From climatological to small-scale applications: simulating water isotopologues with ICON-ART-Iso (version 2.3)

We present the new isotope-enabled model ICON-ART-Iso. The physics package of the global ICOsahedral Nonhydrostatic (ICON) modeling framework has been extended to simulate passive moisture tracers and the stable isotopologues HDO and H182O. The extension builds on the infrastructure provided by ICON-ART, which allows for high flexibility with respect to the number of related water tracers that are simulated. The physics of isotopologue fractionation follow the model COSMOiso. We first present a detailed description of the physics of fractionation that have been implemented in the model. The model is then evaluated on a range of temporal scales by comparing with measurements of precipitation and vapor. A multi-annual simulation is compared to observations of the isotopologues in precipitation taken from the station network GNIP (Global Network for Isotopes in Precipitation). ICON-ART-Iso is able to simulate the main features of the seasonal cycles in δD and δ18O as observed at the GNIP stations. In a comparison with IASI satellite retrievals, the seasonal and daily cycles in the isotopologue content of vapor are examined for different regions in the free troposphere. On a small spatial and temporal scale, ICON-ART-Iso is used to simulate the period of two flights of the IAGOS-CARIBIC aircraft in September 2010, which sampled air in the tropopause region influenced by Hurricane Igor. The general features of this sample as well as those of all tropical data available from IAGOS-CARIBIC are captured by the model. The study demonstrates that ICON-ART-Iso is a flexible tool to analyze the water cycle of ICON. It is capable of simulating tagged water as well as the isotopologues HDO and H182

Ethylene oxide monitor with part-per-trillion precision for in situ measurements

An Aerodyne tunable infrared laser direct absorption spectrometer with a multipass cell with a 413 m pathlength for the detection of ethylene oxide (EtO) is presented (TILDAS-FD-EtO). This monitor achieves precisions of &lt;75 ppt or &lt;0.075 ppb s−1 and &lt;20 ppt in 100 s (1σ). We demonstrate precisions averaging down to 4 ppt h−1 (1σ precision) when operated with frequent humidity-matched zeroes. A months-long record of 2022 ambient concentrations at a site in the eastern United States is presented. Average ambient EtO concentration is on the order of 18 ppt (22 ppt standard deviation, SD). Enhancement events of EtO lasting a few hours are observed, with peaks as high as 600 ppt. Back-trajectory simulations suggest an EtO source nearly 35 km away. This source along with another are confirmed as emitters through mobile near-source measurements, with downwind concentrations in the 0.5 to 700 ppb range depending on source identity and distance downwind.</p

Covalent Modification of Lipids and Proteins in Rat Hepatocytes, and In Vitro, by Thioacetamide Metabolites

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3001658Thioacetamide (TA) is a well-known hepatotoxin in rats. Acute doses cause centrilobular necrosis and hyperbilirubinemia while chronic administration leads to biliary hyperplasia and cholangiocarcinoma. Its acute toxicity requires its oxidation to a stable S-oxide (TASO) that is oxidized further to a highly reactive S,S-dioxide (TASO2). To explore possible parallels between the metabolism, covalent binding and toxicity of TA and thiobenzamide (TB) we exposed freshly isolated rat hepatocytes to [14C]-TASO or [13C2D3]-TASO. TLC analysis of the cellular lipids showed a single major spot of radioactivity that mass spectral analysis showed to consist of N-acetimidoyl PE lipids having the same side chain composition as the PE fraction from untreated cells; no carbons or hydrogens from TASO were incorporated into the fatty acyl chains. Many cellular proteins contained N-acetyl- or N-acetimidoyl lysine residues in a 3:1 ratio (details to be reported separately). We also oxidized TASO with hydrogen peroxide in the presence of dipalmitoyl phosphatidylenthanolamine (DPPE) or lysozyme. Lysozyme was covalently modified at five of its six lysine side chains; only acetamide-type adducts were formed. DPPE in liposomes also gave only amide-type adducts, even when the reaction was carried out in tetrahydrofuran with only 10% water added. The exclusive formation of N-acetimidoyl PE in hepatocytes means that the concentration or activity of water must be extremely low in the region where TASO2 is formed, whereas at least some of the TASO2 can hydrolyze to acetylsulfinic acid before it reacts with cellular proteins. The requirement for two sequential oxidations to produce a reactive metabolite is unusual, but it is even more unusual that a reactive metabolite would react with water to form a new compound that retains a high degree of chemical reactivity toward biological nucleophiles. The possible contribution of lipid modification to the hepatotoxicity of TA/TASO remains to be determined

Using tunable infrared laser direct absorption spectroscopy for ambient hydrogen chloride detection : HCl-TILDAS

The largest inorganic, gas-phase reservoir of chlorine atoms in the atmosphere is hydrogen chloride (HCl), but challenges in quantitative sampling of this compound cause difficulties for obtaining high-quality, high-frequency measurements. In this work, tunable infrared laser direct absorption spectroscopy (TILDAS) was demonstrated to be a superior optical method for sensitive, in situ detection of HCl at the 2925.89645 cm-1 absorption line using a 3 μm inter-band cascade laser. The instrument has an effective path length of 204 m, 1 Hz precision of 7-8 pptv, and 3σ limit of detection ranging from 21 to 24 pptv. For longer averaging times, the highest precision obtained was 0.5 pptv with a 3σ limit of detection of 1.6 pptv at 2.4 min. HCl-TILDAS was also shown to have high accuracy when compared with a certified gas cylinder, yielding a linear slope within the expected 5 % tolerance of the reported cylinder concentration (slope = 0.964 ± 0.008). The use of heated inlet lines and active chemical passivation greatly improve the instrument response times to changes in HCl mixing ratios, with minimum 90 % response times ranging from 1.2 to 4.4 s depending on inlet flow rate. However, these response times lengthened at relative humidities >50 %, conditions under which HCl concentration standards were found to elicit a significantly lower response (-5.8 %). The addition of high concentrations of gas-phase nitric acid (>3.0 ppbv) were found to increase HCl signal (<10 %), likely due to acid displacement with HCl or particulate chloride adsorbed to inlet surfaces. The equilibrium model ISORROPIA suggested a potential of particulate chloride partitioning into HCl gas within the heated inlet system if allowed to thermally equilibrate, but field results did not demonstrate a clear relationship between particulate chloride and HCl signal obtained with a denuder installed on the inlet

Empirical validation and proof of added value of MUSICA\u27s tropospheric δD remote sensing products

The project MUSICA (MUlti-platform remote Sensing of Isotopologues for investigating the Cycle of Atmospheric water) integrates tropospheric water vapour isotopologue remote sensing and in situ observations. This paper presents a first empirical validation of MUSICA\u27s H2O and delta D remote sensing products, generated from ground-based FTIR (Fourier transform infrared), spectrometer and space-based IASI (infrared atmospheric sounding interferometer) observation. The study is made in the area of the Canary Islands in the subtropical northern Atlantic. As reference we use well calibrated in situ measurements made aboard an aircraft (between 200 and 6800 m a.s.l.) by the dedicated ISOWAT instrument and on the island of Tenerife at two different altitudes (at Izaña, 2370 m a.s.l., and at Teide, 3550 m a.s.l.) by two commercial Picarro L2120-i water isotopologue analysers. The comparison to the ISOWAT profile measurements shows that the remote sensors can well capture the variations in the water vapour isotopologues, and the scatter with respect to the in situ references suggests a delta D random uncertainty for the FTIR product of much better than 45‰ in the lower troposphere and of about 15‰ for the middle troposphere. For the middle tropospheric IASI delta D product the study suggests a respective uncertainty of about 15‰. In both remote sensing data sets we find a positive dela D bias of 30-70‰. Complementing H2O observations with delta D data allows moisture transport studies that are not possible with H2O observations alone. We are able to qualitatively demonstrate the added value of the MUSICA delta D remote sensing data. We document that the delta D-H2O curves obtained from the different in situ and remote sensing data sets (ISOWAT, Picarro at Izaña and Teide, FTIR, and IASI) consistently identify two different moisture transport pathways to the subtropical north eastern Atlantic free troposphere

Metabolism and Toxicity of Thioacetamide and Thioacetamide SOxide in Rat Hepatocytes

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3002719The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats, single doses cause centrilobular necrosis accompanied by increases in plasma transaminases and bilirubin. To elicit these effects TA requires oxidative bioactivation leading first to its S-oxide (TASO) and then to its chemically reactive S,S-dioxide (TASO2) which ultimately modifies amine-lipids and proteins. To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis, and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic at concentrations up to 50 mM for 40 hr. On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology and vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole, and was strongly inhibited by TA. Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. The covalent binding of [14C]-TASO is inhibited by unlabeled TA which acts as a “cold-trap” for [14C]-TA and prevents its re-oxidation to [14C]-TASO. This in turn increases the net consumption of [14C]-TASO despite the fact that its oxidation to TASO2 is inhibited. The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA may help explain phenomena previously interpreted as “saturation toxicokinetics” in the in vivo metabolism and toxicity of TA and TASO. The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification