| 1. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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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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| 2. |
- Thiele, I., et al.
(författare)
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A community-driven global reconstruction of human metabolism
- 2013
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
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Tidskriftsartikel (refereegranskat)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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| 3. |
- Andersson, K. G., et al.
(författare)
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Parametric improvement for the ingestion dose module of the European ARGOS and RODOS decision support systems
- 2011
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Ingår i: Radioprotection. - : EDP Sciences. - 0033-8451 .- 1769-700X. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- The European decision support systems ARGOS and RODOS rely on the ECOSYS model for prognoses of ingestion doses. ECOSYS needs an update of various parameter values to provide reliable estimates. This paper reports on some results of a Nordic initiative to derive parameter values that are specific to Nordic conditions, as well as to improve generic parameter values in ECOSYS, taking into account the host of useful measurement data accumulated since ECOSYS was created. © 2011 EDP Sciences.
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| 4. |
- Oei, Ling, et al.
(författare)
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A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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| 5. |
- Pálsson, S.E., et al.
(författare)
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A simple model to estimate deposition based on a statistical reassessment of global fallout data
- 2013
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X. ; 121, s. 75-86
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric testing of nuclear weapons began in 1945 and largely ceased in 1963. Monitoring of the resulting global fallout was carried out globally by the Environmental Measurements Laboratory and the UK Atomic Energy Research Establishment as well as at national level by some countries. A correlation was identified between fallout deposition and precipitation and an uneven distribution with latitude. In this study, the available data from 1954 to 1976 for 90Sr and 137Cs were reanalysed using analysis of covariance (ANCOVA) and logarithmically transformed values of the monthly deposition density as the response variable. Generalized additive models (GAM) were used to explore the relationship of different variables to the response variable and quantify the explanatory power that could be achieved. The explanatory variables which consistently explained most of the variability were precipitation at each site, latitude and change with time and a simple linear model was produced with similar explanatory power as the GAM. The estimates improved as the temporal resolution of the precipitation data increased. A good logelog fit could be obtained if a bias of about 1e6 mm precipitation per month was added, this could be interpreted as dry deposition which is not otherwise accounted for in the model. The deposition rate could then be explained as a simple non-linear power function of the precipitation rate (r0.2e0.6 depending on latitude band). A similar non-linear power function relationship has been the outcome of some studies linking wash-out and rain-out coefficients with rain intensity. Our results showed that the precipitation rate was an important parameter, not just the total amount. The simple model presented here allows the recreation of the deposition history at a site, allowing comparison with time series of activity concentrations for different environmental compartments, which is important for model validation.
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| 6. |
- Andersson, Kasper G, et al.
(författare)
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Revision of deposition and weathering parameters for the ingestion dose module (ECOSYS) of the ARGOS and RODOS decision support systems.
- 2011
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Ingår i: Journal of environmental radioactivity. - : Elsevier BV. - 1879-1700 .- 0265-931X.
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Tidskriftsartikel (refereegranskat)abstract
- The ECOSYS model is the ingestion dose model integrated in the ARGOS and RODOS decision support systems for nuclear emergency management. The parameters used in this model have however not been updated in recent years, where the level of knowledge on various environmental processes has increased considerably. A Nordic work group has carried out a series of evaluations of the general validity of current ECOSYS default parameters. This paper specifically discusses the parameter revisions required with respect to the modelling of deposition and natural weathering of contaminants on agricultural crops, to enable the trustworthy prognostic modelling that is essential to ensure justification and optimisation of countermeasure strategies. New modelling approaches are outlined, since it was found that current ECOSYS approaches for deposition and natural weathering could lead to large prognostic errors.
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| 7. |
- Baldi, A., et al.
(författare)
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Mg/Ti multilayers : Structural and hydrogen absorption properties
- 2010
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 81:22, s. 224203-
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Tidskriftsartikel (refereegranskat)abstract
- Mg-Ti alloys have uncommon optical and hydrogen absorbing properties, originating from a "spinodal-like" microstructure with a small degree of chemical short-range order in the atomic distribution. In the present study we artificially engineer short-range order by depositing Pd-capped Mg/Ti multilayers with different periodicities. Notwithstanding the large lattice mismatch between Mg and Ti, the as-deposited metallic multilayers show good structural coherence. On exposure to H-2 gas a two-step hydrogenation process occurs with the Ti layers forming the hydride before Mg. From in situ measurements of the bilayer thickness Lambda at different hydrogen pressures, we observe large out-of-plane expansions of Mg and Ti layers on hydrogenation, indicating strong plastic deformations in the films and a consequent shortening of the coherence length. On unloading at room temperature in air, hydrogen atoms remain trapped in the Ti layers due to kinetic constraints. Such loading/unloading sequence can be explained in terms of the different thermodynamic properties of hydrogen in Mg and Ti, as shown by diffusion calculations on a model multilayered systems. Absorption isotherms measured by hydrogenography can be interpreted as a result of the elastic clamping arising from strongly bonded Mg/Pd and broken Mg/Ti interfaces.
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| 8. |
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| 9. |
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| 10. |
- Nielsen, Jens B, 1962, et al.
(författare)
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Engineering synergy in biotechnology
- 2014
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 10:5, s. 319-322
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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