The impacts of aviation emissions on current and future year fine particulate matter (PM2.5) were investigated using the Community Multiscale Air Quality model, accounting for aviation emissions from ...99 airports and below 10,000 ft during the landing and takeoff (LTO) cycle. Results indicated that current year aviation emissions increased average PM2.5 concentrations by 0.0032 μg m-3 (0.05%) in the continental U.S. while projected 2025 aviation emissions increased average PM2.5 by 0.0116 μg m-3 (0.21%). Nitrate aerosol was the largest contributor to the increase in PM2.5 concentrations due to aircraft emissions, particularly in the future year. Using an indicator of inorganic PM2.5 change, we attributed nitrate aerosol contributions to excess free ammonia and higher aircraft emissions of NOx (which when converted to HNO3 forms ammonium nitrate aerosol) than SO2 (a precursor of sulfate aerosol).
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS ...outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and
localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low
promoter activity in a variety of lung epithelial cell samples and low
gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein
in airway epithelial cells and confirm broad
protein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.
We call on conservation and space agencies to agree on a definitive set of biodiversity variables and how these will be tracked from space, to address conservation targets. Methods to derive these ...variables and the set of satellites needed to observe them must also be decided, to ensure continuous monitoring. To stimulate discussion, we propose ten variables that capture biodiversity change on the ground and can be monitored from space (see 'Ten variables'). These range from leaf nitrogen and chlorophyll content to seasonal changes in floods and fires.
Background
To define the location of the initial contralateral lymph node (LN) metastasis in patients with oropharynx cancer.
Methods
The location of the LN centroids from patients with oropharynx ...cancer and a single radiographically positive contralateral LN was defined. A clinical target volume (CTV) inclusive of all LN centroids was created, and its impact on dose to organs at risk was assessed.
Results
We identified 55 patients of which 49/55 had a single contralateral LN in level IIA, 4/55 in level III, 1/55 in level IIB, and 1/55 in the retropharynx. Mean radiation dose to the contralateral parotid gland was 15.1 and 21.0 Gy, (p <0.001) using the modeled high‐risk elective CTV and a consensus CTV, respectively.
Conclusions
We present a systematic approach for identifying the contralateral nodal regions at highest risk of harboring subclinical disease in patients with oropharynx cancer that warrants prospective clinical study.
WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in ...cells with faulty mismatch repair mechanisms
. Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214. This compound selectively engages a cysteine (C727) located in a region of the helicase domain subject to interdomain movement during DNA unwinding. VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), but not in microsatellite-stable, cells. The compound was well tolerated in mice and led to robust tumour regression in multiple MSI-H colorectal cancer cell lines and patient-derived xenograft models. Our work shows an allosteric approach for inhibition of WRN function that circumvents competition from an endogenous ATP cofactor in cancer cells, and designates VVD-133214 as a promising drug candidate for patients with MSI-H cancers.
The Breakthrough Listen Initiative is undertaking a comprehensive search for radio and optical signatures from extraterrestrial civilizations. An integral component of the project is the design and ...implementation of wide-bandwidth data recorder and signal processing systems. The capabilities of these systems, particularly at radio frequencies, directly determine survey speed; further, given a fixed observing time and spectral coverage, they determine sensitivity as well. Here, we detail the Breakthrough Listen wide-bandwidth data recording system deployed at the 100 m aperture Robert C. Byrd Green Bank Telescope. The system digitizes up to 6 GHz of bandwidth at 8 bits for both polarizations, storing the resultant 24 GB s−1 of data to disk. This system is among the highest data rate baseband recording systems in use in radio astronomy. A future system expansion will double recording capacity, to achieve a total Nyquist bandwidth of 12 GHz in two polarizations. In this paper, we present details of the system architecture, along with salient configuration and disk-write optimizations used to achieve high-throughput data capture on commodity compute servers and consumer-class hard disk drives.
Estimating the ambient concentration of nitrogen dioxide (NO2) is challenging because NO2 generated by local fossil fuel combustion varies greatly in concentration across space and time. This study ...demonstrates an integrated hybrid approach combining dispersion modeling and land use regression (LUR) to predict daily NO2 concentrations at a high spatial resolution (e.g., 50 m) in the New York tri-state area. The daily concentration of traffic-related NO2 was estimated at the Environmental Protection Agency's NO2 monitoring sites in the study area for the years 2015–2017, using the Research LINE source (R-LINE) model with inputs of traffic data provided by the Highway Performance and Management System and meteorological data provided by the NOAA Integrated Surface Database. We used the R-LINE-predicted daily concentrations of NO2 to build mixed-effects regression models, including additional variables representing land use features, geographic characteristics, weather, and other predictors. The mixed model was selected by the Elastic Net method. Each model's performance was evaluated using the out-of-sample coefficient of determination (R2) and the square root of mean squared error (RMSE) from ten-fold cross-validation (CV). The mixed model showed a good prediction performance (CV R2: 0.75–0.79, RMSE: 3.9–4.0 ppb). R-LINE outputs improved the overall, spatial, and temporal CV R2 by 10.0%, 18.9% and 7.7% respectively. Given the output of R-LINE is point-based and has a flexible spatial resolution, this hybrid approach allows prediction of daily NO2 at an extremely high spatial resolution such as city blocks.
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•The hybrid model can estimate daily NO2 at extremely high resolution.•RLINE improves LUR's prediction precision.•The hybrid model yields an excellent model performance.
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