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Search: WFRF:(Karlsson Max)

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1.
  • Karlsson, Mattias, 1980, et al. (author)
  • Biomimetic nanoscale reactors and networks
  • 2004
  • In: Annual Review of Physical Chemistry. - : Annual Reviews. - 0066-426X .- 1545-1593. ; 55, s. 613-49
  • Journal article (peer-reviewed)abstract
    • Methods based on self-assembly, self-organization, and forced shape transformations to form synthetic or semisynthetic enclosed lipid bilayer structures with several properties similar to biological nanocompartments are reviewed. The procedures offer unconventional micro- and nanofabrication routes to yield complex soft-matter devices for a variety of applications for example, in physical chemistry and nanotechnology. In particular, we describe novel micromanipulation methods for producing fluid-state lipid bilayer networks of nanotubes and surface-immobilized vesicles with controlled geometry, topology, membrane composition, and interior contents. Mass transport in nanotubes and materials exchange, for example, between conjugated containers, can be controlled by creating a surface tension gradient that gives rise to a moving boundary or by induced shape transformations. The network devices can operate with extremely small volume elements and low mass, to the limit of single molecules and particles at a length scale where a continuum mechanics approximation may break down. Thus, we also describe some concepts of anomalous fluctuation-dominated kinetics and anomalous diffusive behaviours, including hindered transport, as they might become important in studying chemistry and transport phenomena in these confined systems. The networks are suitable for initiating and controlling chemical reactions in confined biomimetic compartments for rationalizing, for example, enzyme behaviors, as well as for applications in nanofluidics, bioanalytical devices, and to construct computational and complex sensor systems with operations building on chemical kinetics, coupled reactions and controlled mass transport.
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2.
  • Karlsson, Roger, 1975, et al. (author)
  • Strain-level typing and identification of bacteria using mass spectrometry-based proteomics.
  • 2012
  • In: Journal of proteome research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 11:5, s. 2710-20
  • Journal article (peer-reviewed)abstract
    • Because of the alarming expansion in the diversity and occurrence of bacteria displaying virulence and resistance to antimicrobial agents, it is increasingly important to be able to detect these microorganisms and to differentiate and identify closely related species, as well as different strains of a given species. In this study, a mass spectrometry proteomics approach is applied, exploiting lipid-based protein immobilization (LPI), wherein intact bacterial cells are bound, via membrane-gold interactions, within a FlowCell. The bound cells are subjected to enzymatic digestion for the generation of peptides, which are subsequently identified, using LC-MS. Following database matching, strain-specific peptides are used for subspecies-level discrimination. The method is shown to enable a reliable typing and identification of closely related strains of the same bacterial species, herein illustrated for Helicobacter pylori .
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4.
  • Rhomberg-Kauert, Jan, et al. (author)
  • Using adjusted local assortativity with Molecular Pixelation unveils colocalization of membrane proteins with immunological significance
  • 2024
  • In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 15
  • Journal article (peer-reviewed)abstract
    • Advances in spatial proteomics and protein colocalization are a driving force in the understanding of cellular mechanisms and their influence on biological processes. New methods in the field of spatial proteomics call for the development of algorithms and open up new avenues of research. The newly introduced Molecular Pixelation (MPX) provides spatial information on surface proteins and their relationship with each other in single cells. This allows for in silico representation of neighborhoods of membrane proteins as graphs. In order to analyze this new data modality, we adapted local assortativity in networks of MPX single-cell graphs and created a method that is able to capture detailed information on the spatial relationships of proteins. The introduced method can evaluate the pairwise colocalization of proteins and access higher-order similarity to investigate the colocalization of multiple proteins at the same time. We evaluated the method using publicly available MPX datasets where T cells were treated with a chemokine to study uropod formation. We demonstrate that adjusted local assortativity detects the effects of the stimuli at both single- and multiple-marker levels, which enhances our understanding of the uropod formation. We also applied our method to treating cancerous B-cell lines using a therapeutic antibody. With the adjusted local assortativity, we recapitulated the effect of rituximab on the polarity of CD20. Our computational method together with MPX improves our understanding of not only the formation of cell polarity and protein colocalization under stimuli but also advancing the overall insight into immune reaction and reorganization of cell surface proteins, which in turn allows the design of novel therapies. We foresee its applicability to other types of biological spatial data when represented as undirected graphs.
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5.
  • Sui, Ping, et al. (author)
  • Membrane protein digestion - comparison of LPI HexaLane with traditional techniques.
  • 2011
  • In: Gel-free proteomics. - Germany : Humana Press. - 9781617791482 ; , s. 129-142
  • Book chapter (other academic/artistic)abstract
    • Membrane protein profiling and characterization is of immense importance for the understanding of vital processes taking place across cellular membranes. Traditional techniques used for soluble proteins, such as 2D gel electrophoresis, are sometimes not entirely applicable to membrane protein targets, due to their low abundance and hydrophobic character. New tools have been developed that will accelerate research on membrane protein targets. Lipid-based protein immobilization (LPI) is the core technology in a new approach that enables immobilization and digestion of native membrane proteins inside a flow cell format. The presented method is described in the context of comparing the method to traditional approaches where the sample amount that is digested and analyzed is the same.
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6.
  • Abdellah, Tebani, et al. (author)
  • Integration of molecular profiles in a longitudinal wellness profiling cohort.
  • 2020
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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7.
  • Ahlbeck Bergendahl, Ida, et al. (author)
  • Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
  • 2016
  • Reports (other academic/artistic)abstract
    • I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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8.
  • Alvez, Maria Bueno, et al. (author)
  • Next generation pan-cancer blood proteome profiling using proximity extension assay
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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9.
  • Andernord, Daniel, et al. (author)
  • Surgical Predictors of Early Revision Surgery After Anterior Cruciate Ligament Reconstruction: Results From the Swedish National Knee Ligament Register on 13,102 Patients.
  • 2014
  • In: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 42:7, s. 1574-1582
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:An important objective of anterior cruciate ligament (ACL) registries is to detect and report early graft failure and revision surgery after ACL reconstruction. PURPOSE:To investigate surgical variables and identify predictors of revision surgery after ACL reconstruction. STUDY DESIGN:Prospective cohort study; Level of evidence, 2. METHODS:This prospective cohort study was based on data from the Swedish National Knee Ligament Register during the years 2005 through 2011. Eight surgical variables were investigated: graft selection, graft width, single-bundle or double-bundle techniques, femoral graft fixation, tibial graft fixation, injury-to-surgery interval, injuries to menisci, and injuries to cartilage. The primary endpoint was the 2-year incidence of revision surgery. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated and adjusted for confounders by use of multivariate statistics. RESULTS:A total of 13,102 patients were included (5541 women [42%] and 7561 men [58%]; P < .001). Hamstring tendon autografts accounted for 90% (11,764 patients) of all reconstructions, of which 96% were performed with a single-bundle technique (11,339 patients). Patellar tendon autografts accounted for the remaining 10% (1338 patients). At index reconstruction, observed injuries to menisci and cartilage were common (40% and 28%, respectively). The overall 2-year incidence of revision surgery was 1.60% (women, 1.57%; men, 1.63%; P = .854). Patients with metal interference screw fixation of a semitendinosus tendon autograft on the tibia had a significantly reduced risk of early revision surgery (RR = 0.32; 95% CI, 0.12-0.90; P = .031). CONCLUSION:Metal interference screw fixation of a semitendinosus tendon autograft on the tibia was an independent predictor of significantly lower 2-year incidence of revision surgery. Graft selection, graft width, a single-bundle or a double-bundle technique, femoral graft fixation, the injury-to-surgery interval, and meniscus injury were not predictors of early revision surgery.
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10.
  • Arlen, T., et al. (author)
  • Rapid TeV Gamma-Ray Flaring of BL Lacertae
  • 2013
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 762:2
  • Journal article (peer-reviewed)abstract
    • We report on the detection of a very rapid TeV gamma-ray flare from BL Lacertae on 2011 June 28 with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). The flaring activity was observed during a 34.6 minute exposure, when the integral flux above 200 GeV reached (3.4 ± 0.6) × 10–6 photons m–2 s–1, roughly 125% of the Crab Nebula flux measured by VERITAS. The light curve indicates that the observations missed the rising phase of the flare but covered a significant portion of the decaying phase. The exponential decay time was determined to be 13 ± 4 minutes, making it one of the most rapid gamma-ray flares seen from a TeV blazar. The gamma-ray spectrum of BL Lacertae during the flare was soft, with a photon index of 3.6 ± 0.4, which is in agreement with the measurement made previously by MAGIC in a lower flaring state. Contemporaneous radio observations of the source with the Very Long Baseline Array revealed the emergence of a new, superluminal component from the core around the time of the TeV gamma-ray flare, accompanied by changes in the optical polarization angle. Changes in flux also appear to have occurred at optical, UV, and GeV gamma-ray wavelengths at the time of the flare, although they are difficult to quantify precisely due to sparse coverage. A strong flare was seen at radio wavelengths roughly four months later, which might be related to the gamma-ray flaring activities. We discuss the implications of these multiwavelength results.
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11.
  • Arshad, Usman, et al. (author)
  • Prediction of exposure-driven myelotoxicity of continuous infusion 5-fluorouracil by a semi-physiological pharmacokinetic-pharmacodynamic model in gastrointestinal cancer patients
  • 2020
  • In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 85:4, s. 711-722
  • Journal article (peer-reviewed)abstract
    • PurposeTo describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach.MethodsThirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m2/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m2/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semi-mechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics.ResultsTotal clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 109/L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg).ConclusionsBSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin.
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12.
  • Bandaru, Sashidar, et al. (author)
  • Targeting filamin A reduces macrophage activity and atherosclerosis. : Filamin A in atherogenesis
  • 2019
  • In: Circulation. - 1524-4539. ; 140:1, s. 67-79
  • Journal article (peer-reviewed)abstract
    • The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna o/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC). Atherosclerosis in vivo was studied by transplanting bone marrow from male Flna o/fl/ LC mice to atherogenic low-density lipoprotein receptor-deficient ( Ldlr-/-) mice; and by infecting Flna o/fl and Flna o/fl/ LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Furthermore, C57BL/6 mice were infected with AdPCSK9 and then treated with the calpain inhibitor calpeptin to inhibit FLNA cleavage.We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna o/fl/ LC macrophages proliferated and migrated less than controls; expressed lower levels of phosphorylated AKT and ERK1/2; exhibited reduced foam cell formation and lipid uptake; and excreted more lipids. The deficiency of Flna in macrophages markedly reduced the size of aortic atherosclerotic plaques in both Ldlr-/-BMT: Flnao/fl/LC and AdPCSK9-infected Flna o/fl/ LC mice. Intima/media ratios and numbers of CD68-positive macrophages in atherosclerotic plaques were lower in Flna-deficient mice than in control mice. Moreover, we found that STAT3 interacts with a calpain-cleaved carboxyl-terminal fragment of FLNA. Inhibiting calpain-mediated FLNA cleavage with calpeptin in macrophages reduced nuclear levels of phosphorylated STAT3, interleukin 6 secretion, foam cell formation, and lipid uptake. Finally, calpeptin treatment reduced the size of atherosclerotic plaques in C57BL/6 mice infected with AdPCSK9.Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.
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  • Bogorad, Max I, et al. (author)
  • Review : in vitro microvessel models.
  • 2015
  • In: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 15:22, s. 4242-55
  • Journal article (peer-reviewed)abstract
    • A wide range of perfusable microvessel models have been developed, exploiting advances in microfabrication, microfluidics, biomaterials, stem cell technology, and tissue engineering. These models vary in complexity and physiological relevance, but provide a diverse tool kit for the study of vascular phenomena and methods to vascularize artificial organs. Here we review the state-of-the-art in perfusable microvessel models, summarizing the different fabrication methods and highlighting advantages and limitations.
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15.
  • Boholm, Åsa, 1953, et al. (author)
  • Riskhanteringsbeslut inom transportsektorn: Slutredovisning av forskningsprojektet TRANSAM 2007-2010
  • 2011
  • Reports (other academic/artistic)abstract
    • Inom transportsystemet fattas dagligen otaliga beslut om att hantera risker som hotar människors liv och hälsa, ekonomiska värden eller miljön. Bland beslutsfattarna återfinns statliga och kommunala myndigheter på olika nivåer, privata företag som trafikoperatörer, bygg‐ och konstruktionsentreprenörer och konsultfirmor. Frågor om risk och säkerhet hanteras ofta av grupper och nätverk bestående av privata och offentliga aktörer som samverkar för att utföra och planera offentliga verksamheter. Riskbeslut i infrastruktur‐ och trafikplanering fattas därför ofta gemensamt av aktörer med olika mål, värderingar och prioriteringar. Skiljaktigheter i uppfattningar och erfarenheter bidrar tillsammans med organisatoriska specialiseringar och myndigheters specialiserade sektoriella ansvarsområden och beslutskompetens till hög komplexitet i beslutsprocessen. Syftet med forskningsprojektet Riskhanteringsbeslut inom transportsektorn (2007‐2010), vid Centrum för forskning om offentlig sektor (CEFOS), Göteborgs universitet, har varit att bidra med ökad kunskap om beslutsfattande som sker i komplexa beslutssituationer i samverkan mellan offentliga och privata aktörer. Projektet har varit ett samhällsvetenskapligt mångdisciplinärt forskningsprojekt baserat på ämnesperspektiv från socialantropologi, statsvetenskap, offentlig förvaltning, företagsekonomi, riskforskning och kulturgeografi. Inom ramen för projektet har faktiska beslutsprocesser studerats i realtid och i de institutionella, sociala och politiska sammanhang de ingår i.
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16.
  • Bylesjö, Max, et al. (author)
  • Integrated analysis of transcript, protein and metabolite data to study lignin biosynthesis in hybrid aspen
  • 2009
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 8:1, s. 199-210
  • Journal article (peer-reviewed)abstract
    • Tree biotechnology will soon reach a mature state where it will influence the overall supply of fiber, energy and wood products. We are now ready to make the transition from identifying candidate genes, controlling important biological processes, to discovering the detailed molecular function of these genes on a broader, more holistic, systems biology level. In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples. The aim is to study characteristics of common changes in relation to genotype-specific perturbations affecting the lignin biosynthesis and growth. We show that a considerable part of the systematic effects in the system can be tracked across all platforms and that the approach has a high potential value in functional characterization of candidate genes.
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17.
  • Carlzon, Daniel, et al. (author)
  • Both Low and High Serum IGF-1 Levels Associate With Increased Risk of Cardiovascular Events in Elderly Men
  • 2014
  • In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:11, s. 2308-2316
  • Journal article (peer-reviewed)abstract
    • Context: Most previous prospective studies suggest that low serum IGF-1 associates with increased risk of cardiovascular disease (CVD) events whereas other studies suggest that high serum IGF-1 associates with increased risk of CVD events. Objective: We tested the hypothesis that not only low, but also high serum IGF-1 levels associate with increased risk of CVD events in elderly men. Setting and Design: Serum IGF-1 levels were measured in 2901 elderly men (age 69-81 years) included in the Swedish cohort of the prospective, population-based Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of followup. Results: During followup (median, 5.1 y) 589 participants experienced a CVD event. The association between serum IGF-1 and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-1 associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusions: Both low and high serum IGF-1 levels are risk markers for CVD events in elderly men. The association between high serum IGF-1 and CVD events is mainly driven by CHD events.
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18.
  • Carlzon, Daniel, et al. (author)
  • Both Low and High Serum Insulin-like Growth Factor-I Levels Associate with Increased Risk of Cardiovascular Events in Elderly Men.
  • 2014
  • In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:11
  • Journal article (peer-reviewed)abstract
    • Aims: Most previous prospective studies suggest that low serum insulin-like growth factor-I (IGF-I) associates with increased risk of cardiovascular disease (CVD) events while other studies suggest that high serum IGF-I associates with increased risk of CVD events. We tested the hypothesis that not only low, but also high, serum IGF-I associate with increased risk of CVD events in elderly men. Methods and Results: Serum IGF-I levels were measured in 2901 elderly men (aged 69 to 81 years) included in the prospective population-based MrOS-Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of follow-up. During follow-up (median 5.1 yrs) 589 of the participants experienced a CVD event. The association between serum IGF-I and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CVD events (p<0.01 for nonlinearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio (HR) = 1.25, 95% confidence interval (CI) 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-I associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusion: Both low and high serum IGF-I levels are risk markers for CVD events in elderly men. The association between high serum IGF-I and CVD events is mainly driven by CHD events.
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20.
  • Carney Almroth, Bethanie, 1974, et al. (author)
  • Assessing the effects of textile leachates in fish using multiple testing methods: From gene expression to behavior
  • 2021
  • In: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 207
  • Journal article (peer-reviewed)abstract
    • The textile industry, while of major importance in the world economy, is a toxic industry utilizing and emitting thousands of chemical substances into the aquatic environment. The aim of this project was to study the potentially harmful effects associated with the leaching of chemical residues from three different types of textiles: sportswear, children’s bath towels, and denim using different fish models (cell lines, fish larvae and juvenile fish). A combination of in vitro and in vivo test systems was used. Numerous biomarkers, ranging from gene expression, cytotoxicity and biochemical analysis to behavior, were measured to detect effects of leached chemicals. Principle findings indicate that leachates from all three types of textiles induced cytotoxicity on fish cell lines (RTgill-W1). Leachates from sportswear and towels induced mortality in zebrafish embryos, and chemical residues from sportswear reduced locomotion responses in developing larval fish. Sportswear leachate increased Cyp1a mRNA expression and EROD activity in liver of exposed brown trout. Leachates from towels induced EROD activity and VTG in rainbow trout, and these effects were mitigated by the temperature of the extraction process. All indicators of toxicity tested showed that exposure to textile leachate can cause adverse reactions in fish. These findings suggested that chemical leaching from textiles from domestic households could pose an ecotoxicological threat to the health of the aquatic environment.
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22.
  • Fagbamigbe, A. F., et al. (author)
  • Performance evaluation of survival regression models in analysing Swedish dental implant complication data with frailty
  • 2021
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1
  • Journal article (peer-reviewed)abstract
    • The use of inappropriate methods for estimating the effects of covariates in survival data with frailty leads to erroneous conclusions in medical research. This study evaluated the performance of 13 survival regression models in assessing the factors associated with the timing of complications in implant-supported dental restorations in a Swedish cohort. Data were obtained from randomly selected cohort (n = 596) of Swedish patients provided with dental restorations supported in 2003. Patients were evaluated over 9 years of implant loss, peri-implantitis or technical complications. Best Model was identified using goodness, AIC and BIC. The loglikelihood, the AIC and BIC were consistently lower in flexible parametric model with frailty (df = 2) than other models. Adjusted hazard of implant complications was 45% (adjusted Hazard Ratio (aHR) = 1.449; 95% Confidence Interval (CI): 1.153-1.821, p = 0.001) higher among patients with periodontitis. While controlling for other variables, the hazard of implant complications was about 5 times (aHR = 4.641; 95% CI: 2.911-7.401, p<0.001) and 2 times (aHR = 2.338; 95% CI: 1.553-3.519, p<0.001) higher among patients with full- and partial-jaw restorations than those with single crowns. Flexible parametric survival model with frailty are the most suitable for modelling implant complications among the studied patients.
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23.
  • Grauers, Anna, et al. (author)
  • Candidate gene analysis and exome sequencing confirm LBX1 as a susceptibility gene for idiopathic scoliosis
  • 2015
  • In: The Spine Journal. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1529-9430 .- 1878-1632.
  • Journal article (peer-reviewed)abstract
    • Background: Idiopathic scoliosis is a spinal deformity affecting approximately 3% of otherwise healthy children or adolescents. The etiology is still largely unknown but has an important genetic component. Genome-wide association studies have identified a number of common genetic variants that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding. Purpose: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants. Study design: This was a case control study. Patient sample: A total of 1,739 patients with idiopathic scoliosis and 1,812 controls were included. Outcome measure: The outcome measure was idiopathic scoliosis. Methods: The variants rs10510181, rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5′UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing, were Sanger sequenced in the 100 pooled samples. Results: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10−18). We identified 20 novel variants by exome sequencing after filtration and an initial genotyping validation. However, we could not verify any association to idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. We did not find any variants in the 5′UTR, noncoding exon and promoter regions of LBX1. Conclusions: Here, we confirm LBX1 as a susceptibility gene for idiopathic scoliosis in a Scandinavian population and report that we are unable to find evidence of other genes of similar or stronger effect.
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24.
  • Haraldsson, Joakim, 1990- (author)
  • Improved Energy Efficiency in the Aluminium Industry and its Supply Chains
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • Energy is an essential resource in the daily lives of humans. However, the extraction and use of energy has an impact on the environment. The industrial sector accounts for a large share of the global final energy use and greenhouse gas (GHG) emissions. The largest source of industrial GHG emissions is energy use. The production and processing of aluminium is energy- and GHG-intensive, and uses significant amounts of fossil fuels and electricity. At the same time, the global demand for aluminium is predicted to rise significantly by the year 2050. Improved energy efficiency is one of the most important approaches for reducing industrial GHG emissions. Additionally, improved energy efficiency in industry is a competitive advantage for companies due to the cost reductions that energy efficiency improvements yield.The aim of this thesis was to study improved energy efficiency in the individual companies and the entire supply chains of the aluminium industry. This included studying energy efficiency measures, potentials for energy efficiency improvements and energy savings, and which factors inhibit or drive the work to improve energy efficiency. The aim and the research questions were answered by conducting a literature review, focus groups, questionnaires and calculations of effects on primary energy use, GHG emissions, and energy and CO2 costs.This thesis identified several energy efficiency measures that can be implemented by the individual companies in the aluminium industry and the aluminium casting foundries. The individual companies have large potentials for improving their energy efficiency. Energy efficiency measures within the electrolysis process have significant effects on primary energy use, GHG emissions, and energy and CO2 costs. This thesis showed that joint work between the companies in the supply chains of the aluminium industry is needed in order to achieve further energy efficiency improvements compared to the companies only working on their own. The joint work between the companies in the supply chain is needed to avoid sub-optimisation of the total energy use throughout the entire supply chain. Better communication and closer collaboration between all the companies in the supply chain are two of the most important aspects of the joint work to improve energy efficiency. An energy audit for the entire supply chain could be conducted as a first step in the joint work between the companies in the supply chains. Another important aspect is to increase the use of secondary aluminium or remelted material waste rather than primary aluminium.The companies in the Swedish aluminium industry and the aluminium casting foundries have come some way in their work to improve energy efficiency within their own facilities. However, the results in this thesis indicate that cost-effective technology and improved management can, in total, save 126–185 GWh/year in the Swedish aluminium industry and 8–15 GWh/year in the Swedish aluminium casting foundries.This thesis identified several demands regarding economics, product quality and performance, and environment placed on the companies and products in the supply chains that affect energy use and work to improve energy efficiency. These demands can sometimes counteract each other, and some demands are more important to meet than improving energy efficiency. This implies that improving the energy efficiency of the supply chains as well as designing products so they are energy-efficient in their use phase can sometimes be difficult. The results in this thesis indicate that it would be beneficial if the companies reviewed these demands to see whether any of them could be changed.Both the economic aspects and demands from customers and authorities were shown to be important drivers for improved energy efficiency in the supply chains. However, placing demands on energy-efficient production and a company’s improved energy efficiency would require those placing the demands to have deeper knowledge compared to demanding green energy, for example. Requiring a company to implement an energy management system to ensure active work to improve energy efficiency would be easier for the customer than demanding a certain level of energy efficiency in the company’s processes. Additionally, energy audits and demands on conducted energy audits could act as drivers for improved energy efficiency throughout the supply chains.This thesis showed that the most important barriers to improved energy efficiency within the individual companies include different types of risks as well as the cost of production disruption, complex production processes and technology being inappropriate at the site. Similar to the supply chains, important drivers for improved energy efficiency within the individual companies were shown to be economic aspects and demands from customers and authorities. However, the factors that are most important for driving the work to improve energy efficiency within the individual companies include the access to and utilisation of knowledge within the company, corporate culture, a longterm energy strategy, networking within the sector, information from technology suppliers and energy audits.
  •  
25.
  • Hjorth, Martin, et al. (author)
  • Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
  • 2012
  • In: European journal of haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
  • Journal article (other academic/artistic)abstract
    • Objectives: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions: Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
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26.
  • Jin, Han, et al. (author)
  • Systematic transcriptional analysis of human cell lines for gene expression landscape and tumor representation
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1, s. 5417-
  • Journal article (peer-reviewed)abstract
    • Cell lines are valuable resources as model for human biology and translational medicine. It is thus important to explore the concordance between the expression in various cell lines vis-à-vis human native and disease tissues. In this study, we investigate the expression of all human protein-coding genes in more than 1,000 human cell lines representing 27 cancer types by a genome-wide transcriptomics analysis. The cell line gene expression is compared with the corresponding profiles in various tissues, organs, single-cell types and cancers. Here, we present the expression for each cell line and give guidance for the most appropriate cell line for a given experimental study. In addition, we explore the cancer-related pathway and cytokine activity of the cell lines to aid human biology studies and drug development projects. All data are presented in an open access cell line section of the Human Protein Atlas to facilitate the exploration of all human protein-coding genes across these cell lines.
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27.
  • Karlsson, Johan, et al. (author)
  • Engineered nanoparticles for systemic siRNA delivery to malignant brain tumours.
  • 2019
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 11:42, s. 20045-20057
  • Journal article (peer-reviewed)abstract
    • Improved delivery materials are needed to enable siRNA transport across biological barriers, including the blood-brain barrier (BBB), to treat diseases like brain cancer. We engineered bioreducible nanoparticles for systemic siRNA delivery to patient-derived glioblastoma cells in an orthotopic mouse tumor model. We first utilized a newly developed biomimetic in vitro model to evaluate and optimize the performance of the engineered bioreducible nanoparticles at crossing the brain microvascular endothelium. We performed transmission electron microscopy imaging which indicated that the engineered nanoparticles are able to cross the BBB endothelium via a vesicular mechanism. The nanoparticle formulation engineered to best cross the BBB model in vitro led to safe delivery across the BBB to the brain in vivo. The nanoparticles were internalized by human brain cancer cells, released siRNA to the cytosol via environmentally-triggered degradation, and gene silencing was obtained both in vitro and in vivo. This study opens new frontiers for the in vitro evaluation and engineering of nanomedicines for delivery to the brain, and reports a systemically administered biodegradable nanocarrier for oligonucleotide delivery to treat glioma.
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28.
  • Karlsson, Karolina, 1975, et al. (author)
  • Health economic aspects of implant-supported restorative therapy
  • 2022
  • In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 33:2, s. 221-230
  • Journal article (peer-reviewed)abstract
    • Background: It is poorly understood how much additional dental care patients consume subsequent to implant therapy. The aim of the present study is to evaluate costs associated with implant-supported restorative therapy during the long-term follow-up. Material and Methods: Costs associated with preventive measures and complication-related procedures over a mean follow-up period of 8.2years were assessed in patient files of 514 Swedish subjects provided with implant-supported restorative therapy. The restorative therapy and each of the subsequent interventions were assigned a specific cost. Accumulated costs were calculated in three categories: (i) total cost including initial restorative therapy and complication-related interventions, (ii) cost of preventive measures alone, and (iii) cost of complication-related procedures alone. Potential differences by background variables were analyzed using growth curve models. Results: In the whole sample, costs during follow-up ranged from 878 € (95% CI 743; 1,014) for patients with single-tooth restoration(s) to 1,210 € (95% CI 1,091; 1,329) for subjects with full-jaw restoration(s). The majority of costs during follow-up originated from preventive measures (741 € 95% CI 716; 766). Among individuals receiving ≥1 intervention dealing with a complication (n=253), complication-related costs amounted to 557 € (95% CI 480; 634). For patients with full-jaw restorations, the corresponding amount was 769 € (95% CI 622; 916). Procedures related to peri-implantitis and technical complications resulted in costs similar to each other. Implant loss generated greater costs than any other type of complication. Conclusions: Costs related to implant-supported restorative therapy during follow-up were associated with the extent of initial therapy. The higher costs during follow-up noted in patients provided with full-jaw restorations were explained by complication-associated procedures. Implant loss was the most costly type of complication.
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29.
  • Karlsson, Karolina, 1975, et al. (author)
  • Interventions for peri-implantitis and their effects on further bone loss: A retrospective analysis of a registry-based cohort
  • 2019
  • In: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 46:8, s. 872-879
  • Journal article (peer-reviewed)abstract
    • Objective The aim of the present study was to assess interventions and their consequences with regard to further bone loss at sites diagnosed with peri-implantitis. Materials and Methods In 2017, records of 70 patients diagnosed with moderate/severe peri-implantitis at >= 1 implant sites 4 years earlier were obtained. Changes of marginal bone levels during the study period assessed on radiographs and predictors of disease progression were identified by Cox regression and mixed linear modelling. Patient files were analysed for professional interventions related to the treatment of peri-implantitis. Results Mean bone loss (+/- SD) at implants diagnosed with moderate/severe peri-implantitis was 1.1 +/- 2.0 mm over the observation period of 3.3 years. While non-surgical measures including submucosal and/or supra-mucosal cleaning of implants were provided to almost all patients, surgical treatment of peri-implantitis was limited to a subgroup (17 subjects). Surgically treated implant sites demonstrated a mean bone loss of 1.4 +/- 2.4 mm prior to surgical intervention, while only minor changes (0.2 +/- 1.0 mm) occurred after therapy. Clinical parameters (bleeding/suppuration on probing and probing depth) assessed at diagnosis were statistically significant predictors of disease progression. Conclusions Non-surgical procedures were insufficient to prevent further bone loss at implant sites affected by moderate/severe peri-implantitis. Surgical treatment of peri-implantitis markedly diminished the progression of bone loss. Clinical assessments of bleeding on probing and probing depth at diagnosis predicted further bone loss.
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30.
  • Karlsson, Karolina, 1975, et al. (author)
  • Occurrence and clustering of complications in implant dentistry
  • 2020
  • In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 31:10, s. 1002-1009
  • Journal article (peer-reviewed)abstract
    • Objectives The aim was to evaluate the overall occurrence and potential clustering of biological and technical complications in implant dentistry. Material and Methods 596 patients provided with implant-supported reconstructions were evaluated for the occurrence of (a) technical complications, (b) peri-implantitis and (c) implant loss during a period of 9 years. Time and type of event were scored, and potential risk factors were explored through parametric modelling of survival and hazards. Clustering of complications was assessed at the patient level, and patient satisfaction was evaluated by questionnaire completed at the 9-year examination. Results 42% of patients were affected by technical and/or biological complications during the 9-year observation period. Extent of therapy (Hazard Ratio 2.5: patients with partial jaw restorations; HR 3.9: patients with full jaw restorations) and a history of periodontitis (HR 1.6) were identified as risk factors. While technical complications occurred mostly as isolated events, 41% of subjects identified with peri-implantitis and 52% of subjects with implant loss also presented with other complications. The hazard for technical complications and implant loss peaked at 0.7 years and 0.2 years, respectively, while the hazard for peri-implantitis was consistent throughout the observation period. The overall proportion of satisfied patients at 9 years was high (95%), and only minor differences between individuals with and without complications were noted. Conclusions Complications following implant-supported restorative therapy were common findings. Extent of therapy and periodontitis were identified as risk factors. While technical complications occurred in an isolated pattern, peri-implantitis and implant loss demonstrated clustering with other types of complications.
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31.
  • Karlsson, Karolina, 1975, et al. (author)
  • Technical complications following implant-supported restorative therapy performed in Sweden
  • 2018
  • In: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 29:6, s. 603-611
  • Journal article (peer-reviewed)abstract
    • ObjectiveThe aim of this study was to evaluate the occurrence and consequences of technical complications in implant-supported restorative therapy. Material & MethodsThe occurrence and consequences of technical complications in implant-supported restorative therapy over a mean follow-up period of 5.3years were assessed based on documentation in files from 2,666 patients. Risk indicators were identified by the use of survival models, considering repeated events. Results were expressed as hazard ratios (HR) including 95% confidence intervals. ResultsTechnical complications occurred in 24.8% of the patients. Chipping and loss of retention were the most common, affecting 11.0% and 7.9% of supraconstructions, respectively, while implant-related complications (e.g., implant fracture) were rare. More than 50% of the affected patients experienced technical complications more than once and almost all reported complications led to interventions by a dental professional. The extent of the supraconstruction was the strongest risk indicator for both chipping (HR<0.2) and loss of retention (HR>3). ConclusionOver a 5-year period, technical complications in implant-supported restorative therapy occurred frequently and their management required professional intervention.
  •  
32.
  • Karlsson, Max, et al. (author)
  • A single-cell type transcriptomics map of human tissues
  • 2021
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:31
  • Journal article (peer-reviewed)abstract
    • Advances in molecular profiling have opened up the possibility to map the expression of genes in cells, tissues, and organs in the human body. Here, we combined single-cell transcriptomics analysis with spatial antibody-based protein profiling to create a high-resolution single-cell type map of human tissues. An open access atlas has been launched to allow researchers to explore the expression of human protein-coding genes in 192 individual cell type clusters. An expression specificity classification was performed to determine the number of genes elevated in each cell type, allowing comparisons with bulk transcriptomics data. The analysis highlights distinct expression clusters corresponding to cell types sharing similar functions, both within the same organs and between organs.
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33.
  •  
34.
  • Karlsson, Max, 1990- (author)
  • Dynamics in Blue Emitting Metal Halide Perovskites for Light Emitting Diodes
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Lighting comprises a large part of the global electricity consumption as of today, and the use of lighting in illumination and displays is only projected to grow. It is therefore imperative to meet this energy demand, not only by means of greener energy production, but also with materials that are both more efficient to fabricate as well as to use. Low cost and energy efficient light sources therefore play an important role in minimizing further greenhouse emissions from the way we choose to live.Metal halide perovskites are a group of semiconductors that have received a great amount of attention during the past years due to impressive - and continuously increasing - performance as active materials implemented in solar cells and light emitting diodes. This is due to highly desirable optoelectronic properties combined with low-cost, solution-processable fabrication methods. Simple bandgap-tunability is easily achieved by compositional and dimensional engineering, allowing perovskite emission to span a broad wavelength region from ultraviolet to near infrared. As with previous technologies, attaining stable, bright, and pure blue light has proven difficult also in metal halide perovskites. This thesis investigates some of the challenges in achieving blue emission in mixed-halide and mixed-dimensional perovskites for light-emitting-diode applications.Mixed-halide alloying provides the most straightforward way of tuning the bandgap of perovskites. Unfortunately, mixed bromide/chloride-perovskites (used to achieve blue light) suffer from both spectral and temporal instabilities, as well as severe luminescence quenching at the large chloride contents necessary for blue emission. The spectral instability arises from a segregation of halides into regions of differing halide content, and hence different bandgap, resulting in a shift in emission color during operation. Although the origins of the poor temporal stability of perovskite light emitting diodes are manifold, one of the main problems are the low barriers for halide migration under the applied electric field during operation, rapidly degrading the device properties.We first find that compositional heterogeneities, stemming from rapid uncontrolled film growth, both lowers the threshold for further halide segregation as well as serves as centers for non-radiative recombination, resulting in reduced luminescence yield. We show that by carefully moderating the crystallization dynamics it is possible to achieve films with a homogeneous composition, thereby mitigating the negative effects arising from material inhomogeneities. We identify means of how growth environment, stoichiometric tuning and chelating additives can be used to favorably control film formation and provide guidelines that can be more widely applied in the fabrication of perovskite films and devices. We continue by investigating the role of Br/Cl-alloying on device efficiency and stability in green to blue emitting perovskite LEDs. We find that chloride incorporation, while having only a minor impact on efficiency at moderate levels, detrimentally affects device stability even in small amounts. We ascribe this phenomenon to an increased mobility of halogen ions in the mixed-halide lattice resulting from an increased chemically and structurally disordered landscape with reduced migration barriers. We assign this as the major obstacle towards stable blue-emitting mixed-halide perovskite light emitting diodes.In the last work we investigate blue emitting mixed-dimensional Ruddlesden-Popper perovskites (RPPs) comprising of multiple-quantum-well-structures of varying bandgap. Successful implementation in LEDs has been attributed to efficient carrier funneling from large bandgap (donor) regions to low bandgap regions (acceptors) resulting in improved luminescence yields due to trap state filling from the locally increased carrier density. However, due to the enhanced carrier concentrations in acceptor domains, Auger recombination quickly outcompetes radiative recombination mechanisms already at moderate pump fluences or carrier injection densities in RPPs. We show that by moderating the inter-well carrier transfer, while at the same time providing adequate defect passivation, high quantum yields can be maintained even at large carrier densities. We thereby show that RPPs can support a large density of carriers without compromising luminescence efficiency, paving the way for their use in high brightness applications by engineering the funneling and recombination processes in these materials.The work in this thesis provides new insights on various dynamical processes in metal halide perovskites aimed at light emitting applications. The hope is that it will contribute toward the understanding of these systems and help in bringing these materials closer to practical use.
  •  
35.
  • Karlsson, Max, et al. (author)
  • Genome-wide annotation of protein-coding genes in pig
  • 2022
  • In: BMC Biology. - : Springer Nature. - 1741-7007. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background: There is a need for functional genome-wide annotation of the protein-coding genes to get a deeper understanding of mammalian biology. Here, a new annotation strategy is introduced based on dimensionality reduction and density-based clustering of whole-body co-expression patterns. This strategy has been used to explore the gene expression landscape in pig, and we present a whole-body map of all protein-coding genes in all major pig tissues and organs. Results: An open-access pig expression map (www.rnaatlas.org ) is presented based on the expression of 350 samples across 98 well-defined pig tissues divided into 44 tissue groups. A new UMAP-based classification scheme is introduced, in which all protein-coding genes are stratified into tissue expression clusters based on body-wide expression profiles. The distribution and tissue specificity of all 22,342 protein-coding pig genes are presented. Conclusions: Here, we present a new genome-wide annotation strategy based on dimensionality reduction and density-based clustering. A genome-wide resource of the transcriptome map across all major tissues and organs in pig is presented, and the data is available as an open-access resource (www.rnaatlas.org), including a comparison to the expression of human orthologs.
  •  
36.
  • Karlsson, Max, et al. (author)
  • Genome-wide single cell annotation of the human protein-coding genes
  • Other publication (other academic/artistic)abstract
    • An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new “tau” score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.
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37.
  • Karlsson, Max J., et al. (author)
  • Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy
  • 2021
  • In: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:9, s. 2545-2555
  • Journal article (peer-reviewed)abstract
    • Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort. Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.
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38.
  • Karlsson, Max (author)
  • Mapping and annotating the mammalian body-wide protein-coding gene expression
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • A central aim of fundamental research is to create conditions necessary for fueling further research and innovation. Our understanding of basic biology is central for future developments of tools for diagnosing, monitoring, and treating disease. This doctoral thesis focuses on mapping the mammalian protein-coding gene expression in healthy cells and tissues, and annotation of genes based on their expression patterns, specificity, location, and function. This has in large part been achieved by using large scale transcriptomic and proteomic profiling to describe the gene expression landscape that defines the identities of the great diversity of cells present in mammals. Characterization of gene expression across different tissues and cell types provide fundamental tools to enable the exploration, summary, and ultimately, the annotation of the mammalian proteome, which is still incomplete.The studies comprising this thesis have contributed to the Human Protein Atlas, an online open-access portal for proteomic and transcriptomic data, with the aim to profile each human protein-coding gene to create a spatial map of the molecular organization of the human body, providing basic tools for the scientific community. Paper I comprises an effort to catalogue all proteins that are actively secreted from cells; defining the human secretome. Paper II entails the deep characterization and annotation of the protein-coding transcriptome of 18 peripheral immune cell types. Paper III describes the, to date, most comprehensive tissue-based transcriptomic profiling of protein-coding genes in 98 tissues of the increasingly important model animal pig. Paper IV extends previous tissue-based maps of the human protein-coding genome by integration of 13 single cell transcriptome datasets. Paper V explores the human protein-coding genome in a clustering-based annotation of co-expressed genes across single cells and tissues to provide a framework for finding previously unknown functional relationships between genes by the principle of “guilt-by-association”.In summary, the work described here entails a small contribution to the grand effort of spatially mapping proteins across tissues and cell types, for building a framework of biological knowledge that can lead to increased understanding of the constituents that make us humans.
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39.
  • Karlsson, Max, et al. (author)
  • Mixed halide perovskites for spectrally stable and high-efficiency blue light-emitting diodes
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Bright and efficient blue emission is key to further development of metal halide perovskite light-emitting diodes. Although modifying bromide/chloride composition is straightforward to achieve blue emission, practical implementation of this strategy has been challenging due to poor colour stability and severe photoluminescence quenching. Both detrimental effects become increasingly prominent in perovskites with the high chloride content needed to produce blue emission. Here, we solve these critical challenges in mixed halide perovskites and demonstrate spectrally stable blue perovskite light-emitting diodes over a wide range of emission wavelengths from 490 to 451 nanometres. The emission colour is directly tuned by modifying the halide composition. Particularly, our blue and deep-blue light-emitting diodes based on three-dimensional perovskites show high EQE values of 11.0% and 5.5% with emission peaks at 477 and 467 nm, respectively. These achievements are enabled by a vapour-assisted crystallization technique, which largely mitigates local compositional heterogeneity and ion migration.
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40.
  • Karlsson, Max, et al. (author)
  • Phenotypic and genotypic adaptations in a riverine green alga (Chlorophyceae, Selenastraceae) as a response to long-term exposure to chemical stress
  • 2019
  • In: SETAC Helsinki - SETAC Europe 29th Annual Meeting, 26 - 30 May 2019, Helsinki, Finland.
  • Conference paper (other academic/artistic)abstract
    • Herbicide pollution is a common problem in agricultural streams due to their extensive use and their unwanted effects on non-target species inhabiting these systems. Selanastraceae is a family of green algae that are particularly dominant in freshwater, making them a key component in the base of the food chain and an important part of the oxygen production. Therefore, it is crucial from a conservation point of view to accurately monitor the ecotoxicological impact of herbicides on this group of algae, not only on a short-term scale (e.g. days or weeks), but also in a long-term perspective (e.g. months and years). In this work, phenotypic and genotypic differences are studied between different strains of a population of Kirchneriella (Chlorophyceae, Selenastraceae) isolated from a stream polluted by herbicides over a 20-year period (Skivarpsån, SE Sweden). According to mixture toxicity modelling performed on data obtained from the Swedish pesticide monitoring program, the main drivers of algal toxicity in this river are the herbicides diflufenican (carotenoid synthesis inhibitor) and isoproturon (PSII inhibitor). Three strains of the isolated algae are examined in this study: two strains from the field that have been exposed to different levels of herbicides and one laboratory strain that has never been exposed to herbicide pollution. The taxonomy of this algae is investigated by light microscopy and DNA barcoding analyses (chloroplast 23S rRNA gene). Phenotypic differences between the strains are examined as impacts on growth rate, cell size, photosynthetic activity (chl fluorescence measurements), pigment content and sensitivity to the specific herbicides mentioned earlier (EC50s). Genotypic differences are studied as single nucleotide polymorphisms thought to be induced through exposure to diflufenican and isoproturon on pds and psbA genes via PCR amplification, cloning and sequencing. The results obtained from this project will contribute to a better understanding of genetic and phenotypic adaptations in green algae as a response to herbicide pollution (evolutionary toxicology) and their implications for ecological functions.
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41.
  • Karlsson, Max, et al. (author)
  • Role of chloride on the instability of blue emitting mixed-halide perovskites
  • 2023
  • In: FRONTIERS OF OPTOELECTRONICS. - : HIGHER EDUCATION PRESS. - 2095-2759. ; 16:1
  • Journal article (peer-reviewed)abstract
    • Although perovskite light-emitting diodes (PeLEDs) have seen unprecedented development in device efficiency over the past decade, they suffer significantly from poor operational stability. This is especially true for blue PeLEDs, whose operational lifetime remains orders of magnitude behind their green and red counterparts. Here, we systematically investigate this efficiency-stability discrepancy in a series of green- to blue-emitting PeLEDs based on mixed Br/Cl-perovskites. We find that chloride incorporation, while having only a limited impact on efficiency, detrimentally affects device stability even in small amounts. Device lifetime drops exponentially with increasing Cl-content, accompanied by an increased rate of change in electrical properties during operation. We ascribe this phenomenon to an increased mobility of halogen ions in the mixed-halide lattice due to an increased chemically and structurally disordered landscape with reduced migration barriers. Our results indicate that the stability enhancement for PeLEDs might require different strategies from those used for improving efficiency.
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42.
  • Karlsson, Per Erik, 1957, et al. (author)
  • Ozone concentration gradients and wind conditions in Norway spruce (Picea abies) forests in Sweden
  • 2006
  • In: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 40:9, s. 1610-1618
  • Journal article (peer-reviewed)abstract
    • Ozone concentrations and wind conditions were measured at different heights above ground inside two different Norway spruce forest canopies in Sweden and compared to those outside or above the forests. Compared to high above ground outside or above the canopies, the ozone concentrations inside the Norway spruce forests were reduced 3-8% during mid-day and 10-40% during nighttime. Daylight Accumulated exposure Over a Threshold 40ppb (AOT40) was reduced 15-45% inside as compared to outside the forest. The horizontal concentration differences between inside and outside the forest were in the order of 3-4%, independently of the height above ground. The ozone concentration difference inside and outside the forest depended on the air turbulence as well as the horizontal wind speed inside the forest. It also depended on the distance to the forest edge in relation to the wind direction. The ozone concentration differences inside and outside the Norway spruce forests were explained by the differences in the rate of dry deposition in relation to the rate of replacement of ozone from higher air layers or by the horizontal wind going into the forest. (c) 2005 Elsevier Ltd. All rights reserved.
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43.
  • Karlsson, Sigbritt, et al. (author)
  • Högskolepedagogisk utbildning och pedagogisk meritering som grund för det akademiska lärarskapet
  • 2017
  • Reports (pop. science, debate, etc.)abstract
    • SUHF:s arbetsgrupp för översyn av rekommendationer om mål för behörighetsgivande högskolepedagogisk utbildning lägger här fram sin rapport ”Högskolepedagogisk utbildning och pedagogisk meritering som grund för det akademiska lärarskapet”. I rapporten diskuterar arbetsgruppen sina överväganden i relation till de nya rekommendationer för behörighetsgivande högskolepedagogisk utbildning vid svenska lärosäten som antogs av SUHF:s förbundsförsamling i april 2016.En övergripande princip som har väglett gruppens arbete i formuleringen av de nya rekommendationerna är att högskolepedagogisk utbildning och meritering utgör viktiga aspekter i arbetet med att stärka det akademiska lärarskapet i högskolan. Det är arbetsgruppens förhoppning att rekommendationerna och denna rapport ska bidra till lärosätenas långsiktiga strategier för att säkerställa läraranställdas behov av kontinuerlig högskolepedagogisk kompetensutveckling.Inledningsvis presenteras bakgrunden till den första versionen av SUHF:s rekommendationer som antogs 2005. Rekommendationerna kom att bli en viktig referens för uppbyggnaden av högskolepedagogiska kurser vid högskolor och universitet i Sverige. Därefter beskrivs hur förändringar i det högskolepolitiska landskapet kommit att innebära delvis ändrade förutsättningar för lärarprofessionen i högskolan. Mot bakgrund av dessa förändringar diskuterar och motiverar arbetsgruppen de förändringar som introduceras i de nya rekommendationerna. Huvudsyftet med arbetsgruppens arbete har varit att stärka det akademiska lärarskapet i högskolan.I rapporten presenteras även en studie av lärosätenas anställningsordningar. Syftet var att granska i vilken utsträckning dessa ställer krav på högskolepedagogisk utbildning för olika läraranställningar, och i vilken mån SUHF:s rekommendationer används som måttstock i kraven på högskolepedagogisk utbildning. Arbetsgruppen har dessutom granskat i vilken utsträckning anställningsordningarna reglerar frågan om pedagogisk skicklighet. Resultatet av denna granskning ger vid handen att kravbilden varierar stort bland landets lärosäten och att det i vissa fall saknas tydliga krav på genomgången högskolepedagogisk utbildning. I många anställningsordningar är det också oklart hur pedagogisk skicklighet ska definieras och hur bedömningen av pedagogiska meriter ska ske.Sammanfattningsvis konstaterar arbetsgruppen att SUHF:s rekommendationer för behörighetsgivande högskolepedagogisk utbildning har kommit att spela stor roll för att utveckla grundläggande högskolepedagogisk utbildning vid flertalet lärosäten. Den högskolepedagogiska verksamhet som bedrivs vid svenska universitet och högskolor är dock, i ett internationellt perspektiv, relativt fragmenterad och småskalig. Vår bedömning är att det föreligger ett stort behov av att utveckla system för högskolepedagogisk kompetensutveckling och utvecklingsstöd som kan stärka det akademiska lärarskapet i högskolan.Arbetsgruppen menar att frågan om pedagogisk utveckling i högskolan måste vara en kvalitetsfråga och ett återkommande, långsiktigt utvecklingstema för samtliga lärosäten. Ett strategiskt högskolepedagogiskt kvalitetsarbete förutsätter en stark nationell samverkan inriktad på att skapa systematik och samspel mellan olika system för högskolepedagogisk kompetensutveckling och andra utvecklingsinsatser som syftar till att stärka det akademiska lärarskapet såväl individuellt och kollegialt, som institutionellt.
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44.
  • Karlsson, Therese, 1987, et al. (author)
  • Undersökning av mikroskräp längs bohuslänska stränder och i sediment
  • 2019
  • Reports (other academic/artistic)abstract
    • Mikroplast och andra mikroskräpspartiklar såsom paraffin hittas i miljöprover över hela världen. En stor del av provtagningarna sker i ytvatten och det har gett oss många insikter kring förekomst och transport. På grund av en snabb omsättning och ofta låga antal partiklar per prov är det dock svårt att använda ytvattenprov för analys av mikroskräpssammansättningen. Sammansättningen är dock en viktig komponent för att ge underlag till att utröna såväl källmönster som riskanalyser.Majoriteten av plasten förväntas sjunka eller hamna på stränder. Därför undersöker vi här prover från stränder och sediment på den svenska västkusten. I studien ingår prover från tre exponerade stränder; Tjällsö, Skaftö och Ramsvik, tre stadsnära stränder; Göteborg, Stenungssund och Uddevalla samt prover i sediment utanför Stenungssund.På stränderna provtogs två sorters prover. Ackumulationsprover; prover som togs där skräpet visuellt kunde konstateras ha samlats, och poolade prover; prover där mindre volymer togs över ett större område och lades ihop till ett prov. Ackumulationsproverna togs för att öka chansen att få tillräckligt högt partikelantal och de poolade proverna togs för att ge mer representativa prover för föroreningsnivån på de olika stränderna. Proverna storleksfraktionerades och analyser gjordes visuellt i ljusmikroskop av fraktionerna 1-5 mm, 0,5-1 mm och 0,3-0,5 mm. Vissa partikeltyper analyserades även i FTIR för att även ge materialtyp. Lågt partikelantal i vissa av proverna belyser vikten av att anpassa provvolymen, medan analys av större provvolymer emellertid kan kräva extraktionsmetoder för att analyserna sak bli kostnadseffektiva. På grund av källornas komplexitet ges en så fullständig bild som om miljöanalyser av mikro och makroskräp, geografiska föroreningsmönster samt massbalansberäkningar kombineras. Vid mer specifika frågeställningar om särskilda källor så bör provtagning och analysmetod anpassas specifikt, utifrån storleksfördelning, partikeldensitet och polymertyper. Extraktion av mikroskräp från sedimentproverna är relativt väl utvecklat för miljöövervakning men analysen på mindre storleksfördelningar behöver utvecklas för att bryta ner naturligt material för att underlätta analysen.Resultaten indikerar att strandprover kan vara lämpliga för analys av sammansättningen av flytande mikroskräp, medan sediment är lämpliga för sjunkande partiklar, framförallt de polymerer som har en högre densitet i polymeren men även material som initialt flyter men som sedan på grund av degradationsprocesser och biofilm sjunker.Resultaten från strandproverna visade på höga koncentrationer av mikroskräp; i de poolade proverna låg de mellan 4 000 och 100 000 partiklar över 300 μm per kg torrvikt och koncentrationerna i ackumulationsproverna var upp till 70 gånger högre. Vanligast i samtliga prover var olika typer av plastfragment. Bland dessa var transparanta och semitransparenta fragment de allra vanligaste. De är svåra att spåra till specifika källor, vissa ledtrådar kan dock ges genom att undersöka sammansättningen av större skräp och återkommande resultat av strandinventeringar visar att en stor mängd av skräpet som hittas på svenska stränder är förpackningsplast.På stränderna var expanderad cellplast också en viktig kategori bland fragmenten. Framförallt på de urbana stränderna där de utgjorde en stor del av den identifierade mikroplasten. Åtgärder mot användningen av expanderad polystyren (EPS) i vissa engångartiklar har redan diskuterats på EU-nivå. Merparten av den expanderade polystyrenen som används i Europa används dock till byggmaterial. Det kan därför vara meningsfullt att se över regler om emballage och hantering av EPS och rutiner vid byggnadsarbeten för att säkerhetsställa att minimalt spill sker vid transport, lagring och bearbetning.8Bland de mikroplaster på stränder som inte tycktes vara fragmenterade så var plasttyper kopplat till produktion av plast en betydande del. Antalskoncentrationerna var högre i mindre storleksfraktioner. Den sortens mindre partiklar kan antas vara svårare att undvika spill utav än pellets. Det visar på vikten av att inkludera implementeringen av goda rutiner, miljötillsyn och uppföljning vid produktion, transport och lagring av plastmaterial.En annan återkommande kategori var mikrosfärer. Flera partiklar identifierades som polymetylmetacrylat medan vissa gav liknande spektra som glas. Tidigare studier har även hittat mikrosfärer av polystyren. Mikrosfärer kan därför antas förekomma i olika material med olika sammansättningar. Flera sorter tycks dock hamna i miljön vilket innebär att en översyn av användningsområden kan ge utökad kunskap kring vilka preventiva åtgärder som kan tas för att begränsa spill under produktion, transport, lagring och även användning. Referens bör även ges till det regelverksrevision av primär mikroplast som ECHA arbetar med.Paraffin var också en viktig skräpkategori som utgjorde 21 % av mikroskräpspartiklarna. Det kan därför vara värt att överväga de risker som paraffin kan utgöra samt undersöka möjligheter till att begränsa läckaget av paraffin till miljön.Mikroskräpskategorierna i sediment som gav kompletterade bild av viktiga källor var däckslitagepartiklar, fibrer, industrispill av PVC, samt färgade partiklar som till viss del kan vara färgpartiklar. Men även i sedimenten var de semitransparenta fragmenten av huvudsakligen PP och PE betydande.En litteraturjämförelse mellan sedimentmätningar i denna studie med övriga globala mätningar, visar att dessa svenska, med närliggande urbana-industriella källor, är bland de högsta förekomster som rapporterats från marina sediment. En jämförelse med kunskapsläget kring preliminär riskbedömning är inkluderad.Således sammantaget var majoriteten av partiklarna i sedimentproverna och på stränderna plastfragment. Det innebär att åtgärdsprogram utformade för att minska mängden mikroskräp i miljön bör inkludera åtgärder mot makroskräp med fokus på i) minskning av viss användning, ii) minimering av hantering utomhus, iii) barriärer för läckage och spridning, iv) uppstädningsåtgärder, ej endast på stränder utan även mer nära källorna eller spridningspunkterna.
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45.
  • Kotol, David, et al. (author)
  • Longitudinal Plasma Protein Profiling Using Targeted Proteomics and Recombinant Protein Standards
  • 2020
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:12, s. 4815-4825
  • Journal article (peer-reviewed)abstract
    • Spike-in of standards of known concentrations used in proteomics-based workflows is an attractive approach for both accurate and precise multiplexed protein quantification. Here, a quantitative method based on targeted proteomics analysis of plasma proteins using isotope-labeled recombinant standards originating from the Human Protein Atlas project has been established. The standards were individually quantified prior to being employed in the final multiplex assay. The assays are mainly directed toward actively secreted proteins produced in the liver, but may also originate from other parts of the human body. This study included 21 proteins classified by the FDA as either drug targets or approved clinical protein biomarkers. We describe the use of this multiplex assay for profiling a well-defined human cohort with sample collection spanning over a one-year period. Samples were collected at four different time points, which allowed for a longitudinal analysis to assess the variable plasma proteome within individuals. Two assays toward APOA1 and APOB had available clinical data, and the two assays were benchmarked against each other. The clinical assay is based on antibodies and shows high correlation between the two orthogonal methods, suggesting that targeted proteomics with highly parallel, multiplex analysis is an attractive alternative to antibody-based protein assays.
  •  
46.
  • Lee, James J, et al. (author)
  • Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
  • 2018
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
  • Journal article (peer-reviewed)abstract
    • Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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47.
  • Liljefors, Max, et al. (author)
  • Förflutenhetens bilder
  • 2004
  • In: Historien är nu. En introduktion till historiedidaktiken.
  • Book chapter (other academic/artistic)abstract
    • This essay reflects on the advantages and dangers of using visual art in the teaching of history. It concludes with a number of practical suggestions to teachers who want to use art in their teaching.
  •  
48.
  • Luo, Xiyu, et al. (author)
  • Effects of local compositional heterogeneity in mixed halide perovskites on blue electroluminescence
  • 2024
  • In: Matter. - 2590-2393. ; 7:3, s. 1054-1070
  • Journal article (peer-reviewed)abstract
    • Compositional heterogeneity is commonly observed in mixed bromide/iodide perovskite photoabsorbers, typically with minimal effects on charge carrier recombination and photovoltaic performance. Consistently, it has so far received very limited attention in bromide/chloride-mixed perovskites, which hold particular significance for blue light-emitting diodes. Here, we uncover that even a minor degree of localized halide heterogeneity leads to severe non-radiative losses in mixed bromide/chloride blue perovskite emitters, presenting a stark contrast to general observations in photovoltaics. We not only provide a visualization of the heterogeneity landscape spanning from micro-to sub-microscale but also identify that this issue mainly arises from the initially formed chloride-rich clusters during perovskite nucleation. Our work sheds light on a long-term neglected factor impeding the advancement of blue light-emitting diodes using mixed halide perovskites and provides a practical strategy to mitigate this issue.
  •  
49.
  • Magnusson, Lisa U., 1975, et al. (author)
  • Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
  • 2012
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
  • Journal article (peer-reviewed)abstract
    • Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells) present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr(-/-)) mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role.
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50.
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