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Sökning: WFRF:(Holm Patrik)

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  • Ahola, Virpi, et al. (författare)
  • The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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  • Bungau, Cristian, et al. (författare)
  • Induced activation in accelerator components
  • 2014
  • Ingår i: Physical Review Special Topics. Accelerators and Beams. - 1098-4402. ; 17:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The residual activity induced in particle accelerators is a serious issue from the point of view of radiation safety as the long-lived radionuclides produced by fast or moderated neutrons and impact protons cause problems of radiation exposure for staff involved in the maintenance work and when decommissioning the facility. This paper presents activation studies of the magnets and collimators in the High Energy Beam Transport line of the European Spallation Source due to the backscattered neutrons from the target and also due to the direct proton interactions and their secondaries. An estimate of the radionuclide inventory and induced activation are predicted using the GEANT4 code.
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5.
  • Dam, Veerle, et al. (författare)
  • Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
  • 2019
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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6.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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7.
  • Eklund, Patrik, 1958-, et al. (författare)
  • Rule generation as an alternative to knowledge acquisition : a systems architecture for medical informatics
  • 1994
  • Ingår i: Fuzzy sets and systems (Print). - : Elsevier. - 0165-0114 .- 1872-6801. ; 66:2, s. 195-205
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes a clinical support systems workbench, DiagaiD, based on an efficient transfer of patient data between health care professionals and clinical subsystems. The DiagaiD workbench provides tools for decision support developments for open-loop systems.A leading ambition for our development work has been to establish a data analysis and knowledge elicitation workbench, in which medical professionals entirely by themselves can create stand-alone expert systems.
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  • Erlandsson, Ann, et al. (författare)
  • Studies of the interactions between the anticytokeratin 8 monoclonal antibody TS1, its antigen and its anti-idiotypic antibody αTS1
  • 2003
  • Ingår i: Journal of Molecular Recognition. - : Wiley. - 0952-3499 .- 1099-1352. ; 16:3, s. 157-163
  • Tidskriftsartikel (refereegranskat)abstract
    • The monoclonal antibody TS1 against cytokeratin 8 and its antiidiotype αTS1 have been used for immunotargeting and therapy of carcinomas in experimental tumor model systems. The interaction surfaces between mab TS1, the cytokeratin 8 epitope, and its anti-idiotypic antibody, αTS1, were studied in detail in order to make future veneering of the interactions possible. The V-genes of TS1 and αTS1 were cloned and sequenced and the CDRs and the framework residues were identified. Amino acids participating in the interactions were identified following chemical modifications of residues in non-protected and protected molecules of cytokeratin 8, αTS1 and TS1. From the sequences, the three-dimensional structures were generated using computer modelling of the antibody variable regions. Several charged amino acid, histidine and tyrosine residues were displayed in the antibody surfaces implicated in the interactions and chemical modification confirmed the importance of these amino acids. The cytokeratin 8 epitope has previously been identified by Johansson et al. and it displays negatively charged amino acid residues which could be identified in the chemical modification. It was also revealed that the TS1 binding to cytokeratin 8 and αTS1 respectively are partly overlapping; a histidine identified in TS1 is probably involved only in the interaction with αTS1. Furthermore, the chemical modification demonstrated that exchanging aspartic–glutamic acids to asparagine–glutamine residues in TS1 increased the binding of TS1 to cytokeratin 8, indicating that there is at least one acidic amino acid that is an obstacle in the TS1–CK8 binding. The detailed assembly of the interaction surfaces will facilitate the future use of site directed mutagenesis to improve the TS1–CK8 association rate and the clearing of TS1 with αTS1 in vivo.
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