| 1. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 2. |
- Andersson, Mikael, et al.
(författare)
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Performance modeling of an Apache web server with bursty arrival traffic
- 2003
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Ingår i: IC'03 : proceedings of the international conference on internet computing. - 1932415025 ; , s. 508-511
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Konferensbidrag (refereegranskat)abstract
- Performance modeling is an important topic in capacity planning and overload control for web servers. We present a queueing model of an Apache web server that uses bursty arrival traffic. The arrivals of HTTP requests is assumed to be a Markov Modulated Poisson Process and the service discipline of the server is processor sharing. The total number of requests that can be processed at one time is limited to K. We obtain web server performance metrics such as average response time, throughput and blocking probability by simulations. Compared to other models, our model is conceptually simple. The model has been validated through measurements and simulations in our lab. The performance metrics predicted by the model fit well to the experimental outcome.
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| 3. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 4. |
- Karkela, T., et al.
(författare)
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RECENT FINDINGS ON RUTHENIUM CHEMISTRY IN A SEVERE ACCIDENT
- 2015
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Ingår i: Proceedings of the International OECD-NEA/NUGENIA-SARNET Workshop on the Progress in Iodine Behaviour for NPP Accident Analysis and Management.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The chemistry of radiotoxic ruthenium in a severe nuclear power accident has actively been investigated especially during the last decades. The Ru studies have covered the release from a fuel, the transport in the primary circuit and the behaviour in the containment building. The gathered experimental data have been utilized to understand the key parameters governing the Ru chemistry in a severe accident (SA) and to check the ability of the existing models of SA analysis codes to explain the experimental results. To further increase the knowledge on Ru behaviour, the collaboration on international level has been intensive. Lately, the widest and most active networks have been EU SARNET and EU SARNET2. The valuable effort of these networks on sharing information of e.g. national programs and on interpreting the experimental results is continued in EU NUGENIA program. More detailed studies on separate phenomena have been conducted e.g. as part of OECD/NEA STEM/START and ISTP/VERDON programs. Furthermore, Phébus FP tests have produced valuable data on integral phenomena.The large-scale integral and semi-integral experiments have confirmed that Ru release depends strongly on carrier gas. Ru is significantly released from an irradiated fuel sample under oxidizing conditions, in particular when air is involved. In addition, the oxidation of UO2 fuel seems to lead to a higher Ru release than in case of MOX fuel. Ruthenium can be transported to the containment atmosphere both in gaseous and particulate forms. The small-scale separate-effect experiments gave a detailed view on Ru transport. A high fraction of ruthenium was detected as particles at the outlet of the model primary circuit in an air atmosphere. However, the observed gaseous Ru fraction is higher than what could be expected based on thermodynamic equilibrium calculations. Further studies on the effect of flow residence time in a temperature gradient for the equilibrium of Ru oxides have been conducted.The effect of other fission products in the gas phase, as well as FP deposits on the surface of primary circuit, on the Ru transport has been investigated. For example, caesium containing deposits seemed to trap gaseous ruthenium effectively. Similarly in case of control rod residues, silver particles in the gas phase of the circuit acted as a sink for gaseous Ru. In an air ingress accident, the effect of air radiolysis products on the Ru chemistry becomes important. As the main air radiolysis products can be considered as oxidizing agents, their ability to oxidize the lower oxides of Ru to higher oxidation state has been examined.Most of Ru in the containment building ends up as deposits on the containment surfaces and in the sump. Experiments on the radiolytical revaporisation of ruthenium deposits on the epoxy paint surface indicated the release of gaseous ruthenium and it was enhanced under humid atmosphere and elevated temperature. It appeared that the products of air radiolysis caused by γ-radiation promoted the formation of gaseous ruthenium from Ru oxide deposits on paint in a higher amount than could be expected by pure ozone action. Concerning the irradiation tests of perruthenate aqueous solutions, they indicated the formation of gaseous Ru by γ-radiolysis products in solution.
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| 5. |
- Lindelöf, Linnea, et al.
(författare)
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A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
- 2024
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
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| 6. |
- Roxhed, Niclas, et al.
(författare)
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Multianalyte serology in home-sampled blood enables an unbiased assessment of the immune response against SARS-CoV-2
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Serological testing is essential to curb the consequences of the COVID-19 pandemic. However, most assays are still limited to single analytes and samples collected within healthcare. Thus, we establish a multianalyte and multiplexed approach to reliably profile IgG and IgM levels against several versions of SARS-CoV-2 proteins (S, RBD, N) in home-sampled dried blood spots (DBS). We analyse DBS collected during spring of 2020 from 878 random and undiagnosed individuals from the population in Stockholm, Sweden, and use classification approaches to estimate an accumulated seroprevalence of 12.5% (95% CI: 10.3%-14.7%). This includes 5.4% of the samples being IgG(+)IgM(+) against several SARS-CoV-2 proteins, as well as 2.1% being IgG(-)IgM(+) and 5.0% being IgG(+)IgM(-) for the virus' S protein. Subjects classified as IgG(+) for several SARS-CoV-2 proteins report influenza-like symptoms more frequently than those being IgG(+) for only the S protein (OR=6.1; p<0.001). Among all seropositive cases, 30% are asymptomatic. Our strategy enables an accurate individual-level and multiplexed assessment of antibodies in home-sampled blood, assisting our understanding about the undiagnosed seroprevalence and diversity of the immune response against the coronavirus. Here, Roxhed et al. develop a multiplexed approach to screen IgG and IgM levels against several SARS-CoV-2 proteins in home-sampled dried blood spots and estimate seroprevalence of 12.5% in Stockholm in spring of 2020.
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