Effects of Chemical Feedbacks on Decadal Methane Emissions Estimates

The coupled chemistry of methane, carbon monoxide (CO), and hydroxyl radical (OH) can modulate methane's 9‐year lifetime. This is often ignored in methane flux inversions, and the impacts of neglecting interactive chemistry have not been quantified. Using a coupled‐chemistry box model, we show that neglecting the effect of methane source perturbation on [OH] can lead to a 25% bias in estimating abrupt changes in methane sources after only 10 years. Further, large CO emissions, such as from biomass burning, can increase methane concentrations by extending the methane lifetime through impacts on [OH]. Finally, we quantify the biases of including (or excluding) coupled chemistry in the context of recent methane and CO trends. Decreasing CO concentrations, beginning in the 2000's, have notable impacts on methane flux inversions. Given these nonnegligible errors, decadal methane emissions inversions should incorporate chemical feedbacks for more robust methane trend analyses and source attributions

Interpreting contemporary trends in atmospheric methane

Atmospheric methane plays a major role in controlling climate, yet contemporary methane trends (1982–2017) have defied explanation with numerous, often conflicting, hypotheses proposed in the literature. Specifically, atmospheric observations of methane from 1982 to 2017 have exhibited periods of both increasing concentrations (from 1982 to 2000 and from 2007 to 2017) and stabilization (from 2000 to 2007). Explanations for the increases and stabilization have invoked changes in tropical wetlands, livestock, fossil fuels, biomass burning, and the methane sink. Contradictions in these hypotheses arise because our current observational network cannot unambiguously link recent methane variations to specific sources. This raises some fundamental questions: (i) What do we know about sources, sinks, and underlying processes driving observed trends in atmospheric methane? (ii) How will global methane respond to changes in anthropogenic emissions? And (iii), What future observations could help resolve changes in the methane budget? To address these questions, we discuss potential drivers of atmospheric methane abundances over the last four decades in light of various observational constraints as well as process-based knowledge. While uncertainties in the methane budget exist, they should not detract from the potential of methane emissions mitigation strategies. We show that net-zero cost emission reductions can lead to a declining atmospheric burden, but can take three decades to stabilize. Moving forward, we make recommendations for observations to better constrain contemporary trends in atmospheric methane and to provide mitigation support

Effects of Chemical Feedbacks on Decadal Methane Emissions Estimates

The coupled chemistry of methane, carbon monoxide (CO), and hydroxyl radical (OH) can modulate methane's 9‐year lifetime. This is often ignored in methane flux inversions, and the impacts of neglecting interactive chemistry have not been quantified. Using a coupled‐chemistry box model, we show that neglecting the effect of methane source perturbation on [OH] can lead to a 25% bias in estimating abrupt changes in methane sources after only 10 years. Further, large CO emissions, such as from biomass burning, can increase methane concentrations by extending the methane lifetime through impacts on [OH]. Finally, we quantify the biases of including (or excluding) coupled chemistry in the context of recent methane and CO trends. Decreasing CO concentrations, beginning in the 2000's, have notable impacts on methane flux inversions. Given these nonnegligible errors, decadal methane emissions inversions should incorporate chemical feedbacks for more robust methane trend analyses and source attributions

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial

<div><p>Background</p><p>Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.</p><p>Methods</p><p>The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637.</p><p>Results</p><p>Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment.</p><p>Conclusions</p><p>The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01144637" target="_blank">NCT01144637</a></p></div

Isoniazid as a substrate and inhibitor of myeloperoxidase: Identification of amine adducts and the influence of superoxide dismutase on their formation

Neutrophils ingest Mycobacteria tuberculosis (Mtb) in the lungs of infected individuals. During phagocytosis they use myeloperoxidase (MPO) to catalyze production of hypochlorous acid (HOCl), their most potent antimicrobial agent. Isoniazid (INH),the foremost antibiotic in the treatment oftuberculosis, is oxidized by MPO. It rapidly reduced compound I of MPO [k = (1.22 0.05) 106 M 1 s 1 ] but reacted less favorably with compound II [(9.8 0.6) 102 M 1 s 1 ]. Oxidation of INH by MPO and hydrogen peroxide was unaffected by chloride,the physiological substrate for compound I, and the enzyme was partially converted to compound III. This indicates that INH is oxidized outside the classical peroxidation cycle. In combination with superoxide dismutase (SOD), MPO oxidized INH without exogenous hydrogen peroxide. SOD must favor reduction of oxygen by the INH radical to give superoxide and ultimately hydrogen peroxide. In both oxidation systems, an adduct with methionine was formed and it was a major product with MPO and SOD. We show that it is a conjugate of an acyldiimide with amines. INH substantially inhibited HOCl production by MPO and neutrophils below pharmacological concentrations. The reversible inhibition is explained by diversion of MPO to its ferrous and compound III forms during oxidation of INH. MPO, along with SOD released by Mtb, will oxidize INH at sites of infection and their interactions are likely to limit the efficacy of the drug, promote adverse drug reactions via formation of protein adducts, and impair a major bacterial killing mechanism of neutrophils

Extreme events driving year-to-year differences in gross primary productivity across the US

Solar-Induced chlorophyll Fluorescence (SIF) has previously been shown to strongly correlate with gross primary productivity (GPP), however this relationship has not yet been quantified for the recently launched TROPOspheric Monitoring Instrument (TROPOMI). Here we use a Gaussian mixture model to develop a parsimonious relationship between SIF from TROPOMI and GPP from flux towers across the conterminous United States (CONUS). The mixture model indicates the SIF-GPP relationship can be characterized by a linear model with two terms. We then estimate GPP across CONUS at 500-m spatial resolution over a 16-day moving window. We find that CONUS GPP varies by less than 4% between 2018 and 2019. However, we observe four extreme precipitation events that induce regional GPP anomalies: drought in west Texas, flooding in the midwestern US, drought in South Dakota, and drought in California. Taken together, these events account for 28% of the year-to-year GPP differences across CONUS

A double peak in the seasonality of California's photosynthesis as observed from space

Solar-induced chlorophyll fluorescence (SIF) has been shown to be a powerful proxy for photosynthesis and gross primary productivity (GPP). The recently launched TROPOspheric Monitoring Instrument (TROPOMI) features the required spectral resolution and signal-to-noise ratio to retrieve SIF from space. Here, we present a downscaling method to obtain 500 m spatial resolution SIF over California. We report daily values based on a 14 d window. TROPOMI SIF data show a strong correspondence with daily GPP estimates at AmeriFlux sites across multiple ecosystems in California. We find a linear relationship between SIF and GPP that is largely invariant across ecosystems with an intercept that is not significantly different from zero. Measurements of SIF from TROPOMI agree with MODerate Resolution Imaging Spectroradiometer (MODIS) vegetation indices – the normalized difference vegetation index (NDVI), enhanced vegetation index (EVI), and near-infrared reflectance of vegetation index (NIR_v) – at annual timescales but indicate different temporal dynamics at monthly and daily timescales. TROPOMI SIF data show a double peak in the seasonality of photosynthesis, a feature that is not present in the MODIS vegetation indices. The different seasonality in the vegetation indices may be due to a clear-sky bias in the vegetation indices, whereas previous work has shown SIF to have a low sensitivity to clouds and to detect the downregulation of photosynthesis even when plants appear green. We further decompose the spatiotemporal patterns in the SIF data based on land cover. The double peak in the seasonality of California's photosynthesis is due to two processes that are out of phase: grasses, chaparral, and oak savanna ecosystems show an April maximum, while evergreen forests peak in June. An empirical orthogonal function (EOF) analysis corroborates the phase offset and spatial patterns driving the double peak. The EOF analysis further indicates that two spatiotemporal patterns explain 84 % of the variability in the SIF data. Results shown here are promising for obtaining global GPP at sub-kilometer spatial scales and identifying the processes driving carbon uptake

Extreme events driving year-to-year differences in gross primary productivity across the US

Solar-Induced chlorophyll Fluorescence (SIF) has previously been shown to strongly correlate with gross primary productivity (GPP), however this relationship has not yet been quantified for the recently launched TROPOspheric Monitoring Instrument (TROPOMI). Here we use a Gaussian mixture model to develop a parsimonious relationship between SIF from TROPOMI and GPP from flux towers across the conterminous United States (CONUS). The mixture model indicates the SIF-GPP relationship can be characterized by a linear model with two terms. We then estimate GPP across CONUS at 500-m spatial resolution over a 16-day moving window. We find that CONUS GPP varies by less than 4% between 2018 and 2019. However, we observe four extreme precipitation events that induce regional GPP anomalies: drought in west Texas, flooding in the midwestern US, drought in South Dakota, and drought in California. Taken together, these events account for 28% of the year-to-year GPP differences across CONUS

Unlocking biocatalytic acylations by enzyme repurposing and engineering for amide synthesis

Please click Additional Files below to see the full abstrac

Interpreting contemporary trends in atmospheric methane

Atmospheric methane plays a major role in controlling climate, yet contemporary methane trends (1982–2017) have defied explanation with numerous, often conflicting, hypotheses proposed in the literature. Specifically, atmospheric observations of methane from 1982 to 2017 have exhibited periods of both increasing concentrations (from 1982 to 2000 and from 2007 to 2017) and stabilization (from 2000 to 2007). Explanations for the increases and stabilization have invoked changes in tropical wetlands, livestock, fossil fuels, biomass burning, and the methane sink. Contradictions in these hypotheses arise because our current observational network cannot unambiguously link recent methane variations to specific sources. This raises some fundamental questions: (i) What do we know about sources, sinks, and underlying processes driving observed trends in atmospheric methane? (ii) How will global methane respond to changes in anthropogenic emissions? And (iii), What future observations could help resolve changes in the methane budget? To address these questions, we discuss potential drivers of atmospheric methane abundances over the last four decades in light of various observational constraints as well as process-based knowledge. While uncertainties in the methane budget exist, they should not detract from the potential of methane emissions mitigation strategies. We show that net-zero cost emission reductions can lead to a declining atmospheric burden, but can take three decades to stabilize. Moving forward, we make recommendations for observations to better constrain contemporary trends in atmospheric methane and to provide mitigation support