm) can be observed from one regional site to the other. The more the site is surrounded by urban sources (mostly traffic, residential and commercial heating), the more the CO2 concentration is elevated, as is the associated variability which reflects the variability of the urban sources. Furthermore, two elevated sites (EIF and TRN) show a phase shift of the CO2 diurnal cycle of a few hours compared to lower sites due to a strong coupling with the boundary layer diurnal cycle. As a consequence, the existence of a CO2 vertical gradient above Paris can be inferred, whose amplitude depends on the time of the day and on the season, ranging from a few tenths of ppm during daytime to several ppm during nighttime. The CO2 seasonal cycle inferred from monthly means at our regional sites are driven by the biospheric and anthropogenic CO2 flux seasonal cycles, by the ABLH seasonal cycle and also by synoptic variations. Gradients of several ppm are observed between the rural and peri-urban stations, mostly from the influence of urban emissions that are in the footprint of the peri-urban station. The seasonal cycle observed at the urban station (EIF) is specific and very sensitive to the ABLH cycle. At both the diurnal and the seasonal scales, noticeable differences of several ppm can be observed between the measurements made at regional rural stations and the remote measurements made at MHD, that are shown not to define background concentrations appropriately for quantifying the regional atmospheric impact of urban CO2 emissions. For wind speeds less than 3 m s−1, the accumulation of the local CO2 emissions in the urban atmosphere forms a dome of several tens of ppm at the peri-urban stations, mostly under the influence of relatively local emissions including those from the Charles-De-Gaulle (CDG) airport facility and from aircrafts in flight. When wind speed increases, ventilation transforms the CO2 dome into a plume. Higher CO2 background concentrations of several ppm are advected from the remote Benelux-Ruhr and London regions, impacting concentrations at the five stations of the network even at wind speeds higher than 9 m s−1. For wind speeds ranging between 3 and 8 m s−1, the impact of Paris emissions can be detected in the peri-urban stations when they are downwind of the city, while the rural stations often seem disconnected from the city emission plume. As a conclusion, our study highlights a high sensitivity of the stations to wind speed and direction, to their distance from the city, but also to the ABLH cycle depending on their elevation. We learn some lessons regarding the design of an urban CO2 network: 1/ careful attention should be paid to properly setting background sites that will be representative of the different wind sectors; 2/ the downwind stations should as much as possible be positioned symmetrically in relation to the city centre, at the peri-urban/rural border; 3/ the stations should be installed at ventilated sites (away from strong local sources) and the air inlet set-up above the building or biospheric canopy layer, whichever is the greatest; and 4/ high resolution wind information should be available with the CO2 measurements.

The Paris Agreement requires accurate accounting of greenhouse gases (GHGs) by all countries. Complementary to bottom-up emission inventories, global, regional and national GHG emissions can be estimated using atmospheric measurements and atmospheric models (the "top-down" approach). This report provides an overview of current capabilities, potential, and further perspectives to use the "top-down" approach to evaluate and improve estimates of greenhouse gas emissions in support of the Paris Agreement., JRC.C.5-Air and Climate

Hintergrund: Nationale und internationale Studien konnten zeigen, dass die jüngsten Kinder einer Klasse verglichen mit ihren älteren Mitschülern in der schulischen Leistungsfähigkeit benachteiligt sind. Querschnittstudien berichten von Zusammenhängen zwischen relativ jungem [zum vollständigen Text gelangen Sie über die oben angegebene URL], HEC 2016: Health – Exploring Complexity; Joint Conference of GMDS, DGEpi, IEA-EEF, EFMI

International audience; The ability of a Bayesian atmospheric inversion to quantify the Paris region's fossil fuel CO 2 emissions on a monthly basis, based on a network of three surface stations operated for 1 year as part of the CO 2-MEGAPARIS experiment (August 2010-July 2011), is analysed. Differences in hourly CO 2 atmospheric mole fractions between the near-ground monitoring sites (CO 2 gradients), located at the northeastern and southwestern edges of the urban area, are used to estimate the 6 h mean fossil fuel CO 2 emission. The inversion relies on the CHIMERE transport model run at 2 km × 2 km horizontal resolution, on the spatial distribution of fossil fuel CO 2 emissions in 2008 from a local inventory established at 1 km × 1 km horizontal resolution by the AIRPARIF air quality agency, and on the spatial distribution of the biogenic CO 2 fluxes from the C-TESSEL land surface model. It corrects a prior estimate of the 6 h mean budgets of the fossil fuel CO 2 emissions given by the AIR-PARIF 2008 inventory. We found that a stringent selection of CO 2 gradients is necessary for reliable inversion results, due to large modelling uncertainties. In particular, the most robust data selection analysed in this study uses only mid-afternoon gradients if wind speeds are larger than 3 m s −1 and if the modelled wind at the upwind site is within ±15 • of the transect between downwind and upwind sites. This stringent data selection removes 92 % of the hourly observations. Even though this leaves few remaining data to constrain the emissions, the inversion system diagnoses that their assimilation significantly reduces the uncertainty in monthly emissions: by 9 % in November 2010 to 50 % in October 2010. The inverted monthly mean emissions correlate well with independent monthly mean air temperature. Furthermore, the inverted annual mean emission is consistent with the independent revision of the AIRPARIF inventory for the year 2010, which better corresponds to the measurement period than the 2008 inventory. Several tests of the inversion's sensitivity to prior emission estimates, to the assumed spatial distribution of the emissions, and to the atmospheric transport modelling demonstrate the robustness of the measurement constraint on inverted fossil fuel CO 2 emissions. The results, however, show significant sensitivity to the description of the emissions' spatial distribution in the inversion system , demonstrating the need to rely on high-resolution local inventories such as that from AIRPARIF. Although the inversion constrains emissions through the assimilation of CO 2 gradients, the results are hampered by the improperly modelled influence of remote CO 2 fluxes when air masses originate from urbanised and industrialised areas northeast of Paris. The drastic data selection used in this study limits the ability to continuously monitor Paris fossil fuel CO 2 emissions: the inversion results for specific months such as Published by Copernicus Publications on behalf of the European Geosciences Union. 14704 J. Staufer et al.: 1-year-long inversion of Paris fossil fuel CO 2 emissions September or November 2010 are poorly constrained by too few CO 2 measurements. The high sensitivity of the inverted emissions to the prior emissions' diurnal variations highlights the limitations induced by assimilating data only during the afternoon. Furthermore, even though the inversion improves the seasonal variation and the annual budget of the city's emissions, the assimilation of data during a limited number of suitable days does not necessarily yield robust estimates for individual months. These limitations could be overcome through a refinement of the data processing for a wider data selection, and through the expansion of the observation network.

The present invention relates to compounds for the treatment of chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD) or asthma or bronchiectasis. The present invention further relates to drug delivery devices suitable to be used in the treatment of chronic obstructive airway diseases such as a nebulizer comprising the present compounds. Specifically, the present invention relates to (6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(piperazin-1-yl)methanone or N,6-di-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamide or a pharmaceutically acceptable salt or base thereof for use in the treatment of chronic obstructive airway diseases, preferably chronic obstructive pulmonary disease (COPD) or asthma or bronchiectasis, more preferably chronic obstructive pulmonary disease (COPD).

β3-Adrenoceptors play important roles in the regulation of urogenital and probably gastrointestinal function. However, despite recent progress, their detection at the protein level has remained difficult due to a lack of sufficiently validated selective antibodies. Therefore, we have explored the selectivity of two antibodies for the detection of rodent β3-adrenoceptors in immunoblots and immunohistochemistry. Of two reportedly promising candidates, antibody AB15688 did not exhibit subtype selectivity in immunoblots. In contrast, the antibody Sc1473 exhibited at least some selectivity in immunoblots and more promising results in immunocytochemical and immunohistochemical stains in cells transfected with cloned β-adrenoceptor subtypes and in rat and mouse tissues. In a systematic screening of rat gastrointestinal and urogenital tissues, Sc1473 produced selective staining in the epithelial cell lining of the stomach and the urothelium of ureter and bladder. We conclude that the two tested antibodies are inappropriate or at least insufficient for immunoblotting applications, but Sc1473 appears to be useful for immunohistochemical detection of β3-adrenoceptor protein in rodent tissues. The β3-adrenoceptor protein exhibits a distinct expression pattern in the rat gastrointestinal and urogenital tract, which is at least partly in line with previously reported functional data

Background: The rapid development in technology promotes the increasing use of electronic activity monitors to assess physical activity in large-scale epidemiological studies. Our aim was to explore and discuss both subjective and objective methods assessing physical activity. Methods: Based on a thorough literature search, major strengths and limitations of questionnaires and electronic activity monitors in assessing physical activity are elaborated and discussed, taking into consideration physical activity in all its complexity. Important research questions and the aim and scope of physical activity assessment for next-generation research are defined. Results: Questionnaires can provide details and background information of physical activity, including type of activity, and can identify the activity behaviour patterns that underlie measurable endpoints such as energy expenditure, cardiorespiratory fitness, muscular strength, or certain biomarkers. They can differentiate well between settings and enable retrospective assessment. Electronic activity monitors, on the other hand, are rapidly becoming better at assessing energy expenditure and are good at quantifying the amount and intensity of physical activity and sedentary behaviour. Both methods, however, also have their weaknesses. While questionnaires may not be accurate, due to recall bias or incomplete assessment of all activity domains, electronic activity monitors are not able to provide information about setting, exact type and mode of activity, and cannot recognize and reliably assess resistance exercise or activities with or without carrying weights. Conclusions: Since physical activity is multidimensional and complex, no single method is suitable to capture all aspects and domains. Both methods have their strengths and limitations and do not compete with each other, but should be seen as complementary tools that assess distinct aspects of physical activity. Studies should therefore rely on both methods to enable improved public health recommendations for this complex lifestyle factor., GMS Medizinische Informatik, Biometrie und Epidemiologie; 10(1):Doc06; ISSN 1860-9171

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene–environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10−6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10−4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01–1.16) in nulliparous women and ranged from 1.03 (0.96–1.10) in parous women with one birth to 1.26 (1.16–1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85–0.98) in those with an alcohol intake of

International audience; The development of anthropogenic activities since the pre-industrial era has greatly increased CO2 concentrations in the atmosphere, very likely causing the observed rise in global temperature. Therefore, accurate estimations of CO2 emission fluxes are very important for climate predictions. At the continental scale, CO2 fluxes can be estimated rather precisely using inverse modeling while tower turbulent flux measurements (eddy-covariance or EC) can provide an estimation of local-scale fluxes. However, this method cannot be applied to monitor urban CO2 emissions due to their large horizontal variability, so that a regional scale approach seems more suited. Unfortunately, at this scale, anthropogenic and biospheric fluxes are mixed, diluted and advected in the atmospheric boundary-layer (ABL) and the balance between these processes is not well known. Yet, independent estimations of CO2 fluxes would be needed to verify existing high resolution emission inventories and assess the efficiency of future mitigation policies. Several experiments dedicated to quantifying CO2 emissions from megacities are ongoing, like the CO2-MEGAPARIS research project [a,b]. In this framework, a network of lidars and in-situ sensors has been set up in Paris region. An original ABL mass budget method is used to infer the properties of advected anthropogenic CO2 and CO emissions from Paris urban area [c]. The method is applied in the center of Paris, at neighboring suburban sites located 20 km away, and at a rural station (100 km downwind). The budget uses ABL depths from elastic lidars, CO2 and CO concentrations from both the ICOS [d] and CO2-MEGAPARIS networks to quantify vertical advection and storage terms in the ABL mass budget. EC measurements are used to monitor biospheric surface fluxes. The budget in Paris provides a direct estimation of the average CO2 and CO fluxes from the city, while the budget at the suburban and rural stations provides an estimation of the advected fluxes. These anthropogenic fluxes are compared to the CITEPA and IER emission inventories using the air mass footprint from a Lagrangian Particle Dispersion Model in backward mode. Results from a case study in March 2012 are presented to assess the propagation of Paris CO2 and CO plume, the precision of the method and its ability to provide an independent verification of urban emission inventories.

International audience; [1] A regional variational inverse modeling system for the estimation of European biogenic CO 2 fluxes is presented. This system is based on a 50 km horizontal resolution configuration of a mesoscale atmospheric transport model and on the adjoint of its tracer transport code. It exploits hourly CO 2 in situ data from 15 CarboEurope-Integrated Project stations. Particular attention in the inversion setup is paid to characterizing the transport model error and to selecting the observations to be assimilated as a function of this error. Comparisons between simulations and data of CO 2 and 222 Rn concentrations indicate that the model errors should have a standard deviation which is less than 7 ppm when simulating the hourly variability of CO 2 at low altitude during the afternoon and evening or at high altitude at night. Synthetic data are used to estimate the uncertainty reduction for the fluxes using this inverse modeling system. The improvement brought by the inversion to the prior estimate of the fluxes for both the mean diurnal cycle and the monthly to synoptic variability in the fluxes and associated mixing ratios are checked against independent atmospheric data and eddy covariance flux measurements. Inverse modeling is conducted for summers 2002-2007 which should reduce the uncertainty in the biogenic fluxes by $60% during this period. The trend in the mean flux corrections between June and September is to increase the uptake of CO 2 by $12 gCm À2. Corrections at higher resolution are also diagnosed that reveal some limitations of the underlying prior model of the terrestrial biosphere. Citation: Broquet, G., F. Chevallier, P. Rayner, C. Aulagnier, I. Pison, M. Ramonet, M. Schmidt, A. T. Vermeulen, and P. Ciais (2011), A European summertime CO 2 biogenic flux inversion at mesoscale from continuous in situ mixing ratio measurements

For a long time it was believed that beta(2)-adrenergic receptor agonists used in the treatment of obstructive airway diseases worked primarily on airway smooth muscle cells, causing relaxation, whereas glucocorticoids primarily improved airway function via their anti-inflammatory action, indicating that their clinical synergism occurred at the organism rather than the cellular level. However, it is now becoming clear that both drug classes can affect airway function at multiple levels, including an integrated effect on several cell types. This article summarizes data on the molecular interaction between the two receptor systems, particularly with relevance to phenomena of beta(2)-adrenergic receptor desensitization and glucocorticoid insensitivity in the airways. These molecular interactions may contribute to the observed clinical synergism between both drug classes in the treatment of obstructive airway diseases.

Sepsis is one of the most common diseases on intensive care units all over the world and accounts there for the highest mortality rate. One of the hallmarks of sepsis is an accelerated T-cell apoptosis, resulting in a compromised immune state with the inability to eradicate pathogens. This promotes organ damage or even organ failure. A multiple organ dysfunction evolves, which often ends up in septic shock and death. Recently, it was shown that severe T-cell depletion correlates with sepsis mortality. When inhibiting T-cell apoptosis, an increased mouse survival was observed in experimental sepsis. ... Sepsis ist eine der häufigsten Erkrankungen auf Intensivstationen weltweit und verursacht dort die höchste Mortalitätsrate. Ein besonderes Kennzeichen der Sepsis ist der rapide Verlust von T-Zellen durch Apoptose. Dies hemmt den Immunstatus des Patienten und bewirkt ein Unvermögen gegen Pathogene anzukämpfen. Eine Organdysfunktion oder sogar ein multiples Organversagen wird hervorgerufen. Die T-Zelldepletion korreliert mit der hohen Sepsismortlität und ihre Hemmung führte zu einem verbesserten Überleben in experimenteller Sepsis. ...

Internalization of Listeria monocytogenes into non-phagocytic cells is tightly controlled by host cell actin dynamics and cell membrane alterations. However, knowledge about the impact of phosphatidylcholine cleavage driven by host cell phospholipase D (PLD) on Listeria internalization into epithelial cells is limited. Here, we report that L. monocytogenes activates PLD in Vero cells during the internalization. With immunostaining it was shown that both PLD1 and PLD2 surrounded partially or completely the phagocytic cup of most L. monocytogenes. Either up- or down-regulation of PLD expression (activity) diminished Listeria internalization. Both PLD1 and PLD2 in Vero cells were required for efficient Listeria internalization, and could substitute for each other in the regulation of Listeria internalization. Further, exogenous InlB activated host cell PLD1 and PLD2 via the Met receptor, and restored host PLD activation by InlB-deficient L. monocytogenes. InlB-induced PLD activation and Listeria internalization were tightly controlled by phospho-cycling of cofilin. PLD1, but not PLD2, was involved in cofilin-mediated PLD activation and Listeria internalization. These data indicate that cofilin-dependent PLD activation induced by InlB may represent a novel regulation mechanism for efficient Listeria internalization into epithelial cells.

This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and European surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks, which include continuous measurements performed between mid-2006 and mid-2009. Net H2 surface flux, then deposition velocity and surface emissions and finally, deposition velocity, biomass burning, anthropogenic and N2 fixation-related emissions were simultaneously inverted in several scenarios. These scenarios have focused on the sensibility of the soil uptake value to different spatio-temporal distributions. The range of variations of these diverse inversion sets generate an estimate of the uncertainty for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between −8 and +8 Tg yr−1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on bottom-up and top-down estimations. Our estimate of global H2 soil uptake is −59±9 Tg yr−1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions within the range of their respective uncertainties. Additional constraints, such as isotopic measurements would be needed to infer a more robust partition of H2 sources and sinks.

[no abstract]

BACKGROUND AND PURPOSE Changes in airway smooth muscle (ASM) phenotype may contribute to the pathogenesis of airway disease. Platelet-derived growth factor (PDGF) switches ASM from a contractile to a proliferative, hypo-contractile phenotype, a process requiring activation of extracellular signal-regulated kinase (ERK) and p70S6 Kinase (p70S6K). The effects of cAMP-elevating agents on these processes is unknown. Here, we investigated the effects of cAMP elevation by prostaglandin E(2) (PGE(2)) and the activation of the cAMP effectors, protein kinase A (PKA) and exchange protein activated by cAMP (Epac) on PDGF-induced phenotype switching in bovine tracheal smooth muscle (BTSM). EXPERIMENTAL APPROACH Effects of long-term treatment with the PGE(2) analogue 16,16-dimethyl-PGE(2), the selective Epac activator, 8-pCPT-2'-O-Me-cAMP and the selective PKA activator, 6-Bnz-cAMP were assessed on the induction of a hypo-contractile, proliferative BTSM phenotype and on activation of ERK and p70S6K, both induced by PDGF. KEY RESULTS Treatment with 16,16-dimethyl-PGE(2) inhibited PDGF-induced proliferation of BTSM cells and maintained BTSM strip contractility and contractile protein expression in the presence of PDGF. Activation of both Epac and PKA similarly prevented PDGF-induced phenotype switching and PDGF-induced activation of ERK. Interestingly, only PKA activation resulted in inhibition of PDGF-induced phosphorylation of p70S6K. CONCLUSIONS AND IMPLICATIONS Our data indicate for the first time that both Epac and PKA regulated switching of ASM phenotype via differential inhibition of ERK and p70S6K pathways. These findings suggest that cAMP elevation may be beneficial in the treatment of long-term changes in airway disease.

International audience; Monitoring greenhouse gases (GHGs) in large cities is becoming like air quality one of the priority environmental research areas for scientists and public health authorities. The QualAir platform at University Pierre et Marie Curie (UPMC), is an innovating experimental research platform dedicated to survey GHGs and urban air quality. As one of the major instruments of the QualAir platform, the ground-based Fourier transform spectrometer (QualAir FTS, IFS 125HR model) analyses the composition of the urban atmosphere of Paris, which is the third European megacity. The continous monitoring of GHGs and atmospheric pollutants are essential to improve the estimate of sources and sinks of GHGs and the understanding of urban air pollution processes. Associated with a sun-tracker, the QualAir remote sensing FTS operates in solar infrared absorption and enables to monitor many pollutants and GHGs, and to follow up their variability in the Ile-de-France region. A description of the QualAir FTS will be given. Concentrations of GHGs (CO2, CH4, N2O, …) are retrieved by the radiative transfer model PROFFIT. Located in the centre of Paris, the QualAir FTS can provide new and complementary urban measurements as compared to unpolluted ground-based stations of existing networks (NDACC and TCCON). We will show some first CO2 measurements acquired with our instrument in the framework of the French CO2-MEGAPARIS project, the main goal of which is to quantify CO2 emissions from Paris megacity. Such ground-based information will help to reduce uncertainties in carbon cycle models and to contribute to the characterization of regional GHGs fluxes, especially regarding anthropogenic emissions and trends.

Aus Lithium-bis(trimethylsilyl)phosphid · 2THF1 oder Lithiumdihydrogenarsenid · 2THF und 2,4,6-Trimethylbenzoylchlorid im Molverhältnis 3:2 zugängliches Lithium-bis(2,4,6-trimethylbenzoyl)phosphid · 2THF (1a) bzw. -arsenid · 2THF (1b) [16] setzen sich mit Tetrafluoroborsäure · Diethylether-Addukt in nahezu quantitativer Ausbeute unter Lithium-Wasserstoff-Austausch zu Bis(2,4,6-trimethylbenzoyl)phosphan (2a) sowie zum entsprechenden Arsan 2b um. Nach der Synthese einer nun größeren Zahl von Derivaten [19] lassen sich für die zugehörigen Keto- und Enol-Tautomeren charakteristische NMR-Parameter angeben.Nach den Ergebnissen von Röntgenstrukturanalysen (Raumgruppe Fdd2; a = 1 486,1(4)/1 501,7(4); b = 2975,8(12)/3000,6(6); c = 827,9(2)/822,7(2) pm bei—100° ± 3°C; Z = 8; Rw = 0,034/0,040) liegen die beiden zueinander isotypen Verbindungen 2a und 2b im Festkörper als Enol-Tautomere mit sehr kurzer, symmetrischer O‥H‥O-Brücke (O‥O243/245 pm) vor. Die Moleküle zeigen aufgrund ihrer speziellen Lage die Punktsymmetrie 2; charakteristische Bindungslängen und -winkel sind: P-C 177; As-C 190; C-O 126/128; C-C (Aren) 150/147; O-H 122/128 pm; C-P-C 98° C-As-C 97° P-C-O 125° As-C-O 123° P-C-C 117° As-C-C 118°; C-O-H 99°/116° O-H-O 173°/146°. Die unterschiedliche Geometrie der beiden Enolringe wird diskutiert., Lithium bis(2,4,6-trimethylbenzoyl)phosphide·2THF (1a) and the homologous arsenide 1b [16] are prepared from lithium bis(trimethylsilyl)phosphide·2THF1 and lithium dihydrogenarsenide·2THF, resp., and 2,4,6-trimethylbenzoyl chloride in a molar ratio of 3:2. Subsequent reaction with tetrafluoroboric acid·diethylether adduct results in an exchange of lithium with hydrogen and formation of bis(2,4,6-trimethylbenzoyl)phosphine (2a) and the corresponding arsine 2b in nearly quantitative yields. Characteristic nmr parameters for the keto and enol tautomer could be obtained from a larger number of derivatives [19].X-ray structure determination of the two isotypic compounds 2a and 2b (space group F d d 2; a =1 486.1(4)/1501.7(4); b = 2975.8(12)/3 000.6(6); c = 827.9(2)/822.7(2) pm at −100° ± 3° C; Z = 8; Rw = 0.034/0.040) show enol tautomers with very short symmetrical O‥H‥O-bridges (O‥O 243/245 pm) to be present in the solid state. Due to their special position the molecules are of point symmetry 2; characteristic bond lengths and angles are: P-C 177; As-C 190; C-O 126/128; C-C (arene) 150/147; O-H 122/128 pm; C-P-C 98deg;; C-As-C 97°; P-C-O 125°; As-C-O 123°; P-C-C 117°; As-C-C 118°; C-O-H 99°/116°; O-H-O 173°/146°. The different geometry of the two enol rings is discussed in detail.

Aus Lithium-dihydrogenphosphid · DME (1) [12] und cyclo-Hexoyl- bzw. Adamant-1-oyl-chlorid im Molverhältnis 3:2 zugängliches Lithium-di-cyclo-hexoylphosphid · DME und -diadamant-1-oylphosphid · 2THF 1) reagieren mit 85proz. Tetrafluoroborsäure · Diethylether-Addukt zu Di-cyclo-hexoyl- 1b) und Diadamant-1-oylphosphan (1 c). Die Lage des Keto-Enol-Gleichgewichts zwischen 203 und 343 K sowie thermodynamische Daten zur Bildung des Enol-Isomers ΔH0= −4,3kJ.Mol−1; ΔS0;=−9,2 J · mol−1 · K−1 () wurden NMR-spektroskopisch an einer 2 M Lösung des bei +20°C flüssigen Di-cyclo-Hexoyl-Derivates 1b in d8-Toluol ermittelt und mit Werten von 1,3-Diketonen verglichen.Das farblose, sich aus Benzol in dünnen Plättchen abscheidende Enol-Tautomer des Diadamant-1-oylphosphans (E-1 c) kristallisiert monoklin in der Raumgruppe P21/c {a = 722,2(2) b = 1085,5(4); c = 2434,8(5) pm; ß = 96,43(2)° bei - 100 ± 3°C; Z = 4}. Nach den Ergebnissen der Röntgenstrukturanalyse (Rw=0,033) weist das Molekül in beiden des Hälften des Enolrings nahezu identische Bindungslängen und -winkel auf P-C 179/180; C--O 130/129; C-C(Adamant-1-yl) 152/153 pm; C-P-C 99°; P-C-O 124°/124°; P-C-C 120°/120°; C-C-O 116°/116°. Die Geometrie der sehr starken, aber vermutlich asymmetrischen O‥H‥O-Brücke wird diskutiert (O-H 120/130; O‥O 245 pm)., Lithium dihydrogenphosphide · DME (1) [12] and cyclo-hexoyl or adamant-1-oyl chloride react in a molar ratio of 3:2 to give lithium di-cyclo-hexoylphosphide · DME and the corresponding diadamant-1-oylphosphide.2THF (1) resp. Treatment of these two compounds with 85% tetrafluoroboric acid. diethylether adduct yields di-cyclo-hexoyl- (1b) and diadamant-1-oylphosphine (1c). In nmr spectroscopic studies 1b over a range of 203 to 343 K, a strong temperature dependence of the keto-enol equilibrium is found; thermodynamic data characteristic for the formation of the enol tautomer (ΔH0 = −4.3 kJ. mol−1; ΔS0 = −9.2 J. mol−1. K (−1) are compared of 1,3-diketones.The enol tautomer of diadamant-1-oylphosphine (E-1c) as obtained from a benzene solution in thin colourless plates, crystallizes in the monoclinic space group P21/c {a = 722.2(2); b = 1085.5(4); c = 2434.8(5) pm; ß = 96.43(2)° at –100 ± 3°C; Z = 4}. An X- ray structure analysis (Rw = 0.033) shows bond lengths and angles to be almost identical within the enolic system (P-C 179/180; C-O 130/129; C-C(adamant-1-yl) 152/153 pm; C-P-C 99°; PCO 124°/124°; P-C-C 120°/120°; C-C-O 116°/116°. The geometry of the very strong, but probably asymmetric O‥H‥O bridge is discussed (O-H 120/130, O‥O 245 pm).

The peroxisome proliferator-activated receptor γ (PPARγ) belongs to the nuclear hormone receptor superfamily and regulates gene expression upon heterodimerization with the retinoid X receptor by ligating to peroxisome proliferator response elements (PPREs) in the promoter region of target genes. Originally, PPARγ was identified as being essential for glucose metabolism. Thus, synthetic PPARγ agonists, the thiazolidinediones (TZDs), are used in type 2 diabetes therapy as insulin sensitizers. More recent evidence implied an important role for the nuclear hormone receptor PPARγ in controlling various diseases based on its anti-inflammatory, cell cycle arresting, and proapoptotic properties. In this regard, expression of PPARγ is not restricted to adipocytes, but is also found in immune cells, such as B and T lymphocytes, monocytes, macrophages, dendritic cells, and granulocytes. The expression of PPARγ in lymphoid organs and its modulation of macrophage inflammatory responses, lymphocyte proliferation, cytokine production, and apoptosis underscore its immune regulating functions. Moreover, PPARγ expression is found in tumor cells, where its activation facilitates antitumorigenic actions. This review provides an overview about the role of PPARγ as a possible therapeutic target approaching major, severe diseases, such as sepsis, cancer, and atherosclerosis.

This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks, which include continuous measurements performed between mid-2006 and mid-2009. Net H2 surface flux, soil uptake distinct from surface emissions and finally, soil uptake, biomass burning, anthropogenic emissions and N2 fixation-related emissions separately were inverted in several scenarios. The various inversions generate an estimate for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between −8 and 8 Tg yr−1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on soil uptake measurements. Our estimate of global H2 soil uptake is −59 ± 4.0 Tg yr−1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions considering their respective uncertainties. To constrain a more robust partition of H2 sources and sinks would need additional constraints, such as isotopic measurements.

SummaryMembrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me-cAMP) has been shown to specifically activate cAMP-regulated Epac proteins, without direct effects on protein kinase A and protein kinase G. During isometric tension measurements in thoracic aortic rings from Wistar rats, we observed that 8-pCPT-2'-O-Me-cAMP selectively induced a rightward shift of the concentration response curve for the thromboxane mimetic U46619, without altering the contractile response to noradrenaline. We hypothesised that 8-pCPT-2'-O-Me-cAMP and similar compounds may function as direct thromboxane receptor antagonists. Indeed, in addition to 8-pCPT-2'-OMe-cAMP, also 8-pCPT-cAMP, 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-CPT-cAMPS) and 8-CPT-adenosine, but not 8-Bromo-2'-O-Me-cAMP, induced rightward shifts of the contractile response to U46619. Likewise, 8-pCPT-2'-O- Me-cAMP and Rp-8-CPT-cAMPS, but not 8-Bromo-2'-O-Me-cAMP, specifically reduced U46619-induced aggregation of human platelets. In addition, 8-pCPT-2'-O-Me-cAMP and Rp-8-CPT-cAMPS completely reversed U46619-induced reduction of intercellular adhesion molecule-1 expression and migration of human coronary artery endothelial cells. Most important, the cAMP analogs that reduced the contractile response to U46619 also concentration-dependently inhibited binding of the thromboxane receptor radioligand [5,6-3H]SQ29548 to human platelets. We conclude that 8-pCPT-conjugated cAMP analogs exert competitive thromboxane receptor antagonistic properties.