| 1. |
- Elks, Cathy E, et al.
(författare)
-
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
-
Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
|
|
| 2. |
- Gretarsdottir, Solveig, et al.
(författare)
-
Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
|
|
| 3. |
- Ruderfer, Douglas M., et al.
(författare)
-
Mosaic copy number variation in schizophrenia
- 2013
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 21:9, s. 1007-1011
-
Tidskriftsartikel (refereegranskat)abstract
- Recent reports suggest that somatic structural changes occur in the human genome, but how these genomic alterations might contribute to disease is unknown. Using samples collected as part of the International Schizophrenia Consortium (schizophrenia, n = 3518; control, n = 4238) recruited across multiple university research centers, we assessed single-nucleotide polymorphism genotyping arrays for evidence of chromosomal anomalies. Data from genotyping arrays on each individual were processed using Birdsuite and analyzed with PLINK. We validated potential chromosomal anomalies using custom nanostring probes and quantitative PCR. We estimate chromosomal alterations in the schizophrenia population to be 0.42%, which is not significantly different from controls (0.26%). We identified and validated a set of four extremely large (>10 Mb) chromosomal anomalies in subjects with schizophrenia, including a chromosome 8 trisomy and deletion of the q arm of chromosome 7. These data demonstrate that chromosomal anomalies are present at low frequency in blood cells of both control and schizophrenia subjects.
|
|
| 4. |
- Stacey, Simon N, et al.
(författare)
-
A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
-
Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
|
|
| 5. |
- Stolk, Lisette, et al.
(författare)
-
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
-
Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
|
|
| 6. |
- Audouin, L., et al.
(författare)
-
Quantifying differences between computational results and measurements in the case of a large-scale well-confined fire scenario
- 2011
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 1872-759X .- 0029-5493. ; 241:1, s. 18-31
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this work was to quantify comparisons between several computational results and measurements performed during a pool fire scenario in a well-confined compartment. This collaborative work was initiated under the framework of the OECD fire research program and involves the most frequently used fire models in the fire community, including field and zone models. The experimental scenario was conducted at the French Institut de Radioprotection et de Surete Nucleaire (IRSN) and deals with a full-scale liquid pool fire in a confined and mechanically ventilated compartment representative for nuclear plants. The practical use of different metric operators and their ability to report the capabilities of fire models are presented. The quantitative comparisons between measurements and numerical results obtained from "open" calculations concern six important quantities from a safety viewpoint: gas temperature, oxygen concentration, wall temperature, total heat flux, compartment pressure and ventilation flow rate during the whole fire duration. The results indicate that it is important to use more than one metric for the validation process in order to get information on the uncertainties associated with different aspects of fire safety. (C) 2010 Elsevier B.V. All rights reserved.
|
|
| 7. |
- Bordogna, Marco Tito, et al.
(författare)
-
MUSCAT experiment : active free falling units for in situ measurements of temperature and density in the middle atmosphere
- 2013
-
Ingår i: European Space Agency. - ESTEC, Noordwijk, The Netherlands : ESA Communications. - 9789290922858 ; , s. 575-582
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The main scientific objective of the MUSCAT Experimentis to develop a technique to reconstruct temperatures and density profiles in the middle atmosphere using active spherical probes. The MUSCAT experiment was launched on May 9, 2013 on the REXUS-13 sounding rocket from Esrange, in northern Sweden. The experiment ejected four probes that collected raw GPS signal. The experiment design and preliminary results are presented here.
|
|
| 8. |
- Carlsson, Patrick, 1975-, et al.
(författare)
-
EPR and ab initio calculation study on the EI4 center in 4H and 6H-SiC
- 2010
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 82:23, s. 235203-
-
Tidskriftsartikel (refereegranskat)abstract
- We present new results from electron paramagnetic resonance (EPR) studies of the EI4 EPR center in 4H- and 6H-SiC. The EPR signal of the EI4 center was found to be drastically enhanced in electron-irradiated high-purity semi-insulating materials after annealing at 700-750°C. Strong EPR signals of the EI4 center with minimal interferences from other radiation-induced defects in irradiated high-purity semiinsulating materials allowed our more detailed study of the hyperfine (hf) structures. An additional large-splitting 29Si hf structure and 13C hf lines of the EI4 defect were observed. Comparing the data on the defect formation, the hf interactions and the annealing behavior obtained from EPR experiments and from ab initio supercell calculations of different carbon-vacancy related complexes, we suggest a complex between a carbon vacancy-carbon antisite and a carbon vacancy at the third neighbor site of the antisite in the neutral charge state, (VC-CSiVC)0, as a new defect model for the EI4 center.
|
|
| 9. |
- Carlsson, Patrick, 1975-, et al.
(författare)
-
The EI4 EPR centre in 6H SiC
- 2010
-
Ingår i: Physica Scripta, Vol. T141. - : IOP Publishing. ; , s. 014013-
-
Konferensbidrag (refereegranskat)abstract
- We present the results of our recent electron paramagnetic resonance (EPR) studies of the EI4 EPR centre in electron-irradiated high-purity semi-insulating 6H SiC. Higher signal intensities and better resolution compared with previous studies have enabled a more detailed study of the hyperfine (hf) structure. Based on the observed hf structure due to the interaction with Si and C neighbours, the effective spin S = 1, the C-1h-symmetry and the annealing behaviour, we suggest a carbon vacancy-carbon antisite complex in the neutral charge state, VCVCCSi0, with the vacancies and the antisite in the basal plane, as a new defect model for the centre.
|
|
| 10. |
- Elmendorf, Sarah C., et al.
(författare)
-
Plot-scale evidence of tundra vegetation change and links to recent summer warming
- 2012
-
Ingår i: Nature Climate Change. - : Nature Publishing Group. - 1758-678X .- 1758-6798. ; 2:6, s. 453-457
-
Tidskriftsartikel (refereegranskat)abstract
- Temperature is increasing at unprecedented rates across most of the tundra biome. Remote-sensing data indicate that contemporary climate warming has already resulted in increased productivity over much of the Arctic, but plot-based evidence for vegetation transformation is not widespread. We analysed change in tundra vegetation surveyed between 1980 and 2010 in 158 plant communities spread across 46 locations.We found biome-wide trends of increased height of the plant canopy and maximum observed plant height for most vascular growth forms; increased abundance of litter; increased abundance of evergreen, low-growing and tall shrubs; and decreased abundance of bare ground. Intersite comparisons indicated an association between the degree of summer warming and change in vascular plant abundance, with shrubs, forbs and rushes increasing with warming. However, the association was dependent on the climate zone, the moisture regime and the presence of permafrost. Our data provide plot-scale evidence linking changes in vascular plant abundance to local summer warming in widely dispersed tundra locations across the globe.
|
|
| 11. |
- Ganna, Andrea, et al.
(författare)
-
Utilizing Twins as Controls for Non-Twin Case-Materials in Genome Wide Association Studies
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e83101-
-
Tidskriftsartikel (refereegranskat)abstract
- Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10-5 were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10-8) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.
|
|
| 12. |
- Humphreys, Keith, et al.
(författare)
-
The Genetic Structure of the Swedish Population
- 2011
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e22547-
-
Tidskriftsartikel (refereegranskat)abstract
- Patterns of genetic diversity have previously been shown to mirror geography on a global scale and within continents and individual countries. Using genome-wide SNP data on 5174 Swedes with extensive geographical coverage, we analyzed the genetic structure of the Swedish population. We observed strong differences between the far northern counties and the remaining counties. The population of Dalarna county, in north middle Sweden, which borders southern Norway, also appears to differ markedly from other counties, possibly due to this county having more individuals with remote Finnish or Norwegian ancestry than other counties. An analysis of genetic differentiation (based on pairwise F(st)) indicated that the population of Sweden's southernmost counties are genetically closer to the HapMap CEU samples of Northern European ancestry than to the populations of Sweden's northernmost counties. In a comparison of extended homozygous segments, we detected a clear divide between southern and northern Sweden with small differences between the southern counties and considerably more segments in northern Sweden. Both the increased degree of homozygosity in the north and the large genetic differences between the south and the north may have arisen due to a small population in the north and the vast geographical distances between towns and villages in the north, in contrast to the more densely settled southern parts of Sweden. Our findings have implications for future genome-wide association studies (GWAS) with respect to the matching of cases and controls and the need for within-county matching. We have shown that genetic differences within a single country may be substantial, even when viewed on a European scale. Thus, population stratification needs to be accounted for, even within a country like Sweden, which is often perceived to be relatively homogenous and a favourable resource for genetic mapping, otherwise inferences based on genetic data may lead to false conclusions.
|
|
| 13. |
- Magnusson, Patrick, et al.
(författare)
-
Preliminary results from the RAIN mesospheric and stratospheric aerosol particle collection experiment launched on REXUS-11
- 2013
-
Ingår i: 21st ESA Symposium. - ESTEC, Noordwijk, The Netherlands : ESA Communications. - 9789290922858 ; , s. 511-517
-
Konferensbidrag (refereegranskat)abstract
- The RAIN (Rocket deployed Atmospheric probes conducting Independent measurements in Northern Sweden) experiment demonstrates a technique for collecting aerosol particles in the middle atmosphere using multiple probes ejected from a sounding rocket. Collection samples on each probe are exposed over varying height ranges between 80 and 22 km giving an altitude distribution profile of aerosol particles. The experiment was launched on board the REXUS-11 sounding rocket on November 16, 2012 from Esrange Space Centre. The experiment operated nominally and was recovered. Initial scanning electron microscopy analysis of the collection samples indicates that aerosols were collected during the fall, however detailed analysis over all height ranges is ongoing.
|
|
| 14. |
- Nguyen, Tien Son, et al.
(författare)
-
The carbon vacancy related EI4 defect in 4H-SiC
- 2010
-
Ingår i: Materials Science Forum. Vols. 645-648. - : Trans Tech Publications. ; , s. 399-402
-
Konferensbidrag (refereegranskat)abstract
- Electron paramagnetic resonance (EPR) was used to study high-purity semi-insulating 4H-SiC irradiated with 2 MeV electrons at room temperature. The EPR signal of the EI4 defect was found to be dominating in samples irradiated and annealed at 750 C. Additional large-splitting Si-29 hyperfine (hf) lines and also other C-13 and Si-29 hf structures were observed. Based on the observed hf structures and annealing behaviour, the complex between a negative carbon vacancy-carbon antisite pair (VCCSi-) and a distance positive carbon vacancy (V-C(+)) is tentatively proposed as a possible model for the EIO4 defect.
|
|
| 15. |
- Reid, William, et al.
(författare)
-
Technical Note : A novel rocket-based in situ collection technique for mesospheric and stratospheric aerosol particles
- 2013
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 6:3, s. 777-785
-
Tidskriftsartikel (refereegranskat)abstract
- A technique for collecting aerosol particles between altitudes of 17 and 85 km is described. Spin-stabilized collection probes are ejected from a sounding rocket allowing for multi-point measurements. Each probe is equipped with 110 collection samples that are 3 mm in diameter. The collection samples are one of three types: standard transmission electron microscopy carbon grids, glass fibre filter paper or silicone gel. Collection samples are exposed over a 50 m to 5 km height range with a total of 45 separate ranges. Post-flight electron microscopy will give size-resolved information on particle number, shape and elemental composition. Each collection probe is equipped with a suite of sensors to capture the probe's status during the fall. Parachute recovery systems along with GPS-based localization will ensure that each probe can be located and recovered for post-flight analysis.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Van Hees, Patrick, et al.
(författare)
-
Prediction and validation of pool fire development in enclosures by means of CFD Models for risk assessment of nuclear power plants (Poolfire) – Final Report
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fires in nuclear power plants can be an important hazard for the overall safety of the facility. One of the typical fire sources is a pool fire. It is therefore important to have good knowledge on the fire behaviour of pool fire and be able to predict the heat release rate by prediction of the mass loss rate. This final report describes the state of the art within the area of pool fire modelling and the need for further development of pool fire models. As a result of the research in this project two new models are presented: one pyrolysis model and one engineering model. In the project the models were validated and pool fire experiments were included. Also a number of real case studies were incorporated to show the need for the development of pool fire models.
|
|
| 20. |
- Van Hees, Patrick, et al.
(författare)
-
Validation and development of different calculations methods and software packages for fire safety assessment in swedish nuclear power plants
- 2011
-
Ingår i: 21st International Conference on Structural Mechanics in Reactor Technology (SMiRT 21) - 12th International Pre-Conference Seminar on “FIRE SAFETY IN NUCLEAR POWER PLANTS AND INSTALLATIONS“.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Fire models are used increasingly for fire safety assessment in nuclear power plants. Examples of these fire models are CFD models and zone models. When using these models it is important that they are sufficiently verified and validated. In Sweden the majority of fire safety consultants are using FDS, developed by NIST. The verification and validation of this package is intensively done for a number of scenarios by the developing team. One of the recent modifications in FDS is the implementation of a ventilation module. The first aim of this paper was to validate FDS and ANSYS-CFX within the Swedish part of the OECD/NEA PRISME project using the PRISME SOURCE D1 test. The results are presented in this article and show how powerful the module is for simulation in enclosures with mechanical ventilation. Beside CFD models, fire safety engineers need also simple empirical models for determining temperatures, smoke heights, etc. In the second part of this paper such a model is developed. The model predicts gas temperatures in a room adjacent to a room involved in a pre-flashover fire. The correlation is derived with help of computer simulations and validated by means of a set of fire tests. The results of the correlation model are satisfactory and the correlation formulae will be an additional tool for fire safety engineers.
|
|
