| 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. |
- Li, Shuting, et al.
(författare)
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Direct structure determination of vemurafenib polymorphism from compact spherulites using 3D electron diffraction
- 2023
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Ingår i: Communications Chemistry. - : Springer Science and Business Media LLC. - 2399-3669. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The spherulitic morphology is considered to be the most common morphology of crystalline materials and is particularly apparent in melt-crystallized products. Yet, historically, the polycrystalline nature of spherulites has hindered successful crystal structure determination. Here, we report the direct structure determination of a clinical drug, vemurafenib (VMN), in compact spherulite form using 3D electron diffraction (3D ED). VMN has four known polymorphs. We first solved the crystal structures of α-, β-, and γ-VMN from compact spherulites using 3D ED, and the resulting structures were highly consistent with those obtained by single-crystal X-ray diffraction. We then determined the crystal structure of δ-VMN—the least stable polymorph which cannot be cultivated as a single crystal—directly from the compact spherulite sample. We unexpectedly discovered a new polymorph during our studies, denoted as ε-VMN. Single crystals of ε-VMN are extremely thin and not suitable for study by X-ray diffraction. Again, we determined the structure of ε-VMN in a compact spherulite form. This successful structure elucidation of all five VMN polymorphs demonstrates the possibility of directly determining structures from melt-grown compact spherulite samples. Thereby, this discovery will improve the efficiency and broaden the scope of polymorphism research, especially within the field of melt crystallization.
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| 3. |
- 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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| 4. |
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| 5. |
- Zou, Wei, et al.
(författare)
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Minimising efficiency roll-off in high-brightness perovskite light-emitting diodes
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Efficiency roll-off is a major issue for most types of light-emitting diodes (LEDs), and its origins remain controversial. Here we present investigations of the efficiency roll-off in perovskite LEDs based on two-dimensional layered perovskites. By simultaneously measuring electroluminescence and photoluminescence on a working device, supported by transient photoluminescence decay measurements, we conclude that the efficiency roll-off in perovskite LEDs is mainly due to luminescence quenching which is likely caused by non-radiative Auger recombination. This detrimental effect can be suppressed by increasing the width of quantum wells, which can be easily realized in the layered perovskites by tuning the ratio of large and small organic cations in the precursor solution. This approach leads to the realization of a perovskite LED with a record external quantum efficiency of 12.7%, and the efficiency remains to be high, at approximately 10%, under a high current density of 500 mA cm(-2).
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| 6. |
- Duan, Chunhui, et al.
(författare)
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Improving Performance of All-Polymer Solar Cells Through Backbone Engineering of Both Donors and Acceptors
- 2018
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Ingår i: Solar RRL. - : Wiley. - 2367-198X. ; 2:12
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Tidskriftsartikel (refereegranskat)abstract
- All-polymer solar cells (APSCs), composed of semiconducting donor and acceptor polymers, have attracted considerable attention due to their unique advantages compared to polymer-fullerene-based devices in terms of enhanced light absorption and morphological stability. To improve the performance of APSCs, the morphology of the active layer must be optimized. By employing a random copolymerization strategy to control the regularity of the backbone of the donor polymers (PTAZ-TPDx) and acceptor polymers (PNDI-Tx) the morphology can be systematically optimized by tuning the polymer packing and crystallinity. To minimize effects of molecular weight, both donor and acceptor polymers have number-average molecular weights in narrow ranges. Experimental and coarse-grained modeling results disclose that systematic backbone engineering greatly affects the polymer crystallinity and ultimately the phase separation and morphology of the all-polymer blends. Decreasing the backbone regularity of either the donor or the acceptor polymer reduces the local crystallinity of the individual phase in blend films, affording reduced short-circuit current densities and fill factors. This two-dimensional crystallinity optimization strategy locates a PCE maximum at highest crystallinity for both donor and acceptor polymers. Overall, this study demonstrates that proper control of both donor and acceptor polymer crystallinity simultaneously is essential to optimize APSC performance.
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| 7. |
- 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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| 8. |
- Hu, Min, et al.
(författare)
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Suppression of uterine and placental ferroptosis by N-acetylcysteine in a rat model of polycystic ovary syndrome. : Ferroptosis and N-acetylcysteine
- 2021
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Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 27:12
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms that link hyperandrogenism and insulin resistance to the increased miscarriage rate in women with polycystic ovary syndrome (PCOS) remain elusive. Previous studies demonstrate that increased uterine and placental ferroptosis is associated with oxidative stress-induced fetal loss in a pre-clinical PCOS-like rat model. Here, we investigated the efficacy and molecular mechanism of action of the antioxidant N-acetylcysteine (NAC) in reversing gravid uterine and placental ferroptosis in pregnant rats exposed to 5α-dihydrotestosterone (DHT) and insulin. Molecular and histological analyses showed that NAC attenuated DHT and insulin-induced uterine ferroptosis, including dose-dependent increases in anti-ferroptosis gene content. Changes in other molecular factors after NAC treatment were also observed in the placenta exposed to DHT and insulin, such as increased glutathione peroxidase 4 protein level. Further, increased apoptosis inducing factor mitochondria associated 2 mRNA expression was seen in the placenta but not in the uterus. Additionally, NAC was not sufficient to rescue DHT+insulin-induced mitochondria-morphological abnormalities in the uterus, whereas the same treatment partially reversed such abnormalities in the placenta. Finally, we demonstrated that NAC selectively normalized uterine leukemia inhibitory factor, osteopontin/secreted phosphoprotein 1, progesterone receptor, and homeobox A11 mRNA expression and placental estrogen related receptor beta and trophoblast specific protein alpha mRNA expression. Collectively, our data provide insight into how NAC exerts beneficial effects on differentially attenuating gravid uterine and placental ferroptosis in a PCOS-like rat model with fetal loss. These results indicate that exogenous administration of NAC represents a potential therapeutic strategy in the treatment of hyperandrogenism and insulin resistance-induced uterine and placental dysfunction.
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| 9. |
- Lightowler, Molly, et al.
(författare)
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Indomethacin Polymorph δ Revealed To Be Two Plastically Bendable Crystal Forms by 3D Electron Diffraction : Correcting a 47-Year-Old Misunderstanding
- 2022
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 61:7
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Tidskriftsartikel (refereegranskat)abstract
- Indomethacin is a clinically classical non-steroidal anti-inflammatory drug that has been marketed since 1965. The third polymorph, Form δ, was discovered by both melt and solution crystallization in 1974. δ-indomethacin cannot be cultivated as large single crystals suitable for X-ray crystallography and, therefore, its crystal structure has not yet been determined. Here, we report the structure elucidation of δ-indomethacin by 3D electron diffraction and reveal the truth that melt-crystallized and solution-crystallized δ-indomethacin are in fact two polymorphs with different crystal structures. We propose to keep the solution-crystallized polymorph as Form δ and name the melt-crystallized polymorph as Form θ. Intriguingly, both structures display plastic flexibility based on a slippage mechanism, making indomethacin the first drug to have two plastic polymorphs. This discovery and correction of a 47-year-old misunderstanding signify that 3D electron diffraction has become a powerful tool for polymorphic structural studies.
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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. |
- 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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