Closed (non-steady state) chamber measurements are often used to determine the gas exchange of N₂O. Many researchers have addressed the underestimation of the emission estimates obtained from closed ...chamber measurements when using linear regression methods. However, the linear regression method is still usually applied to derive the flux. The importance of using non-linear regression methods is demonstrated with data from four fertilizing events each consisting of 1 month of automatic chamber measurements at Cabauw in the Netherlands in the period from July 2005 to July 2006. It is presented that the cumulative emission estimates with the exponential regression method are close to the cumulative emissions estimates with the intercept method. The linear estimates differ by up to 60% of the estimates with the exponential method. The performance of each method is validated using a C₂H₆ tracer and a goodness-of-fit analysis. The goodness-of-fit is much better for the exponential than the linear regression method. The systematic error due to linear regression is of the same order as the estimated uncertainty due to temporal variation. Therefore, closed-chamber data should be tested for non-linearity and an appropriate method should be used to calculate the flux.
Since 1992 semi-continuous in-situ observations of greenhouse gas concentrations have been performed at the tall tower of Cabauw (4.927° E, 51.971° N, −0.7 m a.s.l.). Through 1992 up to now, the ...measurement system has been gradually extended and improved in precision, starting with CO2 and CH4 concentrations from 200 m a.g.l. in 1992 to vertical gradients at 4 levels of the gases CO2, CH4, SF6, N2O, H2, CO and gradients at 2 levels for 222Rn. In this paper the measurement systems and measurement results are described for the main greenhouse gases and CO, for the whole period. The automatic measurement system now provides half-hourly concentration gradients with a precision better than or close to the WMO recommendations. The observations at Cabauw show a complex pattern caused by the influence of sources and sinks from a large area around the tower with significant contributions of sources and sinks at distances up to 500–700 km. The concentration footprint area of Cabauw is one the most intensive and complex source areas of greenhouse gases in the world. Despite this, annual mean trends for the most important greenhouse gases, compatible with the values derived using the global network, can be reproduced from the measured concentrations at Cabauw over the entire measurement period, with a measured increase in the period 2000–2009 for CO2 of 1.90 ± 0.1 ppm yr−1, for CH4 of 4.4 ± 0.6 ppb yr−1, for N2O of 0.86 ± 0.04 ppb yr−1, and for SF6 of 0.27 ± 0.01 ppt yr−1; for CO no significant trend could be detected. The influences of strong local sources and sinks are reflected in the amplitude of the mean seasonal cycles observed at Cabauw, that are larger than the mean Northern Hemisphere average; Cabauw mean seasonal amplitude for CO2 is 25–30 ppm (higher value for lower sampling levels). The observed CH4 seasonal amplitude is 50–110 ppb. All gases except N2O show highest concentrations in winter and lower concentrations in summer, N2O observations show two additional concentration maxima in early summer and in autumn. Seasonal cycles of the day-time mean concentrations show that surface concentrations or high elevation concentrations alone do not give a representative value for the boundary layer concentrations, especially in winter time, but that the vertical profile data along the mast can be used to construct a useful boundary layer mean value. The variability at Cabauw in the atmospheric concentrations of CO2 on time scales of minutes to hours is several ppm and is much larger than the precision of the measurements (0.1 ppm). The diurnal and synoptical variability of the concentrations at Cabauw carry information on the sources and sinks in the footprint area of the mast, that will be useful in combination with inverse atmospheric transport model to verify emission estimates and improve ecosystem models. For this purpose a network of tall tower stations like Cabauw forms a very useful addition to the existing global observing network for greenhouse gases.
Background
Component‐resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to ...combining them with clinical factors in predicting severity.
Aim
To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy.
Methods
Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double‐blind placebo‐controlled food challenge DBPCFC) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD‐ and extract‐based). Odds ratios (ORs) and areas under receiver‐operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value.
Results
Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70‐073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker.
Conclusion
A model combining CRD with clinical background and extract‐based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.
Ammonia exchange fluxes between grassland and the atmosphere were modelled on the basis of stomatal compensation points and leaf surface chemistry, and compared with measured fluxes during the ...GRAMINAE intensive measurement campaign in spring 2000 near Braunschweig, Germany. Leaf wetness and dew chemistry in grassland were measured together with ammonia fluxes and apoplastic NH4+ and H+ concentration, and the data were used to apply, validate and further develop an existing model of leaf surface chemistry and ammonia exchange. Foliar leaf wetness which is known to affect ammonia fluxes may be persistent after the end of rainfall, or sustained by recondensation of water vapour originating from the ground or leaf transpiration, so measured leaf wetness values were included in the model. pH and ammonium concentrations of dew samples collected from grass were compared to modelled values. The measurement period was divided into three phases: a relatively wet phase followed by a dry phase in the first week before the grass was cut, and a second drier week after the cut. While the first two phases were mainly characterised by ammonia deposition and occasional short emission events, regular events of strong ammonia emissions were observed during the post-cut period. A single-layer resistance model including dynamic cuticular and stomatal exchange could describe the fluxes well before the cut, but after the cut the stomatal compensation points needed to numerically match measured fluxes were much higher than the ones measured by bioassays, suggesting another source of ammonia fluxes. Considerably better agreement both in the direction and the size range of fluxes were obtained when a second layer was introduced into the model, to account for the large additional ammonia source inherent in the leaf litter at the bottom of the grass canopy. Therefore, this was found to be a useful extension of the mechanistic dynamic chemistry model by keeping the advantage of requiring relatively little site-specific information.
A major international experiment on ammonia (NH3) biosphere-atmosphere exchange was conducted over intensively managed grassland at Braunschweig, Germany. The experimental strategy was developed to ...allow an integrated analysis of different features of NH3 exchange including: a) quantification of nearby emissions and advection effects, b) estimation of net NH3 fluxes with the canopy by a range of micrometeorological measurements, c) analysis of the sources and sinks of NH3 within the plant canopy, including soils and bioassay measurements, d) comparison of the effects of grassland management options on NH3 fluxes and e) assessment of the interactions of NH3 fluxes with aerosol exchange processes. Additional technical objectives included the inter-comparison of different estimates of sensible and latent heat fluxes, as well as continuous-gradient and Relaxed Eddy Accumulation (REA) systems for NH3 fluxes. The prior analysis established the spatial and temporal design of the experiment, allowing significant synergy between these objectives. The measurements were made at 7 measurement locations, thereby quantifying horizontal and vertical profiles, and covered three phases: a) tall grass canopy prior to cutting (7 days), b) short grass after cutting (7 days) and c) re-growing sward following fertilization with ammonium nitrate (10 days). The sequential management treatments allowed comparison of sources-sinks, advection and aerosol interactions under a wide range of NH3 fluxes. This paper describes the experimental strategy and reports the grassland management history, soils, environmental conditions and air chemistry during the experiment, finally summarizing how the results are coordinated in the accompanying series of papers.
Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience ...to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis.
Drainage affects inflammatory and fibrotic gene signatures
Measurements of the stable isotopic composition (δD(H2) or δD) of atmospheric molecular hydrogen (H2) are a useful addition to mixing ratio (χ(H2)) measurements for understanding the atmospheric H2 ...cycle. δD datasets published so far consist mostly of observations at background locations. We complement these with observations from the Cabauw tall tower at the CESAR site, situated in a densely populated region of the Netherlands. Our measurements show a large anthropogenic influence on the local H2 cycle, with frequently occurring pollution events that are characterized by χ(H2) values that reach up to ≈1 ppm and low δD values. An isotopic source signature analysis yields an apparent source signature below −400‰, which is much more D-depleted than the fossil fuel combustion source signature commonly used in H2 budget studies. Two diurnal cycles that were sampled at a suburban site near London also show a more D-depleted source signature (≈−340‰), though not as extremely depleted as at Cabauw. The source signature of the Northwest European vehicle fleet may have shifted to somewhat lower values due to changes in vehicle technology and driving conditions. Even so, the surprisingly depleted apparent source signature at Cabauw requires additional explanation; microbial H2 production seems the most likely cause. The Cabauw tower site also allowed us to sample vertical profiles. We found no decrease in χ(H2) at lower sampling levels (20 and 60 m) with respect to higher sampling levels (120 and 200 m). There was a significant shift to lower median δD values at the lower levels. This confirms the limited role of soil uptake around Cabauw, and again points to microbial H2 production during an extended growing season, as well as to possible differences in average fossil fuel combustion source signature between the different footprint areas of the sampling levels. So, although knowledge of the background cycle of H2 has improved over the last decade, surprising features come to light when a non-background location is studied, revealing remaining gaps in our understanding.
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•Multi-year time series of H2 and δD(H2) were measured at a regional tall tower site.•The dataset contains the first measured δD height profiles in the boundary layer.•The features of the time series are consistent with large anthropogenic influences.•The apparent δD source signature is much lower than fossil fuel combustion estimates.•Both source signature and profiles suggest microbial H2 production around the tower.
Context.
Meteorites preserve an imprint of conditions in the early Solar System. By studying the distribution of calcium-aluminium-rich inclusions (CAIs) that are embedded within meteorites, we can ...learn about the dynamical history of the protoplanetary disk from which our Solar System formed. A long-standing problem concerning CAIs is the CAI storage problem. CAIs are thought to have formed at high temperatures near the Sun, but they are primarily found in carbonaceous chondrites, which formed much further out, beyond the orbit of Jupiter. Additionally, radial drift of CAI particles should have removed them from the solar protoplanetary disk several million years before the parent bodies of meteorites in which they are encountered would have accreted.
Aims.
We revisit a previously suggested solution to the CAI storage problem by Desch, Kalyaan, and Alexander which proposed that CAIs were mixed radially outward through the disk and subsequently got trapped in a pressure maximum created by Jupiter’s growing core opening a planet gap. Our aim is to investigate whether their solution still works when we take into account the infall phase during which the disk builds up from the collapse of a molecular cloud core.
Methods.
We build a 1D numerical code in Python using the DISKLAB package to simulate the evolution of the solar protoplanetary disk, starting with a collapsing molecular cloud. CAIs are created in the model by thermal processing of solar nebula composition dust, and subsequently transported through the disk by turbulent diffusion, radial drift and advection by the gas.
Results.
We find that outward transport of CAIs during the infall phase is very efficient, possibly mixing them all the way into the far outer disk. Subsequent inward radial drift collects CAIs in the pressure maximum beyond Jupiter’s orbit while draining the inner disk, roughly reproducing parts of the result by Desch et al. By introducing CAI formation so early, abundances out to 100 AU remain significant, possibly not consistent with some meteoritic data. It is possible to create a disk that does not expand as far out and also does not push CAIs as far out by using a very slowly rotating cloud.
Using exome sequencing and linkage analysis in a three-generation family with a unique dominant myoclonus-dystonia-like syndrome with cardiac arrhythmias, we identified a mutation in the CACNA1B ...gene, coding for neuronal voltage-gated calcium channels CaV2.2. This mutation (c.4166G>A;p.Arg1389His) is a disruptive missense mutation in the outer region of the ion pore. The functional consequences of the identified mutation were studied using whole-cell and single-channel patch recordings. High-resolution analyses at the single-channel level showed that, when open, R1389H CaV2.2 channels carried less current compared with WT channels. Other biophysical channel properties were unaltered in R1389H channels including ion selectivity, voltage-dependent activation or voltage-dependent inactivation. CaV2.2 channels regulate transmitter release at inhibitory and excitatory synapses. Functional changes could be consistent with a gain-of-function causing the observed hyperexcitability characteristic of this unique myoclonus-dystonia-like syndrome associated with cardiac arrhythmias.
Janus kinases (JAKs) mediate cytokine signaling involved in inflammatory bowel disease. The pan-JAK inhibitor tofacitinib has shown efficacy in the treatment of ulcerative colitis. However, concerns ...regarding adverse events due to their wide spectrum inhibition fueled efforts to develop selective JAK inhibitors. Given the crucial role of myeloid cells in intestinal immune homeostasis, we evaluated the effect of pan-JAK and selective JAK inhibitors on pro- and anti-inflammatory macrophage polarization and function (M1/M2) and in experimental colitis.
Murine bone marrow-derived macrophages or human monocytes were treated using JAK1 and JAK3 selective inhibitors (JAK1i;JAK3i) and tofacitinib and were evaluated by transcriptional, functional, and metabolic analyses. In vivo, oral administration of JAK1i and tofacitinib (10 or 30 mg/kg) was tested in both acute and acute rescue dextran sodium sulfate (DSS) colitis.
Both tofacitinib and JAK1i but not JAK3i effectively inhibited STAT1 phosphorylation and interferon gamma-induced transcripts in M1 polarized macrophages. Strikingly, transcriptional profiling suggested a switch from M1 to M2 type macrophages, which was supported by increased protein expression of M2-associated markers. In addition, both inhibitors enhanced oxidative phosphorylation rates. In vivo, JAK1i and tofacitinib did not protect mice from acute DSS-induced colitis but ameliorated recovery from weight loss and disease activity during acute rescue DSS-induced colitis at the highest dose.
JAK1i and tofacitinib but not JAK3i induce phenotypical and functional characteristics of anti-inflammatory macrophages, suggesting JAK1 as the main effector pathway for tofacitinib in these cells. In vivo, JAK1i and tofacitinib modestly affect acute rescue DSS-induced colitis.
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