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1.
  • Justice, Anne E., et al. (author)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Journal article (peer-reviewed)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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2.
  • Surendran, Praveen, et al. (author)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
  • Journal article (peer-reviewed)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
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3.
  • Turcot, Valerie, et al. (author)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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4.
  • Ahlm, Lars, 1976-, et al. (author)
  • A comparison of dry and wet season aerosol number fluxes over the Amazon rain forest
  • 2010
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 10:6, s. 3063-3079
  • Journal article (peer-reviewed)abstract
    • Vertical number fluxes of aerosol particles and vertical fluxes of CO2 were measured with the eddy covariance method at the top of a 53m high tower in the Amazon rain forest as part of the LBA (The Large Scale Biosphere Atmosphere Experiment in Amazonia) experiment. The observed aerosol number fluxes included particles with sizes down to 10 nm in diameter. The measurements were carried out during the wet and dry season in 2008. In this study focus is on the dry season aerosol fluxes, with significant influence from biomass burning, and these are compared with aerosol fluxes measured during the wet season. Net particle deposition fluxes dominated in daytime in both seasons and the deposition flux was considerably larger in the dry season due to the much higher dry season particle concentration. The particle transfer velocity increased linearly with increasing friction velocity in both seasons. The difference in transfer velocity between the two seasons was small, indicating that the seasonal change in aerosol number size distribution is not enough for causing any significant change in deposition velocity. In general, particle transfer velocities in this study are low compared to studies over boreal forests. The reasons are probably the high percentage of accumulation mode particles and the low percentage of nucleation mode particles in the Amazon boundary layer, both in the dry and wet season, and low wind speeds in the tropics compared to the midlatitudes. In the dry season, nocturnal particle fluxes behaved very similar to the nocturnal CO2 fluxes. Throughout the night, the measured particle flux at the top of the tower was close to zero, but early in the morning there was an upward particle flux peak that is not likely a result of entrainment or local pollution. It is possible that these morning upward particle fluxes are associated with emission of primary biogenic particles from the rain forest. Emitted particles may be stored within the canopy during stable conditions at nighttime, similarly to CO2, and being released from the canopy when conditions become more turbulent in the morning.
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5.
  • Ahlm, Lars, 1976-, et al. (author)
  • Aerosol number fluxes over the Amazon rain forest during the wet season
  • 2009
  • In: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 9:24, s. 9381-9400
  • Journal article (peer-reviewed)abstract
    • Number fluxes of particles with diameter larger than 10 nm were measured with the eddy covariance method over the Amazon rain forest during the wet season as part of the LBA (The Large Scale Biosphere Atmosphere Experiment in Amazonia) campaign 2008. The primary goal was to investigate whether sources or sinks dominate the aerosol number flux in the tropical rain forest-atmosphere system. During the measurement campaign, from 12 March to 18 May, 60% of the particle fluxes pointed downward, which is a similar fraction to what has been observed over boreal forests. The net deposition flux prevailed even in the absolute cleanest atmospheric conditions during the campaign and therefore cannot be explained only by deposition of anthropogenic particles. The particle transfer velocity vt increased with increasing friction velocity and the relation is described by the equation vt=2.4×10−3×u* where u* is the friction velocity. Upward particle fluxes often appeared in the morning hours and seem to a large extent to be an effect of entrainment fluxes into a growing mixed layer rather than primary aerosol emission. In general, the number source of primary aerosol particles within the footprint area of the measurements was small, possibly because the measured particle number fluxes reflect mostly particles less than approximately 200 nm. This is an indication that the contribution of primary biogenic aerosol particles to the aerosol population in the Amazon boundary layer may be low in terms of number concentrations. However, the possibility of horizontal variations in primary aerosol emission over the Amazon rain forest cannot be ruled out.
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6.
  • Ahlm, Lars, et al. (author)
  • Emission and dry deposition of accumulation mode particles in the Amazon Basin
  • 2010
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 10:21, s. 10237-10253
  • Journal article (peer-reviewed)abstract
    • Size-resolved vertical aerosol number fluxes of particles in the diameter range 0.25–2.5 μm were measured with the eddy covariance method from a 53 m high tower over the Amazon rain forest, 60 km NNW of Manaus, Brazil. This study focuses on data measured during the relatively clean wet season, but a shorter measurement period from the more polluted dry season is used as a comparison. Size-resolved net particle fluxes of the five lowest size bins, representing 0.25–0.45 μm in diameter, pointed downward in more or less all wind sectors in the wet season. This is an indication that the source of primary biogenic aerosol particles may be small in this particle size range. In the diameter range 0.5–2.5 μm, vertical particle fluxes were highly dependent on wind direction. In wind sectors where anthropogenic influence was low, net emission fluxes dominated. However, in wind sectors associated with higher anthropogenic influence, net deposition fluxes dominated. The net emission fluxes were interpreted as primary biogenic aerosol emission, but deposition of anthropogenic particles seems to have masked this emission in wind sectors with higher anthropogenic influence. The emission fluxes were at maximum in the afternoon when the mixed layer is well developed, and these emissions were best correlated with horizontal wind speed by the equation log10F=0.47·U+2.26 where F is the emission number flux of 0.5–2.5 μm particles [m−2s−1] and U is the horizontal wind speed [ms−1] at the top of the tower.
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8.
  • Aranda-Guillén, Maribel, et al. (author)
  • A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
  • 2023
  • In: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
  • Journal article (peer-reviewed)abstract
    • Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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9.
  • David, Romain, et al. (author)
  • Converging on a Semantic Interoperability Framework for the European Data Space for Science, Research and Innovation (EOSC)
  • 2023
  • Conference paper (peer-reviewed)abstract
    • Semantic interoperability (SI) is at the heart of the FAIR principles and of the design of large scale cross disciplinary infrastructures. The European Open Science Cloud (EOSC) is a European-wide effort towards such an infrastructure, aiming to deepen the regional research collaboration and realising a shared data space for science, research and innovation. In this context, the research community’s voice is represented by the EOSC Association (EOSC-A) and a number of advisory groups with a broad range of representatives from different stakeholder organisations. The advisory group on metadata and data quality has formed a task force focusing on developing and implementing recommendations for SI (EOSC SI Task Force) with the ambition to converge on globally relevant and scalable SI solutions for EOSC. This paper provides context to SI in EOSC, the various components contributing to it, as well as some views on the socio-technical challenges to arriving at a consensus. In particular, the paper provides motivation for exploring the heterogeneity of SI solutions demonstrated across scientific communities and insight into the task force’s planned approach to conduct a survey to identify relevant components and structures. The paper is also an invitation to the global community to align and engage with the task force’s activities going forward.
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10.
  • Deans, Andrew R, et al. (author)
  • Finding Our Way through Phenotypes.
  • 2015
  • In: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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11.
  • Delle, M., et al. (author)
  • Celiac trunk coverage in endovascular aneurysm repair
  • 2010
  • In: Scandinavian Journal of Surgery. - : SAGE Publications. - 1457-4969. ; 99:4, s. 226-229
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: This retrospective study was undertaken to examine the risks associated with obstruction of the coeliac trunk in the process of treating aneurysms with endografting. MATERIAL AND METHODS: 120 patients were treated by endografting for aneurysmal disease. Of these, a subgroup of 9 patients had their celiac trunk covered. If possible, a preoperative angiography was performed to evaluate collateral flow from the superior mesenteric artery. This was considered to predict the risk for ischemia. RESULTS: None of the patients had any severe clinical event of the celiac trunk occlusion or clinical signs of intestinal ischemia. Three patients had transient increase of liver enzymes. CONCLUSIONS: In cases where the distal landing zone of the descending thoracic aorta is to short for endografting, covering of the celiac trunk may be an option if no other surgical alter-native is apparent. Preoperative angiography to visualise the presence of collateral vessels from the superior mesenteric artery is recommended.
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13.
  • Frey, H U, et al. (author)
  • Freja and ground-based analysis of inverted-V events
  • 1998
  • In: JOURNAL OF GEOPHYSICAL RESEARCH-SPACE PHYSICS. - 0148-0227. ; 103:A3, s. 4303-4314
  • Journal article (peer-reviewed)abstract
    • During two campaigns, ground-based auroral observations were performed in coordination with Freja. The high temporal and spatial resolution of the satellite instruments as well as the real-time recording with a stereoscopic camera system from the ground enabled detailed comparison of small- and large-scale optical phenomena with particle and field data measured by the satellite. Three passes of the satellite over inverted-V auroral arcs and over precipitation regions with strong field-aligned electron spectra are investigated. Brightness modulations within auroral arcs coincide with modulations of primary electron fluxes. The dynamics of small-scale structures within arcs as well as the proper motion of arcs are analyzed and compared with electric fields measured by the satellite and with BARS radar measurements. Energy fluxes independently determined from the ground and from the satellite are used to calculate the field-aligned conductance. The results agree with predictions of the kinetic theory of the mirror force, if we allow for variations of the density and thermal energy of the electrons in the source region of the magnetosphere. Detailed comparison of electron spectra and electric and magnetic field perturbations provide evidence of different acceleration mechanisms for the electrons, electrostatic acceleration inside inverted-V's, and wave acceleration in transient regions.
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14.
  • Hendriks, Kasper P., et al. (author)
  • Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
  • 2023
  • In: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
  • Journal article (peer-reviewed)abstract
    • The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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15.
  • Kurek, Magdalena, et al. (author)
  • Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
  • 2021
  • In: Cells. - : MDPI AG. - 2073-4409. ; 10:2
  • Journal article (peer-reviewed)abstract
    • Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
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16.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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17.
  • Nyberg Åkerström, Wolmar, et al. (author)
  • Developing and implementing the semantic interoperability recommendations of the EOSC Interoperability Framework
  • 2024
  • Reports (other academic/artistic)abstract
    • This document expands on and provides nuance to some of the concepts defined in the EOSC Interoperability Framework report from the EOSC Executive Board Working Groups (WG) FAIR and Architecture published in 2021 and the conceptualisation of an EOSC Interoperability Framework that it embodies (EOSC-IF). It accounts for a deep-dive into the landscape of semantic interoperability implementations and a wide range of interoperability scenarios focused around the Semantic Interoperability Specification, some subtypes of Semantic Business Objects, as well as the Semantic Artefact Catalogue and Mapping Repository. A small set of new concepts of relevance to this work and to EOSC at large have also been added.The introduction provides context to the creation of this report, the basic concepts section provides and overview of the related components of the EOSC-IF, and the following four sections summarise explorations that frame the concluding set of recommendations to the EOSC community at large.The explorations that frame the recommendations are titled as follows:The Semantic Interoperability Specification: Implementation profiles for communitiesThe Semantic Artefact Catalogue: Twelve maturity dimensionsThe Mapping Repository: Making a case for FAIR mappings and crosswalksImplementation examples: Common use cases and real-world case studiesThe recommendations themselves are organised under the following five broad categories:Align emerging adaptations and implementations to the Semantic View of the EOSC-IF (pp. 39–42)  reference architecture.Identify and consolidate different approaches to representing and exchanging (meta)data with the FAIR Digital Objects model described in the EOSC-IF (pp. 29–34).Extend the EOSC-IF to include a research process perspective that can support convergence on solutions for common use cases.Extend the set of Semantic Business Objects described in the EOSC-IF (pp. 40–41) to include artefacts such as mappings and crosswalks.Recognise Semantic Artefact Catalogue component described in the EOSC-IF (p. 42) as a critical part of the long-term viability of any research data infrastructure.
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18.
  • Orlando, Ludovic, et al. (author)
  • Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
  • 2013
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74-
  • Journal article (peer-reviewed)abstract
    • The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
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19.
  • Peng, Guotao, et al. (author)
  • Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract
  • 2020
  • In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 12:32, s. 16730-16737
  • Journal article (peer-reviewed)abstract
    • Understanding the biological fate of graphene-based materials such as graphene oxide (GO) is crucial to assess adverse effects following intentional or inadvertent exposure. Here we provide first evidence of biodegradation of GO in the gastrointestinal tract using zebrafish as a model. Raman mapping was deployed to assess biodegradation. The degradation was blocked upon knockdown ofnos2aencoding the inducible nitric oxide synthase (iNOS) or by pharmacological inhibition of NOS usingl-NAME, demonstrating that the process was nitric oxide (NO)-dependent. NO-dependent degradation of GO was further confirmedin vitroby combining a superoxide-generating system, xanthine/xanthine oxidase (X/XO), with an NO donor (PAPA NONOate), or by simultaneously producing superoxide and NO by decomposition of SIN-1. Finally, by using the transgenic strainTg(mpx:eGFP) to visualize the movement of neutrophils, we could show that inhibition of the degradation of GO resulted in increased neutrophil infiltration into the gastrointestinal tract, indicative of inflammation.
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  • Sunnerhagen, Torgny, et al. (author)
  • Biofilm formation on endovascular aneurysm repair (EVAR) grafts– a proof of concept in vitro model
  • 2023
  • In: Clinical Microbiology and Infection. - 1469-0691. ; 29:12, s. 1-1600
  • Journal article (peer-reviewed)abstract
    • ObjectivesAn endovascular aneurysm repair (EVAR) graft is a catheter-implanted vascular prosthesis and is the preferred treatment for patients with aortic aneurysm. If an EVAR graft becomes the focus of infection, the treatment possibilities are limited as it is technically difficult to remove the graft to obtain source control. This study examines whether Pseudomonas aeruginosa and Staphylococcus aureus form biofilm on EVAR prostheses.MethodsEVAR graft sections were exposed to bacteria at 102 or 108 colony forming units (CFU)/ml in lysogeny broth and Krebs-Ringer at 37°C, bacterial biofilm formation was evaluated by scanning electron microscopy (SEM) and counting CFU on the graft sections following antibiotic exposure at x10 minimal inhibitory concentration (MIC). Bacteria were tested for tolerance to benzyl penicillin, tobramycin and ciprofloxacin.ResultsBacterial exposure for 15 minutes established biofilms on all prosthesis fragments (6/6 replicates). After 4 hours, bacteria were firmly attached to the EVAR prostheses and resisted washing. After 18 to 24 hours the median CFU/g of EVAR graft reached 5.2 x 108 (1.15 x 108 – 1.1 x 109) for S. aureus and 9.1 x 107 (3.5 x 107 – 6.25 x 108) for P. aeruginosa. SEM showed bacterial attachment to the graft pieces. There was a time-dependent development of tolerance with approximately 20 (tobramycin), 560 (benzyl penicillin), and 600 (ciprofloxacin) times more S. aureus surviving antibiotic exposure in 24 compared to 0 hours old biofilm. Five (tobramycin) and 170 times (ciprofloxacin) more P. aeruginosa survived antibiotic exposure in 24 compared to 0 hours old biofilms.ConclusionsOur results show that bacteria can rapidly adhere to and subsequently form antibiotic tolerant biofilms on EVAR graft material in concentrations equivalent to levels seen in transient bacteremia in vivo. Potentially, the system can be used for identifying optimal treatment combinations for infected EVAR prosthesis.
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21.
  • Vogt, Matthias, et al. (author)
  • Heated submicron particle fluxes using an optical particle counter in urban environment
  • 2013
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 13:6, s. 3087-3096
  • Journal article (peer-reviewed)abstract
    • From May 2008 to March 2009 aerosol emissions were measured using the eddy covariance method covering the size range 0.25 to 2.5 mu m diameter (D-p) from a 105m tower, in central Stockholm, Sweden. Supporting chemical aerosol data were collected at roof and street level. Results show that the inorganic fraction of sulfate, nitrate, ammonium and sea salt accounts for approximately 15% of the total aerosol mass < 1 mu m D-p (PM1) with water soluble soil contributing 11% and water insoluble soil 47%. Carbonaceous compounds were at the most 27% of PM1 mass. It was found that heating the air from the tower to 200 degrees C resulted in the loss of approximately 60% of the aerosol volume at 0.25 mu m D-p whereas only 40% of the aerosol volume was removed at 0.6 mu m D-p. Further heating to 300 degrees C caused very little additional losses < 0.6 mu m D-p. The chemical analysis did not include carbonaceous compounds, but based on the difference between the total mass concentration and the sum of the analyzed non-carbonaceous materials, it can be assumed that the non-volatile particulate material (heated to 300 degrees C) consists mainly of carbonaceous compounds, including elemental carbon. Furthermore, it was found that the nonvolatile particle fraction < 0.6 mu m D-p correlated (r(2) = 0.4) with the BC concentration at roof level in the city, supporting the assumption that the non-volatile material consists of carbonaceous compounds. The average diurnal cycles of the BC emissions from road traffic (as inferred from the ratio of the incremental concentrations of nitrogen oxides (NOx) and BC measured on a densely trafficked street) and the fluxes of non-volatile material at tower level are in close agreement, suggesting a traffic source of BC. We have estimated the emission factors (EFs) for non-volatile particles < 0.6 mu m D-p to be 2.4 +/- 1.4 mg veh(-1) km(-1) based on either CO2 fluxes or traffic activity data. Light (LDV) and heavy duty vehicle (HDV) EFs were estimated using multiple linear regression and reveal that for non-volatile particulate matter in the 0.25 to 0.6 mu m D-p range, the EFHDV is approximately twice as high as the EFLDV, the difference not being statistically significant.
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  • Vogt, Matthias, et al. (author)
  • Seasonal and diurnal cycles of 0.25–2.5 μm aerosol fluxes over urban Stockholm, Sweden
  • 2011
  • In: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 63:5, s. 935-951
  • Journal article (peer-reviewed)abstract
    • Size resolved aerosol and gas fluxes were measured in Stockholm from 1 April 2008 to 15 April 2009 over both urban and green sectors. CO2 and H2O fluxes peaked in daytime for all seasons. CO2 concentrations peaked in winter. Due to vegetation influence the CO2 fluxes had different diurnal cycles and magnitude in the two sectors. In the urban sector, CO2 fluxes indicated a net source. The sector dominated by residential areas and green spaces had its highest aerosol fluxes in winter. In spring, super micrometer concentrations for both sectors were significantly higher, as were the urban sector rush hour fluxes. The submicrometer aerosol fluxes had a similar diurnal pattern with daytime maxima for all seasons. This suggests that only the super micrometer aerosol emissions are dependent on season. During spring there was a clear difference in super micrometer fluxes between wet and dry streets. Our direct flux measurements have improved the understanding of the processes behind these aerosol emissions. They support the hypothesis that the spring peak in aerosol emissions are due to road dust, produced during the winter, but not released in large quantities until the roads dry up during spring, and explain why Stockholm has problems meeting the EU directive for aerosol mass (PM10).
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26.
  • Vogt, Matthias, et al. (author)
  • The relationship between 0.25-2.5 mu m aerosol and CO2 emissions over a city
  • 2011
  • In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:10, s. 4851-4859
  • Journal article (peer-reviewed)abstract
    • Unlike exhaust emissions, non-exhaust traffic emissions are completely unregulated and in addition, there are large uncertainties in the non-exhaust emission factors required to estimate the emissions of these aerosols. This study provides the first published results of direct measurements of size resolved emission factors for particles in the size range 0.25-2.5 mu m using a new approach to derive aerosol emission factors based on carbon dioxide (CO2) emission fluxes. Aerosol fluxes were measured over one year using the eddy covariance method at the top of a 105m high communication tower in Stockholm, Sweden. Maximum CO2 and particle fluxes were found when the wind direction coincided with the area of densest traffic within the footprint area. Negative fluxes (uptake of CO2 and deposition of particles) coincided with periods of sampling from an urban forest area. The fluxes of CO2 were used to obtain emission factors for particles by assuming that the CO2 fluxes could be directly related to the amount of fuel burnt by vehicles in the footprint area. The estimated emission factor for the fleet mix in the measurement area was, in number 1.8 x 10(11) particle veh(-1) km(-1) (for 0.25-2.5 mu m size range). Assuming spherical particles of density 1600 kg m(-3) this corresponds to 27.5 mg veh(-1) km(-1). For particles (0.8-2.5 mu m) the emission factors were 5.1 x 10(9) veh(-1) km(-1) for number and 11.5 mg veh(-1) km(-1) for mass. But a wind speed dependence was noted for high wind speeds. Thus, for wind speeds larger than 9 ms(-1), as measured in the tower at 105m (U-105), the emission factor for particle number and mass was parameterised as: E-f(Number, 0.8-2.5 mu m) = (6.1 +/- 1.7)10(9)U(105)-50+/-188 and E-f(Mass, 0.8-2.5 mu m) = (20+/-12)U-105-171+/-122.
  •  
27.
  • Vogt, Matthias, et al. (author)
  • Traffic Aerosol emission velocity derived from direct flux measurements over urban Stockholm, Sweden
  • 2011
  • In: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 45:32, s. 5725-5731
  • Journal article (peer-reviewed)abstract
    • Size-resolved aerosol vertical number fluxes were measured using the eddy covariance method, 105 meters above the ground over the city of Stockholm, Sweden, between 1st April 2008 and 15th April 2009. The size range of the measurements cover particles from 0.25 to 2.5 μm diameter (Dp). Emission velocities (ve) were calculated for the same size range and were found to be well correlated with friction velocity (u*) and CO2 fluxes (FCO2). These variables were used to parameterize the emission velocity aswhere ve and u* are given in [m s−1], Dp in [μm], and FCO2 in [mmol m−2s−1]. The parameterization reproduces the average diurnal cycle from the observations well for particles sizes up to 0.6 μm Dp. For larger particles the parameterization tends to over predict the emission velocity. These larger particles are not believed to be produced by combustion and therefore not well represented by FCO2, which represents the traffic source through its fossil fuel consumption and the related CO2 emissions.
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