The preservation of atmospheric nitrate in snow at Summit, Greenland

There is great interest in using nitrate NO3 isotopic composition in ice cores to track the history of precursor nitrogen oxides (NOx = NO + NO2) in the atmosphere. Nitrate NO3 however can be lost from the snow by surface processes, such as photolysis back to NOx upon exposure to sunlight, making it difficult to interpret records of NO3 as a tracer of atmospheric NOx loading. In a campaign consisting of two field seasons (May–June) at Summit, Greenland, high temporal frequency surface snow samples were collected and analyzed for the oxygen isotopic composition of NO3. The strong, linear relationship observed between the oxygen isotopes of NO3 in both 2010 and 2011, is difficult to explain in the presence of significant post depositional processing of NO3 unless several unrelated variables change in concert. Therefore, the isotopic signature of NO3 in the snow at Summit is most feasibly explained as preserved atmospheric NO3 deposition

Isotopic evidence for dominant secondary production of HONO in near-ground wildfire plumes

Nitrous acid (HONO) is an important precursor to hydroxyl radical (OH) that determines atmospheric oxidative capacity and thus impacts climate and air quality. Wildfire is not only a major direct source of HONO, it also results in highly polluted conditions that favor the heterogeneous formation of HONO from nitrogen oxides (NOx= NO + NO2) and nitrate on both ground and particle surfaces. However, these processes remain poorly constrained. To quantitatively constrain the HONO budget under various fire and/or smoke conditions, we combine a unique dataset of field concentrations and isotopic ratios (15N / 14N and 18O / 16O) of NOx and HONO with an isotopic box model. Here we report the first isotopic evidence of secondary HONO production in near-ground wildfire plumes (over a sample integration time of hours) and the subsequent quantification of the relative importance of each pathway to total HONO production. Most importantly, our results reveal that nitrate photolysis plays a minor role (\u3c5 %) in HONO formation in daytime aged smoke, while NO2-to-HONO heterogeneous conversion contributes 85 %–95 % to total HONO production, followed by OH + NO (5 %–15 %). At nighttime, heterogeneous reduction of NO2 catalyzed by redox active species (e.g., iron oxide and/or quinone) is essential (≥ 75 %) for HONO production in addition to surface NO2 hydrolysis. Additionally, the 18O / 16O of HONO is used for the first time to constrain the NO-to-NO2 oxidation branching ratio between ozone and peroxy radicals. Our approach provides a new and critical way to mechanistically constrain atmospheric chemistry and/or air quality models on a diurnal timescale

BK Channels Regulate Spontaneous Action Potential Rhythmicity in the Suprachiasmatic Nucleus

Background: Circadian (,24 hr) rhythms are generated by the central pacemaker localized to the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the basis for intrinsic rhythmicity is generally understood to rely on transcription factors encoded by ‘‘clock genes’’, less is known about the daily regulation of SCN neuronal activity patterns that communicate a circadian time signal to downstream behaviors and physiological systems. Action potentials in the SCN are necessary for the circadian timing of behavior, and individual SCN neurons modulate their spontaneous firing rate (SFR) over the daily cycle, suggesting that the circadian patterning of neuronal activity is necessary for normal behavioral rhythm expression. The BK K + channel plays an important role in suppressing spontaneous firing at night in SCN neurons. Deletion of the Kcnma1 gene, encoding the BK channel, causes degradation of circadian behavioral and physiological rhythms. Methodology/Principal Findings: To test the hypothesis that loss of robust behavioral rhythmicity in Kcnma1 2/2 mice is due to the disruption of SFR rhythms in the SCN, we used multi-electrode arrays to record extracellular action potentials from acute wild-type (WT) and Kcnma1 2/2 slices. Patterns of activity in the SCN were tracked simultaneously for up to 3 days, and the phase, period, and synchronization of SFR rhythms were examined. Loss of BK channels increased arrhythmicity but also altered the amplitude and period of rhythmic activity. Unexpectedly, Kcnma1 2/2 SCNs showed increased variability in the timing of the daily SFR peak

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Triple oxygen stable isotope analysis of nitrite measured using continuous flow isotope ratio mass spectrometry

Oxygen stable isotopes (i.e., 16O, 17O, 18O) of nitrite (NO2−) are useful for investigating chemical processes and sources contributing to this important environmental contaminant and nutrient. However, it remains difficult to quantify the oxygen isotope compositions of NO2− due to the lack of internationally recognized NO2− reference materials with a well-known Δ(17O) value. Here we have adopted a combination of methodologies to develop a technique for measuring Δ(17O) of NO2− by reducing nitrate (NO3−) materials with internationally recognized Δ(17O) values to NO2− using activated cadmium catalyzed by chloride in a basic solution while conserving Δ(17O). The NO3− reference materials reduced to NO2− and sample NO2− unknowns are converted to N2O using sodium azide/acetic acid reagent and decomposed to O2 by passing through a heated gold tube and introduced into a continuous flow isotope ratio mass spectrometer for analysis at m/z 32, 33, and 34 for Δ(17O) quantification.The adapted method involves the following main points: • NO3− reference materials with internationally recognized oxygen isotope composition are reduced to NO2− under high pH conditions that conserve Δ(17O) values. • The NO3− reference materials reduced to NO2− and sample NO2− with unknown Δ(17O) values are reduced to N2O using chemical methods involving sodium azide/acetic acid. • The product N2O is extracted, purified, decomposed to O2, and analyzed for its isotope composition using a continuous flow isotope ratio mass spectrometer for Δ(17O) quantification. The Δ(17O) of NO2− samples are calibrated with respect to the NO3− reference materials with known Δ(17O) values

Collection Method for Isotopic Analysis of Gaseous Nitrous Acid

The sources and chemistry of gaseous nitrous acid (HONO) in the environment are of great interest. HONO is a major source of atmospheric hydroxyl radical (OH), which impacts air quality and climate. HONO is also a major indoor pollutant that threatens human health. However, the large uncertainty of HONO sources and chemistry hinders an accurate prediction of the OH budget. Isotopic analysis of HONO may provide a tool for tracking the sources and chemistry of HONO. In this study, a modified annular denuder system (ADS) was developed to quantitatively capture HONO for offline nitrogen and oxygen isotopic analysis (δ¹⁵N and δ¹⁸O) using the denitrifier method. The ADS method was tested using laboratory generated HONO (400 ppbv to 1 ppmv) and validated by parallel HONO collection with a standard, basic impinger (BI) method. The ADS system shows complete capture of HONO without isotopic fractionation. The uncertainty (1σ) based on repeated measurements across the entire analytical procedure is 0.6‰ for δ¹⁵N and 0.5‰ for δ¹⁸O. The ADS method was also tested in roadside collections of ambient HONO (0.4–1.3 ppbv) for isotopic analysis and was found to be robust for low concentration collections over 3 and 12 h collection times. In order to ensure ability to use this method in the laboratory and in the field, storage conditions for the collected HONO samples were tested and samples can be stored with consistent δ¹⁵N and δ¹⁸O for 60 days. This method enables future work to utilize the isotopic composition of HONO for studying HONO chemical formation pathways, as well as atmospheric sources and chemistry