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| 6. |
- Tanskanen, T., et al.
(author)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
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In: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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| 7. |
- Cirasuolo, M., et al.
(author)
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MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT
- 2014
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In: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 1996-756X .- 0277-786X. ; 9147, s. 91470-91470
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Conference paper (peer-reviewed)abstract
- MOONS (the Multi-Object Optical and Near-infrared Spectrograph) has been selected by ESO as a third-generation instrument for the Very Large Telescope (VLT). The light grasp of the large collecting area offered by the VLT (8.2m diameter), combined with the large multiplex and wavelength coverage (optical to near-IR: 0.8 -1.8 mu m) of MOONS will provide the European astronomical community with a powerful, unique instrument able to pioneer a wide range of Galactic, extragalactic and cosmological studies, and it will provide crucial follow-up for major facilities such as Gaia, VISTA, Euclid and LSST. MOONS has the observational power needed to unveil galaxy formation and evolution over the entire history of the Universe, from stars in our Milky Way, through the redshift desert, and up to the epoch of very first galaxies and reionization of the Universe at redshifts of z > 8-9, just a few million years after the Big Bang. From five years of observations MOONS will provide high-quality spectra for > 3M stars in our Galaxy and the Local Group, and for 1-2M galaxies at z > 1 (for an SDSS-like survey), promising to revolutionize our understanding of the Universe. The baseline design consists of similar to 1000 fibres, deployable over a field-of-view of similar to 500 arcmin(2), the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8 -1.8 mu m with two spectral resolving powers: in the medium-resolution mode (R similar to 4,000-6,000) the entire wavelength range is observed simultaneously, while the high-resolution mode will cover three selected sub-regions simultaneously: one region with R similar to 8,000 near the Ca II triplet to measure stellar radial velocities, and two regions at R similar to 20,000 (one in each of the J- and H-bands), for precision measurements of chemical abundances.
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| 8. |
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| 9. |
- Jiang, X., et al.
(author)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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| 11. |
- Zaborowski, AM, et al.
(author)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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In: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Journal article (peer-reviewed)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 12. |
- Arnau-Soler, A, et al.
(author)
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Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland
- 2019
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 14-
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Journal article (peer-reviewed)abstract
- Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 × 10−6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 × 10−9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 × 10−8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 × 10−8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 × 10−6). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 × 10−3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.
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| 13. |
- Berthomier, M., et al.
(author)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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In: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Journal article (peer-reviewed)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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| 14. |
- Cheng, THT, et al.
(author)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Journal article (peer-reviewed)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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| 16. |
- Freitag, Daniel F., et al.
(author)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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In: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Journal article (peer-reviewed)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 17. |
- Koettgen, Anna, et al.
(author)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Journal article (peer-reviewed)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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| 18. |
- Lockwood, M, et al.
(author)
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Coordinated Cluster and ground-based instrument observations of transient changes in the magnetopause boundary layer during an interval of predominantly northward IMF : relation to reconnection pulses and FTE signatures
- 2001
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In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 19:10-12, s. 1613-1640
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Research review (peer-reviewed)abstract
- We study a series of transient entries into the low-latitude boundary layer (LLBL) of all four Cluster spacecraft during an outbound pass through the mid-afternoon magnetopause ([X(GSM), Y(GSM), Z(GSM)] approximate to [2, 7, 9] R(E)). The events take place during an interval of northward IMF, as seen in the data from the ACE satellite and lagged by a propagation delay of 75 min that is well-defined by two separate studies: (1) the magnetospheric variations prior to the northward turning (Lockwood et al., 2001, this issue) and (2) the field clock angle seen by Cluster after it had emerged into the magnetosheath (Opgenoorth et al., 2001, this issue). With an additional lag of 16.5 min, the transient LLBL events cor-relate well with swings of the IMF clock angle (in GSM) to near 90degrees. Most of this additional lag is explained by ground-based observations, which reveal signatures of transient reconnection in the pre-noon sector that then take 10-15 min to propagate eastward to 15 MLT, where they are observed by Cluster. The eastward phase speed of these signatures agrees very well with the motion deduced by the cross-correlation of the signatures seen on the four Cluster spacecraft. The evidence that these events are reconnection pulses includes: transient erosion of the noon 630 nm (cusp/cleft) aurora to lower latitudes; transient and travelling enhancements of the flow into the polar cap, imaged by the AMIE technique; and poleward-moving events moving into the polar cap, seen by the EISCAT Svalbard Radar (ESR). A pass of the DMSP-F15 satellite reveals that the open field lines near noon have been opened for some time: the more recently opened field lines were found closer to dusk where the flow transient and the poleward-moving event intersected the satellite pass. The events at Cluster have ion and electron characteristics predicted and observed by Lockwood and Hapgood (1998) for a Flux Transfer Event (FTE), with allowance for magnetospheric ion reflection at Alfvenic disturbances in the magnetopause reconnection layer. Like FTEs, the events are about 1 R(E) in their direction of motion and show a rise in the magnetic field strength, but unlike FTEs, in general, they show no pressure excess in their core and hence, no characteristic bipolar signature in the boundary-normal component. However, most of the events were observed when the magnetic field was southward, i.e. on the edge of the interior magnetic cusp, or when the field was parallel to the magnetic equatorial plane. Only when the satellite begins to emerge from the exterior boundary (when the field was northward), do the events start to show a pressure excess in their core and the consequent bipolar signature. We identify the events as the first observations of FTEs at middle altitudes.
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| 19. |
- Bourne, N., et al.
(author)
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Evolution of cosmic star formation in the SCUBA-2 Cosmology Legacy Survey
- 2017
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 467:2, s. 1360-1385
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Journal article (peer-reviewed)abstract
- We present a new exploration of the cosmic star formation history and dust obscuration in massive galaxies at redshifts 0.5 10(10) M-O galaxies at 0.5 10. One third of this is accounted for by 450 mu m-detected sources, while one-fifth is attributed to UV-luminous sources (brighter than L-UV(*)), although even these are largely obscured. By extrapolating our results to include all stellar masses, we estimate a total SFRD that is in good agreement with previous results from IR and UV data at z
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| 20. |
- Coppin, K. E. K., et al.
(author)
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Herschel-PACS observations of [O I]63 μm towards submillimetre galaxies at z~1
- 2012
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 427:1, s. 520-532
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Journal article (peer-reviewed)abstract
- We present Herschel-PACS spectroscopy of the [O I]63 μm far-infrared cooling line from a sample of six unlensed and spectroscopically confirmed 870 μm selected submillimetre (submm) galaxies (SMGs) at 1.1
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| 21. |
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| 22. |
- Geach, J.E., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: 850 μm maps, catalogues and number counts
- 2017
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 465:2, s. 1789-1806
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Journal article (peer-reviewed)abstract
- We present a catalogue of similar to 3000 submillimetre sources detected (>= 3.5 sigma) at 850 mu m over similar to 5 deg(2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 mu m, increasing the sample size of 850 mu m selected submillimetre galaxies by an order of magnitude. The wide 850 mu m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1s depth of S2CLS is 1.2 mJy beam(-1), approaching the SCUBA-2 850 mu m confusion limit, which we determine to be sigma(c) approximate to 0.8 mJy beam(-1). We measure the 850 mu m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S-850 approximate to 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5 degrees-1 degrees scales are generally within 50 per cent of the S2CLS mean for S-850 > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2 sigma) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S-850 < 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S-850 > 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 mu m emission
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| 23. |
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| 24. |
- Moukaddam, M., et al.
(author)
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In-beam internal conversion electron spectroscopy with the SPICE detector
- 2018
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 905, s. 180-187
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Journal article (peer-reviewed)abstract
- The SPectrometer for Internal Conversion Electrons (SPICE) has been commissioned for use in conjunction with the TIGRESS γ-ray spectrometer at TRIUMF's ISAC-II facility. SPICE features a permanent rare-earth magnetic lens to collect and direct internal conversion electrons emitted from nuclear reactions to a thick, highly segmented, lithium-drifted silicon detector. This arrangement, combined with TIGRESS, enables in-beam γ-ray and internal conversion electron spectroscopy to be performed with stable and radioactive ion beams. Technical aspects of the device, capabilities, and initial performance are presented.
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| 27. |
- Savin, S., et al.
(author)
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Experimental study of nonlinear interaction of plasma flow with charged thin current sheets : 2. Hall dynamics, mass and momentum transfer
- 2006
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In: Nonlinear processes in geophysics. - 1023-5809 .- 1607-7946. ; 13:4, s. 377-392
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Journal article (peer-reviewed)abstract
- Proceeding with the analysis of Amata et al. (2005), we suggest that the general feature for the local transport at a thin magnetopause (MP) consists of the penetration of ions from the magnetosheath with gyroradius larger than the MP width, and that, in crossing it, the transverse potential difference at the thin current sheet (TCS) is acquired by these ions, providing a field-particle energy exchange without parallel electric fields. It is suggested that a part of the surface charge is self-consistently produced by deflection of ions in the course of inertial drift in the nonuniform electric field at MP. Consideration of the partial moments of ions with different energies demonstrates that the protons having gyro-radii of roughly the same size or larger than the MP width carry fluxes normal to MP that are about 20% of the total flow in the plasma jet under MP. This is close to the excess of the ion transverse velocity over the cross-field drift speed in the plasma flow just inside MP (Amata et al., 2005), which conforms to the contribution of the finite-gyroradius inflow across MP. A linkage through the TCS between different plasmas results from the momentum conservation of the higher-energy ions. If the finite-gyroradius penetration occurs along the MP over similar to 1.5 R-E from the observation site, then it can completely account for the formation of the jet under the MP. To provide the downstream acceleration of the flow near the MP via the cross-field drift, the weak magnetic field is suggested to rotate from its nearly parallel direction to the unperturbed flow toward being almost perpendicular to the accelerated flow near the MP. We discuss a deceleration of the higher-energy ions in the MP normal direction due to the interaction with finite-scale electric field bursts in the magnetosheath flow frame, equivalent to collisions, providing a charge separation. These effective collisions, with a nonlinear frequency proxy of the order of the proton cyclotron one, in extended turbulent zones are a promising alternative in place of the usual parallel electric fields invoked in the macro-reconnection scenarios. Further cascading towards electron scales is supposed to be due to unstable parallel electron currents, which neutralize the potential differences, either resulted from the ion-burst interactions or from the inertial drift. The complicated MP shape suggests its systematic velocity departure from the local normal towards the average one, inferring domination for the MP movement of the non-local processes over the small-scale local ones. The measured Poynting vector indicates energy transmission from the MP into the upstream region with the waves triggering impulsive downstream flows, providing an input into the local flow balance and the outward movement of the MP. Equating the transverse electric field inside the MP TCS by the Hall term in the Ohm's law implies a separation of the different plasmas primarily by the Hall current, driven by the respective part of the TCS surface charge. The Hall dynamics of TCS can operate either without or as a part of a macro-reconnection with the magnetic field annihilation.
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| 28. |
- Simpson, J. M., et al.
(author)
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THE SCUBA-2 COSMOLOGY LEGACY SURVEY: ALMA RESOLVES the BRIGHT-END of the SUB-MILLIMETER NUMBER COUNTS
- 2015
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In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 807:2
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Journal article (peer-reviewed)abstract
- We present high-resolution 870 μm Atacama Large Millimeter/sub-millimeter Array (ALMA) continuum maps of 30 bright sub-millimeter sources in the UKIDSS UDS field. These sources are selected from deep, 1 degree2 850 μm maps from the SCUBA-2 Cosmology Legacy Survey, and are representative of the brightest sources in the field (median SSCUBA-2= 8.7 ± 0.4 mJy). We detect 52 sub-millimeter galaxies (SMGs) at >4σ significance in our 30 ALMA maps. In 61-15+19% of the ALMA maps the single-dish source comprises a blend of ≥2 SMGs, where the secondary SMGs are Ultra-luminous Infrared Galaxies (ULIRGs) with LIR ≳ 1012 L⊙. The brightest SMG contributes on average 80-2+6% of the single-dish flux density, and in the ALMA maps containing ≥2 SMGs the secondary SMG contributes 25-5+1% of the integrated ALMA flux. We construct source counts and show that multiplicity boosts the apparent single-dish cumulative counts by 20% at S870 > 7.5 mJy, and by 60% at S870 > 12 mJy. We combine our sample with previous ALMA studies of fainter SMGs and show that the counts are well-described by a double power law with a break at 8.5 ± 0.6 mJy. The break corresponds to a luminosity of ∼6 × 1012 L⊙ or a star formation rate (SFR) of ∼103 M⊙ yr-1. For the typical sizes of these SMGs, which are resolved in our ALMA data with Re = 1.2 ± 0.1 kpc, this yields a limiting SFR density of ∼100 M⊙ yr-1 kpc-2 Finally, the number density of S870 ≳ 2 mJy SMGs is 80 ± 30 times higher than that derived from blank-field counts. An over-abundance of faint SMGs is inconsistent with line-of-sight projections dominating multiplicity in the brightest SMGs, and indicates that a significant proportion of these high-redshift ULIRGs are likely to be physically associated.
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| 29. |
- Thomas, Minta, et al.
(author)
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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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| 30. |
- Thompson, Deborah J, et al.
(author)
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Genetic predisposition to mosaic Y chromosome loss in blood
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 575, s. 652-657
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Journal article (peer-reviewed)abstract
- Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.
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| 31. |
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| 32. |
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| 33. |
- Bethlehem, RAI, et al.
(author)
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Brain charts for the human lifespan
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Journal article (peer-reviewed)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 34. |
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| 35. |
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| 36. |
- Carter, J. A., et al.
(author)
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Ground-based and additional science support for SMILE
- 2024
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In: Earth and Planetary Physics. - : Science Press. - 2096-3955. ; 8:1, s. 275-298
-
Journal article (peer-reviewed)abstract
- The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions, and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere. Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission. Here, we describe current community efforts to prepare for SMILE, and the benefits and context various experiments that have explicitly expressed support for SMILE can offer. A dedicated group of international scientists representing many different experiment types and geographical locations, the Ground-based and Additional Science Working Group, is facilitating these efforts. Preparations include constructing an online SMILE Data Fusion Facility, the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar, and the consideration of particular observing strategies and spacecraft conjunctions. We anticipate growing interest and community engagement with the SMILE mission, and we welcome novel ideas and insights from the solar-terrestrial community.
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| 37. |
- Chen, Zhishan, et al.
(author)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 38. |
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| 39. |
- Coppin, K. E. K., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: the submillimetre properties of Lyman-break galaxies at z=3-5
- 2015
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 446:2, s. 1293-1304
-
Journal article (peer-reviewed)abstract
- We present detections at 850 mu m of the Lyman-break galaxy (LBG) population at z approximate to 3, 4, and 5 using data from the Submillimetre Common User Bolometer Array 2 Cosmology Legacy Survey in the United Kingdom Infrared Deep Sky Survey 'Ultra Deep Survey' field. We employ stacking to probe beneath the survey limit, measuring the average 850 mu m flux density of LBGs at z approximate to 3, 4, and 5 with typical ultraviolet luminosities of L-1700 approximate to 10(29) erg s(-1) Hz(-1). We measure 850 mu m flux densities of (0.25 +/- 0.03), (0.41 +/- 0.06), and (0.88 +/- 0.23) mJy, respectively, finding that they contribute at most 20 per cent to the cosmic far-infrared (IR) background at 850 mu m. Fitting an appropriate range of spectral energy distributions to the z similar to 3, 4, and 5 LBG stacked 24-850 mu m fluxes, we derive IR luminosities of L8-1000 (mu m) approximate to 3.2, 5.5, and 11.0 x 10(11) L-circle dot [and star formation rates (SFRs) of approximate to 50-200M(circle dot) yr(-1)], respectively. We find that the evolution in the IR luminosity density of LBGs is broadly consistent with model predictions for the expected contribution of luminous-to-ultraluminous IR galaxies at these epochs. We observe a positive correlation between stellar mass and IR luminosity and confirm that, for a fixed mass, the reddest LBGs (UV slope beta -> 0) are redder due to dust extinction, with SFR (IR)/SFR (UV) increasing by about an order of magnitude over -2
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| 40. |
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| 41. |
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| 42. |
- Dunlop, R., et al.
(author)
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β decay and β-delayed neutron decay of the N=82 nucleus 13149In82
- 2019
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In: Physical Review C: covering nuclear physics. - 2469-9985.
-
Journal article (peer-reviewed)abstract
- The half-lives of three β-decaying states of 13149In82 have been measured with the GRIFFIN γ-ray spectrometer at the TRIUMF-ISAC facility to be T1/2(1/2−)=328(15)ms, T1/2(9/2+)=265(8)ms, and T1/2(21/2+)=323(55)ms, respectively. The first observation of γ rays following the βn decay of 131In into 130Sn is reported. The β-delayed neutron emission probability is determined to be P1n=12(7)% for the 21/2+ state and 2.3(3)% from the combined 1/2− and 9/2+ states of 13149In82 observed in this experiment. A significant expansion of the decay scheme of 131In, including 17 new excited states and 35 new γ-ray transitions in 13150Sn81 is also reported. This leads to large changes in the deduced β-branching ratios to some of the low-lying states of 131Sn compared to previous work with implications for the strength of the first-forbidden β transitions in the vicinity of doubly magic 13250Sn82.
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| 43. |
- Geach, J.E., et al.
(author)
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The SCUBA-2 Cosmology Legacy Survey: blank-field number counts of 450-mu m-selected galaxies and their contribution to the cosmic infrared background
- 2013
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 432:1, s. 53-61
-
Journal article (peer-reviewed)abstract
- The first deep blank-field 450 mu m map (1 sigma approximate to 1.3 mJy) from the Submillimetre Common-User Bolometer Array-2 SCUBA-2 Cosmology Legacy Survey (S2CLS), conducted with the James Clerk Maxwell Telescope (JCMT) is presented. Our map covers 140 arcmin(2) of the Cosmological Evolution Survey field, in the footprint of the Hubble Space Telescope (HST) Cosmic Assembly Near-Infrared Deep Extragalactic Legacy Survey. Using 60 submillimetre galaxies detected at >= 3.75s, we evaluate the number counts of 450-mu m-selected galaxies with flux densities S-450 > 5 mJy. The 8 arcsec JCMT beam and high sensitivity of SCUBA-2 now make it possible to directly resolve a larger fraction of the cosmic infrared background (CIB, peaking at. similar to 200 mu m) into the individual galaxies responsible for its emission than has previously been possible at this wavelength. At S450 > 5 mJy, we resolve (7.4 +/- 0.7) x 10(-2) MJy sr(-1) of the CIB at 450 mu m (equivalent to 16 +/- 7 per cent of the absolute brightness measured by the Cosmic Background Explorer at this wavelength) into point sources. A further similar to 40 per cent of the CIB can be recovered through a statistical stack of 24 mu m emitters in this field, indicating that the majority (approximate to 60 per cent) of the CIB at 450 mu m is emitted by galaxies with S450 > 2 mJy. The average redshift of 450 mu m emitters identified with an optical/near-infrared counterpart is estimated to be = 1.3, implying that the galaxies in the sample are in the ultraluminous class (LIR approximate to 1.1 x 1012 L approximate to). If the galaxies contributing to the statistical stack lie at similar redshifts, then the majority of the CIB at 450 mu m is emitted by galaxies in the luminous infrared galaxy (LIRG) class with LIR > 3.6 x 1011 L-circle dot.
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| 44. |
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| 45. |
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| 46. |
- Koprowski, M. P., et al.
(author)
-
A direct calibration of thtae IRX-β relation in Lyman-break Galaxies at z = 3-5
- 2018
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 479:4, s. 4355-4366
-
Journal article (peer-reviewed)abstract
- We use a sample of 4209 Lyman-break galaxies (LBGs) at z ≃ 3, 4, and 5 in the UKIRT Infrared Deep Sky Survey Ultra Deep Survey field to investigate the relationship between the observed slope of the stellar continuum emission in the ultraviolet, β, and the thermal dust emission, as quantified via the so-called 'infrared excess' (IRX=LIR/LUV). Through a stacking analysis, we directly measure the 850-μm flux density of LBGs in our deep (0.9 mJy) James Clerk Maxwell Telescope SCUBA-2 850-μm map as well as deep public Herschel/SPIRE 250-, 350-, and 500-μm imaging. We establish functional forms for the IRX-β relation to z ~ 5, confirming that there is no significant redshift evolution of the relation, and that the resulting average IRX-β curve is consistent with a Calzetti-like attenuation law. Comparing our results with recent works in the literature, we confirm that discrepancies in the slope of the IRX-β relation are driven by biases in the methodology used to determine the ultraviolet slopes. Consistent results are found when IRX-β is evaluated by stacking in bins of stellar mass, and we argue that the near-linear IRX-M* relationship is a better proxy for correcting observed ultraviolet luminosities to total star formation rates, provided an accurate handle on M* and also gives clues as to the physical driver of the role of dust-obscured star formation in high-redshift galaxies.
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| 47. |
- Law, Philip J., et al.
(author)
-
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 48. |
- Lockwood, M., Fazakerley, A., Opgenoorth, H., Moen, J., van Eyken, A.P., Dunlop, M., Bosqued, J.M., Lu, G., Cully, C., Eglitis, P., McCrea, I., Hapgood, M. A., Wild, M.N., Stamper, R., Denig, W., Taylor, M., . Wild, J.A., Provan, G., Amm, O., Kauristie
(author)
-
Coordinated Cluster, ground-based instrumentation and low-altitude satellite observations of transient poleward-moving events in the ionosphere and in the tail lobe
- 2001
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In: Annales Geophysicae. ; 19:10, s. 1589-1612
-
Journal article (peer-reviewed)abstract
- During the interval between 8:00–9:30 on 14 January 2001, the four Cluster spacecraft were moving from the central magnetospheric lobe, through the dusk sector mantle, on their way towards intersecting the magnetopause near 15:00 MLT and 15:00 UT. Throug
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| 49. |
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| 50. |
- Marklund, G.T., Ivchenko, N., Karlsson, T., Fazakerley, A., Dunlop, M., Lindqvist, P.A., Buchert, S., Owen, C., Taylor, M., Vaivalds, A., Carter, P., Andre, M. and Balogh, A.
(author)
-
Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere.
- 2001
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In: Nature. ; 414:6865, s. 724-727
-
Journal article (peer-reviewed)abstract
- The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field(1-3). On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric fie
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