| 1. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Echelmeier, A., et al.
(författare)
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Segmented flow generator for serial crystallography at the European X-ray free electron laser
- 2020
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.
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| 9. |
- Kirkwood, S., et al.
(författare)
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Polar mesosphere winter echoes by ESRAD, EISCAT and lidar
- 2002
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- The ESRAD 52 MHz MST radar (67° 53 ‘ N, 21 ° 06 ‘ E) has observed thin layers of enhanced radar echoes in the winter mesosphere during several recent solar proton events. The detection of these polar mesosphere winter echoes (PMWE) is generally found to correlates well with low values of λ (the ratio of negative ion density to electron density). However PMWE are found to persist for values of λ up to ~100. Present knowledge of the nature of neutral turbulence in the winter mesosphere suggests that such turbulence cannot generate electron density fluctuations with scale-sizes as short as the 3 m needed to produce radar echoes at 52 MHz. This is particularly true as λ increases to ~100. Joint observations from ESRAD and the EISCAT 224 MHz radar suggest that PMWE is also detectable at 67 cm scale-sizes, further increasing the difficulty in explaining the echoes by neutral turbulence. Joint observations from ESRAD and lidar are also inconsistent with the expected behaviour of turbulence. Together with results concerning the thickness, echo aspect-sensitivity and echo spectral-width of the PMWE, these observation leads to the conclusion that the layers cannot be explained by turbulence alone. A role for charged aerosols in creating PMWE is proposed. The presence of aerosols is supported by the lidar observations.
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| 11. |
- Ayyer, Kartik, et al.
(författare)
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3D diffractive imaging of nanoparticle ensembles using an x-ray laser
- 2021
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Ingår i: Optica. - : Optical Society of America. - 2334-2536. ; 8:1, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- Single particle imaging at x-ray free electron lasers (XFELs) has the potential to determine the structure and dynamics of single biomolecules at room temperature. Two major hurdles have prevented this potential from being reached, namely, the collection of sufficient high-quality diffraction patterns and robust computational purification to overcome structural heterogeneity. We report the breaking of both of these barriers using gold nanoparticle test samples, recording around 10 million diffraction patterns at the European XFEL and structurally and orientationally sorting the patterns to obtain better than 3-nm-resolution 3D reconstructions for each of four samples. With these new developments, integrating advancements in x-ray sources, fast-framing detectors, efficient sample delivery, and data analysis algorithms, we illuminate the path towards sub-nano meter biomolecular imaging. The methods developed here can also be extended to characterize ensembles that are inherently diverse to obtain their full structural landscape. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.
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| 12. |
- Barrington, Sally F, et al.
(författare)
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PET-CT for staging and early response : results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 127:12, s. 1531-1538
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Tidskriftsartikel (refereegranskat)abstract
- International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.
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| 13. |
- Belova, E., et al.
(författare)
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Multi-radar observations of polar mesosphere summer echoes during the PHOCUS campaign on 20-22 July 2011
- 2014
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Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 118, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- During the PHOCUS rocket campaign, on 20-22 July 2011, the observations of polar mesosphere summer echoes (PMSE) were made by three mesosphere-stratosphere-troposphere radars, operating at about 50 MHz. One radar, ESRAD is located at Esrange in Sweden, where the rocket was launched, two other radars, MAARSY and MORRO, are located 250 km north-west and 200 km north of the ESRAD, respectively, on the other side of the Scandinavian mountain ridge. We compared PMSE as measured by these three radars in terms of their strength, spectral width and wave modulation. Time-altitude maps of PMSE strength look very similar for all three radars. Cross-correlations with maximum values 0.5-0.6 were found between the signal powers over the three days of observations for each pair of radars. By using cross-spectrum analysis of PMSE signals, we show that some waves with periods of a few hours were observed by all three radars. Unlike the strengths, simultaneous values of PMSE spectral width, which is related to turbulence, sometimes differ significantly between the radars. For interpretation of the results we suggested that large-scale fields of neutral temperature, ice particles and electron density, which are more or less uniform over 150-250 km horizontal extent were 'modulated' by waves and smaller patches of turbulence.
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| 14. |
- Belova, E., et al.
(författare)
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The dynamical background of polar mesosphere winter echoes from simultaneous EISCAT and ESRAD observations
- 2005
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Ingår i: Annales Geophysicae. - : European Geosciences Union. - 0992-7689 .- 1432-0576. ; 23:4, s. 1239-1247
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Tidskriftsartikel (refereegranskat)abstract
- On 30 October 2004 during a strong solar proton event, layers of enhanced backscatter from altitudes between 55 and 75km have been observed by both ESRAD (52MHz) and the EISCAT VHF (224MHz) radars. These echoes have earlier been termed Polar Mesosphere Winter Echoes, PMWE. After considering the morphology of the layers and their relation to observed atmospheric waves, we conclude that the radars have likely seen the same phenomenon even though the radars' scattering volumes are located about 220km apart and that the most long-lasting layer is likely associated with wind-shear in an inertio-gravity wave. An ion-chemistry model is used to determine parameters necessary to relate wind-shear induced turbulent energy dissipation rates to radar backscatter. The model is verified by comparison with electron density profiles measured by the EISCAT VHF radar. Observed radar signal strengths are found to be 2-3 orders of magnitude stronger than the maximum which can be expected from neutral turbulence alone, assuming that previously published results relating radar signal scatter to turbulence parameters, and turbulence parameters to wind shear, are correct. The possibility remains that some additional or alternative mechanism may be involved in producing PMWE, such as layers of charged dust/smoke particles or large cluster ions.
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| 15. |
- Costello, David M., et al.
(författare)
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Global patterns and controls of nutrient immobilization on decomposing cellulose in riverine ecosystems
- 2022
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Ingår i: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:3
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Tidskriftsartikel (refereegranskat)abstract
- Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter.
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| 18. |
- Lossow, Stefan, et al.
(författare)
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Middle atmospheric water vapour and dynamics in the vicinity of the polar vortex during the Hygrosonde-2 campaign
- 2009
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 9, s. 4407-4417
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Tidskriftsartikel (refereegranskat)abstract
- The Hygrosonde-2 campaign took place on 16 December 2001 at Esrange/Sweden (68° N, 21° E) with the aim to investigate the small scale distribution of water vapour in the middle atmosphere in the vicinity of the Arctic polar vortex. In situ balloon and rocket-borne measurements of water vapour were performed by means of OH fluorescence hygrometry. The combined measurements yielded a high resolution water vapour profile up to an altitude of 75 km. Using the characteristic of water vapour being a dynamical tracer it was possible to directly relate the water vapour data to the location of the polar vortex edge, which separates air masses of different character inside and outside the polar vortex. The measurements probed extra-vortex air in the altitude range between 45 km and 60 km and vortex air elsewhere. Transitions between vortex and extra-vortex usually coincided with wind shears caused by gravity waves which advect air masses with different water vapour volume mixing ratios. From the combination of the results from the Hygrosonde-2 campaign and the first flight of the optical hygrometer in 1994 (Hygrosonde-1) a clear picture of the characteristic water vapour distribution inside and outside the polar vortex can be drawn. Systematic differences in the water vapour concentration between the inside and outside of the polar vortex can be observed all the way up into the mesosphere. It is also evident that in situ measurements with high spatial resolution are needed to fully account for the small-scale exchange processes in the polar winter middle atmosphere.
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| 19. |
- Metra, Marco, et al.
(författare)
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y Effects of Serelaxin in Patients with Acute Heart Failure
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:8, s. 716-726
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.) In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
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| 20. |
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| 21. |
- Sobolev, Egor, et al.
(författare)
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Megahertz single-particle imaging at the European XFEL
- 2020
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Ingår i: Communications Physics. - : Springer Science and Business Media LLC. - 2399-3650. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of high repetition-rate X-ray free-electron lasers (XFELs) powered by superconducting accelerator technology enables the measurement of significantly more experimental data per day than was previously possible. The European XFEL is expected to provide 27,000 pulses per second, over two orders of magnitude more than any other XFEL. The increased pulse rate is a key enabling factor for single-particle X-ray diffractive imaging, which relies on averaging the weak diffraction signal from single biological particles. Taking full advantage of this new capability requires that all experimental steps, from sample preparation and delivery to the acquisition of diffraction patterns, are compatible with the increased pulse repetition rate. Here, we show that single-particle imaging can be performed using X-ray pulses at megahertz repetition rates. The results obtained pave the way towards exploiting high repetition-rate X-ray free-electron lasers for single-particle imaging at their full repetition rate.
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| 22. |
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| 23. |
- Tiegs, Scott D., et al.
(författare)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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Ingår i: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 24. |
- Zhuang, Yulong, et al.
(författare)
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Unsupervised learning approaches to characterizing heterogeneous samples using X-ray single-particle imaging
- 2022
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Ingår i: IUCrJ. - : International Union of Crystallography (IUCr). - 2052-2525. ; 9, s. 204-214
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Tidskriftsartikel (refereegranskat)abstract
- One of the outstanding analytical problems in X-ray single-particle imaging (SPI) is the classification of structural heterogeneity, which is especially difficult given the low signal-to-noise ratios of individual patterns and the fact that even identical objects can yield patterns that vary greatly when orientation is taken into consideration. Proposed here are two methods which explicitly account for this orientation-induced variation and can robustly determine the structural landscape of a sample ensemble. The first, termed common-line principal component analysis (PCA), provides a rough classification which is essentially parameter free and can be run automatically on any SPI dataset. The second method, utilizing variation auto-encoders (VAEs), can generate 3D structures of the objects at any point in the structural landscape. Both these methods are implemented in combination with the noise-tolerant expand-maximizecompress (EMC) algorithm and its utility is demonstrated by applying it to an experimental dataset from gold nanoparticles with only a few thousand photons per pattern. Both discrete structural classes and continuous deformations are recovered. These developments diverge from previous approaches of extracting reproducible subsets of patterns from a dataset and open up the possibility of moving beyond the study of homogeneous sample sets to addressing open questions on topics such as nanocrystal growth and dynamics, as well as phase transitions which have not been externally triggered.
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