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Sökning: WFRF:(Vermeulen Michiel)

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1.
  • Fallows, Richard A., et al. (författare)
  • A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
  • 2020
  • Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18-19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10-80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of similar to 20-40 ms(-1) with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of similar to 110 ms(-1) with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported.
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2.
  • Fang, Jun, et al. (författare)
  • Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
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3.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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4.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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6.
  • Van Der Laan, Sander, et al. (författare)
  • Inferring 222Rn soil fluxes from ambient 222Rn activity and eddy covariance measurements of CO2
  • 2016
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:11, s. 5523-5533
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a new methodology, which we call Single Pair of Observations Technique with Eddy Covariance (SPOT-EC), to estimate regional-scale surface fluxes of 222Rn from tower-based observations of 222Rn activity concentration, CO2 mole fractions and direct CO2 flux measurements from eddy covariance. For specific events, the regional (222Rn) surface flux is calculated from short-term changes in ambient (222Rn) activity concentration scaled by the ratio of the mean CO2 surface flux for the specific event to the change in its observed mole fraction. The resulting 222Rn surface emissions are integrated in time (between the moment of observation and the last prior background levels) and space (i.e. over the footprint of the observations). The measurement uncertainty obtained is about ±15 % for diurnal events and about ±10 % for longer-term (e.g. seasonal or annual) means. The method does not provide continuous observations, but reliable daily averages can be obtained. We applied our method to in situ observations from two sites in the Netherlands: Cabauw station (CBW) and Lutjewad station (LUT). For LUT, which is an intensive agricultural site, we estimated a mean 222Rn surface flux of (0.29±0.02)atomscm-2s-1 with values > 0.5atomscm-2s-1 to the south and south-east. For CBW we estimated a mean 222Rn surface flux of (0.63±0.04)atomscm-2s-1. The highest values were observed to the south-west, where the soil type is mainly river clay. For both stations good agreement was found between our results and those from measurements with soil chambers and two recently published 222Rn soil flux maps for Europe. At both sites, large spatial and temporal variability of 222Rn surface fluxes were observed which would be impractical to measure with a soil chamber. SPOT-EC, therefore, offers an important new tool for estimating regional-scale 222Rn surface fluxes. Practical applications furthermore include calibration of process-based 222Rn soil flux models, validation of atmospheric transport models and performing regional-scale inversions, e.g. of greenhouse gases via the SPOT 222Rn-tracer method.
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  • Resultat 1-6 av 6

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