We developed a system that links a thermal desorption oven for aerosol filter samples to an isotope ratio mass spectrometer (IRMS) via a combustion interface. Organic compounds are desorbed from the ...filter sample in He at 7 temperature steps between 100 and 400°C and subsequently oxidized to CO2, which is analyzed for δ13C. We tested the system for isotopic fractionation, reproducibility and linearity using organic test compounds and aerosol filter samples. An oxalic acid standard with known δ13C value shows no isotopic fractionation when it is desorbed at temperatures well above its melting point. When organic acids are heated at a temperature close to their melting point only a fraction of the compound (10–80%) evaporates which shows depleted δ13C values at this temperature step. At the next higher temperature step, when the rest of the compound is desorbed, δ13C values are enriched. This effect is stronger for compounds with a lower molecular weight than for compounds with a higher molecular weight. In ambient samples this should only have a moderate effect on the overall δ13C value, since hundreds of different compounds are desorbed at each temperature step. Choosing different values for temperature steps does not strongly change the δ13C values for ambient aerosol filter samples. For typical ambient samples the reproducibility lies below ±0.3‰ for oven temperatures below 200°C and below ±0.5‰ for oven temperatures above 200°C. Tests with oxalic acid and ambient filter samples show that the IRMS is linear for peak areas in the operational range of 1–20Vs.
•A step-wise thermal desorption system for measuring δ13C values of organic aerosol.•The results are independent of the chosen temperature steps.•The system is linear, i.e. δ13C values are independent of the analyzed peak area.•No isotopic fractionation for fully desorbed compounds.•The reproducibility of δ13C values is below 0.5‰.
We report the detection of a class of related oxygenated compounds by proton‐transfer‐reaction mass‐spectrometry (PTR‐MS) that have rarely or never been observed as a group using in situ ...instrumentation. Measurements were made as part of the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) 2004 in Chebogue Point, Nova Scotia. The detected class of compounds discussed here includes acetic acid, formaldehyde, acetaldehyde, tentatively identified formic acid and hydroxyacetone, and unidentified compounds detected at mass to charge ratios 85, 87, 99, 101, 113, 115, and 129. Typical concentrations were 800, 2500, 450, 700, 85, 25, 50, 50, 60, 35, 20, and 25 ppt, respectively. The uniqueness of this class of compounds is illustrated by showing they were poorly related to trace gases found in the US outflow, local pollution, primary biogenic emissions and other oxygenated compounds such as acetone, methanol, and MEK measured by other in situ instrumentation. On the other hand these oxidized volatile organic compounds were related to chemical species in aerosols and their abundance was high during nucleation events. Thus they likely are gas phase species that are formed in parallel to biogenic secondary organic aerosol production. We clearly show these compounds do not originate from local sources. We also show these compounds match the oxidation products of isoprene observed in smog chamber studies, and we therefore suggest they must be mainly produced by oxidation of biogenic precursor compounds.
Airborne measurements of acetone, methanol, PAN, acetonitrile (by Proton Transfer Reaction Mass Spectrometry), and CO (by Tunable Diode Laser Absorption Spectroscopy) have been performed during the ...Mediterranean Intensive Oxidants Study (MINOS August 2001). We have identified ten biomass burning plumes from strongly elevated acetonitrile mixing ratios. The characteristic biomass burning signatures obtained from these plumes reveal secondary production of acetone and methanol, while CO photochemically declines in the plumes. Mean excess mixing ratios - normalized to CO - of 1.8%, 0.20%, 3.8%, and 0.65% for acetone, acetonitrile, methanol, and PAN, respectively, were found. By scaling to an assumed global annual source of 663-807Tg CO, biomass burning emissions of 25-31 and 29-35 Tg/yr for acetone and methanol are estimated, respectively. Our measurements suggest that the present biomass burning contributions of acetone and methanol are significantly underestimated due to the neglect of secondary formation within the plume. Median acetonitrile mixing ratios throughout the troposphere were around 150pmol/mol, in accord with current biomass burning inventories and an atmospheric lifetime of ~6 months.
OBJECTIVESPrior candidate gene studies have associated CYP2B6 516G→T rs3745274 and 983T→C rs28399499 with increased plasma efavirenz exposure. We sought to identify novel variants associated with ...efavirenz pharmacokinetics.
MATERIALS AND METHODSAntiretroviral therapy-naive AIDS Clinical Trials Group studies A5202, A5095, and ACTG 384 included plasma sampling for efavirenz pharmacokinetics. Log-transformed trough efavirenz concentrations (Cmin) were previously estimated by population pharmacokinetic modeling. Stored DNA was genotyped with Illumina HumanHap 650Y or 1MDuo platforms, complemented by additional targeted genotyping of CYP2B6 and CYP2A6 with MassARRAY iPLEX Gold. Associations were identified by linear regression, which included principal component vectors to adjust for genetic ancestry.
RESULTSAmong 856 individuals, CYP2B6 516G→T was associated with efavirenz estimated Cmin (P=8.5×10). After adjusting for CYP2B6 516G→T, CYP2B6 983T→C was associated (P=9.9×10). After adjusting for both CYP2B6 516G→T and 983T→C, a CYP2B6 variant (rs4803419) in intron 3 was associated (P=4.4×10). After adjusting for all the three variants, non-CYP2B6 polymorphisms were associated at P-value less than 5×10. In a separate cohort of 240 individuals, only the three CYP2B6 polymorphisms replicated. These three polymorphisms explained 34% of interindividual variability in efavirenz estimated Cmin. The extensive metabolizer phenotype was best defined by the absence of all three polymorphisms.
CONCLUSIONThree CYP2B6 polymorphisms were independently associated with efavirenz estimated Cmin at genome-wide significance, and explained one-third of interindividual variability. These data will inform continued efforts to translate pharmacogenomic knowledge into optimal efavirenz utilization.
We present setup, testing and initial results from a new automated system for stable carbon isotope ratio measurements on C2 to C6 atmospheric hydrocarbons. The inlet system allows analysis of trace ...gases from air samples ranging from a few liters for urban samples and samples with high mixing ratios, to many tens of liters for samples from remote unpolluted regions with very low mixing ratios. The centerpiece of the sample preparation is the separation trap, which is used to separate CO2 and methane from the compounds of interest. The main features of the system are (i) the capability to sample up to 300 l of air, (ii) long term (since May 2009) operational δ13C accuracy levels in the range 0.3–0.8 ‰ (1-σ), and (iii) detection limits of order 1.5–2.5 ngC (collected amount of substance) for all reported compounds. The first application of this system was the analysis of 21 ambient air samples taken during 48 h in August 2009 in Utrecht, the Netherlands. Results obtained are generally in good agreement with those from similar urban ambient air studies. Short sample intervals allowed by the design of the instrument help to illustrate the complex diurnal behavior of hydrocarbons in an urban environment, where diverse sources, dynamical processes, and chemical reactions are present.
Volatile organic compound (VOC) emissions of the Mediterranean holm oak (Quercus ilex L.) were investigated using a fast Proton Transfer Reaction Mass Spectrometry (PTR‐MS) instrument for analysis. ...This technique is able to measure compounds with a proton affinity higher than water with a high time resolution of 1 s per compound. Hence nearly all VOCs can be detected on‐line. We could clearly identify the emission of methanol, acetaldehyde, ethanol, acetone, acetic acid, isoprene, monoterpenes, toluene, and C10‐benzenes. Some other species could be tentatively denominated. Among these are the masses 67 (cyclo pentadiene), mass 71 (tentatively attributed to methyl vinyl ketone (MVK) and metacrolein (MACR)), 73 (attributed to methyl ethyl ketone (MEK)), 85 (C6H12 or hexanol), and 95 (vinylfuran or phenol). The emissions of all these compounds (identified as well as nonidentified) together represent 99% of all masses detected and account for a carbon loss of 0.7–2.9% of the net photosynthesis. Of special interest was a change in the emission behavior under changing environmental conditions such as flooding or fast light/dark changes. Flooding of the root system caused an increase of several VOCs between 60 and 2000%, dominated by the emission of ethanol and acetaldehyde, which can be explained by the well described production of ethanol under anoxic conditions of the root system and the recently described subsequent transport and partial oxidation to acetaldehyde within the green leaves. However, ethanol emissions were dominant. Additionally, bursts of acetaldehyde with lower ethanol emission were also found under fast light/dark changes. These bursts are not understood.
A series of 12 high volume air samples collected from the S2 firn core during the North Greenland Eemian Ice Drilling (NEEM) 2009 campaign have been measured for mixing ratio and stable carbon ...isotope composition of the chlorofluorocarbon CFC-12 (CCl2F2). While the mixing ratio measurements compare favorably to other firn air studies, the isotope results show extreme 13C depletion at the deepest measurable depth (65 m), to values lower than δ13C = −80‰ vs. VPDB (the international stable carbon isotope scale), compared to present day surface tropospheric measurements near −40‰. Firn air modeling was used to interpret these measurements. Reconstructed atmospheric time series indicate even larger depletions (to −120‰) near 1950 AD, with subsequent rapid enrichment of the atmospheric reservoir of the compound to the present day value. Mass-balance calculations show that this change is likely to have been caused by a large change in the isotopic composition of anthropogenic CFC-12 emissions, probably due to technological advances in the CFC production process over the last 80 yr, though direct evidence is lacking.
This study presents measurements of acetonitrile, benzene, toluene, methanol and acetone made using the proton-transfer-reaction mass spectrometry (PTR-MS) technique at the Finokalia ground station ...in Crete during the Mediterranean INtensive Oxidant Study (MINOS) in July-August 2001. Three periods during the campaign with broadly consistent back trajectories are examined in detail. In the first, air was advected from Eastern Europe without significant biomass burning influence (mean acetonitrile mixing ratio 154 pmol/mol). In the second period, the sampled air masses originated in Western Europe, and were advected approximately east-south-east, before turning south-west over the Black Sea and north-western Turkey. The third well-defined period included air masses advected from Eastern Europe passing east and south of/over the Sea of Azov, and showed significant influence by biomass burning (mean acetonitrile mixing ratio 436 pmol/mol), confirmed by satellite pictures. The mean toluene:benzene ratios observed in the three campaign periods described were 0.35, 0.37 and 0.22, respectively; the use of this quantity to determine air mass age is discussed. Methanol and acetone were generally well-correlated both with each other and with carbon monoxide throughout the campaign. Comparison of the acetone and methanol measurements with the MATCH-MPIC model showed that the model underestimated both species by a factor of 4, on average. The correlations between acetone, methanol and CO implied that the relatively high levels of methanol observed during MINOS were largely due to direct biogenic emissions, and also that biogenic sources of acetone were highly significant during MINOS (~35%). This in turn suggests that the model deficit in both species may be due, at least in part, to missing biogenic emissions.
The current paradigm of human genetics research is to analyze variation of a single data type (i.e., DNA sequence or RNA levels) to detect genes and pathways that underlie complex traits such as ...disease state or drug response. While these studies have detected thousands of variations that associate with hundreds of complex phenotypes, much of the estimated heritability, or trait variability due to genetic factors, remain unexplained. We may be able to account for a portion of the missing heritability if we incorporate a systems biology approach into these analyses. Rapid technological advances will make it possible for scientists to explore this hypothesis via the generation of high-throughput omics data - transcriptomic, proteomic and methylomic to name a few. Analyzing this 'meta-dimensional' data will require clever statistical techniques that allow for the integration of qualitative and quantitative predictor variables. For this article, we examine two major categories of approaches for integrated data analysis, give examples of their use in experimental and in silico datasets, and assess the limitations of each method.
The spatial distribution of the deuterium content of precipitation has a well-established latitudinal variation that is reflected in organic molecules in plants growing at different locations. Some ...laboratory and field studies have already shown that the deuterium content of methane emitted from methanogens can be partially related to δD variations of the water in the surrounding environment. Here we present a similar relation for the methane emitted from plant biomass under UV radiation. To show this relation, we determined the hydrogen isotopic composition of methane released from leaves of a range of plants grown with water of different deuterium content (δD
=
−130‰ to +115‰). The plant leaves were irradiated with UV light and the CH
4 isotopic composition was measured by continuous flow isotope ratio mass spectrometry (CF-IRMS). Furthermore, the deuterium content of bulk biomass and of the methoxyl (OCH
3) groups of the biomass was measured. The D/H ratio successively decreases from bulk biomass (δD
=
−106‰ to −50‰) via methoxyl groups (δD
=
−310‰ to −115‰) to the CH
4 emitted (δD
=
−581‰ to −196‰). The range of isotope ratios in bulk biomass and OCH
3 groups is smaller than in the water used to grow the plants. Methoxyl groups, which contain only non-exchangeable hydrogen, can be used to assess the fraction of external water that was incorporated before OCH
3 groups were formed. Surprisingly, the CH
4 formed under UV irradiation has a wider isotopic range than the OCH
3 groups. Although the precise production pathway cannot be fully determined, the presented experiments indicate that methoxyl groups are not the only source substrate for CH
4, but that other sources, including very depleted ones, must contribute. The main limitation to the interpretation of the data is the possible influence of exchangeable water, which could not be quantified. Future studies should include measurements of leaf water and avoid interaction between different plants via the gas phase. Despite these deficiencies, the results suggest that the deuterium content of the methane generated from plants under UV irradiation is closely linked to δD in precipitation. This dependency, which should also exist for other biogenic methane sources could be evaluated with global isotope models.
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