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1.
  • Sarwar, Nadeem, et al. (författare)
  • Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
  • 2012
  • Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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2.
  • Zheng, Hou-Feng, et al. (författare)
  • Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
  • Tidskriftsartikel (refereegranskat)abstract
    • The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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3.
  • Becker, Joel, et al. (författare)
  • Resource profile and user guide of the Polygenic Index Repository
  • 2021
  • Ingår i: Nature Human Behaviour. - : Nature Research (part of Springer Nature). - 2397-3374. ; 51:6, s. 694-695
  • Tidskriftsartikel (refereegranskat)abstract
    • Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies—some not previously published—from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
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4.
  • Bekele, Maheteme, et al. (författare)
  • Tumor and immune cell profiling in breast cancer using highly multiplexed imaging mass cytometry single-cell technology demonstrates tumor heterogeneity and immune phenotypic abnormality in Ethiopian women
  • 2020
  • Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 80:21 Suppl.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Tumor heterogeneity represents a complex challenge to cancer treatment, disease recurrence, and patient survival. Imaging mass cytometry (IMC) is an emerging proteomic tool for cancer profiling in tumor tissue samples. IMC enables digital image analysis by multiplexed immunostaining of cells and proteins within tissue and preserves spatial relations within tumor environment. We have applied IMC based approach to study the heterogeneity of invasive breast carcinoma protein expression pattern in formalin fixed paraffin embedded tissues.Methods: A total of 10 region of interest (ROI) derived from 5 patients with primary invasive breast carcinoma representing three molecular subclasses (HR+/HER2-,HER2+/HR- and TNBC) were stained with a 30-marker IMC metal labeled antibody panel (α-SMA, EGFR, p53, CD33, CD16, CD163, CD11b, PDL1, CD31, CD45, D44,Vimentin, FoxP3, CD4, ECadherin, CD68, CD20, CD8a, Cytokeratin7, PD1, GranzymeB, Ki67, ColTypeI, CD3, CD45RO, HLADR, DARC & CD11c). Tissue imaging was done by quantifying the abundance of bound antibody with a Hyperion IMC. MCD Viewer was used for visualization purpose and to export raw 16-bit tiff images for segmentation on CellProfiler. Segmentation masks were combined with the individual tiff files to extract single-cell information from each individual image. HistoCAT was applied to perform unbiased clustering of cell populations using the PhenoGraph algorithm and clustered cell populations was overlaid on t-SNE plot. The relative marker expression was used to generate heat-maps and each cluster was manually assigned a phenotype based on its expression profile.Results: The t-SNE generated from each ROI revealed different distinct cell populations and we report the presence of diverse tumor and immune cell populations in our samples. The (min, max) number of PhenoGraph clustered tumor cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. Similarly, the (min, max) number of PhenoGraph clustered immune cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. We also document the presence of inter and intra-tumor heterogeniety in expression of PD1 and PDL1 in all the tumor subtypes studied. Additionally, we report a phenotypic abnormality in the immune cell populations identified with dual or triple markers expression of the canonical CD antigens of T-Cells, B-Cells and macrophages.Conclusion: The current study demonstrates high-dimensional visualization with the simultaneous analysis of epithelial, immune, and stromal components using IMC can be used to explore cell populations in tumor tissue to quantify tumor heterogeneity or identification of novel clustering patterns that has potential for translational research and clinical practice. Significance: This study presents the potential of Imaging Mass Cytometry and single cell analysis algorithms in multiplex high throughput tumor tissue studies.
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5.
  • Bergström, Ann-Kristin, et al. (författare)
  • Contrasting plankton stoichiometry and nutrient regeneration in northern arctic and boreal lakes
  • 2018
  • Ingår i: Aquatic Sciences. - : Springer. - 1015-1621 .- 1420-9055. ; 80:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Contrasting carbon: nitrogen: phosphorus (C: N: P) stoichiometry between phytoplankton and zooplankton affect consumer growth and phytoplankton nutrient limitation via nutrient recycling by zooplankton. However, no study has assessed how regional differences in terrestrial loadings of organic matter affect plankton N: P stoichiometry and recycling in systems with low N deposition and N-limited phytoplankton. We address this question by using data from 14 unproductive headwater arctic and boreal lakes. We found that boreal lakes had higher lake water-and seston C, N and P concentrations than arctic lakes, whereas seston C: N, C: P and N: P ratios did not differ among regions. Boreal zooplankton were also richer in N and P relative to C, with lower somatic N: P ratios, compared to arctic lakes. Consequently, the estimated N: P imbalances between seston and zooplankton were negative in arctic lakes, indicating zooplankton feeding on phytoplankton of suboptimal N content, resulting in low consumer driven N: P recycling (medians arctic sub-mid and high altitude lakes: 11 and 13). In boreal lakes, estimated N: P imbalance did not differ from zero, with a seston N: P stoichiometry matching the N: P requirements of zooplankton, which resulted in higher consumer driven N: P recycling (median 18). Our results imply that regional climate induced catchment differences, through enhanced terrestrial nutrient inputs, affect plankton stoichiometry by raising consumer N: P recycling ratio and changing zooplankton from being mainly N-(arctic) to NP co-limited (boreal). Browning of lakes, in regions with low N deposition, may therefore promote large-scale regional changes in plankton nutrient limitation with potential feedbacks on pelagic food webs.
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6.
  • Bergström, Ann-Kristin, et al. (författare)
  • N-limited consumer growth and low nutrient regeneration N:P ratios in lakes with low N deposition
  • 2015
  • Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Nutrient limitation of primary producers and their consumers can have a large influence on ecosystem productivity. The nature and strength of nutrient limitation is driven both by external factors (e.g., nutrient loading) and internal processes (e.g., consumer-driven nutrient regeneration). Here we present results from a field study in 10 low productive headwater lakes in northern subarctic Sweden, where nitrogen (N) deposition is low and phytoplankton is primarily N-limited. We assessed the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of seston and zooplankton and estimated the N:P ratio of consumer-driven nutrient regeneration. Based on stoichiometric models, the estimated elemental imbalances between seston and zooplankton suggest that zooplankton were mainly N-limited and regenerated nutrients with low N:P ratios (median 11.9, atomic ratio). The predicted N:P regeneration ratios were consistent with results from phytoplankton nutrient limitation bioassays in mid-summer, i.e., the N:P regeneration was predicted to be low when phytoplankton were N-limited, and high when phytoplankton were P-limited. During other seasons, when water discharge was high, nutrient loading from the surrounding catchments apparently had the strongest effect on phytoplankton nutrient limitation. We propose that lakes with higher N:P ratios than the open ocean is an effect of N deposition, that N-limitation of consumers and phytoplankton is further enhanced by low nutrient regeneration N:P ratios, and that in the absence of N deposition, lake and ocean N:P stoichiometry are similar.
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7.
  • Bergström, Ann-Kristin, et al. (författare)
  • Nitrogen deposition and warming  – effects on phytoplankton nutrient limitation in subarctic lakes
  • 2013
  • Ingår i: Global Change Biology. - Hoboken, NJ : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 19:8, s. 2557-2568
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to predict the combined effects of enhanced nitrogen (N) deposition and warming on phytoplankton development in high latitude and mountain lakes. Consequently, we assessed, in a series of enclosureexperiments, how lake water nutrient stoichiometry and phytoplankton nutrient limitation varied over the growingseason in 11 lakes situated along an altitudinal/climate gradient with low N-deposition (<1 kg N ha1yr1) in northern subarctic Sweden. Short-term bioassay experiments with N- and P-additions revealed that phytoplankton inhigh-alpine lakes were more prone to P-limitation, and with decreasing altitude became increasingly N- andNP-colimited. Nutrient limitation was additionally most obvious in midsummer. There was also a strong positivecorrelation between phytoplankton growth and water temperature in the bioassays. Although excess nutrients wereavailable in spring and autumn, on these occasions growth was likely constrained by low water temperatures. Theseresults imply that enhanced N-deposition over the Swedish mountain areas will, with the exception of high-alpinelakes, enhance biomass and drive phytoplankton from N- to P-limitation. However, if not accompanied by warming,N-input from deposition will stimulate limited phytoplankton growth due to low water temperatures during largeparts of the growing season. Direct effects of warming, allowing increased metabolic rates and an extension of thegrowing season, seem equally crucial to synergistically enhance phytoplankton development in these lakes.
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8.
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9.
  • Blomqvist, Per, et al. (författare)
  • Characterisation of fire generated particles : BRANDFORSK project 700-061, FireTechnology, SP Report 2010:01
  • 2010
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Characterisation of fire generated particlesThe present project has examined the question of distribution patterns of important chemical compounds between gas phase and particle phase. It has also, in some cases, addressed the question of the distribution of individual particle-associated species between the different size-ranges of particles produced in a fire. The chemical compounds studied were hydrogen chloride (HCl), polycyclic aromatic hydrocarbons (PAHs), and isocyanates.The steady-state tube furnace, ISO/TS 19700, was chosen as the physical fire model in order to study the production of particles from different types of fire exposure. Three different fire types were investigated: oxidative pyrolysis, well-ventilated flaming fires and vitiated post flashover. Two materials were chosen for investigation, PVC-carpet and wood board, based on their prevalence fire exposure scenarios and their chemical composition. The particle production from the two materials investigated varied both concerning the amounts produced and the particle size distributions. The production of particles on a mass basis was generally significantly lower from the wood board compared with the PVC-carpet. The tests with the PVC-carpet showed that relatively large particles are produced from all combustion conditions examined. The tests made with the wood board show preferably predisposition towards the production of small-sized particles during flaming combustion.The analysis of PAHs in the tests with the PVC-carpet showed that volatile PAHs were dominate during all types of combustion. However, when the toxicity of the individual species was taken into account, the relative importance between volatile and particle associated PAHs changed. From the tests with the wood board material (OSB) it was noted that the highest yields of total PAHs were found from under ventilated conditions, and the volatile part of the total PAH dominated for this material as well. The yields found from the well-ventilated tests were very low. Toxicity weighted data showed that the particle associated part dominated the toxicity both for under ventilated and well-ventilated conditions.A study made of the presence of chlorine on particles showed that it is clear that the major part of the HCl produced during combustion of the PVC-carpet is present in the gas phase. Chlorine was found associated with particulates but these results were, however, inconclusive due to the difficulty in determining the source of the chlorine found in the soot fractions studied.The low polyurethane (PUR) content and the substantial degradation of the PUR in the tests resulted in no or very small amounts of quantifiable isocyanate dimers (i.e. high molecular species). Monoisocyanates such as ICA and MIC dominated in the emitted degradation products. These kinds of monoisocyanates are volatile compounds and almost exclusively present in the gas phase. 
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10.
  • Blomqvist, Per, et al. (författare)
  • Detailed study of distribution patterns of polycyclic aromatic hydrocarbons and isocyanates under different fire conditions
  • 2014
  • Ingår i: Fire and Materials. - : Wiley. - 0308-0501 .- 1099-1018. ; 38:1, s. 125-144
  • Tidskriftsartikel (refereegranskat)abstract
    • This study has examined the distribution patterns between gas phase and particle phase of some chemical compounds produced in fires. It has also addressed the question of the distribution of individual particle-associated species between the different size-ranges of particles. The chemical compounds studied and discussed in this paper are polycyclic aromatic hydrocarbons (PAHs), and isocyanates. The steady-state tube furnace, ISO/TS 19700, was chosen as the physical fire model in order to study the production of particles from different types of fire exposure, that is, oxidative pyrolysis, well-ventilated flaming fires and under-ventilated flaming post-flashover fires. Two materials were chosen for investigation, a polyvinyl chloride (PVC) carpet and a wood board. The particle production from the two materials investigated varied concerning both the amounts produced and the particle size distributions. The analysis of PAHs showed that volatile PAHs were generally dominant. However, when the toxicity of the individual species was taken into account, the relative importance between volatile and particle-associated PAHs shifted the dominance to particle-bound PAH for both materials. The substantial degradation in the tests of the low polyurethane content of the PVC carpet, and the (4,4′-methylenediphenyl diisocyanate)-based binder in the wood board resulted in no or very small amount of quantifiable diisocyanates.
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11.
  • Campbell, Walter S., et al. (författare)
  • A computable pathology report for precision medicine: extending an observables ontology unifying SNOMED CT and LOINC
  • 2018
  • Ingår i: JAMIA Journal of the American Medical Informatics Association. - : OXFORD UNIV PRESS. - 1067-5027 .- 1527-974X. ; 25:3, s. 259-266
  • Tidskriftsartikel (refereegranskat)abstract
    • The College of American Pathologists (CAP) introduced the first cancer synoptic reporting protocols in 1998. However, the objective of a fully computable and machine-readable cancer synoptic report remains elusive due to insufficient definitional content in Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) and Logical Observation Identifiers Names and Codes (LOINC). To address this terminology gap, investigators at the University of Nebraska Medical Center (UNMC) are developing, authoring, and testing a SNOMED CT observable ontology to represent the data elements identified by the synoptic worksheets of CAP. Investigators along with collaborators from the US National Library of Medicine, CAP, the International Health Terminology Standards Development Organization, and the UK Health and Social Care Information Centre analyzed and assessed required data elements for colorectal cancer and invasive breast cancer synoptic reporting. SNOMED CT concept expressions were developed at UNMC in the Nebraska LexiconA (c) SNOMED CT namespace. LOINC codes for each SNOMED CT expression were issued by the Regenstrief Institute. SNOMED CT concepts represented observation answer value sets. UNMC investigators created a total of 194 SNOMED CT observable entity concept definitions to represent required data elements for CAP colorectal and breast cancer synoptic worksheets, including biomarkers. Concepts were bound to colorectal and invasive breast cancer reports in the UNMC pathology system and successfully used to populate a UNMC biobank. The absence of a robust observables ontology represents a barrier to data capture and reuse in clinical areas founded upon observational information. Terminology developed in this project establishes the model to characterize pathology data for information exchange, public health, and research analytics.
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12.
  • Christmas, Matthew, et al. (författare)
  • Evolutionary constraint and innovation across hundreds of placental mammals
  • 2023
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
  • Tidskriftsartikel (refereegranskat)abstract
    • Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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13.
  • Eriksson, Joel, et al. (författare)
  • Limited Clinical Utility of a Genetic Risk Score for the Prediction of Fracture Risk in Elderly Subjects
  • 2015
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 30:1, s. 184-194
  • Tidskriftsartikel (refereegranskat)abstract
    • It is important to identify the patients at highest risk of fractures. A recent large-scale meta-analysis identified 63 autosomal single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD), of which 16 were also associated with fracture risk. Based on these findings, two genetic risk scores (GRS63 and GRS16) were developed. Our aim was to determine the clinical usefulness of these GRSs for the prediction of BMD, BMD change, and fracture risk in elderly subjects. We studied two male (Osteoporotic Fractures in Men Study [MrOS] US, MrOS Sweden) and one female (Study of Osteoporotic Fractures [SOF]) large prospective cohorts of older subjects, looking at BMD, BMD change, and radiographically and/or medically confirmed incident fractures (8067 subjects, 2185 incident nonvertebral or vertebral fractures). GRS63 was associated with BMD (3% of the variation explained) but not with BMD change. Both GRS63 and GRS16 were associated with fractures. After BMD adjustment, the effect sizes for these associations were substantially reduced. Similar results were found using an unweighted GRS63 and an unweighted GRS16 compared with those found using the corresponding weighted risk scores. Only minor improvements in C-statistics (AUC) for fractures were found when the GRSs were added to a base model (age, weight, and height), and no significant improvements in C-statistics were found when they were added to a model further adjusted for BMD. Net reclassification improvements with the addition of the GRSs to a base model were modest and substantially attenuated in BMD-adjusted models. GRS63 is associated with BMD, but not BMD change, suggesting that the genetic determinants of BMD differ from those of BMD change. When BMD is known, the clinical utility of the two GRSs for fracture prediction is limited in elderly subjects. (c) 2014 American Society for Bone and Mineral Research.
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14.
  • Estrada, Karol, et al. (författare)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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15.
  • Frazier-Wood, Alexis C., et al. (författare)
  • Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
  • 2016
  • Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
  • Tidskriftsartikel (refereegranskat)abstract
    • Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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16.
  • Gebregzabher, Endale, et al. (författare)
  • Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women
  • 2021
  • Ingår i: International Journal of Breast Cancer. - : Hindawi Publishing Corporation. - 2090-3170 .- 2090-3189. ; 2021
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women.Methods: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link.Results: Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39.Conclusion: The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.
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17.
  • Gustavsson, Marcus, et al. (författare)
  • Adsorption Efficiency of Respirator Filter Cartridges for Isocyanates
  • 2010
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 54:4, s. 377-390
  • Tidskriftsartikel (refereegranskat)abstract
    • In some industries, the temperature and the humidity will vary greatly between different work places, such as outdoor work in arctic or tropical climates. There is therefore a need to test respirator filters at conditions that simulate conditions that are relevant for the industries that they are used in. Filter cartridges were exposed to controlled atmospheres of varying isocyanate concentration, air humidity, and temperature in an exposure chamber. For isocyanic acid (ICA) and methyl isocyanate (MIC), the exposure concentrations were between 100 and 200 p.p.b., monitored using a proton transfer reaction mass spectrometer. ICA and MIC were generated by continuous thermal degradation of urea and dimethylurea. The breakthrough was studied by collecting air samples at the outlet of the filter cartridges using impinger flasks or dry samplers with di-n-butylamine as derivatization reagent for isocyanates followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. For hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI), the exposure concentrations were between 4 and 20 p.p.b. and were generated by wet membrane permeation. To reveal the profile of adsorption in different layers of the respirator filters, representative samples from each of the layers were hydrolyzed. The hydrolysis products hexamethylene diamine and isophorone diamine were determined after derivatization with pentafluoropropionic anhydride (PFPA) followed by LC-MS/MS analysis. The two filter types studied efficiently absorbed both ICA and MIC. There was no trend of impaired performance throughout 48-h exposure tests. Even when the filters were exposed to high concentrations (similar to 200 p.p.b.) of ICA and MIC for 96 h, the isocyanates were efficiently absorbed with only a limited breakthrough. The majority of the HDI and IPDI (> 90%) were absorbed in the top layers of the absorbant, but HDI and IPDI penetrated farther down into the respirator filters during 120 h of exposure as compared to 16 h exposure.
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18.
  • Gylestam, Daniel, 1979-, et al. (författare)
  • Determination of Gas Phase Isocyanates Using Proton Transfer Reaction Mass Spectrometry
  • 2011
  • Ingår i: Analytical Chemistry Letters. - : Informa UK Limited. - 2229-7928 .- 2230-7532. ; 1:4, s. 261-271
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the development of proton transfer reaction-mass spectrometry (PTR-MS) methodology for on-line monitoring, using a direct reading instrument, of several typical gas phase isocyanates, including isocyanic acid (ICA), ethyl isocyanate (EIC), phenyl isocyanate (PhI), hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI). In the study, ICA and MIC were generated by thermal degradation of urea and 1,3-dimethylurea, respectively, while the other isocyanates were generated by liquid and gas permeation techniques. Comparative, reference measurements were made by sampling isocyanate atmosphere using impinger flasks containing the reagent di-n-butyl amine (DBA) then determining the resulting DBA derivatives by liquid chromatography (LC)-MS/MS. Reproducible measurements were obtained, with a <10 % drift in PTR-MS responses during a 12 month period. Further, there were linear correlations (R2>0.99) between the data acquired by the PTR-MS technique and air sampling followed by LC-MS/MS for all tested isocyanates in the concentration range 2-100 ppb, with a PTR-MS detection limits in the low ppb range. For all isocyanates except EIC, BIC, HDI and IPDI, the protonated molecular ions were the most abundant ions in the PTR mass spectra. Overall, the results show that the developed method enables sensitive, time-resolved measurements of airborne isocyanates to be acquired over several weeks.
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19.
  • Gylestam, Daniel, 1979-, et al. (författare)
  • Dry Sampling of Gas-Phase Isocyanates and Isocyanate Aerosols from Thermal Degradation of Polyurethane
  • 2014
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 58:1, s. 28-49
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of a dry sampler, with an impregnated denuder in series with a glass fibre filter, using di-n-butylamine (DBA) for airborne isocyanates (200ml min−1) is investigated and compared with an impinger flask with a glass fibre filter in series (1 l min−1). An exposure chamber containing 1,6-hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), and 2,4- and 2,6-toluene diisocyanate (TDI) in the concentration range of 5–205 μg m−3 [0.7–33 p.p.b.; relative humidity (RH) 50%], generated by gas- and liquid-phase permeation, was used for the investigation. The precision for the dry sampling for five series with eight samplers were in the range of 2.0–6.1% with an average of 3.8%. During 120-min sampling (n = 4), no breakthrough was observed when analysing samplers in series. Sixty-four exposed samplers were analysed after storage for 0, 7, 14, and 21 days. No breakdown of isocyanate derivatives was observed. Twenty-eight samplers in groups of eight were collecting isocyanates during 0.5–32h. Virtually linear relationships were obtained with regard to sampling time and collected isocyanates with correlation coefficients in the range of 0.998–0.999 with the intercept close to the origin. Pre- or post-exposure to ambient air did not affect the result. Dry sampling (n = 48) with impinger-filter sampling (n = 48) of thermal decomposition product of polyurethane polymers, at RH 20, 40, 60, and 90%, was compared for 11 isocyanate compounds. The ratio between the different isocyanates collected with dry samplers and impinger-filter samplers was in the range of 0.80–1.14 for RH = 20%, 0.8–1.25 for RH = 40%, 0.76–1.4 for RH = 60%, and 0.72–3.7 for RH = 90%. Taking into account experimental errors, it seems clear that isocyanic acid DBA derivatives are found at higher levels in the dry samples compared with impinger-filter samplers at elevated humidity. The dry sampling using DBA as the reagent enables easy and robust sampling without the need of field extraction.
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20.
  • Gylestam, Daniel, 1979- (författare)
  • Isocyanates - methodology for gas and particle generation, sampling and detection
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Isocyanates are mainly used in the industry for the production of polyurethane (PUR) plastics. Workers are at risk of being exposed during the manufacturing of PUR. During thermal degradation of PUR, isocyanates are released and workers involved in hot work such as fire-fighting, welding etc. may also be exposed.Isocyanates are known to cause allergic diseases and are the most common cause of occupational asthma. Some of the isocyanates used are suspected human carcinogens. Exposure among workers occurs frequently.Isocyanates are reactive unstable compounds that need to be converted to stabile derivatives immediately during sampling to avoid underestimation of the exposure. Di-n-ButylAmine (DBA) was used as derivatising reagent to form stable urea derivatives. The DBA derivatives were analysed using LC-MS/MS.In this thesis a novel technology for the direct monitoring of isocyanates using a Proton Transfer Reaction Mass Spectrometry (PTR-MS) is presented. Advancement of technology for the generation of isocyanates in an environmental chamber, dry sampling, particle-size fractionated sampling and the testing of respirator filter cartridges are described.The dry sampler was demonstrated to be robust and enabled sampling up to 32 h. Precise sampling without the need of field extraction was made possible.The particle-size fractionated sampling efficiently separated gas-phase and respirable particle-borne isocyanates (< 4µm in diameter).Two personal protective respirator filter cartridges were studied. No trend of impaired performance for mono-isocyanates throughout 48-h exposure tests was found.The distribution patterns, in a steady-state tube-furnace oven, between gas phase and different particle-phase fractions of isocyanates produced in fires were investigated. The substantial degradation of a PVC-carpet containing PUR and a wood board with a MDI based binder resulted mainly in the formation of high levels of monoisocyanates.
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21.
  • Gylestam, Daniel, 1979-, et al. (författare)
  • Sampling of Respirable Isocyanate Particles
  • 2014
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 58:3, s. 340-354
  • Tidskriftsartikel (refereegranskat)abstract
    • An advanced design of a denuder impactor (DI) sampler has been developed for characterization of possible airborne isocyanate exposure in different particle size fractions. The sampler is equipped with 12 different parallel denuder tubes, 4 impaction stages with the cut-off values (d50) of: 9.5, 4, 2.5 and 1 µm, and an end filter that collects particles < 1 µm. All collecting parts were impregnated with di-n-butylamine DBA as the reagent in a mixture with acetic acid. The performance of the DI sampler was studied on a standard atmosphere containing gas and particulate isocyanates. The isocyanate atmosphere was generated by liquid permeation of 2,4-, 2,6-Toluene Diisocyanate (TDI), 1,6-Hexamethylene Diisocyanate (HDI) and Isophorone Diisocyanate (IPDI). 4,4’-Methylene Diphenyl Diisocyanate (MDI) particles were generated by heating of technical MDI and condensing the mixture of gas and particle-borne MDI in an atmosphere containing mixed salt particles. The study was performed in a 0.85 m3 environmental chamber with stainless steel walls. With the advancement of the DI sampler it is now possible to collect isocyanate particle samples for up to 320min. The performance of the DI sampler is essentially unaffected by the humidity. The DI sampler and the ASSET™ EZ4-NCO sampler (Sigma-Aldrich/Supelco, Bellefonte, PA, USA) gave similar results. Sample losses within the DI sampler are low. In the environmental chamber it was observed that the particle distribution may be affected by the humidity and ageing. A scanning mobility particle sizer (SMPS) was used to separate a flow of selected fractions containing MDI particles from mixed MDI and salt particles. The particle-size distribution had a maximum at about 300nm, but later in the environmental chamber 1 µm dominated. The distribution was very different as compared to with only NaCl or MDI present. The biological relevance for studying isocyanate nano particles is significant as these have the possibility to reach the lower airways where allergic reactions may occur. SMPS and isocyanate air sampling can be used for the investigation of isocyanate nano particles.
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22.
  • Hadgu, Endale, et al. (författare)
  • Breast cancer in Ethiopia : evidence for geographic difference in the distribution of molecular subtypes in Africa
  • 2018
  • Ingår i: BMC Women's Health. - : BioMed Central. - 1472-6874. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2). Limited data from East Africa including Ethiopia however shows hormone receptor negative tumors to account for a lower proportion of all breast cancers than has been reported from elsewhere in Africa.METHODS: In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were assessed using immunohistochemistry from tissue microarrays. FISH was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases.RESULTS: The distribution of molecular subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER were positive in 65% of all tumors and 43% the cases were positive for PR. There was statistically significant difference in median age at diagnosis between the molecular subtypes (P < 0.05). There was a bimodal distribution of molecular subtypes in different age ranges with Luminal B subtype being more common at younger ages (median = 36) and Luminal A subtype more prevalent at older ages (median = 42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer.CONCLUSION: The present study detected Luminal A breast cancer to be the most common subtype and reveals a relatively low rate of hormone receptor negative and TNBC. Our findings and results from other East African studies suggest geographic variability in the distribution of the molecular subtypes of breast cancer in Africa and hence have important clinical and policy implications for breast cancer control and treatment in Ethiopia.
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23.
  • Hadgu, Endale, et al. (författare)
  • Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia : A cross sectional study
  • 2020
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 15:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.
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24.
  • Karlsson, Christofer M. G., et al. (författare)
  • Different gene expression responses in two Baltic Sea heterotrophic model bacteria to dinoflagellate dissolved organic matter
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Phytoplankton release massive amounts of dissolved organic matter (DOM) into the water column during recurring blooms in coastal waters and inland seas. The released DOM includes dissolved organic carbon, nitrogen and phosphorus, in a complex mixture of both known and unknown compounds, and is a rich nutrient source for heterotrophic bacteria. The metabolic activity of heterotrophic bacteria during and after phytoplankton blooms can hence be expected to reflect the characteristics of the released DOM. With this in mind, we wanted to investigate if bacterioplankton could be used as “living sensors” of phytoplankton DOM quantity and quality, and to trace the flow of nutrients in the ecosystem. We used transcriptional activity from Baltic Sea bacterial isolates (Polaribacter sp. BAL334 (Flavobacteriia) and Brevundimonas sp. BAL450 (Alphaproteobacteria)) exposed to DOM derived from the dinoflagellate Prorocentrum minimum in exponential and stationary growth phases respectively. We observed strong responses both in terms of physiology – bacterial abundance – and the expressed metabolic pathways – e.g. Membrane Transport, Fatty Acids, Lipids and Isoprenoids – of the populations in samples exposed to dinoflagellate DOM compared with controls. Particularly striking was the increased expression of Ton and Tol transport systems, commonly associated with uptake of complex molecules, in both isolates. Equally important were the differences in metabolic responses between the two isolates, caused by differences in gene repertoire between them, emphasizing the importance of separating the responses of different taxa in analyses of community sequence data. Differences in response to DOM sourced from exponentially and stationary growing dinoflagellates were less pronounced, although not absent, than differences between the bacterial isolates. This suggests that shifts in metabolism during the different phases of a phytoplankton bloom might be detectable in individual bacterial populations. To conclude, our work opened a door to the future use of bacterioplankton as living sensors of environmental status, particularly with respect to phytoplankton blooms.
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25.
  • Karlsson, Christofer M. G., et al. (författare)
  • Direct effects of organic pollutants on the growth and gene expression of the Baltic Sea model bacterium Rheinheimera sp. BAL341
  • 2019
  • Ingår i: Microbial Biotechnology. - : John Wiley & Sons. - 1751-7907 .- 1751-7915. ; 12:5, s. 892-906
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic pollutants (OPs) are critically toxic, bioaccumulative and globally widespread. Moreover, several OPs negatively influence aquatic wildlife. Although bacteria are major drivers of the ocean carbon cycle and the turnover of vital elements, there is limited knowledge of OP effects on heterotrophic bacterioplankton. We therefore investigated growth and gene expression responses of the Baltic Sea model bacterium Rheinheimera sp. BAL341 to environmentally relevant concentrations of distinct classes of OPs in 2-h incubation experiments. During exponential growth, exposure to a mix of polycyclic aromatic hydrocarbons, alkanes and organophosphate esters (denoted MIX) resulted in a significant decrease (between 9% and 18%) in bacterial abundance and production compared with controls. In contrast, combined exposure to perfluorooctanesulfonic acids and perfluorooctanoic acids (denoted PFAS) had no significant effect on growth. Nevertheless, MIX and PFAS exposures both induced significant shifts in gene expression profiles compared with controls in exponential growth. This involved several functional metabolism categories (e.g. stress response and fatty acids metabolism), some of which were pollutant-specific (e.g. phosphate acquisition and alkane-1 monooxygenase genes). In stationary phase, only two genes in the MIX treatment were significantly differentially expressed. The substantial direct influence of OPs on metabolism during bacterial growth suggests that widespread OPs could severely alter biogeochemical processes governed by bacterioplankton.
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26.
  • Karlsson, Daniel, et al. (författare)
  • Experimental and theoretical study of the photodissociation of bromo-3-fluorobenzene
  • 2008
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 128:3, s. 034307-
  • Tidskriftsartikel (refereegranskat)abstract
    • The UV photodissociation of bromo-3-fluorobenzene under collisionless conditions has been studied as a function of the excitation wavelength between 255 and 265 nm. The experiments were performed using ultrafast pump-probe laser spectroscopy. To aid in the interpretation of the results, it was necessary to extend the theoretical framework substantially compared to previous studies, to also include quantum dynamical simulations employing a two-dimensional nuclear Hamiltonian. The nonadiabatic potential energy surfaces (PES) were parameterized against high-level MS-CASTP2 quantum chemical calculations, using both the C–Br distance and the out-of-plane bending of the bromine as nuclear parameters. We show that the wavelength dependence of the photodissociation via the S0→1ππ*→1πσ* channel, accessible with a ∼ 260 nm pulse, is captured in this model. We thereby present the first correlation between experiments and theory within the quantitative regime.
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27.
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28.
  • Karlsson, Roger, 1975, et al. (författare)
  • Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping
  • 2020
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 19:3, s. 518-528
  • Tidskriftsartikel (refereegranskat)abstract
    • Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.
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29.
  • Karlsson, Roger, 1975, et al. (författare)
  • Proteotyping bacteria: Characterization, differentiation and identification of pneumococcus and other species within the Mitis Group of the genus Streptococcus by tandem mass spectrometry proteomics
  • 2018
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A range of methodologies may be used for analyzing bacteria, depending on the purpose and the level of resolution needed. The capability for recognition of species distinctions within the complex spectrum of bacterial diversity is necessary for progress in microbiological research. In clinical settings, accurate, rapid and cost-effective methods are essential for early and efficient treatment of infections. Characterization and identification of microorganisms, using, bottom-up proteomics, or "proteotyping", relies on recognition of species-unique or associated peptides, by tandem mass spectrometry analyses, dependent upon an accurate and comprehensive foundation of genome sequence data, allowing for differentiation of species, at amino acid-level resolution. In this study, the high resolution and accuracy of MS/MS-based proteotyping was demonstrated, through analyses of the three phylogenetically and taxonomically most closely-related species of the Mitis Group of the genus Streptococcus: i.e., the pathogenic species, Streptococcus pneumoniae (pneumococcus), and the commensal species, Streptococcus pseudopneumoniae and Streptococcus mitis. To achieve high accuracy, a genome sequence database used for matching peptides was created and carefully curated. Here, MS-based, bottom-up proteotyping was observed and confirmed to attain the level of resolution necessary for differentiating and identifying the most-closely related bacterial species, as demonstrated by analyses of species of the Streptococcus Mitis Group, even when S. pneumoniae were mixed with S. pseudopneumoniae and S. mitis, by matching and identifying more than 200 unique peptides for each species.
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30.
  • Kondori, Nahid, 1967, et al. (författare)
  • Mass Spectrometry Proteotyping-Based Detection and Identification of Staphylococcus aureus, Escherichia coli, and Candida albicans in Blood
  • 2021
  • Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Bloodstream infections (BSIs), the presence of microorganisms in blood, are potentially serious conditions that can quickly develop into sepsis and life-threatening situations. When assessing proper treatment, rapid diagnosis is the key; besides clinical judgement performed by attending physicians, supporting microbiological tests typically are performed, often requiring microbial isolation and culturing steps, which increases the time required for confirming positive cases of BSI. The additional waiting time forces physicians to prescribe broad-spectrum antibiotics and empirically based treatments, before determining the precise cause of the disease. Thus, alternative and more rapid cultivation-independent methods are needed to improve clinical diagnostics, supporting prompt and accurate treatment and reducing the development of antibiotic resistance. In this study, a culture-independent workflow for pathogen detection and identification in blood samples was developed, using peptide biomarkers and applying bottom-up proteomics analyses, i.e., so-called "proteotyping". To demonstrate the feasibility of detection of blood infectious pathogens, using proteotyping, Escherichia coli and Staphylococcus aureus were included in the study, as the most prominent bacterial causes of bacteremia and sepsis, as well as Candida albicans, one of the most prominent causes of fungemia. Model systems including spiked negative blood samples, as well as positive blood cultures, without further culturing steps, were investigated. Furthermore, an experiment designed to determine the incubation time needed for correct identification of the infectious pathogens in blood cultures was performed. The results for the spiked negative blood samples showed that proteotyping was 100- to 1,000-fold more sensitive, in comparison with the MALDI-TOF MS-based approach. Furthermore, in the analyses of ten positive blood cultures each of E. coli and S. aureus, both the MALDI-TOF MS-based and proteotyping approaches were successful in the identification of E. coli, although only proteotyping could identify S. aureus correctly in all samples. Compared with the MALDI-TOF MS-based approaches, shotgun proteotyping demonstrated higher sensitivity and accuracy, and required significantly shorter incubation time before detection and identification of the correct pathogen could be accomplished.
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31.
  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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32.
  • Liptzin, Daniel, et al. (författare)
  • Spatial and Temporal Patterns in Atmospheric Deposition of Dissolved Organic Carbon
  • 2022
  • Ingår i: Global Biogeochemical Cycles. - : American Geophysical Union (AGU). - 0886-6236 .- 1944-9224. ; 36:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric deposition of dissolved organic carbon (DOC) to terrestrial ecosystems is a small, but rarely studied component of the global carbon (C) cycle.Emissions of volatile organic compounds (VOC) and organic particulates are the sources of atmospheric C and deposition represents a major pathway for the removal of organic C from the atmosphere.Here, we evaluate the spatial and temporal patterns of DOC deposition using 70 data sets at least one year in length ranging from 40° south to 66° north latitude. Globally, the median DOC concentration in bulk deposition was 1.7 mg L −1. The DOC concentrations were significantly higher in tropical (<25°) latitudes compared to temperate (>25°) latitudes.DOC deposition was significantly higher in the tropics because of both higher DOC concentrations and precipitation. Using the global median or latitudinal specific DOC concentrations leads to a calculated global deposition of 202 or 295 Tg C yr −1 respectively.Many sites exhibited seasonal variability in DOC concentration. At temperate sites, DOC concentrations were higher during the growing season; at tropical sites, DOC concentrations were higher during the dry season. Thirteen of the thirty-four long-term (>10 years) data sets showed significant declines in DOC concentration over time with the others showing no significant change.Based on the magnitude and timing of the various sources of organic C to the atmosphere, biogenic VOCs likely explain the latitudinal pattern and the seasonal pattern at temperate latitudes while decreases in anthropogenic emissions are the most likely explanation for the declines in DOC  concentration.
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33.
  • Liu, Ya-Jun, et al. (författare)
  • Photodissociation of Bromobenzene, Dibromobenzene, and 1,3,5-Tribromobenzene
  • 2004
  • Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 120:14, s. 6502-
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantum chemical calculations have been performed on the ground state and several low-lying excited states of bromobenzene, ortho-, meta-, and para-dibromobenzene, and 1,3,5-tribromobenzene using high-level ab initio and hybrid density-functional methods. Experimental observations of ultrafast predissociation in these molecules are clarified from extensive theoretical information about all low-energy potential-energy curves together with symmetry arguments. The intriguing observation that o- and m-dibromobenzene have two ultrafast predissociation channels while bromobenzene, p-dibromobenzene, and 1,3,5-tribromobenzene only have one such channel is explained from the calculated potential-energy curves. These show that the lowering of point-group symmetry from C2v to Cs along the main photodissociation reaction coordinate, which only occurs in o- and m-dibromobenzene, opens up a new predissociation channel. Dynamical quantum simulations based on the calculated potential-energy curves are used to estimate the coupling strength at the intersystem crossing point in bromobenzene.
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34.
  • Lundgren, Markus, et al. (författare)
  • Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
  • 2017
  • Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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35.
  •  
36.
  • Momcilovic, Dane, et al. (författare)
  • Derivatization using dimethylamine for tandem mass spectrometric structure analysis of enzymatically and acidically depolymerized methyl cellulose
  • 2005
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:9, s. 2948-2959
  • Tidskriftsartikel (refereegranskat)abstract
    • Structure analysis of partially depolymerized methyl cellulose was performed by nanoelectrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) and by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS). Dimethylamine (DMA) was used for the first time as a reducing end derivatization reagent for oligosaccharides. This is an attractive reagent since it could be easily removed from the reaction mixture. Most important it also introduces a basic functional group that increased the sensitivity in both MALDI and nano-ESI. Depolymerization was made in two ways: one by the cellulose selective endoglucanase 5A from Bacillus agaradhaerens (Ba Ce15A) and the other by trifluoroacetic acid. The DMA derivatives formed both protonated and sodiated molecules in nano-ESI and MALDI. Tandem MS of protonated molecules yielded predominantly Y fragments from which the distribution of the substituents in the oligomers could be measured. Fragments obtained in tandem MS of sodiated molecules provided information regarding the positions of the substituents within the anhydroglucose units (AGUs). It was found that Ba Ce15A could cleave glucosidic bonds also if the AGU on the reducing side of the bond was fully methylated. The combination of DMA derivatization and tandem MS was demonstrated as a tool for the characterization of endoglucanase selectivity.
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37.
  • Nordanstig, Annika, 1974, et al. (författare)
  • EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
  •  
38.
  • Sartor, Oliver, et al. (författare)
  • Re-treatment with radium-223 : 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases
  • 2019
  • Ingår i: The Prostate. - : Wiley Periodicals. - 0270-4137 .- 1097-0045. ; 79:14, s. 1683-1691
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study.Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported.Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months.Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.
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39.
  • Stec, A. A., et al. (författare)
  • Analysis of toxic effluents released from PVC carpet under different fire conditions
  • 2013
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 90:1, s. 65-71
  • Tidskriftsartikel (refereegranskat)abstract
    • A large number of investigations have been reported on minimising the PAH and PCDD/F yields during controlled combustion, such as incineration. This study is an attempt to quantify acute and chronic toxicants including PAH and PCDD/F in conditions relating to unwanted fires. This paper investigates distribution patterns of fire effluents between gas and aerosol phase, and the different particle size-ranges produced under different fire conditions. PVC carpet was selected as the fuel as a precursor for both PAH and PCDD/F. In order to generate fire effluents under controlled fire conditions, the steady-state tube furnace, was chosen as the physical fire model. Fire scenarios included oxidative pyrolysis, well-ventilated and under-ventilated fires. Fire effluent measurements included: carbon monoxide, carbon dioxide, hydrogen chloride, polycyclic aromatic hydrocarbons, chlorinated dibenzo-dioxins and furans and soot. The distribution patterns between gas and particle phase, and the size-ranges of the particles produced in these fires together with their chemical composition is also reported. Significant quantities of respirable submicron particles were detected, together with a range of PAHs. Lower levels of halogenated dioxins were detected in the fire residue compared with those found in other studies. Nevertheless, the findings do have implications for the health and safety of fire and rescue personnel, fire investigators, and other individuals exposed to the residue from unwanted fires.
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40.
  • Zeng, Chenjie, et al. (författare)
  • Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
  • 2016
  • Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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41.
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42.
  • Abramowski, A., et al. (författare)
  • The 2010 very high energy gamma-RAY flare and 10 years of multi-wavelength observations of M 87
  • 2012
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 746:2, s. 151-
  • Tidskriftsartikel (refereegranskat)abstract
    • The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
  •  
43.
  • Acciari, V. A., et al. (författare)
  • Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
  • 2009
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
  • Tidskriftsartikel (refereegranskat)abstract
    • The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.
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44.
  • Actis, M., et al. (författare)
  • Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
  • 2011
  • Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
  •  
45.
  • Adams, Kelly L., et al. (författare)
  • Steady-State Electrochemical Determination of Lipidic Nanotube Diameter Utilizing an Artificial Cell Model
  • 2010
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 82:3, s. 1020-1026
  • Tidskriftsartikel (refereegranskat)abstract
    • By exploiting the capabilities of steady-state electrochemical measurements, we have measured the inner diameter of a lipid nanotube using Fick’s first law of diffusion in conjunction with an imposed linear concentration gradient of electroactive molecules over the length of the nanotube. Fick’s law has been used in this way to provide a direct relationship between the nanotube diameter and the measurable experimental parameters Δi (change in current) and nanotube length. Catechol was used to determine the Δi attributed to its flux out of the nanotube. Comparing the nanotube diameter as a function of nanotube length revealed that membrane elastic energy was playing an important role in determining the size of the nanotube and was different when the tube was connected to either end of two vesicles or to a vesicle on one end and a pipet tip on the other. We assume that repulsive interaction between neck regions can be used to explain the trends observed. This theoretical approach based on elastic energy considerations provides a qualitative description consistent with experimental data.
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46.
  • Adolfsson, Daniel, 1992-, et al. (författare)
  • TBV Radar SLAM - Trust but Verify Loop Candidates
  • 2023
  • Ingår i: IEEE Robotics and Automation Letters. - : IEEE. - 2377-3766. ; 8:6, s. 3613-3620
  • Tidskriftsartikel (refereegranskat)abstract
    • Robust SLAM in large-scale environments requires fault resilience and awareness at multiple stages, from sensing and odometry estimation to loop closure. In this work, we present TBV (Trust But Verify) Radar SLAM, a method for radar SLAM that introspectively verifies loop closure candidates. TBV Radar SLAM achieves a high correct-loop-retrieval rate by combining multiple place-recognition techniques: tightly coupled place similarity and odometry uncertainty search, creating loop descriptors from origin-shifted scans, and delaying loop selection until after verification. Robustness to false constraints is achieved by carefully verifying and selecting the most likely ones from multiple loop constraints. Importantly, the verification and selection are carried out after registration when additional sources of loop evidence can easily be computed. We integrate our loop retrieval and verification method with a robust odometry pipeline within a pose graph framework. By evaluation on public benchmarks we found that TBV Radar SLAM achieves 65% lower error than the previous state of the art. We also show that it generalizes across environments without needing to change any parameters. We provide the open-source implementation at https://github.com/dan11003/tbv_slam_public
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47.
  • Ahlgren, Erik, 1962, et al. (författare)
  • Biokombi Rya - slutrapporter från ingående delprojekt
  • 2007
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Inom projektet Biokombi Rya har ett flertal olika forskargrupper samarbetat för att studera system¬effekterna av förgasning av biobränsle ur olika aspekter. Syftet med projektet är att öka kunskapen om biobränsleförgasning i Sverige samt att utreda förutsättningar för att sådana anläggningar ska vara ekonomiskt och miljömässigt intressanta. En referensgrupp har varit kopplad till projektet där förutsättningar, resultat och slutsatser har behandlats.I denna underlagsrapport har slutrapporterna från projektets delprojekt samlats. De beskriver förutsättningar, metodansatser, använda data och resultat utförligt och utgör på så sätt ett viktigt komplement till den mer övergripande beskrivningen i projektets syntesrapport. De delrapporter som ingår har valts för att täcka in samtliga delar av projektet som är av allmänt intresse. Projektresultat som publicerats på annat sätt berörs dock mer kortfattat.Projektet Biokombi Rya har pågått under två år (2005-2006) och drivits av Chalmers EnergiCentrum. Förutom de omfattande analysinsatser som författarna till denna rapport står för, har Avdelningen för kemisk teknologi vid KTH, Siemens Industrial Turbines AB och Göteborg Energi AB bidragit med expertstöd. CIT Industriell Energianalys, med undertecknad som projektledare, har stått för projektledning och koordination.Projektet har finansierats av Energimyndigheten, Göteborg Energis forsknings¬stiftelse samt Göteborg Energi AB.
  •  
48.
  • Ahlström, Christoffer, et al. (författare)
  • Optimus Pråm - Semi-submersible wind farm installation vessel for Blekinge Offshore
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden the government is investing lots of resources in order to meet the energy need with clean and renewable alternatives. Since wind is an unlimited source of energy the exploitations of wind farms is of great interest. This report describes a conceptual design of an innovative offshore wind turbine installation vessel for inland sea conditions, with highest possible energy efficiency and environmental friendly performance in every detail. The customer, Blekinge Offshore, main requirement is to receive a concept with an as low installation cost as possible.The final concept Optimus Pråm includes one installation vessel, which is a semi-submersible barge, and one support vessel that supply the installation vessel with power and propulsion. The power is distributed from the support vessel to the installation vessel through a power cable. The installation vessel will be self-propelled during the installation phase using electrical motors and thrusters.The installation vessel shall be able to handle gravity foundations and fully assembled wind turbines, transported vertically to the installation site. Foundations and windmills will be fully assembled in Karlshamn port before transit to site. During transit the installation and support vessel are connected to each other in all motions except pitch. This almost total fixed connection makes the two vessels acts like one, which gives the joint vessel excellent manoeuvrability. When installing foundations, the installation vessel and the support vessel disconnect. The installation vessel places the foundation at the planned location by ballasting until the foundation has reached the seabed. After de-ballasting the installation vessel and support vessel connects again and transit back to the harbour. When installing wind turbines the two vessels are kept connected and makes highly accurate positioning for the installation possible
  •  
49.
  • Alfredsson, Eva C., et al. (författare)
  • Industrial climate mitigation strategies and the remaining fair carbon budget – The case of Sweden
  • 2024
  • Ingår i: Next Sustainability. - 2949-8236. ; 3, s. 100031-100031
  • Tidskriftsartikel (refereegranskat)abstract
    • This article explores the climate mitigation strategies of the 15 industries with the largest carbon dioxide emissions in Sweden. Starting from two carbon budget alternatives, we analyse the mitigation projections of the companies in relation to what can be considered their fair share of the remaining carbon budget for Sweden.We furthermore determine the uncertainties associated with the strategies. The results suggest that if the communicated mitigation plans are implemented as planned, the companies overdraft our main, 1.5-degree, budget option but stay within the alternative 1.7-degree budget. The analysis shows, however, that the timing and efficiency of emission reductions are crucial.Already small delays or lower efficiency in implementation, result in evident overdrafts of also the alternative budget. There are also substantial political and technical risks which can prevent timely mitigations. The article makes a novel contribution by analyzing industries’ mitigation strategies relative to their share of the remaining carbon budget.The article demonstrates the importance of transparent industrial climate mitigation strategies and in particular the need for policymakers to set incentive structures to promote strategy implementation.
  •  
50.
  • Alfredsson, Eva, 1963-, et al. (författare)
  • Investeringar för en rättvis klimatomställning
  • 2023
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Inom forskningsprogrammet FAIRTRANS har en workshop hållits om investeringars roll i klimatomställningen. Syftet var att lyfta fram olika gruppers behov av investeringar för en rättvis fossilfri framtid inom ramen för en svensk koldioxidbudget.
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