Varying the effective mass of geophones

This is the published version. Reuse is subject to the Society of Exploration Geophysicists terms of use and conditions.Traditionally, acquiring seismic data has rested on the assumption that geophone mass should be as small as possible. When Steeples and coworkers in 1999 planted 72 geophones automatically and simultaneously with a farm tillage implement, the effective mass of each of the geophones was significantly increased. We examined how the mass of a geophone affects changes in traveltime, amplitude, frequency, and overall data quality by placing various external masses on top of 100‐Hz vertical geophones. Circular barbell weights of 1.1‐, 11.3‐, and 22.7 kg; an 8.2‐kg bag of lead shot; and a 136‐kg stack of barbell weights were placed on top of geophones during data acquisition. In addition, a very large mass in the form of a truck was parked on top of two of the geophones. Four seismic sources supplying a broad range of energies were tested: a sledgehammer, a .22‐caliber rifle, a 30.06 rifle, and an 8‐gauge Betsy Seisgun. Spectral analysis revealed that the smaller weights had the greatest effects on the capacities of the geophones to replicate the earth’s motion. Consequently, using geophones with a large effective mass as part of an automatic geophone‐planting device would not necessarily be detrimental to the collection of high‐quality near‐surface seismic data

Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies

We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly active α-glucosidase inhibitors were discovered, where one of them is the most potent iminosugar-based anti-SARS-CoV-2 agent to date (EC90 = 1.94 µM in A549-ACE2 cells against Omicron BA.1 strain). However, galactosidase inhibitors did not exhibit antiviral activity, whereas mannosidase inhibitors were both active and cytotoxic. As our iminosugar-based drug candidates act by a host-directed mechanism, they should be more resilient to drug resistance. Moreover, this strategy could be extended to identify potential drug candidates for other viral infections

A global observational analysis to understand changes in air quality during exceptionally low anthropogenic emission conditions

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015-2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O-3 and the total gaseous oxidant (O-X = NO2 + O-3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015-2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples' mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality. As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015-2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O-3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of similar to 70%. The SO2 anomalies were negative for 2020 compared to 2015-2019 (between similar to 25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to similar to 40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of similar to 60%). Analysis of the total oxidant (OX = NO2 + O-3) showed that primary NO2 emissions at urban locations were greater than the O-3 production, whereas at background sites, O-X was mostly driven by the regional contributions rather than local NO2 and O-3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.Peer reviewe

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

A global observational analysis to understand changes in air quality during exceptionally low anthropogenic emission conditions

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015–2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O3 and the total gaseous oxidant (OX = NO2 + O3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015–2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples’ mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality. As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015–2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of ~70%. The SO2 anomalies were negative for 2020 compared to 2015–2019 (between ~25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to ~40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of ~60%). Analysis of the total oxidant (OX = NO2 + O3) showed that primary NO2 emissions at urban locations were greater than the O3 production, whereas at background sites, OX was mostly driven by the regional contributions rather than local NO2 and O3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.World Meteorological Organization Global Atmospheric Watch programme is gratefully acknowledged for initiating and coordinating this study and for supporting this publication. We acknowledge the following projects for supporting the analysis contained in this article: Air Pollution and Human Health for an Indian Megacity project PROMOTE funded by UK NERC and the Indian MOES, Grant reference number NE/P016391/1; Regarding project funding from the European Commission, the sole responsibility of this publication lies with the authors. The European Commission is not responsible for any use that may be made of the information contained therein. This project has received funding from the European Commission’s Horizon 2020 research and innovation program under grant agreement No 874990 (EMERGE project). European Regional Development Fund (project MOBTT42) under the Mobilitas Pluss programme; Estonian Research Council (project PRG714); Estonian Research Infrastructures Roadmap project Estonian Environmental Observatory (KKOBS, project 2014-2020.4.01.20-0281). European network for observing our changing planet project (ERAPLANET, grant agreement no. 689443) under the European Union’s Horizon 2020 research and innovation program, Estonian Ministry of Sciences projects (grant nos. P180021, P180274), and the Estonian Research Infrastructures Roadmap project Estonian Environmental Observatory (3.2.0304.11-0395). Eastern Mediterranean and Middle East—Climate and Atmosphere Research (EMME-CARE) project, which has received funding from the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 856612) and the Government of Cyprus. INAR acknowledges support by the Russian government (grant number 14.W03.31.0002), the Ministry of Science and Higher Education of the Russian Federation (agreement 14.W0331.0006), and the Russian Ministry of Education and Science (14.W03.31.0008). We are grateful to to the following agencies for providing access to data used in our analysis: A.M. Obukhov Institute of Atmospheric Physics Russian Academy of Sciences; Agenzia Regionale per la Protezione dell’Ambiente della Campania (ARPAC); Air Quality and Climate Change, Parks and Environment (MetroVancouver, Government of British Columbia); Air Quality Monitoring & Reporting, Nova Scotia Environment (Government of Nova Scotia); Air Quality Monitoring Network (SIMAT) and Emission Inventory, Mexico City Environment Secretariat (SEDEMA); Airparif (owner & provider of the Paris air pollution data); ARPA Lazio, Italy; ARPA Lombardia, Italy; Association Agr´e´ee de Surveillance de la Qualit´e de l’Air en ˆIle-de- France AIRPARIF / Atmo-France; Bavarian Environment Agency, Germany; Berlin Senatsverwaltung für Umwelt, Verkehr und Klimaschutz, Germany; California Air Resources Board; Central Pollution Control Board (CPCB), India; CETESB: Companhia Ambiental do Estado de S˜ao Paulo, Brazil. China National Environmental Monitoring Centre; Chandigarh Pollution Control Committee (CPCC), India. DCMR Rijnmond Environmental Service, the Netherlands. Department of Labour Inspection, Cyprus; Department of Natural Resources Management and Environmental Protection of Moscow. Environment and Climate Change Canada; Environmental Monitoring and Science Division Alberta Environment and Parks (Government of Alberta); Environmental Protection Authority Victoria (Melbourne, Victoria, Australia); Estonian Environmental Research Centre (EERC); Estonian University of Life Sciences, SMEAR Estonia; European Regional Development Fund (project MOBTT42) under the Mobilitas Pluss programme; Finnish Meteorological Institute; Helsinki Region Environmental Services Authority; Haryana Pollution Control Board (HSPCB), IndiaLondon Air Quality Network (LAQN) and the Automatic Urban and Rural Network (AURN) supported by the Department of Environment, Food and Rural Affairs, UK Government; Madrid Municipality; Met Office Integrated Data Archive System (MIDAS); Meteorological Service of Canada; Minist`ere de l’Environnement et de la Lutte contre les changements climatiques (Gouvernement du Qu´ebec); Ministry of Environment and Energy, Greece; Ministry of the Environment (Chile) and National Weather Service (DMC); Moscow State Budgetary Environmental Institution MOSECOMONITORING. Municipal Department of the Environment SMAC, Brazil; Municipality of Madrid public open data service; National institute of environmental research, Korea; National Meteorology and Hydrology Service (SENAMHI), Peru; New York State Department of Environmental Conservation; NSW Department of Planning, Industry and Environment; Ontario Ministry of the Environment, Conservation and Parks, Canada; Public Health Service of Amsterdam (GGD), the Netherlands. Punjab Pollution Control Board (PPCB), India. R´eseau de surveillance de la qualit´e de l’air (RSQA) (Montr´eal); Rosgydromet. Mosecomonitoring, Institute of Atmospheric Physics, Russia; Russian Foundation for Basic Research (project 20–05–00254) SAFAR-IITM-MoES, India; S˜ao Paulo State Environmental Protection Agency, CETESB; Secretaria de Ambiente, DMQ, Ecuador; Secretaría Distrital de Ambiente, Bogot´a, Colombia. Secretaria Municipal de Meio Ambiente Rio de Janeiro; Mexico City Atmospheric Monitoring System (SIMAT); Mexico City Secretariat of Environment, Secretaría del Medio Ambiente (SEDEMA); SLB-analys, Sweden; SMEAR Estonia station and Estonian University of Life Sciences (EULS); SMEAR stations data and Finnish Center of Excellence; South African Weather Service and Department of Environment, Forestry and Fisheries through SAAQIS; Spanish Ministry for the Ecological Transition and the Demographic Challenge (MITECO); University of Helsinki, Finland; University of Tartu, Tahkuse air monitoring station; Weather Station of the Institute of Astronomy, Geophysics and Atmospheric Science of the University of S˜ao Paulo; West Bengal Pollution Control Board (WBPCB).http://www.elsevier.com/locate/envintam2023Geography, Geoinformatics and Meteorolog

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large