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Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke
Get PDFThe blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions. We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis. Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.publishedVersio
New advanced models (NAMs) for risk assessment of bisphenol A alternatives
Get PDFThe safety of bisphenol A (BPA) due to its adverse effects on the immune system has led to an increasing concern and a significant regulatory shift. The European Food Safety Authority (EFSA) proposed a reduction in the tolerable daily intake (TDI) of BPA in food in their 2023 scientific opinion, highlighting the need for stricter regulations compared to their previous assessment in 2015. This regulatory action has spurred the production of BPA alternatives, raising concerns about their safety due to insufficient toxicological data. Addressing this gap is crucial for ensuring human and environmental health. In this project, multiple genotoxicity endpoints were applied for testing of two regulatory relevant BPA alternatives, bisphenol E (BPE) and bisphenol P (BPP), in different human models: 2D HepG2 liver cells, 3D liver spheroids and primary human peripheral blood lymphocytes. DNA strand breaks and oxidised base lesions were evaluated by the enzyme-modified version of the comet assay, while clastogenicity and aneugenicity were analysed by the in vitro micronucleus assay (OECD TG 487, 2016), together with cytotoxicity. Development of new advanced models (NAMs), as 3D spheroids, are essential for next-generation risk assessment (NGRA) in line with the 3R's to replace, reduce or refine animal experiments. In this aspect, validation and standardisation of NAMs are needed to reach regulatory readiness level and development of OECD Test Guidelines. Therefore, a standardisation and pre-validation of the advanced 3D liver spheroid model was performed by using multiple genotoxicity endpoints and by comparing the obtained results with standard genotoxicity models.publishedVersio
FLEXPART version 11: improved accuracy, efficiency, and flexibility
Get PDFNumerical methods and simulation codes are essential for the advancement of our understanding of complex atmospheric processes. As technology and computer hardware continue to evolve, the development of sophisticated code is vital for accurate and efficient simulations. In this paper, we present the recent advancements made in the FLEXible PARTicle dispersion model (FLEXPART), a Lagrangian particle dispersion model, which has been used in a wide range of atmospheric transport studies over the past 3 decades, extending from tracing radionuclides from the Fukushima nuclear disaster, to inverse modelling of greenhouse gases, and to the study of atmospheric moisture cycles. This version of FLEXPART includes notable improvements in accuracy and computational efficiency. (1) By leveraging the native vertical coordinates of European Centre for Medium Range Weather Forecasts (ECMWF) Integrated Forecasting System (IFS) instead of interpolating to terrain-following coordinates, we achieved an improvement in trajectory accuracy, leading to a ∼8 %–10 % reduction in conservation errors for quasi-conservative quantities like potential vorticity. (2) The shape of aerosol particles is now accounted for in the gravitational settling and dry-deposition calculation, increasing the simulation accuracy for non-spherical aerosol particles such as microplastic fibres. (3) Wet deposition has been improved by the introduction of a new below-cloud scheme, by a new cloud identification scheme, and by improving the interpolation of precipitation. (4) Functionality from a separate version of FLEXPART, the FLEXPART CTM (chemical transport model), is implemented, which includes linear chemical reactions. Additionally, the incorporation of Open Multi-Processing parallelisation makes the model better suited for handling large input data. Furthermore, we introduced novel methods for the input and output of particle properties and distributions. Users now have the option to run FLEXPART with more flexible particle input data, providing greater adaptability for specific research scenarios (e.g. effective backward simulations corresponding to satellite retrievals). Finally, a new user manual (https://flexpart.img.univie.ac.at/docs/, last access: 11 September 2024) and restructuring of the source code into modules will serve as a basis for further development
The Troll Observing Network (TONe): plugging observation holes in Dronning Maud Land, Antarctica
Get PDFUnderstanding how Antarctica is changing and how these changes influence the rest of the Earth is fundamental to the future robustness of human society. Strengthening our understanding of these changes and their implications requires dedicated, sustained and coordinated observations of key Antarctic indicators. The Troll Observing Network (TONe), now under development, is Norway’s contribution to the global need for sustained, coordinated, complementary and societally relevant observations from Antarctica. When fully implemented within the coming three years, TONe will be a state-of-the-art, multi-platform, multi-disciplinary observing network in data-sparse Dronning Maud Land. A critical part of the network is a data management system that will ensure broad, free access to all TONe data to the international research community.publishedVersio
Recent advances and current challenges of new approach methodologies in developmental and adult neurotoxicity testing
Get PDFAdult neurotoxicity (ANT) and developmental neurotoxicity (DNT) assessments aim to understand the adverse effects and underlying mechanisms of toxicants on the human nervous system. In recent years, there has been an increasing focus on the so-called new approach methodologies (NAMs). The Organization for Economic Co-operation and Development (OECD), together with European and American regulatory agencies, promote the use of validated alternative test systems, but to date, guidelines for regulatory DNT and ANT assessment rely primarily on classical animal testing. Alternative methods include both non-animal approaches and test systems on non-vertebrates (e.g., nematodes) or non-mammals (e.g., fish). Therefore, this review summarizes the recent advances of NAMs focusing on ANT and DNT and highlights the potential and current critical issues for the full implementation of these methods in the future. The status of the DNT in vitro battery (DNT IVB) is also reviewed as a first step of NAMs for the assessment of neurotoxicity in the regulatory context. Critical issues such as (i) the need for test batteries and method integration (from in silico and in vitro to in vivo alternatives, e.g., zebrafish, C. elegans) requiring interdisciplinarity to manage complexity, (ii) interlaboratory transferability, and (iii) the urgent need for method validation are discussed.publishedVersio
Revealing the significant acceleration of hydrofluorocarbon (HFC) emissions in eastern Asia through long-term atmospheric observations
Get PDFHydrofluorocarbons (HFCs) are powerful anthropogenic greenhouse gases (GHGs) with high global-warming potentials (GWPs). They have been widely used as refrigerants, insulation foam-blowing agents, aerosol propellants, and fire suppression agents. Since the mid-1990s, emissions of HFCs have been increasing rapidly as they are used in many applications to replace ozone-depleting chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs) whose consumption and production have been phased out under the Montreal Protocol (MP). Due to the high GWP of HFCs, the Kigali Amendment to the MP requires the phasedown of production and consumption of HFCs to gradually achieve an 80 %–85 % reduction by 2047, starting in 2019 for non-Article 5 (developed) countries with a 10 % reduction against each defined baseline and later schedules for Article 5 (developing) countries. In this study, we have examined long-term high-precision measurements of atmospheric abundances of five major HFCs (HFC-134a, HFC-143a, HFC-32, HFC-125, and HFC-152a) at Gosan station, Jeju Island, South Korea, from 2008 to 2020. Background abundances of HFCs gradually increased, and the inflow of polluted air masses with elevated abundances from surrounding source regions were detected over the entire period. From these pollution events, we inferred regional and country-specific HFC emission estimates using two independent Lagrangian particle dispersion models and Bayesian inversion frameworks (FLEXPART-FLEXINVERT+ and NAME-InTEM). The spatial distribution of the derived “top-down” (measurement based) emissions for all HFCs shows large fluxes from megacities and industrial areas in the region. Our most important finding is that HFC emissions in eastern China and Japan have sharply increased from 2016 to 2018. The contribution of East Asian HFC emissions to the global total increased from 9 % (2008–2014) to 13 % (2016–2020). In particular, HFC emissions in Japan (Annex I country) rose rapidly from 2016 onward, with accumulated total inferred HFC emissions being ∼ 114 Gg yr−1, which is ∼ 76 Gg yr−1 higher for 2016–2020 than the “bottom-up” (i.e., based on activity data and emission factors) emissions of ∼ 38 Gg yr−1 reported to the United Nations Framework Convention on Climate Change (UNFCCC). This is likely related to the increase in domestic demand in Japan for refrigerants and air-conditioning-system-related products and incomplete accounting. A downward trend of HFC emissions that started in 2019 reflects the effectiveness of the F-gas policy in Japan. Eastern China and South Korea, though not obligated to report to the UNFCCC, voluntarily reported emissions, which also show differences between top-down and bottom-up emission estimates, demonstrating the need for atmospheric measurements, comprehensive data analysis, and accurate reporting for precise emission management. Further, the proportional contribution of each country's CO2-equivalent HFC emissions has changed over time, with HFC-134a decreasing and HFC-125 increasing. This demonstrates the transition in the predominant HFC substances contributing to global warming in each country.publishedVersio
NERVE – an emission model for road traffic. Documentation of revised emission model from road traffic in Norwegian municipalities
No full textNILU og Transportøkonomisk institutt (TØI) har på oppdrag fra Miljødirektoratet videreutviklet modellen NERVE («Norwegian Emissions from Road Vehicle Exhaust») for beregning av klimagassutslipp fra veitrafikken i norske kommuner. NERVE-modellen anvender de mest detaljerte datasettene for bilpark, utslippsfaktorer, trafikk og veier for spesifikke lokale forhold. Datasettene er kombinert i en datastruktur som gjør at resultat kan aggregeres på et lite eller et stort geografisk område. NERVE kan således betegnes som en «bottom-up»-utslippsmodell, fordi den er bygget opp «nedenfra» fra detaljerte datakilder. Denne rapporten presenterer metodikken og antagelsene bak beregningene med NERVE, og sammenligner resultat aggregert på nasjonalt nivå med annen tilgjengelig nasjonal statistikk.NILU and the Institute of Transport Economics (TØI), commissioned by the Norwegian Environment Agency, have further developed the NERVE model (“Norwegian Emissions from Road Vehicle Exhaust”) for calculating greenhouse gas emissions from road traffic in Norwegian municipalities. The NERVE model uses the most detailed datasets for vehicle fleet composition, emission factors, traffic, and roads tailored to specific local conditions. These datasets are combined into a data structure that allows results to be aggregated for small or large geographical areas. NERVE can thus be described as a “bottom-up” emissions model. This report presents the methodology and assumptions behind the calculations with NERVE, and compares results aggregated at the national level with other available national statistics.publishedVersio
New Sewage Treatment Plant at Nordbykollen - Drammen. Dispersion calculations emissions to air
No full textNILU har på oppdrag fra Multiconsult AS gjort spredningsberegninger av utslipp til luft fra fremtidig renseanlegg i Nordbykollen i Drammen, samt pumpestasjon ved Solumstrand. Det er gjort beregninger for tre utslippspunkter ved Nordbykollen, 15 moh., 45 moh. og 85 moh. og det er beregnet grad av fortynning ved ulike naboer. Vurderingen er at ved normale driftsforhold vil plasseringen 15 moh. være tilstrekkelig for å minimere risiko for lukt. Men ved spesielle værforhold som inversjon kan det oppstå situasjoner med stabil luft og dårlig fortynning med økt risiko for følbar lukt hos nærmeste naboer. For pumpestasjonen ved Solumstrand bør det velges en løsning med minimum 10-12 m skorstein og vertikal utgangshastighet 5-6 m/s for å sikre god spredning og fortynning av utslippet.NILU has carried out dispersion calculations of emissions to air from a future sewage treatment plant at Nordbykollen in Drammen, as well as the pumping station at Solumstrand. Calculations have been made for three different emission points at Nordbykollen, 15, 45 and 85 meters above sea level, and the dilution factor at receptor points at various neighbours is calculated. The main conclusion is that under normal operating conditions, the stack located at 15 m will be sufficient to minimize the risk of odour. However, in special meteorological situations such as inversion, characterized by stable air and poor dilution, there is enhanced risk of perceptible odours for the nearest neighbours. For the pumping station at Solumstrand, a minimum stack height of 10-12 m is advised, and a minimum vertical exit velocity of 5-6 m/s should be applied to ensure good dispersion and dilution.publishedVersio
European pollen reanalysis, 1980–2022, for alder, birch, and olive
No full textThe dataset presents a 43 year-long reanalysis of pollen seasons for three major allergenic genera of trees in Europe: alder (Alnus), birch (Betula), and olive (Olea). Driven by the meteorological reanalysis ERA5, the atmospheric composition model SILAM predicted the flowering period and calculated the Europe-wide dispersion pattern of pollen for the years 1980–2022. The model applied an extended 4-dimensional variational data assimilation of in-situ observations of aerobiological networks in 34 European countries to reproduce the inter-annual variability and trends of pollen production and distribution. The control variable of the assimilation procedure was the total pollen release during each flowering season, implemented as an annual correction factor to the mean pollen production. The dataset was designed as an input to studies on climate-induced and anthropogenically driven changes in the European vegetation, biodiversity monitoring, bioaerosol modelling and assessment, as well as, in combination with intra-seasonal observations, for health-related applications.publishedVersio
The FAIRness av ACTRIS Data Centre
Get PDFThe purpose of this report is to document the status and implementation of FAIRness within ACTRIS Data centre as of March 2023, developed over the period January 2019 – March 2023. The report is an extended version of ENVRI-FAIR deliverable D8.4 due March 2023 and available through Zenodo: ENVRI-FAIR D8.4: The FAIRness of ACTRIS | Zenodo, only including the work until autumn 2022. This present report adds more information to the implementation of the FAIR principles by ACTRIS Data Centre over the period January 2019 – March 2023. In addition to D8.4, the present report provides a comprehensive external FAIRness assessment covering the entire period 2019 - 2023, along with an evaluation of the implementation in the years 2022 and the first half of 2023. It's important to note that the project deliverable only encompasses the period from 2019 to 2021.Formålet med denne rapporten er å dokumentere status for implementeringen av FAIRness i ACTRIS Data senter frem til juni 2023, over perioden januar 2019 – mars 2023. Rapporten er en utvidet versjon av ENVRI-FAIR D8.4 som ble levert i mars 2023 og er tilgjengelig via Zenodo: ENVRI-FAIR D8.4: The FAIRness of ACTRIS | Zenodo Den rapporten inkluderer kun arbeidet frem til høsten 2022. Denne rapporten som publiseres her legger til mer informasjon om implementeringen av FAIR-prinsippene av ACTRIS data senter i perioden januar 2019 – juni 2023. Sammenlignet med D8.4 dekker denne rapporten også fullstendig ekstern FAIRness-vurdering av implementeringen siden år 2019 inkludert også implementeringen i år 2022. Prosjektleveransen i Zenodo inkluderer kun året 2019-2021.publishedVersio