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1.
  • Cerhan, James R., et al. (författare)
  • Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1233-1238
  • Tidskriftsartikel (refereegranskat)abstract
    • Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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2.
  • Callegaro, Sara, et al. (författare)
  • Upper and lower crust recycling in the source of CAMP basaltic dykes from southeastern North America
  • 2013
  • Ingår i: Earth and Planetary Science Letters. - 0012-821X .- 1385-013X. ; 376, s. 186-199
  • Tidskriftsartikel (refereegranskat)abstract
    • The densest dykes swarm of the Central Atlantic magmatic province (CAMP) occur in southeastern North America (SENA) and were intruded between 202 and 195 Ma during Pangea break-up. New combined geochemical data (major and trace elements, Sr–Nd–Pb–Os isotopes) constrain the mantle source of these magmatic bodies and their evolution path. While Sr–Nd isotopic compositions for SENA rocks (87Sr/86Sr200Ma 0.70438–0.70880 and 143Nd/144Nd200Ma 0.51251–0.51204) fall within the low-Ti CAMP field, Pb–Pb isotopes (206Pb/204Pb200Ma 17.46–18.85, 207Pb/204Pb200Ma 15.54–15.65, 208Pb/204Pb200Ma 37.47–38.76) are peculiar to this area of the CAMP and cover a considerable span of compositions, especially in 206Pb/204Pb200Ma. Given the generally unradiogenic Os isotopic compositions (187Os/188Os200Ma 0.127–0.144) observed and the lack of correlation between these and other geochemical markers, crustal contamination during the evolution of SENA dykes must have been limited (less than 10%). Thus the isotopic variation is interpreted to reside primarily within the mantle source. These observations, coupled with typical continental signatures in trace elements (positive anomaly in Pb and negative anomalies in Ti and Nb), require another means of conveying a continental flavor to these magmas, which is here hypothesized to be the shallow recycling within the upper mantle of subducted lower and upper crustal materials. Pseudo-ternary mixing models show that a maximum of 10% recycled crust is enough to explain their trace element patterns as well as their isotopic heterogeneity. Looking at the larger picture of the origin of the CAMP, the thermal contribution of a mantle plume cannot be ruled out due to the relatively high mantle potential temperatures (1430–1480 °C) calculated for high-Fo SENA olivines. Nevertheless, our results suggest that the chemical involvement of a mantle plume is negligible (less than 5%) if either a C- or an EM-flavored plume is considered. Rather, the possibility of a PREMA-flavored mantle plume, enriched by 5–20% recycled crustal material, remains a possible, though less plausible, source for these tholeiites.
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3.
  • de Kocka, Michiel O., et al. (författare)
  • Dykes of the 1.11 Ga Umkondo LIP, Southern Africa: Clues to a complex plumbing system
  • 2014
  • Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 249, s. 129-143
  • Tidskriftsartikel (refereegranskat)abstract
    • The Umkondo Large Igneous Province (LIP) is represented by widespread (similar to 2.0 x 10(6) km(2)) mafic intrusions that were rapidly emplaced (1112-1108 Ma) into the Kalahari craton of southern Africa and the formerly adjacent Grunehogna Province of Antarctica during Rodinia assembly. Very few Umkondo-aged dykes have been identified before, resulting in a poor understanding of this LIP's plumbing system and origin. Here we report six new similar to 1110 Ma U-Pb TIMS baddeleyite ages for various dolerite dykes, which, when coupled with geochemistry from some of the dykes, suggest association with the Umkondo LIP. The distribution of dykes defines distinct radiating swarms, which locate two separate magmatic centers on the northern margin of the Kalahari craton, and a third less robust center on the SE margin. The Umkondo intrusions' geochemistry indicates significant partial melting of the sub-continental mantle lithosphere (SCLM) and requires a transient thermal anomaly in the mantle. A viable model sees a mantle plume ascend beneath the craton and split into different portions that moved and ascended to different lithospheric thin-spots along the margins of the craton. As an alternative, the rise in mantle temperature associated with continental aggregation at this time is considered sufficient to cause partial melting of the SCLM without any plume involvement. Specific features of the Umkondo LIP's plumbing system are supportive of either model, and an approach of multiple working hypotheses is recommended. (C) 2014 Elsevier B.V. All rights reserved.
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4.
  • Kouyate, Djiky, et al. (författare)
  • U-Pb baddeleyite and zircon ages of 2040 Ma, 1650 Ma and 885 Ma on dolerites in the West African Craton (Anti-Atlas inliers): Possible links to break-up of Precambrian supercontinents
  • 2013
  • Ingår i: Lithos. - : Elsevier BV. - 0024-4937. ; 174, s. 71-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Precambrian inliers of the Anti-Atlas belt in the southern part of Morocco contain numerous dolerite dyke and sill swarms which were previously poorly dated. Four dykes and two sills dated by the U-Pb TIMS method on baddeleyite and zircon provide the first steps toward a magmatic 'barcode' for the West African Craton (WAC) and constraints on the timing of breakup of the WAC from Precambrian supercontinents. A 2040 +/- 2 Ma (U-Pb zircon) age for a WNW dyke in the Zenaga inlier, matches the published age of a dyke in the Tagragra of Tata inlier, and also those of Eburnean granites observed in several inliers, which are collectively interpreted to represent ca. 2040 Ma bimodal magmatism due to a mantle plume. Based on the presence of matching 2040 Ma ages, the WAC may have been connected to the North Atlantic Craton at the initial stage of fragmentation of a late Archean continent. U-Pb baddeleyite ages of 1656 9 Ma and ca. 1655 Ma from sills in the Zenaga inlier and 1654 +/- 16 Ma from a NE-trending dyke in the Agadir Melloul inlier are similar to intraplate magmatic ages in eastern and northern Baltica, and support the SAMBA reconstruction (part of the Nuna supercontinent) of the WAC adjacent to Baltica. Approximate U-Pb ages of 885 Ma for two dykes in the Iguerda-Taifast and Zenaga inliers date a NE trending swarm (named herein the Iguerda-Taifast swarm) which is connected to the initial breakup of the supercontinent Rodinia, and a specific link with the Sao Francisco/Congo and North China craton is considered. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.
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5.
  • Merle, Renaud E., 1976-, et al. (författare)
  • 40Ar/39Ar ages and Sr–Nd–Pb–Os geochemistry of CAMP tholeiites from Western Maranhão basin (NE Brazil)
  • 2011
  • Ingår i: Lithos. - 0024-4937 .- 1872-6143. ; 122:3, s. 137-151
  • Tidskriftsartikel (refereegranskat)abstract
    • The Central Atlantic Magmatic Province (CAMP), emplaced at the Triassic–Jurassic (T–J) boundary (~200Ma), is among the largest igneous provinces on Earth. The Maranhão basin in NE Brazil is located around 700km inland and 2000km from the site of the earliest Pangea disruption. The CAMP tholeiites occur only in the western part of the basin and have been described as low and high-Ti. Here we document the occurrence of two sub-groups among the high-Ti tholeiites in the Western Maranhão basin. The major and trace elements and the Sr–Nd–Pb isotopic ratios define three chemical groups corresponding to the low-Ti (TiO2<1.3wt.%), high-Ti (TiO2~2.0wt.%) and evolved high-Ti (TiO2>3wt.%) western Maranhão basin tholeiites (WMBT). The new 40Ar/39Ar plateau ages obtained on plagioclase separates for high-Ti (199.7±2.4Ma) and evolved high-Ti WMBT (197.2±0.5Ma and 198.2±0.6Ma) are indistinguishable and identical to those of previously analyzed low-Ti WMBT (198.5±0.8Ma) and to the mean 40Ar/39Ar age of the CAMP (199±2.4Ma). We also present the first Re–Os isotopic data for CAMP basalts. The low and high-Ti samples display mantle-like initial (187Os/188Os)i ranging from 0.1267 to 0.1299, while the evolved high-Ti samples are more radiogenic ((187Os/188Os)i up to 0.184) We propose that the high-Ti WMBT were derived from the sub-lithospheric asthenosphere, and contaminated during ascent by interaction with the subcontinental lithospheric mantle (SCLM). The evolved high-Ti WMBT were derived from the same asthenospheric source but experienced crustal contamination. The chemical characteristics of the low-Ti group can be explained by partial melting of the most fertile portions of the SCLM metasomatized during paleo-subduction. Alternatively, the low-Ti WMBT could be derived from the sub-lithospheric asthenosphere but the resulting melts may have undergone contamination by the SCLM. The occurrences of high-Ti basalts are apparently not restricted to the area of initial continental disruption which may bring into question previous interpretations such as those relating high-Ti CAMP magmatism to the initiation of Atlantic ridge spreading or as the expression of a deep mantle plume. We propose that the CAMP magmatism in the Maranhão basin may be attributed to local hotter mantle conditions due to the combined effects of edge-driven convection and large-scale mantle warming under the Pangea supercontinent. The involvement of a mantle-plume with asthenosphere-like isotopic characteristics cannot be ruled out either as one of the main source components of the WMBT or as a heat supplier.
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6.
  • Merle, Renaud E., 1976-, et al. (författare)
  • Sr, Nd, Pb and Os Isotope Systematics of CAMP Tholeiites from Eastern North America (ENA) : Evidence of a Subduction-enriched Mantle Source
  • 2013
  • Ingår i: Journal of Petrology. - : Oxford University Press (OUP). - 0022-3530 .- 1460-2415. ; 55:1, s. 133-180
  • Tidskriftsartikel (refereegranskat)abstract
    • The Central Atlantic Magmatic Province (CAMP) is one of the largest igneous provinces on Earth, with an areal extent exceeding 107 km2. Here we document the geochemical characteristics of CAMP basalts from Triassic–Jurassic basins in northeastern USA and Nova Scotia (Canada). The CAMP rocks occur as lava flows, sills and dykes. All of our analysed samples show chemical characteristics typical of CAMP basalts with low titanium content, which include enrichment in the most incompatible elements and negative Nb anomalies. All the basalts also show enriched Sr–Nd–Pb initial (t = 201 Ma) isotopic compositions (206Pb/204Pbini. = 18·155–18·691, 207Pb/204Pbini. = 15·616–15·668, 208Pb/204Pbini. = 38·160–38·616, 143Nd/144Ndini. = 0·512169–0·512499). On the basis of stratigraphy, rare earth element (REE) chemistry and Sr–Nd–Pb isotope composition, three chemical groups are defined. The Hook Mountain group, with the lowest La/Yb ratios, initial 206Pb/204Pbini. >18·5 and 143Nd/144Ndini. > 0·51238, comprises all the lastest and upper stratigraphic units. The Preakness group, with intermediate La/Yb ratios, 206Pb/204Pbini. > 18·5 and 0·51233 > 143Nd/144Ndini. > 0·51225, comprises the intermediate units. The Orange Mountain group has the highest La/Yb ratios and 143Nd/144Ndini. < 0·51235 and involves all the earliest and stratigraphically lowest units, including the entire North Mountain basalts from Nova Scotia. In this last group, three sub-groups may be distinguished: the Rapidan sill, which has 206Pb/204Pbini. higher than 18·5, the Shelburne sub-group, which has 143Nd/144Ndini. < 0·51225, and the remaining Orange Mt samples. With the exception of one sample, the Eastern North America (ENA) CAMP basalts display initial 187Os/188Os ratios in the range of mantle-derived magmas (<0·15). Simple modelling shows that the composition of the ENA CAMP basalts cannot plausibly be explained solely by crustal contamination of oceanic island basalt (OIB), mid-ocean ridge basalt (MORB) or oceanic plateau basalt (OPB) magmas. Mixing of such magma compositions with sub-continental lithospheric mantle (SCLM)-derived melts followed by crustal contamination, by either assimilation–fractional crystallization (AFC) or assimilation through turbulent ascent (ATA) processes is somewhat more successful. However, this latter scenario does not reproduce the REE and isotopic composition of the ENA CAMP in a fully satisfactory manner. Alternatively, we propose a model in which asthenospheric mantle overlying a subducted slab (i.e. mantle wedge) was enriched during Cambrian to Devonian subduction by sedimentary material, isotopically equivalent to Proterozoic–Lower Paleozoic crustal rocks. Subsequently, after subduction ceased, the isotopic composition of this mantle evolved by radioactive decay for another 170 Myr until the CAMP magmatic event. Varying amounts and compositions of the incorporated sedimentary component coupled with radiogenic ingrowth over time can account for the main geochemical characteristics of the ENA CAMP (enriched incompatible element patterns, negative Nb anomalies, enriched Sr–Nd–Pb isotopic composition) and the differences between the three chemical groups.
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7.
  • Schael, S., et al. (författare)
  • Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
  • 2013
  • Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
  • Forskningsöversikt (refereegranskat)abstract
    • Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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8.
  • Skibola, Christine F, et al. (författare)
  • Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 95:4, s. 462-471
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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9.
  • Youbi, Nasrrddine, et al. (författare)
  • The 1750 Ma Magmatic Event of the West African Craton (Anti-Atlas, Morocco)
  • 2013
  • Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 236, s. 106-123
  • Tidskriftsartikel (refereegranskat)abstract
    • The Precambrian inliers of the Anti Atlas belt located at the southern part of Morocco contain numerous mafic dyke and sill swarms thought to represent the erosional remnants of Proterozoic Large Igneous Provinces (LIPS). As part of a continuing research campaign to date and characterize these LIPs, four dykes have been dated by the U-Pb TIMS (Thermal Ionization Mass Spectrometry) method on baddeleyite and zircon: ca. 1758 Ma in the Tagragra of Akka inlier, 1741 +/- 10 Ma in the Tafeltast-Kerdous inlier, 1746.8 +/- 3.7 Ma in the Iguerda-Tanst and 1734 +/- 5 Ma in the Zenaga inlier. The age matches (and chemical features akin to continental flood basalts) confirm a widespread intraplate magmatic event at 1750 Ma, herein termed the Tagragra of Akka LIP, that represents an important new magmatic tarcode' line for the West African Craton (WAC). Contemporaneous 1750 Ma LIP magmatism is reported in other crustal blocks including northwestern Laurentia and Siberia; together with the newly defined Tagragra of Akka event of the Anti Atlas region of the WAC this widespread 1750 Ma magmatism is postulated to collectively constitute a single huge LIP associated with a breakup attempt of Nuns (Columbia) shortly after its final assembly at ca. 1.8 Ga. (C) 2013 Elsevier B.V. All rights reserved.
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10.
  • Zadravec, Damir, 1980-, et al. (författare)
  • Ablation of the very-long-chain fatty acid elongase ELOVL3 in mice leads to constrained lipid storage and resistance to diet-induced obesity.
  • 2010
  • Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860 .- 0892-6638. ; 24:11, s. 4366-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Although saturated and monounsaturated very-long-chain fatty acids (VLCFAs) have long been associated with undesirable effects on health, including obesity, heart failure, and atherosclerosis, the physiological role of endogenous synthesis is largely unknown. The fatty acid elongase ELOVL3 is involved in the synthesis of C20-C24 saturated and monounsaturated VLCFAs mainly in liver, brown and white adipose tissue, and triglyceride-rich glands such as the sebaceous and meibomian glands. Here we show that ablation of ELOVL3 leads to reduced adiponectin levels, constrained expansion of adipose tissue, and resistance against diet-induced obesity, a situation that is more exaggerated in female mice. Both female and male knockout mice show reduced hepatic lipogenic gene expression and triglyceride content, a situation that is associated with reduced de novo fatty acid synthesis and uptake. As a consequence, the VLDL-triglyceride level in serum is significantly reduced. Remarkably, despite increased energy expenditure, markedly reduced serum levels of leptin, and increased expression of orexigenic peptides in the hypothalamus, the Elovl3(-/-) mice do not compensate by increased food intake. Thus, these results reveal that C20-C22 saturated and monounsaturated VLCFAs produced by ELOVL3 are indispensable for appropriate synthesis of liver triglycerides, fatty acid uptake, and storage in adipose tissue.
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