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1.
  • Pedersoli, E., et al. (författare)
  • Mesoscale morphology of airborne core-shell nanoparticle clusters : x-ray laser coherent diffraction imaging
  • 2013
  • Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16 SI, s. 164033-
  • Tidskriftsartikel (refereegranskat)abstract
    • Unraveling the complex morphology of functional materials like core-shell nanoparticles and its evolution in different environments is still a challenge. Only recently has the single-particle coherent diffraction imaging (CDI), enabled by the ultrabright femtosecond free-electron laser pulses, provided breakthroughs in understanding mesoscopic morphology of nanoparticulate matter. Here, we report the first CDI results for Co@SiO2 core-shell nanoparticles randomly clustered in large airborne aggregates, obtained using the x-ray free-electron laser at the Linac Coherent Light Source. Our experimental results compare favourably with simulated diffraction patterns for clustered Co@SiO2 nanoparticles with similar to 10 nm core diameter and similar to 30 nm shell outer diameter, which confirms the ability to resolve the mesoscale morphology of complex metastable structures. The findings in this first morphological study of core-shell nanomaterials are a solid base for future time-resolved studies of dynamic phenomena in complex nanoparticulate matter using x-ray lasers.
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3.
  • Loh, N. D., et al. (författare)
  • Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7404, s. 513-517
  • Tidskriftsartikel (refereegranskat)abstract
    • The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology(1) to climate science(2), yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate(3); visible light scattering provides insufficient resolution(4); and X-ray synchrotron studies have been limited to ensembles of particles(5). Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source(6) free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins(7), vibrational energy transfer by the hydrodynamic interaction of amino acids(8), and large-scale production of nanoscale structures by flame synthesis(9).
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4.
  • Duane Loh, N., et al. (författare)
  • Profiling structured beams using injected aerosols
  • 2012
  • Ingår i: Proceedings of SPIE. - : SPIE. - 9780819492210 ; , s. 850403-
  • Konferensbidrag (refereegranskat)abstract
    • Profiling structured beams produced by X-ray free-electron lasers (FELs) is crucial to both maximizing signal intensity for weakly scattering targets and interpreting their scattering patterns. Earlier ablative imprint studies describe how to infer the X-ray beam profile from the damage that an attenuated beam inflicts on a substrate. However, the beams in-situ profile is not directly accessible with imprint studies because the damage profile could be different from the actual beam profile. On the other hand, although a Shack-Hartmann sensor is capable of in-situ profiling, its lenses may be quickly damaged at the intense focus of hard X-ray FEL beams. We describe a new approach that probes the in-situ morphology of the intense FEL focus. By studying the translations in diffraction patterns from an ensemble of randomly injected sub-micron latex spheres, we were able to determine the non-Gaussian nature of the intense FEL beam at the Linac Coherent Light Source (SLAC National Laboratory) near the FEL focus. We discuss an experimental application of such a beam-profiling technique, and the limitations we need to overcome before it can be widely applied.
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5.
  • Charette, M. A., et al. (författare)
  • The Transpolar Drift as a Source of Riverine and Shelf-Derived Trace Elements to the Central Arctic Ocean
  • 2020
  • Ingår i: Journal of Geophysical Research-Oceans. - : American Geophysical Union (AGU). - 2169-9275 .- 2169-9291. ; 125:5
  • Tidskriftsartikel (refereegranskat)abstract
    • A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river-influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high-resolution pan-Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and similar to 25-50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle-reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the open ocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 +/- 0.4 Sv (10(6) m(3)s(-1)). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologic cycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean. Plain Language Summary A major feature of the Arctic Ocean circulation is the Transpolar Drift (TPD), a surface current that carries ice and continental shelf-derived materials from Siberia across the North Pole to the North Atlantic Ocean. In 2015, an international team of oceanographers conducted a survey of trace elements in the Arctic Ocean, traversing the TPD. Near the North Pole, they observed much higher concentrations of trace elements in surface waters than in regions on either side of the current. These trace elements originated from land, and their journey across the Arctic Ocean is made possible by chemical reactions with dissolved organic matter that originates mainly in Arctic rivers. This study reveals the importance of rivers and shelf processes combined with strong ocean currents in supplying trace elements to the central Arctic Ocean and onward to the Atlantic. These trace element inputs are expected to increase as a result of permafrost thawing and increased river runoff in the Arctic, which is warming at a rate much faster than anywhere else on Earth. Since many of the trace elements are essential building blocks for ocean life, these processes could lead to significant changes in the marine ecosystems and fisheries of the Arctic Ocean.
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6.
  • Charette, M, et al. (författare)
  • The Transpolar Drift as a Source of Riverine and Shelf‐Derived Trace Elements to the Central Arctic Ocean
  • 2020
  • Ingår i: Journal of Geophysical Research - Oceans. - 2169-9275 .- 2169-9291. ; 125, s. 1-34
  • Tidskriftsartikel (refereegranskat)abstract
    • A major surface circulation feature of the Arctic Ocean is the Transpolar Drift (TPD), a current that transports river‐influenced shelf water from the Laptev and East Siberian Seas toward the center of the basin and Fram Strait. In 2015, the international GEOTRACES program included a high‐resolution pan‐Arctic survey of carbon, nutrients, and a suite of trace elements and isotopes (TEIs). The cruises bisected the TPD at two locations in the central basin, which were defined by maxima in meteoric water and dissolved organic carbon concentrations that spanned 600 km horizontally and ~25–50 m vertically. Dissolved TEIs such as Fe, Co, Ni, Cu, Hg, Nd, and Th, which are generally particle‐reactive but can be complexed by organic matter, were observed at concentrations much higher than expected for the openocean setting. Other trace element concentrations such as Al, V, Ga, and Pb were lower than expected due to scavenging over the productive East Siberian and Laptev shelf seas. Using a combination of radionuclide tracers and ice drift modeling, the transport rate for the core of the TPD was estimated at 0.9 ± 0.4 Sv(106m3 s−1). This rate was used to derive the mass flux for TEIs that were enriched in the TPD, revealing the importance of lateral transport in supplying materials beneath the ice to the central Arctic Ocean and potentially to the North Atlantic Ocean via Fram Strait. Continued intensification of the Arctic hydrologicc ycle and permafrost degradation will likely lead to an increase in the flux of TEIs into the Arctic Ocean.
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7.
  • Chapman, H N, et al. (författare)
  • Coherent imaging at FLASH
  • 2009
  • Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 186:1, s. 012051-
  • Tidskriftsartikel (refereegranskat)abstract
    • We have carried out high-resolution single-pulse coherent diffractive imaging at the FLASH free-electron laser. The intense focused FEL pulse gives a high-resolution low-noise coherent diffraction pattern of an object before that object turns into a plasma and explodes. In particular we are developing imaging of biological specimens beyond conventional radiation damage resolution limits, developing imaging of ultrafast processes, and testing methods to characterize and perform single-particle imaging.
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9.
  • Arsava, E. M., et al. (författare)
  • The Causative Classification of Stroke system An international reliability and optimization study
  • 2010
  • Ingår i: Neurology. - 1526-632X. ; 75:14, s. 1277-1284
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results: The kappa value for causative classification was 0.80 (95% confidence interval [ CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: kappa = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The kappa value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. Conclusions: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras. Neurology (R) 2010;75:1277-1284
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10.
  • Bogan, M. J., et al. (författare)
  • Single-shot femtosecond x-ray diffraction from randomly oriented ellipsoidal nanoparticles
  • 2010
  • Ingår i: Physical Review Special Topics - Accelerators and Beams. - 1098-4402. ; 13:9, s. 094701-
  • Tidskriftsartikel (refereegranskat)abstract
    • Coherent diffractive imaging of single particles using the single-shot "diffract and destroy" approach with an x-ray free electron laser (FEL) was recently demonstrated. A high-resolution low-noise coherent diffraction pattern, representative of the object before it turns into a plasma and explodes, results from the interaction of the FEL with the particle. Iterative phase retrieval algorithms are used to reconstruct two-dimensional projection images of the object from the recorded intensities alone. Here we describe the first single-shot diffraction data set that mimics the data proposed for obtaining 3D structure from identical particles. Ellipsoidal iron oxide nanoparticles (250 nm x 50 nm) were aerosolized and injected through an aerodynamic lens stack into a soft x-ray FEL. Particle orientation was not controlled with this injection method. We observed that, at the instant the x-ray pulse interacts with the particle, a snapshot of the particle's orientation is encoded in the diffraction pattern. The results give credence to one of the technical concepts of imaging individual nanometer and subnanometer-sized objects such as single molecules or larger clusters of molecules using hard x-ray FELs and will be used to help develop robust algorithms for determining particle orientations and 3D structure.
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11.
  • Garsen, Marjolein, et al. (författare)
  • Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis
  • 2016
  • Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 186:4, s. 805-815
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparanase, a heparan sulfate (HS)-specific endoglucuronidase, mediates the onset of proteinuria and renal damage during experimental diabetic nephropathy. Glomerular heparanase expression is increased in most proteinuric diseases. Herein, we evaluated the role of heparanase in two models of experimental glomerulonephritis, being anti-glomerular basement membrane and lipopolysaccharide-induced glomerulonephritis, in wild-type and heparanase-deficient mice. Induction of experimental glomerulonephritis Led to an increased heparanase expression in wild-type mice, which was associated with a decreased glomerular expression of a highly sulfated HS domain, and albuminuria. Albuminuria was reduced in the heparanase-deficient mice in both models of experimental glomerulonephritis, which was accompanied by a better renal function and less renal damage. Notably, glomerular HS expression was preserved in the heparanase-deficient mice. Glomerular leukocyte and macrophage influx was reduced in the heparanase-deficient mice, which was accompanied by a reduced expression of both types 1 and 2 helper T-cell cytokines. In vitro, tumor necrosis factor-alpha and Lipopolysaccharide directly induced heparanase expression and increased transendothelial albumin passage. Our study shows that heparanase contributes to proteinuria and renal damage in experimental glomerulonephritis by decreasing glomerular HS expression, enhancing renal leukocyte and macrophage influx, and affecting the Local cytokine milieu.
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12.
  • Akbari, Parsa, et al. (författare)
  • Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 373:6550
  • Tidskriftsartikel (refereegranskat)abstract
    • Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ∼4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.
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13.
  • Daurer, Benedikt J., et al. (författare)
  • Experimental strategies for imaging bioparticles with femtosecond hard X-ray pulses
  • 2017
  • Ingår i: IUCrJ. - : INT UNION CRYSTALLOGRAPHY. - 2052-2525. ; 4, s. 251-262
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of similar to 40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from similar to 35 to similar to 300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 * 10(12) photons per mu m(2) per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.
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14.
  • Frank, Matthias, et al. (författare)
  • Femtosecond X-ray diffraction from two-dimensional protein crystals
  • 2014
  • Ingår i: IUCrJ. - 2052-2525. ; 1:2, s. 95-100
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are presented. To date, it has not been possible to acquire transmission X-ray diffraction patterns from individual 2-D protein crystals due to radiation damage. However, the intense and ultrafast pulses generated by an XFEL permit a new method of collecting diffraction data before the sample is destroyed. Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source, Bragg diffraction was acquired to better than 8.5 Å resolution for two different 2-D protein crystal samples each less than 10 nm thick and maintained at room temperature. These proof-of-principle results show promise for structural analysis of both soluble and membrane proteins arranged as 2-D crystals without requiring cryogenic conditions or the formation of three-dimensional crystals.
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15.
  • Langfeldt, Liv, et al. (författare)
  • Excellence and growth dynamics: A comparative study of the Matthew effect
  • 2015
  • Ingår i: Science and Public Policy. - : Oxford University Press (OUP). - 1471-5430 .- 0302-3427. ; 42:5, s. 661-675
  • Tidskriftsartikel (refereegranskat)abstract
    • In the past two decades, centres of excellence (CoE) and other ‘research excellence initiatives’ likely to increase the cumulative advantages and stratification of science, have been implemented in many countries. Based on empirical studies of CoE in four Nordic countries, this paper examines how the resources provided by CoE schemes (generous long-term funding, prestige and visibility) add to the success and growth dynamics of the CoE. The data indicate a modified Matthew effect with ceilings and limits avoiding excessive accumulation of resources. Important impacts of the CoE are found, in particular in terms of enabling more interdisciplinary collaboration and risk-taking and enhancing international recruitment to the research areas involved. But, in contrast to what might be expected, the CoE grant seem to add less to the relative citation rate of those already performing at the highest level, than for those performing at a somewhat lower level prior to the CoE grant.
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