| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Wang, Nana, et al.
(författare)
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Perovskite light-emitting diodes based on solution-processed self-organized multiple quantum wells
- 2016
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Ingår i: Nature Photonics. - : NATURE PUBLISHING GROUP. - 1749-4885 .- 1749-4893. ; 10:11, s. 699-
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Tidskriftsartikel (refereegranskat)abstract
- Organometal halide perovskites can be processed from solutions at low temperatures to form crystalline direct-bandgap semiconductors with promising optoelectronic properties(1-5). However, the efficiency of their electroluminescence is limited by non-radiative recombination, which is associated with defects and leakage current due to incomplete surface coverage(6-9). Here we demonstrate a solution-processed perovskite light-emitting diode (LED) based on self-organized multiple quantum wells (MQWs) with excellent film morphologies. The MQW-based LED exhibits a very high external quantum efficiency of up to 11.7%, good stability and exceptional highpower performance with an energy conversion efficiency of 5.5% at a current density of 100 mA cm(-2). This outstanding performance arises because the lower bandgap regions that generate electroluminescence are effectively confined by perovskite MQWs with higher energy gaps, resulting in very efficient radiative decay. Surprisingly, there is no evidence that the large interfacial areas between different bandgap regions cause luminescence quenching.
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| 3. |
- Cheung, Ho-Nam, et al.
(författare)
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Assessing the influence of sea surface temperature and arctic sea ice cover on the uncertainty in the boreal winter future climate projections
- 2022
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 59:1-2, s. 433-454
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the uncertainty (i.e., inter-model spread) in future projections of the boreal winter climate, based on the forced response of ten models from the CMIP5 following the RCP8.5 scenario. The uncertainty in the forced response of sea level pressure (SLP) is large in the North Pacific, the North Atlantic, and the Arctic. A major part of these uncertainties (31%) is marked by a pattern with a center in the northeastern Pacific and a dipole over the northeastern Atlantic that we label as the Pacific–Atlantic SLP uncertainty pattern (PA∆SLP). The PA∆SLP is associated with distinct global sea surface temperature (SST) and Arctic sea ice cover (SIC) perturbation patterns. To better understand the nature of the PA∆SLP, these SST and SIC perturbation patterns are prescribed in experiments with two atmospheric models (AGCMs): CAM4 and IFS. The AGCM responses suggest that the SST uncertainty contributes to the North Pacific SLP uncertainty in CMIP5 models, through tropical–midlatitude interactions and a forced Rossby wavetrain. The North Atlantic SLP uncertainty in CMIP5 models is better explained by the combined effect of SST and SIC uncertainties, partly related to a Rossby wavetrain from the Pacific and air-sea interaction over the North Atlantic. Major discrepancies between the CMIP5 and AGCM forced responses over northern high-latitudes and continental regions are indicative of uncertainties arising from the AGCMs. We analyze the possible dynamic mechanisms of these responses, and discuss the limitations of this work.
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| 4. |
- Döscher, Ralf, et al.
(författare)
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The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6
- 2022
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 15:7, s. 2973-3020
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Tidskriftsartikel (refereegranskat)abstract
- The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.
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| 5. |
- Fan, Zhiwen, et al.
(författare)
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Porous Ionic Network/CNT Composite Separator as a Polysulfide Snaring Shield for High Performance Lithium–Sulfur Battery
- 2023
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Ingår i: Macromolecular rapid communications. - 1022-1336 .- 1521-3927. ; 44:24
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Tidskriftsartikel (refereegranskat)abstract
- Lithium–sulfur (Li–S) battery features a high theoretical energy density, but the shuttle of soluble polysulfides between the two electrodes often results in a rapid capacity decay. Herein, a straightforward electrostatic adsorption strategy based on a cross-linked polyimidazolium separator as a snaring shield of polysulfides is reported, which suppresses the undesirable migration of polysulfides to the anode. The porous ionic network (PIN)-modified carbon nanotubes (CNTs) are successfully prepared and coated onto a commercial porous polypropylene membrane in a vacuum-filtration step. The favorable affinity of the imidazolium ring toward polysulfide via the polar interaction and the electrostatic effect of ions mitigates the undesirable shuttle of polysulfides in the electrolyte, improving the Li─S battery in terms of rate performance and cycling life. Compared to the reference PIN-free CNT-coated separator, the PIN/CNT-coated one has an increased initial capacity of 1.3 folds (up to 1394.8 mAh g−1 for PIN/CNT/PP-3) at 0.1 C.
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| 6. |
- Helsen, Michiel M., et al.
(författare)
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On the importance of the albedo parameterization for the mass balance of the Greenland ice sheet in EC-Earth
- 2017
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 11:4, s. 1949-1965
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Tidskriftsartikel (refereegranskat)abstract
- The albedo of the surface of ice sheets changes as a function of time due to the effects of deposition of new snow, ageing of dry snow, bare ice exposure, melting and run-off. Currently, the calculation of the albedo of ice sheets is highly parameterized within the earth system model EC-Earth by taking a constant value for areas with thick perennial snow cover. This is an important reason why the surface mass balance (SMB) of the Greenland ice sheet (GrIS) is poorly resolved in the model. The purpose of this study is to improve the SMB forcing of the GrIS by evaluating different parameter settings within a snow albedo scheme. By allowing ice-sheet albedo to vary as a function of wet and dry conditions, the spatial distribution of albedo and melt rate improves. Nevertheless, the spatial distribution of SMB in EC-Earth is not significantly improved. As a reason for this, we identify omissions in the current snow albedo scheme, such as separate treatment of snow and ice and the effect of refreezing. The resulting SMB is downscaled from the lower-resolution global climate model topography to the higher-resolution ice-sheet topography of the GrIS, such that the influence of these different SMB climatologies on the long-term evolution of the GrIS is tested by ice-sheet model simulations. From these ice-sheet simulations we conclude that an albedo scheme with a short response time of decaying albedo during wet conditions performs best with respect to long-term simulated ice-sheet volume. This results in an optimized albedo parameterization that can be used in future EC-Earth simulations with an interactive ice-sheet component.
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| 7. |
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| 8. |
- Lightowler, Molly, et al.
(författare)
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Phase identification and discovery of an elusive polymorph of drug-polymer inclusion complex using automated 3D electron diffraction
- 2024
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Ingår i: Angewandte Chemie International Edition. - 1433-7851 .- 1521-3773. ; 63:16
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Tidskriftsartikel (refereegranskat)abstract
- 3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low-dose and low-bias 3D ED protocol has been implemented to identify six phases from a multiple-phase melt-crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low-dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell parameters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF-PEG IC-I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF-PEG IC-II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF-PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam-sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.
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| 9. |
- Meccia, Virna L., et al.
(författare)
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Internal multi-centennial variability of the Atlantic Meridional Overturning Circulation simulated by EC-Earth3
- 2023
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 60:11-12, s. 3695-3712
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Tidskriftsartikel (refereegranskat)abstract
- We report a multi-centennial oscillation of the Atlantic Meridional Overturning Circulation (AMOC) simulated by the EC-Earth3 climate model under the pre-industrial climate. This oscillation has an amplitude of ~ 6 Sv and a period of ~ 150 years and significantly impacts the atmosphere. We find that it is a self-sustained low-frequency internal variability, driven by the accumulation of salinity anomalies in the Arctic and their release into the North Atlantic, affecting the water column stability and the deep convection. Sea ice plays a major role in creating the salinity anomaly in the Arctic, while the anomalous Arctic oceanic circulation, which drives the exchange of liquid freshwater between the Arctic and the open ocean, is the main responsible for its southward propagation. Interestingly, EC-Earth3 simulations with increased greenhouse concentrations, and therefore under a warmer climate, do not exhibit these strong AMOC fluctuations. We hypothesize that in a quasi-equilibrium climate with a global air surface temperature 4.5° higher than the pre-industrial period, the low amount of sea ice in the high latitudes of the North Atlantic is no longer able to trigger the mechanism.
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| 10. |
- Rugenstein, Maria, et al.
(författare)
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Equilibrium Climate Sensitivity Estimated by Equilibrating Climate Models
- 2020
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 47:4
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Tidskriftsartikel (refereegranskat)abstract
- The methods to quantify equilibrium climate sensitivity are still debated. We collect millennial-length simulations of coupled climate models and show that the global mean equilibrium warming is higher than those obtained using extrapolation methods from shorter simulations. Specifically, 27 simulations with 15 climate models forced with a range of CO2 concentrations show a median 17% larger equilibrium warming than estimated from the first 150 years of the simulations. The spatial patterns of radiative feedbacks change continuously, in most regions reducing their tendency to stabilizing the climate. In the equatorial Pacific, however, feedbacks become more stabilizing with time. The global feedback evolution is initially dominated by the tropics, with eventual substantial contributions from the mid-latitudes. Time-dependent feedbacks underscore the need of a measure of climate sensitivity that accounts for the degree of equilibration, so that models, observations, and paleo proxies can be adequately compared and aggregated to estimate future warming.
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| 11. |
- Rugenstein, Maria, et al.
(författare)
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LongRunMIP : Motivation and Design for a Large Collection of Millennial-Length AOGCM Simulations
- 2019
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 100:12, s. 2551-2570
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Tidskriftsartikel (refereegranskat)abstract
- We present a model intercomparison project, LongRunMIP, the first collection of millennial-length (1,000+ years) simulations of complex coupled climate models with a representation of ocean, atmosphere, sea ice, and land surface, and their interactions. Standard model simulations are generally only a few hundred years long. However, modeling the long-term equilibration in response to radiative forcing perturbation is important for understanding many climate phenomena, such as the evolution of ocean circulation, time- and temperature-dependent feedbacks, and the differentiation of forced signal and internal variability. The aim of LongRunMIP is to facilitate research into these questions by serving as an archive for simulations that capture as much of this equilibration as possible. The only requirement to participate in LongRunMIP is to contribute a simulation with elevated, constant CO2 forcing that lasts at least 1,000 years. LongRunMIP is an MIP of opportunity in that the simulations were mostly performed prior to the conception of the archive without an agreed-upon set of experiments. For most models, the archive contains a preindustrial control simulation and simulations with an idealized (typically abrupt) CO2 forcing. We collect 2D surface and top-of-atmosphere fields and 3D ocean temperature and salinity fields. Here, we document the collection of simulations and discuss initial results, including the evolution of surface and deep ocean temperature and cloud radiative effects. As of October 2019, the collection includes 50 simulations of 15 models by 10 modeling centers. The data of LongRunMIP are publicly available. We encourage submissions of more simulations in the future.
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| 12. |
- Sterl, Andreas, et al.
(författare)
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A look at the ocean in the EC-Earth climate model
- 2012
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 39:11, s. 2631-2657
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Tidskriftsartikel (refereegranskat)abstract
- EC-Earth is a newly developed global climate system model. Its core components are the Integrated Forecast System (IFS) of the European Centre for Medium Range Weather Forecasts (ECMWF) as the atmosphere component and the Nucleus for European Modelling of the Ocean (NEMO) developed by Institute Pierre Simon Laplace (IPSL) as the ocean component. Both components are used with a horizontal resolution of roughly one degree. In this paper we describe the performance of NEMO in the coupled system by comparing model output with ocean observations. We concentrate on the surface ocean and mass transports. It appears that in general the model has a cold and fresh bias, but a much too warm Southern Ocean. While sea ice concentration and extent have realistic values, the ice tends to be too thick along the Siberian coast. Transports through important straits have realistic values, but generally are at the lower end of the range of observational estimates. Exceptions are very narrow straits (Gibraltar, Bering) which are too wide due to the limited resolution. Consequently the modelled transports through them are too high. The strength of the Atlantic meridional overturning circulation is also at the lower end of observational estimates. The interannual variability of key variables and correlations between them are realistic in size and pattern. This is especially true for the variability of surface temperature in the tropical Pacific (El Nio). Overall the ocean component of EC-Earth performs well and helps making EC-Earth a reliable climate model.
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| 13. |
- Tian, Tian, et al.
(författare)
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Benefits of sea ice initialization for the interannual-to-decadal climate prediction skill in the Arctic in EC-Earth3
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:7, s. 4283-4305
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Tidskriftsartikel (refereegranskat)abstract
- A substantial part of Arctic climate predictability at interannual timescales stems from the knowledge of the initial sea ice conditions. Among all sea ice properties, its volume, which is a product of sea ice concentration (SIC) and thickness (SIT), is the most responsive parameter to climate change. However, the majority of climate prediction systems are only assimilating the observed SIC due to lack of long-term reliable global observation of SIT. In this study, the EC-Earth3 Climate Prediction System with anomaly initialization to ocean, SIC and SIT states is developed. In order to evaluate the regional benefits of specific initialized variables, three sets of retrospective ensemble prediction experiments are performed with different initialization strategies: ocean only; ocean plus SIC; and ocean plus SIC and SIT initialization. In the Atlantic Arctic, the Greenland–Iceland–Norway (GIN) and Barents seas are the two most skilful regions in SIC prediction for up to 5–6 lead years with ocean initialization; there are re-emerging skills for SIC in the Barents and Kara seas in lead years 7–9 coinciding with improved skills of sea surface temperature (SST), reflecting the impact of SIC initialization on ocean–atmosphere interactions for interannual-to-decadal timescales. For the year 2–9 average, the region with significant skill for SIT is confined to the central Arctic Ocean, covered by multi-year sea ice (CAO-MYI). Winter preconditioning with SIT initialization increases the skill for September SIC in the eastern Arctic (e.g. Kara, Laptev and East Siberian seas) and in turn improve the skill of air surface temperature locally and further expanded over land. SIT initialization outperforms the other initialization methods in improving SIT prediction in the Pacific Arctic (e.g. East Siberian and Beaufort seas) in the first few lead years. Our results suggest that as the climate warming continues and the central Arctic Ocean might become seasonal ice free in the future, the controlling mechanism for decadal predictability may thus shift from sea ice volume to ocean-driven processes.
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| 14. |
- Tilmes, Simone, et al.
(författare)
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The hydrological impact of geoengineering in the Geoengineering Model Intercomparison Project (GeoMIP)
- 2013
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Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-897X. ; 118:19, s. 11036-11058
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Tidskriftsartikel (refereegranskat)abstract
- The hydrological impact of enhancing Earth's albedo by solar radiation management is investigated using simulations from 12 Earth System models contributing to the Geoengineering Model Intercomparison Project (GeoMIP). We contrast an idealized experiment, G1, where the global mean radiative forcing is kept at preindustrial conditions by reducing insolation while the CO2 concentration is quadrupled to a 4×CO2 experiment. The reduction of evapotranspiration over land with instantaneously increasing CO2 concentrations in both experiments largely contributes to an initial reduction in evaporation. A warming surface associated with the transient adjustment in 4×CO2 generates an increase of global precipitation by around 6.9% with large zonal and regional changes in both directions, including a precipitation increase of 10% over Asia and a reduction of 7% for the North American summer monsoon. Reduced global evaporation persists in G1 with temperatures close to preindustrial conditions. Global precipitation is reduced by around 4.5%, and significant reductions occur over monsoonal land regions: East Asia (6%), South Africa (5%), North America (7%), and South America (6%). The general precipitation performance in models is discussed in comparison to observations. In contrast to the 4×CO2 experiment, where the frequency of months with heavy precipitation intensity is increased by over 50% in comparison to the control, a reduction of up to 20% is simulated in G1. These changes in precipitation in both total amount and frequency of extremes point to a considerable weakening of the hydrological cycle in a geoengineered world.
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| 15. |
- Van Noije, Twan, et al.
(författare)
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EC-Earth3-AerChem : A global climate model with interactive aerosols and atmospheric chemistry participating in CMIP6
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:9, s. 5637-5668
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the global climate model EC-Earth3-AerChem, one of the members of the EC-Earth3 family of models participating in the Coupled Model Intercomparison Project Phase 6 (CMIP6). EC-Earth3-AerChem has interactive aerosols and atmospheric chemistry and contributes to the Aerosols and Chemistry Model Intercomparison Project (AerChemMIP). In this paper, we give an overview of the model, describe in detail how it differs from the other EC-Earth3 configurations, and outline the new features compared with the previously documented version of the model (EC-Earth 2.4). We explain how the model was tuned and spun up under preindustrial conditions and characterize the model's general performance on the basis of a selection of coupled simulations conducted for CMIP6. The net energy imbalance at the top of the atmosphere in the preindustrial control simulation is on average -0.09 W m-2 with a standard deviation due to interannual variability of 0.25 W m-2, showing no significant drift. The global surface air temperature in the simulation is on average 14.08 ∼ C with an interannual standard deviation of 0.17 ∼ C, exhibiting a small drift of 0.015 ± 0.005 ∼ C per century. The model's effective equilibrium climate sensitivity is estimated at 3.9 ∼ C, and its transient climate response is estimated at 2.1 ∼ C. The CMIP6 historical simulation displays spurious interdecadal variability in Northern Hemisphere temperatures, resulting in a large spread across ensemble members and a tendency to underestimate observed annual surface temperature anomalies from the early 20th century onwards. The observed warming of the Southern Hemisphere is well reproduced by the model. Compared with the ECMWF (European Centre for Medium-Range Weather Forecasts) Reanalysis version 5 (ERA5), the surface air temperature climatology for 1995-2014 has an average bias of -0.86 ± 0.05 ∼ C with a standard deviation across ensemble members of 0.35 ∼ C in the Northern Hemisphere and 1.29 ± 0.02 ∼ C with a corresponding standard deviation of 0.05 ∼ C in the Southern Hemisphere. The Southern Hemisphere warm bias is largely caused by errors in shortwave cloud radiative effects over the Southern Ocean, a deficiency of many climate models. Changes in the emissions of near-term climate forcers (NTCFs) have significant effects on the global climate from the second half of the 20th century onwards. For the SSP3-7.0 Shared Socioeconomic Pathway, the model gives a global warming at the end of the 21st century (2091-2100) of 4.9 ∼ C above the preindustrial mean. A 0.5 ∼ C stronger warming is obtained for the AerChemMIP scenario with reduced emissions of NTCFs. With concurrent reductions of future methane concentrations, the warming is projected to be reduced by 0.5 ∼ C.
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| 16. |
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| 17. |
- Yang, Shuting, et al.
(författare)
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Mechanical sensitivity changes in pericranial muscles after local anesthesia and experimentally induced pain in the temporalis tendon : Implications for headache and facial pain
- 2022
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Ingår i: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 42:11-12, s. 1127-1137
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess changes in mechanical sensitivity of the pericranial muscles in healthy individuals after a local anesthetic block of the temporalis tendon. In addition, to assess, if experimentally induced temporalis tendon pain, can lead to an increase in mechanical sensitivity of the pericranial muscles and reports of headache.METHODS: 40 healthy participants were recruited for this randomized, double-blinded, controlled experiment, and were randomly injected with mepivacaine and isotonic saline into the dominant-side temporalis tendon in two different sessions, and either nerve growth factor (n = 20) or isotonic saline (n = 20) in a third session. Mechanical sensitivity was assessed in the temporalis, masseter, and trapezius muscles as well as in the temporalis tendon, on the dominant side, before and 10 minutes after each injection, and in a fourth session two days after the third session. Pain drawings and headache diaries were kept for 30 days after the final session to register any developing pain or headache.RESULTS: Mepivacaine injection into the temporalis tendon caused a significant decrease in mechanical sensitivity in the temporal tendon (-54.5%) and the masseter (-15.4%) muscle (P < 0.05) but not the temporalis (-12.1%) and trapezius muscles (-12.7%) (P > 0.05). Nerve growth factor injection into the temporalis tendon caused a significant increase in mechanical sensitivity in the tendon (+15.4%) and masseter muscle (+14.4%) (P < 0.05) but not the temporalis (+2.8%) or trapezius muscles (+3.1%) (P > 0.05). A significant increase was found for headache frequency in the first seven days (P < 0.05) after nerve growth factor injection compared to after isotonic saline injection, but not intensity (P > 0.05).CONCLUSION: These findings suggest that the therapeutic effect of temporalis tendon anesthetic injections on facial pain and headaches are most likely not only due to a direct effect of the local anesthetic on the temporalis tendon but rather to a more generalized block of the nerves in the area. In addition, the temporal tendon may contribute to the pathophysiological processes of headache.
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| 18. |
- Zhang, Qiong, et al.
(författare)
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Simulating the mid-Holocene, last interglacial and mid-Pliocene climate with EC-Earth3-LR
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:2, s. 1147-1169
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Tidskriftsartikel (refereegranskat)abstract
- As global warming is proceeding due to rising greenhouse gas concentrations, the Earth system moves towards climate states that challenge adaptation. Past Earth system states are offering possible modelling systems for the global warming of the coming decades. These include the climate of the mid-Pliocene (similar to 3 Ma), the last interglacial (similar to 129-116 ka) and the mid-Holocene (similar to 6 ka). The simulations for these past warm periods are the key experiments in the Paleoclimate Model Intercomparison Project (PMIP) phase 4, contributing to phase 6 of the Coupled Model Intercomparison Project (CMIP6). Paleoclimate modelling has long been regarded as a robust out-of-sample test bed of the climate models used to project future climate changes. Here, we document the model setup for PMIP4 experiments with EC-Earth3-LR and present the large-scale features from the simulations for the mid-Holocene, the last interglacial and the mid-Pliocene. Using the pre-industrial climate as a reference state, we show global temperature changes, large-scale Hadley circulation and Walker circulation, polar warming, global monsoons and the climate variability modes - El Nino-Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO). EC-Earth3-LR simulates reasonable climate responses during past warm periods, as shown in the other PMIP4-CMIP6 model ensemble. The systematic comparison of these climate changes in past three warm periods in an individual model demonstrates the model's ability to capture the climate response under different climate forcings, providing potential implications for confidence in future projections with the EC-Earth model.
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| 19. |
- Zhang, Yuehui, et al.
(författare)
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Increased uterine androgen receptor protein abundance results in implantation and mitochondrial defects in pregnant rats with hyperandrogenism and insulin resistance. : Deciphering the role of uterine AR in PCOS during early pregnancy
- 2021
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Ingår i: Journal of molecular medicine (Berlin, Germany). - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 99, s. 1427-1446
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we show that during normal rat pregnancy, there is a gestational stage-dependent decrease in androgen receptor (AR) abundance in the gravid uterus and that this is correlated with the differential expression of endometrial receptivity and decidualization genes during early and mid-gestation. In contrast, exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) or DHT alone significantly increased AR protein levels in the uterus in association with the aberrant expression of endometrial receptivity and decidualization genes, as well as disrupted implantation. Next, we assessed the functional relevance of the androgen-AR axis in the uterus for reproductive outcomes by treating normal pregnant rats and pregnant rats exposed to DHT and INS with the anti-androgen flutamide. We found that AR blockage using flutamide largely attenuated the DHT and INS-induced maternal endocrine, metabolic, and fertility impairments in pregnant rats in association with suppressed induction of uterine AR protein abundance and androgen-regulated response protein and normalized expression of several endometrial receptivity and decidualization genes. Further, blockade of AR normalized the expression of the mitochondrial biogenesis marker Nrf1 and the mitochondrial functional proteins Complexes I and II, VDAC, and PHB1. However, flutamide treatment did not rescue the compromised mitochondrial structure resulting from co-exposure to DHT and INS. These results demonstrate that functional AR protein is an important factor for gravid uterine function. Impairments in the uterine androgen-AR axis are accompanied by decreased endometrial receptivity, decidualization, and mitochondrial dysfunction, which might contribute to abnormal implantation in pregnant PCOS patients with compromised pregnancy outcomes and subfertility. KEY MESSAGES: The proper regulation of uterine androgen receptor (AR) contributes to a normal pregnancy process, whereas the aberrant regulation of uterine AR might be linked to polycystic ovary syndrome (PCOS)-induced pregnancy-related complications. In the current study, we found that during normal rat pregnancy there is a stage-dependent decrease in AR abundance in the gravid uterus and that this is correlated with the differential expression of the endometrial receptivity and decidualization genes Spp1, Prl, Igfbp1, and Hbegf. Pregnant rats exposed to 5α-dihydrotestosterone (DHT) and insulin (INS) or to DHT alone show elevated uterine AR protein abundance and implantation failure related to the aberrant expression of genes involved in endometrial receptivity and decidualization in early to mid-gestation. Treatment with the anti-androgen flutamide, starting from pre-implantation, effectively prevents DHT + INS-induced defects in endometrial receptivity and decidualization gene expression, restores uterine mitochondrial homeostasis, and increases the pregnancy rate and the numbers of viable fetuses. This study adds to our understanding of the mechanisms underlying poor pregnancy outcomes in PCOS patients and the possible therapeutic use of anti-androgens, including flutamide, after spontaneous conception.
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