| 1. |
- Vicari, Marco, et al.
(författare)
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Spatial multimodal analysis of transcriptomes and metabolomes in tissues
- 2024
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Ingår i: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 42:7, s. 1046-1050
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Tidskriftsartikel (refereegranskat)abstract
- We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson’s disease.
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| 2. |
- Amann, Peter, et al.
(författare)
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A high-pressure x-ray photoelectron spectroscopy instrument for studies of industrially relevant catalytic reactions at pressures of several bars
- 2019
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Ingår i: Review of Scientific Instruments. - : American Institute of Physics (AIP). - 0034-6748 .- 1089-7623. ; 90:10
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Tidskriftsartikel (refereegranskat)abstract
- We present a new high-pressure x-ray photoelectron spectroscopy system dedicated to probing catalytic reactions under realistic conditions at pressures of multiple bars. The instrument builds around the novel concept of a "virtual cell" in which a gas flow onto the sample surface creates a localized high-pressure pillow. This allows the instrument to be operated with a low pressure of a few millibar in the main chamber, while simultaneously a local pressure exceeding 1 bar can be supplied at the sample surface. Synchrotron based hard x-ray excitation is used to increase the electron mean free path in the gas region between sample and analyzer while grazing incidence <5 degrees close to total external refection conditions enhances surface sensitivity. The aperture separating the high-pressure region from the differential pumping of the electron spectrometer consists of multiple, evenly spaced, micrometer sized holes matching the footprint of the x-ray beam on the sample. The resulting signal is highly dependent on the sample-to-aperture distance because photoemitted electrons are subject to strong scattering in the gas phase. Therefore, high precision control of the sample-to-aperture distance is crucial. A fully integrated manipulator allows for sample movement with step sizes of 10 nm between 0 and -5 mm with very low vibrational amplitude and also for sample heating up to 500 degrees C under reaction conditions. We demonstrate the performance of this novel instrument with bulk 2p spectra of a copper single crystal at He pressures of up to 2.5 bars and C1s spectra measured in gas mixtures of CO + H-2 at pressures of up to 790 mbar. The capability to detect emitted photoelectrons at several bars opens the prospect for studies of catalytic reactions under industrially relevant operando conditions.
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| 3. |
- Ameur, Adam, et al.
(författare)
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SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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| 4. |
- Asp, Michaela, et al.
(författare)
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A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
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Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
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| 5. |
- Eck, Joakim A.T., et al.
(författare)
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Pressure Evolution in Ceramic Stopper in a Liquid Metal Continuous Casting Simulator
- 2022
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Ingår i: 8th International Congress on the Science and Technology of Steelmaking, ICS 2022. - : Association for Iron and Steel Technology. ; , s. 398-402
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Konferensbidrag (refereegranskat)abstract
- Stopper controls see considerable use in Continuous Casting (CC) throughput control. The flow regulation results in a narrow gap between the stopper and the SEN throat which can result in considerable under-pressures. Large pressure gradients across the refractory material lead to air infiltration through joints and porous refractory material which result in oxidation and corresponding issues such as inclusions, clogging, with adverse effect on product quality. Improving the CC process makes it necessary to understand how the pressure evolves in the continuous caster. Swerim and SSAB investigated the pressure in the argon line of a ceramic stopper for different casting conditions in a liquid metal continuous casting simulator. The results showed a narrow operational region for positive pressures in stopper and an occurrence of considerably low pressures at levels down to -741 mbar relative pressure. At these under-pressures the risk for air infiltration, and thus product issues, is considerable.
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| 6. |
- Ek, Patrik, 1980-
(författare)
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Mass Spectrometry with Electrospray Ionization from an Adjustable Gap
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis the fabrication and analytical evaluation of two new electrospray emitters utilized for mass spectrometry analysis is presented. The emitters are based on a new concept, where the spray orifice can be varied in size. The thesis is based on two papers. All present-day nanoelectrospray emitters have fixed dimensions. The range of the applicable flow rate for such an emitter is therefore rather limited and exchange of emitters may be necessary from one experiment to another. Optimization of the signal of the analyte ions is also limited to adjustments of the applied voltage or the distance between the emitter and the mass spectrometer inlet. Furthermore, clogging can occur in emitters with fixed dimensions of narrow orifice sizes. In this thesis, electrospray emitters with a variable size of the spray orifice are proposed. An open gap between two thin substrates is filled with sample solution via a liquid bridge from a capillary. Electrospray is generated at the end point of the gap, which can be varied in width. In Paper I, electrospray emitters fabricated in polyethylene terephthalate have been evaluated. Triangular tips are manually cut from the polymer film. The tips are mounted to form a gap between the edges of the tips. The gap wall surfaces are subjected to a hydrophilic surface treatment to increase the wetting of the gap walls. In Paper II, silicon electrospray chips with high precision are fabricated and evaluated. A thin beam, elevated from the bulk silicon chip is fabricated by means of deep reactive ion etching. The top surfaces of the beams of two chips act as a sample conduit when mounted in the electrospray setup. An anisotropic etching step with KOH of the intersecting <100> crystal planes results in a very sharp spray point. The emitters were given a hydrophobic surface treatment except for the hydrophilic gap walls. For both emitter designs, the gap width has been adjusted during the experiments without any interruption of the electrospray. For a continuously applied peptide mixture, a shift towards higher charge states and increased signal to noise ratios could be observed when decreasing the gap width. The limit of detection has been investigated and the silicon chips have been interfaced with capillary electrophoresis.
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| 7. |
- Hamrin, Maria, et al.
(författare)
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Evidence for the braking of flow bursts as they propagate toward the Earth
- 2014
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 119:11, s. 9004-9018
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Tidskriftsartikel (refereegranskat)abstract
- In this article we use energy conversion arguments to investigate the possible braking of flow bursts as they propagate toward the Earth. By using EJ data (E and J are the electric field and the current density) observed by Cluster in the magnetotail plasma sheet, we find indications of a plasma deceleration in the region -20 R-E < X < - 15 R-E. Our results suggest a braking mechanism where compressed magnetic flux tubes in so-called dipolarization fronts (DFs) can decelerate incoming flow bursts. Our results also show that energy conversion arguments can be used for studying flow braking and that the position of the flow velocity peak with respect to the DF can be used as a single-spacecraft proxy when determining energy conversion properties. Such a single-spacecraft proxy is invaluable whenever multispacecraft data are not available. In a superposed epoch study, we find that a flow burst with the velocity peak behind the DF is likely to decelerate and transfer energy from the particles to the fields. For flow bursts with the peak flow at or ahead of the DF we see no indications of braking, but instead we find an energy transfer from the fields to the particles. From our results we obtain an estimate of the magnitude of the deceleration of the flow bursts, and we find that it is consistent with previous investigations.
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| 8. |
- Hamrin, Maria, et al.
(författare)
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The evolution of flux pileup regions in the plasma sheet : Cluster observations
- 2013
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Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-9380 .- 2169-9402. ; 118:10, s. 6279-6290
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Tidskriftsartikel (refereegranskat)abstract
- Bursty bulk flows (BBFs) play an important role for the mass, energy, and magnetic flux transport in the plasma sheet, and the flow pattern in and around a BBF has important consequences for the localized energy conversion between the electromagnetic and plasma mechanical energy forms. The plasma flow signature in and around BBFs is often rather complicated. Return flows and plasma vortices are expected to exist at the flanks of the main flow channel, especially near the inner plasma sheet boundary, but also farther down-tail. A dipolarization front (DF) is often observed at the leading edge of a BBF, and a flux pileup region (FPR) behind the DF. Here we present Cluster data of three FPRs associated with vortex flows observed in the midtail plasma sheet on 15 August 2001. According to the principles of Fu et al. (2011, 2012c), two of the FPRs are considered to be in an early stage of evolution (growing FPRs). The third FPR is in a later stage of evolution (decaying FPR). For the first time, the detailed energy conversion properties during various stages of the FPR evolution have been measured. We show that the later stage FPR has a more complex vortex pattern than the two earlier stage FPRs. The two early stage FPR correspond to generators, EJ<0, while the later stage FPR only shows weak generator characteristics and is instead dominated by load signatures at the DF, EJ>0. Moreover, to our knowledge, this is one of the first times BBF-related plasma vortices have been observed to propagate over the spacecraft in the midtail plasma sheet at geocentric distances of about 18R(E). Our observations are compared to recent simulation results and previous observations.
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| 9. |
- Hong, Mun-Gwan, et al.
(författare)
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Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
- 2020
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:10, s. e202000817-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.
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| 10. |
- Lindstrand, Anna, et al.
(författare)
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From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
- 2019
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Ingår i: Genome Medicine. - : BMC. - 1756-994X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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