| 1. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 2. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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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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| 3. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 4. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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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).
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| 5. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 6. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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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.
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| 7. |
- Abu-Elyazeed, R R, et al.
(författare)
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Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age : results from a randomised, controlled, double-blind trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:51, s. 6136-6143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.
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| 8. |
- Agnarsson, Björn, et al.
(författare)
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The effect of hard nitridation on Al(2)O(3) using a radio frequency operated plasma cell
- 2011
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 519:22, s. 7796-7802
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Tidskriftsartikel (refereegranskat)abstract
- We report on an atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) investigation of hard nitridation of sapphire (alpha.-Al(2)O(3)) substrate, using an Epi UNI-Bulb RF plasma cell at substrate temperatures ranging from 250 to 600 degrees C. Our results show that an AlN(1-x)O(x) layer forms on sapphire after extended nitridation at all temperatures, following a Stranski-Krastanov growth mode, with less islands forming at higher temperatures. We also observe a layer-dependent charging shift in XPS, separating smooth AlN(1-x)O(x) layers from rough AlN(1-x)O(x) islands due to their different electronic coupling to the substrate. Although the island growth is suppressed at higher temperatures, the surface roughness increases at higher temperatures as seen by AFM. We also observe sputtering effects with protrusions and pits.
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| 9. |
- Dagsson-Waldhauserova, P., et al.
(författare)
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Physical properties of suspended dust during moist and low wind conditions in Iceland
- 2014
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Ingår i: Icelandic Agricultural Sciences. - 1670-567X. ; 27, s. 25-39
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Tidskriftsartikel (refereegranskat)abstract
- We measured a dust event which occurred during wet and low wind/windless conditions as the result of surface heating in August 2013. Maximum particle number concentration (PM similar to 0.3-10 mu m) reached 149,954 particles cm(-3) min(-1) while mass concentration (PM<10 m) was 1757 g m-3 min-1. The suspended dust was very fine with the highest number of particles in the size range 0.3-0.337 mu m, followed by particles 1.5-5 mu m in diameter. Close-to-ultrafine particle size distributions showed a significant increase in number with the severity of the measured dust event (during dust peaks). Number concentrations were well correlated with mass concentrations. The mineralogy and geochemical compositions showed that glaciogenic dust contains sharp-tipped shards with bubbles and 80 % of the particulate matter is volcanic glass rich in heavy metals. Wet dust particles were mobilized within < 4 hours. This is the first scientific study of particle size distributions in an Icelandic dust event including findings on initiation of dust suspension.
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| 10. |
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| 11. |
- Qi, B., et al.
(författare)
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A micro-spectroscopy study on the influence of chemical residues from nanofabrication on the nitridation chemistry of Al nanopatterns
- 2012
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 258:10, s. 4497-4506
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Tidskriftsartikel (refereegranskat)abstract
- We applied spatially resolved photoelectron spectroscopy implemented with an X-ray photoemission electron microscopy (XPEEM) using soft X-ray synchrotron radiation to identify the compositional and morphological inhomogeneities of a SiO2/Si substrate surface nanopatterned with Al before and after nitridation. The nanofabrication was conducted by a polymethylmethacrylate (PMMA)-based e-beam lithography and a fluorine-based reactive ion etching (RIE), followed by Al metalization and acetone lift-off. Three types of chemical residues were identified before nitridation: (1) fluorocarbons produced and accumulated mainly during RIE process on the sidewalls of the nanopatterns; (2) a thick Al-bearing PMMA layer and/or (3) a thin PMMA residue layer owing to unsuccessful or partial lift-off of the e-beam unexposed PMMA between the nanopatterns. The fluorocarbons actively influenced the surface chemical composition of the nanopatterns by forming Al-F compounds. After nitridation, in the PMMA residue-free area, the Al-F compounds on the sidewalls were decomposed and transformed to AIN. The PMMA residues between the nanopatterns had no obvious influence on the surface chemical composition and nitridation properties of the Al nanopatterns. They were only partially decomposed by the nitridation. The regional surface morphology of the nanopatterns revealed by the secondary electron XPEEM was consistent with the scanning electron microscopy results.
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| 12. |
- Qi, B., et al.
(författare)
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Formation and nitridation of InGa composite droplets on Si(111) : In-situ study by high resolution X-ray photoelectron spectroscopy
- 2014
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 303, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate applying synchrotron radiation based high resolution X-ray photoelectron spectroscopy as a versatile in-situ tool to study the step-wise formation and nitridation of indium gallium (InGa) composite droplets on Si(1 1 1) 7 x 7. This includes analysis of initial interactions of Ga and In with Si(1 1 1)7x7, and characterization of formation and nitridation of InGa droplets. The results show that after stabilization of Si(1 1 1) 7 x 7 structure with Ga and In at 750 degrees C and formation of Ga nanodroplets as the bases, the InGa composite droplets (In:Ga approximate to 3:1) were formed at RT and 200 degrees C in a coverage range 3-14 monolayers. The nitridation efficiency and structure of the droplets/Si(1 1 1) with NH3 were temperature dependent. At or below 350 degrees C, the droplets were hardly nitridated. At 670 degrees C, the nitridation of InGa was more completed, which however caused an unavoidable nitridation of Si surface. The optimum nitridation occurred around 480 degrees C and proceed in a 2D mode. Further simultaneous growth and nitridation of the InGa droplets on the 2D nitridated surface at 400 degrees C resulted in a complex surface composition and structure. An ex-situ atomic force microscopy reveals both the aligned metallic droplet-island assemblies and the fractured nitridated island bases with small droplets on top for the final surface.
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| 13. |
- Qi, B., et al.
(författare)
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High-resolution X-ray photoemission spectroscopy study of AlN nano-columns grown by nitridation of Al nano-squares on Si(111) substrates with ammonia
- 2010
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 518:14, s. 3632-3639
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Tidskriftsartikel (refereegranskat)abstract
- The growth of AlN nano-columns by ammonium nitridation of Al nano-squares embedded in SiO2 on Si(111) substrates was studied by high-resolution X-ray photoemission spectroscopy from a synchrotron radiation source and scanning electron microscopy (SEM). Selective nitridation of the Al nano-squares on the SiO2 mask was obtained in the temperature window of 600 degrees C-700 degrees C. The well-shaped AlN nano-column arrays with diameters confined by the lateral size of the Al nano-squares (similar to 100 nm) were observed in SEM.
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| 14. |
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| 15. |
- Qi, B., et al.
(författare)
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Photoemission and low energy electron microscopy study on the formation and nitridation of indium droplets on Si (111)7 x 7 surfaces
- 2013
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 531, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- The formation and nitridation of indium(In) droplets on Si (1 1 1)7 x 7, with regard to In droplet epitaxy growth of InN nanostructures, were studied using a spectroscopic photoemission and low energy electron microscopy, for the In coverages from 0.07 to 2.3 monolayer (ML). The results reveal that the In adatoms formed well-ordered clusters while keeping the Si (1 1 1)7 x 7 surface periodicity at 0.07 ML and a single root 3 x root 3 phase at 0.3 ML around 440-470 degrees C. At 0.82 ML, owing to the presence of structurally defect areas beside the 7 x 7 domains, 3-D In droplets evolved concomitantly with the formation of 4 x 1-In cluster chains, accompanied by a transition in surface electric property from semiconducting to metallic. Further increasing the In to 2.3 ML led to a moderate increase in number density and an appreciable lateral growth of the droplets, as well as the multi-domain In phases. Upon nitridation with NH3 at similar to 480 degrees C, besides the nitridation of the In droplets, the N radicals also dissociated the In - Si bonds to form Si - N. This caused a partial disintegration of the ordered In phase and removal of the In adatoms between the In droplets.
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| 16. |
- Qi, B., et al.
(författare)
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Room temperature deposition of self-assembled Al nanoclusters on stepped sapphire (0001) surface and subsequent nitridation
- 2011
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 520:1, s. 64-73
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Tidskriftsartikel (refereegranskat)abstract
- Self-assembled growth and nitridation of ultrathin Al nanoclusters on a stepped sapphire (0001) surface were studied by high-resolution X-ray photoemission spectroscopy, atomic force microscopy and low-energy electron diffraction (LEED). Upon room temperature deposition, in the coverage range of similar to 0.79 to 2.3 monolayer (ML), Al nanoclusters were uniformly nucleated over the entire surface of defect-free atomically smooth terraces as well as step edges. Subsequent nitridation at elevated temperatures by ammonia did not alter the morphology of the nanoclusters. The global morphology of the stepped sapphire (0001) surface such as terrace width, step height and facet orientation had no obvious influence on the nucleation morphology of the nanoclusters in the given Al coverage range. However, local structural defects at the joints of short facets and step edges played a noticeable role on the local morphology of the nanoclusters and subsequently the nitridation chemistry. The Al nanoclusters were uniformly nitridated from surface and downwards through the 3D structures. The LEED pattern indicated a certain degree of crystallinity on the nitridated surface at a nominal Al coverage less than 2 ML, whereas at 2.3 ML Al coverage, the nitridated surface became amorphous. Thus there is a critical coverage for good surface order.
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| 17. |
- Qi, B., et al.
(författare)
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Study of spatial homogeneity and nitridation of an Al nanopattern template with spectroscopic photoemission and low energy electron microscopy
- 2013
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 264, s. 349-357
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Tidskriftsartikel (refereegranskat)abstract
- We report a study on the spatial homogeneity and nitridation of a nanopattern template using a spectroscopic photoemission and low energy electron microscopy. The template was composed of Al nanodots which were patterned into a SiO2/Si(1 1 1) surface using e-beam lithography and reactive ion etching. The template exhibited a global inhomogeneity in terms of the local topography, Al composition and structure of the individual nanopatterns. After nitridation, the individual nanopatterns were diminished, more corrugated and faceted. The nitridated nanopatterns were structurally ordered but differently orientated. The nitridation effectively removed the fluorine contaminants by decomposition of the fluorocarbon sidewalls, resulting in the AlN nanopatterns and partially nitridated Si substrate surface outside the nanopattern domains.
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| 18. |
- Shapiro, M, et al.
(författare)
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An Earth-system prediction initiative for the twenty-first century: An international interdisciplinary initiative to accelerate advances in knowledge, prediction, use and value of weather, climate and Earth-system information
- 2010
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007. ; 91:10, s. 1377-1388
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Tidskriftsartikel (refereegranskat)abstract
- The necessity and benefits for establishing the international Earth-system Prediction Initiative (EPI) are discussed by scientists associated with the World Meteorological Organization (WMO) World Weather Research Programme (WWRP), World Climate Research Programme (WCRP), International Geosphere–Biosphere Programme (IGBP), Global Climate Observing System (GCOS), and natural-hazards and socioeconomic communities. The proposed initiative will provide research and services to accelerate advances in weather, climate, and Earth system prediction and the use of this information by global societies. It will build upon the WMO, the Group on Earth Observations (GEO), the Global Earth Observation System of Systems (GEOSS) and the International Council for Science (ICSU) to coordinate the effort across the weather, climate, Earth system, natural-hazards, and socioeconomic disciplines. It will require (i) advanced high-performance computing facilities, supporting a worldwide network of research and operational modeling centers, and early warning systems; (ii) science, technology, and education projects to enhance knowledge, awareness, and utilization of weather, climate, environmental, and socioeconomic information; (iii) investments in maintaining existing and developing new observational capabilities; and (iv) infrastructure to transition achievements into operational products and services.
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| 19. |
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