| 1. |
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| 2. |
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| 3. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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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.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Arvidson, R. E., et al.
(författare)
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Opportunity Mars Rover mission : Overview and selected results from Purgatory ripple to traverses to Endeavour crater
- 2011
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Ingår i: Journal of Geophysical Research. - Hoboken : Wiley-Blackwell. - 0148-0227 .- 2156-2202. ; 116, s. E00F15-
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Tidskriftsartikel (refereegranskat)abstract
- Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.
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| 8. |
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| 9. |
- Peloso, Gina M, et al.
(författare)
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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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| 10. |
- Vaniman, D.T., et al.
(författare)
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Mineralogy of a mudstone at Yellowknife Bay, Gale Crater, Mars
- 2014
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
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Tidskriftsartikel (refereegranskat)abstract
- Sedimentary rocks at Yellowknife Bay (Gale crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, calcium sulfates, iron oxide or hydroxides, iron sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 angstroms, indicating little interlayer hydration. The Cumberland smectite has basal spacing at both ~13.2 and ~10 angstroms. The larger spacing suggests a partially chloritized interlayer or interlayer magnesium or calcium facilitating H2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time.
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| 11. |
- Anderson, Beverley H., et al.
(författare)
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Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 338-342
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Tidskriftsartikel (refereegranskat)abstract
- Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
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| 12. |
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| 13. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 14. |
- Scott, Robert A, et al.
(författare)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Tidskriftsartikel (refereegranskat)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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| 15. |
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| 16. |
- 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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| 17. |
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| 18. |
- Lin, Y., et al.
(författare)
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Ion cyclotron range of frequency mode conversion flow drive in D(He-3) plasmas on JET
- 2012
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 54:7, s. 074001-
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Tidskriftsartikel (refereegranskat)abstract
- Ion cyclotron range of frequency (ICRF) mode conversion has been shown to drive toroidal flow in JET D(He-3) L-mode plasmas: B-t0 = 3.45 T, n(e0) similar to 3x10(19) m(-3), I-p = 2.8 and 1.8 MA, P-RF <= 3MW at 33MHz and -90 degrees phasing. Central toroidal rotation in the counter-I-p direction, with omega(phi 0) up to 10 krad s(-1) (V-phi 0 similar to 30 km s(-1), central thermal Mach number M-th(0) similar to 0.07 and Alfven Mach number M-A(0) similar to 0.003) has been observed. The flow drive effect is sensitive to the He-3 concentration and the largest rotation is observed in the range X[He-3] = n(He3)/n(e) similar to 10-17%. The rotation profile is peaked near the magnetic axis, and the central rotation scales with the input RF power. The effective torque density profile from the RF power has been calculated and the total torque is estimated to be as high as 50% of the same power from neutral beam injection, and a factor of 5 larger than the direct momentum injection from the RF waves. RF physics modeling using the TORIC code shows that the interaction between the mode converted ion cyclotron wave and the He-3 ions, and associated asymmetry in space and momentum, may be key for flow drive.
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| 19. |
- Mathews, G. S., et al.
(författare)
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GAS in Protoplanetary Systems (GASPS) I. First results
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L127
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Tidskriftsartikel (refereegranskat)abstract
- Context. Circumstellar discs are ubiquitous around young stars, but rapidly dissipate their gas and dust on timescales of a few Myr. The Herschel Space Observatory allows for the study of the warm disc atmosphere, using far-infrared spectroscopy to measure gas content and excitation conditions, and far-IR photometry to constrain the dust distribution. Aims. We aim to detect and characterize the gas content of circumstellar discs in four targets as part of the Herschel science demonstration phase. Methods. We carried out sensitive medium resolution spectroscopy and high sensitivity photometry at gimel similar to 60-190 mu m using the Photodetector Array Camera and Spectrometer instrument on the Herschel Space Observatory. Results. We detect [OI] 63 mu m emission from the young stars HD 169142, TW Hydrae, and RECX 15, but not HD 181327. No other lines, including [CII] 158 and [OI] 145, are significantly detected. All four stars are detected in photometry at 70 and 160 mu m. Extensive models are presented in associated papers.
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| 20. |
- Meeus, G., et al.
(författare)
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Gas in the protoplanetary disc of HD 169142: Herschel's view
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L124
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Tidskriftsartikel (refereegranskat)abstract
- In an effort to simultaneously study the gas and dust components of the disc surrounding the young Herbig Ae star HD 169142, we present far-IR observations obtained with the PACS instrument onboard the Herschel Space Observatory. This work is part of the open time key program GASPS, which is aimed at studying the evolution of protoplanetary discs. To constrain the gas properties in the outer disc, we observed the star at several key gas-lines, including [OI] 63.2 and 145.5 mu m, [CII] 157.7 mu m, CO 72.8 and 90.2 mu m, and o-H2O 78.7 and 179.5 mu m. We only detect the [OI] 63.2 mu m line in our spectra, and derive upper limits for the other lines. We complement our data set with PACS photometry and (CO)-C-12/13 data obtained with the Submillimeter Array. Furthermore, we derive accurate stellar parameters from optical spectra and UV to mm photometry. We model the dust continuum with the 3D radiative transfer code MCFOST and use this model as an input to analyse the gas lines with the thermo-chemical code ProDIMo. Our dataset is consistent with a simple model in which the gas and dust are well-mixed in a disc with a continuous structure between 20 and 200 AU, but this is not a unique solution. Our modelling effort allows us to constrain the gas-to-dust mass ratio as well as the relative abundance of the PAHs in the disc by simultaneously fitting the lines of several species that originate in different regions. Our results are inconsistent with a gas-poor disc with a large UV excess; a gas mass of 5.0 +/- 2.0 x 10(-3) M-circle dot is still present in this disc, in agreement with earlier CO observations.
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| 21. |
- Montazeri, Mohammad, et al.
(författare)
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Direct Measure of Strain and Electronic Structure in GaAs/GaP Core-Shell Nanowires
- 2010
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 10:3, s. 880-886
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Tidskriftsartikel (refereegranskat)abstract
- Highly strained GaAs/GaP nanowires of excellent optical quality were grown with 50 nm diameter GaAs cores and 25 nm GaP shells. Photoluminescence from these nanowires is observed at energies dramatically shifted from the unstrained GaAs free exciton emission energy by 260 meV. Using Raman scattering, we show that it is possible to separately measure the degree of compressive and shear strain of the GaAs core and show that the Raman response of the GaP shell is consistent with tensile strain. The Raman and photoluminescence measurement are both on good agreement with 8 band k.p calculations, This result opens up new possibilities for engineering the electronic properties of the nanowires for optimal design of one-dimensional nanodevices by controlling the strain of the core and shell by varying the nanowire geometry.
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| 22. |
- Pinte, C., et al.
(författare)
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The Herschel view of GAS in Protoplanetary Systems (GASPS) First comparisons with a large grid of models
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L126
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Tidskriftsartikel (refereegranskat)abstract
- The Herschel GASPS key program is a survey of the gas phase of protoplanetary discs, targeting 240 objects which cover a large range of ages, spectral types, and disc properties. To interpret this large quantity of data and initiate self-consistent analyses of the gas and dust properties of protoplanetary discs, we have combined the capabilities of the radiative transfer code MCFOST with the gas thermal balance and chemistry code ProDiMo to compute a grid of approximate to 300 000 disc models (DENT). We present a comparison of the first Herschel/GASPS line and continuum data with the predictions from the DENT grid of models. Our objective is to test some of the main trends already identified in the DENT grid, as well as to define better empirical diagnostics to estimate the total gas mass of protoplanetary discs. Photospheric UV radiation appears to be the dominant gas-heating mechanism for Herbig stars, whereas UV excess and/or X-rays emission dominates for T Tauri stars. The DENT grid reveals the complexity in the analysis of far-IR lines and the difficulty to invert these observations into physical quantities. The combination of Herschel line observations with continuum data and/or with rotational lines in the (sub-)millimetre regime, in particular CO lines, is required for a detailed characterisation of the physical and chemical properties of circumstellar discs.
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| 23. |
- Pinto, Dalila, et al.
(författare)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Tidskriftsartikel (refereegranskat)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 24. |
- Rajaraman, Preetha, et al.
(författare)
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Genome-wide association study of glioma and meta-analysis
- 2012
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 131:12, s. 1877-1888
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
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| 25. |
- Rissanen, J., et al.
(författare)
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Decay of the High-K Isomeric State to a Rotational Band in 257Rf
- 2013
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
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Tidskriftsartikel (refereegranskat)abstract
- The 257Rf isotope has been populated via the 208Pb(50Ti, n) fusion-evaporation reaction and delayed gamma-ray and electron decay spectroscopy has been performed. The existence of a high-K isomeric state in 257Rf has been confirmed. The isomeric state decays into a rotational band based on the 11/2(-)[725] excitation, which was observed up to spin of (23/2(-)). Three multipolarity-E1 gamma transitions depopulating the isomeric state have been observed, which fixes the spin for that state to (21/2(+)). This assignment agrees with theoretical predictions calculated with the microscopic-macroscopic approach, which suggest the isomeric state to be formed by coupling an unpaired 11/2(-)[725] quasineutron to the (1/2(-)[521] circle times 9/2(+)[624])(5)- two-quasiproton state. The same two-quasiproton excitation is possible for the lowest isomer in 256Rf.
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| 26. |
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| 27. |
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| 28. |
- Thi, W. F., et al.
(författare)
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Herschel-PACS observation of the 10 Myr old T Tauri disk TW Hya Constraining the disk gas mass
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L125
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Tidskriftsartikel (refereegranskat)abstract
- Planets are formed in disks around young stars. With an age of similar to 10 Myr, TW Hya is one of the nearest T Tauri stars that is still surrounded by a relatively massive disk. In addition a large number of molecules has been found in the TW Hya disk, making TW Hya the perfect test case in a large survey of disks with Herschel-PACS to directly study their gaseous component. We aim to constrain the gas and dust mass of the circumstellar disk around TW Hya. We observed the fine-structure lines of [OI] and [CII] as part of the open-time large program GASPS. We complement this with continuum data and ground-based (12) CO 3-2 and (CO)-C-13 3-2 observations. We simultaneously model the continuum and the line fluxes with the 3D Monte-Carlo code MCFOST and the thermo-chemical code ProDiMo to derive the gas and dust masses. We detect the [OI] line at 63 mu m. The other lines that were observed, [OI] at 145 mu m and [CII] at 157 mu m, are not detected. No extended emission has been found. Preliminary modeling of the photometric and line data assuming [(CO)-C-12]/[(CO)-C-13] = 69 suggests a dust mass for grains with radius
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| 29. |
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| 30. |
- Abbott, R., et al.
(författare)
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Hybridization and speciation
- 2013
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Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 26:2, s. 229-246
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Forskningsöversikt (refereegranskat)abstract
- Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.
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| 31. |
- Alexander, Naomi E., et al.
(författare)
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IMAGINE project : A low cost, high performance, monolithic passive mm-wave imager front-end
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819492852
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Konferensbidrag (refereegranskat)abstract
- The FP7 Research for SME project IMAGINE - a low cost, high performance monolithic passive mm-wave imager front-end is described in this paper. The main innovation areas for the project are: i) the development of a 94 GHz radiometer chipset and matching circuits suitable for monolithic integration. The chipset consists of a W-band low noise amplifier, fabricated using the commercially available OMMIC D007IH GaAs mHEMT process, and a zero bias resonant interband tunneling diode, fabricated using a patented epi-layer structure that is lattice matched to the same D007IH process; ii) the development of a 94 GHz antenna adapted for low cost manufacturing methods with performance suitable for real-time imaging; iii) the development of a low cost liquid crystal polymer PCB build-up technology with performance suitable for the integration and assembly of a 94 GHz radiometer module; iv) the assembly of technology demonstrator modules. The results achieved in these areas are presented.
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| 32. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Damm, S., et al.
(författare)
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Formation of ferroelectrically defined Ag nanoarray patterns
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9781628410747
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Konferensbidrag (refereegranskat)abstract
- In order to produce the most effective Ag nanoarrays for plasmon enhanced fluorescence and Raman scattering made using ferroelectric substrates, the optimum conditions for the creation of arrays must be identified. We study here Ag nanopattern arrays formed using ferroelectric lithography based on periodically proton exchanged (PPE) template methods. We examine different conditions in regard to deposition of Ag nanoparticles and analyze the plasmon enhanced signal from the resulting nanoarray. We apply FLIM (fluorescence lifetime imaging) to assess different Ag nanoarray preparation conditions on fluorescence emission from selected fluorphores. In addition, we apply Raman and luminescence spectroscopy with AFM (atomic force microscopy) to study the plasmon enhancement of luminescence and Raman from the Ag nanoarrays.
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| 37. |
- Damm, Signe, et al.
(författare)
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Surface enhanced luminescence and Raman scattering from ferroelectrically defined Ag nanopatterned arrays
- 2013
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 103:8, s. 083105-
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Tidskriftsartikel (refereegranskat)abstract
- Ag nanopatterned arrays prepared using periodically proton exchanged templates have been demonstrated to support surface enhanced luminescence. Fluorescence lifetime imaging reveals that luminescence intensity is greatest on Ag and that the lifetime of the molecular probe is reduced, in line with a surface enhanced luminescence mechanism. Studies establish that the substrate simultaneously supports surface enhanced luminescence and Raman scattering. Spatial dependence along the nanopatterned arrays shows <7% variation in Raman scattering signal intensity, offering high reproducibility for practical applications. Fluorophores emitting near the plasmon absorption maxima are enhanced 4-fold.
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| 38. |
- Davison, Lucy J, et al.
(författare)
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Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 322-333
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Tidskriftsartikel (refereegranskat)abstract
- The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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| 39. |
- Ellinor, Patrick T., et al.
(författare)
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Meta-analysis identifies six new susceptibility loci for atrial fibrillation
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:6, s. 88-670
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
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| 40. |
- Herman, Jonathan D., et al.
(författare)
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A genomic and evolutionary approach reveals non-genetic drug resistance in malaria
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:11, s. 511-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use.
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| 41. |
- Lucas, W. E., et al.
(författare)
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Misaligned streamers around a Galactic Centre black hole from a single cloud's infall
- 2013
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 433:1, s. 353-365
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Tidskriftsartikel (refereegranskat)abstract
- We follow the near radial infall of a prolate cloud on to a 4 x 10(6) M-circle dot supermassive black hole in the Galactic Centre using smoothed particle hydrodynamics. We show that a prolate cloud oriented perpendicular to its orbital plane naturally produces a spread in angular momenta in the gas which can translate into misaligned discs as is seen in the young stars orbiting Sagittarius A*. A turbulent or otherwise highly structured cloud is necessary to avoid cancelling too much angular momentum through shocks at closest approach. Our standard model of a 2 x 10(4) M-circle dot gas cloud brought about the formation of a disc within 0.3 pc from the black hole and a larger, misaligned streamer at 0.5 pc. A total of 1.5 x 10(4) M-circle dot of gas formed these structures. Our exploration of the simulation parameter space showed that when star formation occurred, it resulted in top-heavy initial mass functions with stars on eccentric orbits with semi-major axes 0.02-0.3 pc and inclinations following the gas discs and streamers. We suggest that the single event of an infalling prolate cloud can explain the occurrence of multiple misaligned discs of young stars.
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| 42. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 43. |
- Rice, J. E., et al.
(författare)
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The Ar(17+) Ly(alpha 2)/Ly(alpha 1) ratio in Alcator C-Mod tokamak plasmas
- 2011
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 44:16, s. 165702-
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Tidskriftsartikel (refereegranskat)abstract
- High-quality spectra of hydrogen-like Ar(17+) have been obtained from Alcator C-Mod tokamak plasmas using a spatially imaging high-resolution x-ray spectrometer system in an extensive study of the underlying high-n satellite lines. The ratio of Ly(alpha 2) (1S(1/2)-2P(1/2)) to Ly(alpha 1) (1S(1/2)-2P(3/2)) was found to be similar to 0.52 regardless of plasma parameters, which is somewhat greater than the ratio of the statistical weights of the upper n = 2 levels, 0.5. This difference is mainly due to the effects of collisional excitation of fine-structure sub-levels. For the observations presented here, electron densities were in an extended range from 3 x 10(19) to 4 x 10(20) m(-3) with electron and ion temperatures between 1 and 4 keV. Experimental results are compared to calculations from COLRAD, a collisional-radiative modelling code, and good agreement is shown.
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| 44. |
- Schank, Jesse R., et al.
(författare)
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Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429
- 2011
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Ingår i: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 218:1, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Genetic inactivation or pharmacological antagonism of neurokinin 1 (NK1) receptors blocks morphine and alcohol reward in rodents, while NK1 antagonism decreases alcohol craving in humans. The role of the NK1 system for relapse-like behavior has not previously been examined.OBJECTIVE: Divergence between human and rodent NK1 receptors has limited the utility of NK1 antagonists developed for the human receptor species for preclinical studies of addiction-related behaviors in rats. Here we used L822429, an NK1 antagonist specifically engineered to bind at high affinity to the rat receptor, to assess the effects of NK1 receptor antagonism on alcohol-seeking behaviors in rats.METHODS: L822429 (15 and 30 mg/kg) was used to examine effects of NK1 receptor antagonism on operant self-administration of 10% alcohol in 30-min daily sessions, as well as intermittent footshock stress- and cue-induced reinstatement of alcohol-seeking after extinction of lever responding.RESULTS: At the doses used, L822429 did not significantly affect alcohol self-administration or cue-induced reinstatement, but potently and dose dependently suppressed stress-induced reinstatement of alcohol seeking, with an essentially complete suppression at the highest dose. The effect of L822429 on stress-induced reinstatement was behaviorally specific. The drug had no effect on conditioned suppression of operant responding following fear conditioning, locomotor activity, or self-administration of a sucrose solution.CONCLUSIONS: To the degree that the reinstatement model provides a model of drug relapse, the results provide support for NK1 antagonism as a promising mechanism for pharmacotherapy of alcoholism, acting through suppression of stress-induced craving and relapse.
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| 45. |
- Schunkert, Heribert, et al.
(författare)
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
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Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 46. |
- Smith, P., et al.
(författare)
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How much land-based greenhouse gas mitigation can be achieved without compromising food security and environmental goals?
- 2013
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Ingår i: Global Change Biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 19:8, s. 2285-2302
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Forskningsöversikt (refereegranskat)abstract
- Feeding 9-10billion people by 2050 and preventing dangerous climate change are two of the greatest challenges facing humanity. Both challenges must be met while reducing the impact of land management on ecosystem services that deliver vital goods and services, and support human health and well-being. Few studies to date have considered the interactions between these challenges. In this study we briefly outline the challenges, review the supply- and demand-side climate mitigation potential available in the Agriculture, Forestry and Other Land Use AFOLU sector and options for delivering food security. We briefly outline some of the synergies and trade-offs afforded by mitigation practices, before presenting an assessment of the mitigation potential possible in the AFOLU sector under possible future scenarios in which demand-side measures codeliver to aid food security. We conclude that while supply-side mitigation measures, such as changes in land management, might either enhance or negatively impact food security, demand-side mitigation measures, such as reduced waste or demand for livestock products, should benefit both food security and greenhouse gas (GHG) mitigation. Demand-side measures offer a greater potential (1.5-15.6Gt CO2-eq. yr(-1)) in meeting both challenges than do supply-side measures (1.5-4.3Gt CO2-eq. yr(-1) at carbon prices between 20 and 100US$ tCO(2)-eq. yr(-1)), but given the enormity of challenges, all options need to be considered. Supply-side measures should be implemented immediately, focussing on those that allow the production of more agricultural product per unit of input. For demand-side measures, given the difficulties in their implementation and lag in their effectiveness, policy should be introduced quickly, and should aim to codeliver to other policy agenda, such as improving environmental quality or improving dietary health. These problems facing humanity in the 21st Century are extremely challenging, and policy that addresses multiple objectives is required now more than ever.
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| 47. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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