| 1. |
- Erni, W., et al.
(författare)
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Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
- 2013
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 4. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 5. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 6. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 7. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 8. |
- Casazza, P. G., et al.
(författare)
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Preface
- 2012
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Ingår i: Numerical Functional Analysis and Optimization. - : Informa UK Limited. - 0163-0563 .- 1532-2467. ; 33:7-9, s. 705-707
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Dixon, Keri L., et al.
(författare)
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The large-scale observational signatures of low-mass galaxies during reionization
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:3, s. 3011-3029
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the epoch of reionization give us clues about the nature and evolution of the sources of ionizing photons, or early stars and galaxies. We present a new suite of structure formation and radiative transfer (RT) simulations from the PRACE4LOFAR project designed to investigate whether the mechanism of radiative feedback, or the suppression of star formation in ionized regions from UV radiation, can be inferred from these observations. Our source halo mass extends down to 10(8) M-circle dot, with sources in the mass range 10(8)-10(9) M-circle dot expected to be particularly susceptible to feedback from ionizing radiation, and we vary the aggressiveness and nature of this suppression. Not only do we have four distinct source models, we also include two box sizes (67 and 349 Mpc), each with two grid resolutions. This suite of simulations allows us to investigate the robustness of our results. All of our simulations are broadly consistent with the observed electron-scattering optical depth of the cosmic microwave background and the neutral fraction and photoionization rate of hydrogen at z similar to 6. In particular, we investigate the redshifted 21-cm emission in anticipation of upcoming radio interferometer observations. We find that the overall shape of the 21-cm signal and various statistics are robust to the exact nature of source suppression, the box size, and the resolution. There are some promising model discriminators in the non-Gaussianity and small-scale power spectrum of the 21-cm signal.
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| 10. |
- Giri, Sambit K., et al.
(författare)
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Bubble size statistics during reionization from 21-cm tomography
- 2018
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 473:3, s. 2949-2964
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming SKA1-Low radio interferometer will be sensitive enough to produce tomographic imaging data of the redshifted 21-cm signal from the Epoch of Reionization. Due to the non-Gaussian distribution of the signal, a power spectrum analysis alone will not provide a complete description of its properties. Here, we consider an additional metric which could be derived from tomographic imaging data, namely the bubble size distribution of ionized regions. We study three methods that have previously been used to characterize bubble size distributions in simulation data for the hydrogen ionization fraction-the spherical-average (SPA), mean-free-path (MFP) and friends-of-friends (FOF) methods -and apply them to simulated 21-cm data cubes. Our simulated data cubes have the (sensitivity-dictated) resolution expected for the SKA1-Low reionization experiment and we study the impact of both the light-cone (LC) and redshift space distortion (RSD) effects. To identify ionized regions in the 21-cm data we introduce a new, self-adjusting thresholding approach based on the K-Means algorithm. We find that the fraction of ionized cells identified in this way consistently falls below the mean volume-averaged ionized fraction. From a comparison of the three bubble size methods, we conclude that all three methods are useful, but that the MFP method performs best in terms of tracking the progress of reionization and separating different reionization scenarios. The LC effect is found to affect data spanning more than about 10 MHz in frequency (Delta z similar to 0.5). We find that RSDs only marginally affect the bubble size distributions.
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| 11. |
- Giri, Sambit K., et al.
(författare)
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Neutral island statistics during reionization from 21-cm tomography
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:2, s. 1590-1605
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Tidskriftsartikel (refereegranskat)abstract
- We present the prospects of extracting information about the epoch of reionization by identifying the remaining neutral regions, referred to as islands, in tomographic observations of the redshifted 21-cm signal. Using simulated data sets we show that at late times the 21-cm power spectrum is fairly insensitive to the details of the reionization process but that the properties of the neutral islands can distinguish between different reionization scenarios. We compare the properties of these islands with those of ionized bubbles. At equivalent volume-filling fractions, neutral islands tend to be fewer in number but larger compared to the ionized bubbles. In addition, the evolution of the size distribution of neutral islands is found to be slower than that of the ionized bubbles and also their percolation behaviour differs substantially. Even though the neutral islands are relatively rare, they will be easier to identify in observations with the low frequency component of the Square Kilometre Array due to their larger size and the lower noise levels at lower redshifts. The size distribution of neutral islands at the late stages of reionization is found to depend on the source properties, such as the ionizing efficiency of the sources and their minimum mass. We find the longest line of sight through a neutral region to be more than 100 comoving Mpc until very late stages (90-95 per cent reionized), which may have relevance for the long absorption trough at z = 5.6-5.8 in the spectrum of quasar ULAS J0148+0600.
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| 12. |
- Jensen, Hannes, et al.
(författare)
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The wedge bias in reionization 21-cm power spectrum measurements
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:1, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- A proposed method for dealing with foreground emission in upcoming 21-cm observations from the epoch of reionization is to limit observations to an uncontaminated window in Fourier space. Foreground emission can be avoided in this way, since it is limited to a wedge-shaped region in k(parallel to), k(perpendicular to) space. However, the power spectrum is anisotropic owing to redshift-space distortions from peculiar velocities. Consequently, the 21-cm power spectrum measured in the foreground avoidance window - which samples only a limited range of angles close to the line-of-sight direction - differs from the full redshift-space spherically averaged power spectrum which requires an average over all angles. In this paper, we calculate the magnitude of this 'wedge bias' for the first time. We find that the bias amplifies the difference between the real-space and redshift-space power spectra. The bias is strongest at high redshifts, where measurements using foreground avoidance will overestimate the redshift-space power spectrum by around 100 per cent, possibly obscuring the distinctive rise and fall signature that is anticipated for the spherically averaged 21-cm power spectrum. In the later stages of reionization, the bias becomes negative, and smaller in magnitude (less than or similar to 20 per cent).
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| 13. |
- Kakiichi, Koki, et al.
(författare)
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Recovering the H II region size statistics from 21-cm tomography
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 471:2, s. 1936-1954
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a novel technique, called 'granulometry', to characterize and recover the mean size and the size distribution of HII regions from 21-cm tomography. The technique is easy to implement, but places the previously not very well-defined concept of morphology on a firm mathematical foundation. The size distribution of the cold spots in 21-cm tomography can be used as a direct tracer of the underlying probability distribution of HII region sizes. We explore the capability of the method using large-scale reionization simulations and mock observational data cubes while considering capabilities of SquareKilometreArray 1 (SKA1) low and a future extension to SKA2. We show that the technique allows the recovery of the HII region size distribution with a moderate signal-to-noise ratio from wide-field imaging (SNR less than or similar to 3), for which the statistical uncertainty is sample variance dominated. We address the observational requirements on the angular resolution, the field of view, and the thermal noise limit for a successful measurement. To achieve a full scientific return from 21-cm tomography and to exploit a synergy with 21-cm power spectra, we suggest an observing strategy using widefield imaging (several tens of square degrees) by an interferometric mosaicking/multibeam observation with additional intermediate baselines (similar to 2-4 km) in an SKA phase 2.
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| 14. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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| 15. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 16. |
- Majumdar, Suman, et al.
(författare)
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Effects of the sources of reionization on 21-cm redshift-space distortions
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:2, s. 2080-2094
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Tidskriftsartikel (refereegranskat)abstract
- The observed 21 cm signal from the epoch of reionization will be distorted along the line of sight by the peculiar velocities of matter particles. These redshift-space distortions will affect the contrast in the signal and will also make it anisotropic. This anisotropy contains information about the cross-correlation between the matter density field and the neutral hydrogen field, and could thus potentially be used to extract information about the sources of reionization. In this paper, we study a collection of simulated reionization scenarios assuming different models for the sources of reionization. We show that the 21 cm anisotropy is best measured by the quadrupole moment of the power spectrum. We find that, unless the properties of the reionization sources are extreme in some way, the quadrupole moment evolves very predictably as a function of global neutral fraction. This predictability implies that redshift-space distortions are not a very sensitive tool for distinguishing between reionization sources. However, the quadrupole moment can be used as a model-independent probe for constraining the reionization history. We show that such measurements can be done to some extent by first-generation instruments such as LOFAR, while the SKA should be able to measure the reionization history using the quadrupole moment of the power spectrum to great accuracy.
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| 17. |
- Moores, John E., et al.
(författare)
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Atmospheric movies acquired at the Mars Science Laboratory landing site : Cloud Morphology, Frequency and Significance to the Gale Crater Water Cycle and Phoenix Mission Results
- 2015
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 55:9, s. 2217-2238
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first 360 sols (LS 150° to 5°), representing just over half a Martian year, of atmospheric monitoring movies acquired using the NavCam imager from the Mars Science Laboratory (MSL) Rover Curiosity. Such movies reveal faint clouds that are difficult to discern in single images. The data set acquired was divided into two different classifications depending upon the orientation and intent of the observation. Up to sol 360, 73 Zenith Movies and 79 Supra-Horizon Movies have been acquired and time-variable features could be discerned in 25 of each. The data set from MSL is compared to similar observations made by the Surface Stereo Imager (SSI) onboard the Phoenix Lander and suggests a much drier environment at Gale Crater (4.6°S) during this season than was observed in Green Valley (68.2°N) as would be expected based on latitude and the global water cycle. The optical depth of the variable component of clouds seen in images with features are up to 0.047 ± 0.009 with a granularity to the features observed which averages 3.8 degrees. MCS also observes clouds during the same period of comparable optical depth at 30 and 50 km that would suggest a cloud spacing of 2.0 to 3.3 km. Multiple motions visible in atmospheric movies support the presence of two distinct layers of clouds. At Gale Crater, these clouds are likely caused by atmospheric waves given the regular spacing of features observed in many Zenith movies and decreased spacing towards the horizon in sunset movies consistent with clouds forming at a constant elevation. Reanalysis of Phoenix data in the light of the NavCam equatorial dataset suggests that clouds may have been more frequent in the earlier portion of the Phoenix mission than was previously thought.
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| 18. |
- Moores, John E., et al.
(författare)
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Observational evidence of a suppressed planetary boundary layer in northern Gale Crater, Mars as seen by the Navcam instrument onboard the Mars Science Laboratory rover
- 2015
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Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 249, s. 129-142
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Tidskriftsartikel (refereegranskat)abstract
- The Navigation Cameras (Navcam) of the Mars Science Laboratory rover, Curiosity, have been used to examine two aspects of the planetary boundary layer: vertical dust distribution and dust devil frequency. The vertical distribution of dust may be obtained by using observations of the distant crater rim to derive a line-of-sight optical depth within Gale Crater and comparing this optical depth to column optical depths obtained using Mastcam observations of the solar disc. The line of sight method consistently produces lower extinctions within the crater compared to the bulk atmosphere. This suggests a relatively stable atmosphere in which dust may settle out leaving the air within the crater clearer than air above and explains the correlation in observed column opacity between the floor of Gale Crater and the higher elevation Meridiani Planum. In the case of dust devils, despite an extensive campaign only one optically thick vortex (τ=1.5±0.5×10-3) was observed compared to 149 pressure events > 0.5Pa observed in REMS pressure data. Correcting for temporal coverage by REMS and geographic coverage by Navcam still suggests 104 vortices should have been viewable, suggesting that most vortices are dustless. Additionally, the most intense pressure excursions observed on other landing sites (pressure drop >2.5Pa) are lacking from the observations by the REMS instrument. Taken together, these observations are consistent with pre-landing circulation modeling of the crater showing a suppressed, shallow boundary layer. They are further consistent with geological observations of dust that suggests the northern portion of the crater is a sink for dust in the current era.
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| 19. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 20. |
- Ross, Hannah E., et al.
(författare)
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Evaluating the QSO contribution to the 21-cm signal from the Cosmic Dawn
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 487:1, s. 1101-1119
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming radio interferometer Square Kilometre Array (SKA) is expected to directly detect the redshifted 21-cm signal from the neutral hydrogen present during the Cosmic Dawn. Temperature fluctuations from X-ray heating of the neutral intergalactic medium can dominate the fluctuations in the 21-cm signal from this time. This heating depends on the abundance, clustering, and properties of the X-ray sources present, which remain highly uncertain. We present a suite of three new large-volume, 349 Mpc a side, fully numerical radiative transfer simulations including QSO-like sources, extending the work previously presented in Ross et al. (2017). The results show that our QSOs have a modest contribution to the heating budget, yet significantly impact the 21-cm signal. Initially, the power spectrum is boosted on large scales by heating from the biased QSO-like sources, before decreasing on all scales. Fluctuations from images of the 21-cm signal with resolutions corresponding to SKA1-Low at the appropriate redshifts are well above the expected noise for deep integrations, indicating that imaging could be feasible for all the X-ray source models considered. The most notable contribution of the QSOs is a dramatic increase in non-Gaussianity of the signal, as measured by the skewness and kurtosis of the 21-cm probability distribution functions. However, in the case of late Lyman-alpha saturation, this non-Gaussianity could be dramatically decreased particularly when heating occurs earlier. We conclude that increased non-Gaussianity is a promising signature of rare X-ray sources at this time, provided that Lyman-a saturation occurs before heating dominates the 21-cm signal.
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| 21. |
- Ross, Hannah E., et al.
(författare)
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Redshift-space distortions in simulations of the 21-cm signal from the cosmic dawn
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 506:3, s. 3717-3733
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Tidskriftsartikel (refereegranskat)abstract
- The 21-cm signal from the Cosmic Dawn (CD) is likely to contain large fluctuations, with the most extreme astrophysical models on the verge of being ruled out by observations from radio interferometers. It is therefore vital that we understand not only the astrophysical processes governing this signal, but also other inherent processes impacting the signal itself, and in particular line-of-sight effects. Using our suite of fully numerical radiative transfer simulations, we investigate the impact on the redshifted 21-cm from the CD from one of these processes, namely the redshift-space distortions (RSDs). When RSDs are added, the resulting boost to the power spectra makes the signal more or equally detectable for our models for all redshifts, further strengthening hopes that a power spectra measurement of the CD will be possible. RSDs lead to anisotropy in the signal at the beginning and end of the CD, but not while X-ray heating is underway. The inclusion of RSDs, however, decreases detectability of the non-Gaussianity of fluctuations from inhomogeneous X-ray heating as measured by the skewness and kurtosis. On the other hand, mock observations created from all our simulations that include telescope noise corresponding to 1000 h of observation with the Square Kilometre Array telescope show that we may be able to image the CD for all heating models considered and suggest RSDs dramatically boost fluctuations coming from the inhomogeneous Ly α background.
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| 22. |
- Ross, Hannah E., et al.
(författare)
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Simulating the impact of X-ray heating during the cosmic dawn
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 468:4, s. 3785-3797
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Tidskriftsartikel (refereegranskat)abstract
- Upcoming observations of the 21-cm signal from the epoch of reionization will soon provide the first direct detection of this era. This signal is influenced by many astrophysical effects, including long-range X-ray heating of the intergalactic gas. During the preceding cosmic dawn era, the impact of this heating on the 21-cm signal is particularly prominent, especially before spin temperature saturation. We present the largest volume (349 Mpc comoving = 244 h(-1) Mpc) full numerical radiative transfer simulations to date of this epoch which include the effects of helium and multifrequency heating, both with and without X-ray sources. We show that X-ray sources contribute significantly to early heating of the neutral intergalactic medium and, hence, to the corresponding 21-cm signal. The inclusion of hard, energetic radiation yields an earlier, extended transition from absorption to emission compared to the stellar-only case. The presence of X-ray sources decreases the absolute value of the mean 21-cm differential brightness temperature. These hard sources also significantly increase the 21-cm fluctuations compared to the common assumption of temperature saturation. The 21-cm differential brightness temperature power spectrum is initially boosted on large scales, before decreasing on all scales. Compared to the case of the cold, unheated intergalactic medium, the signal has lower rms fluctuations and increased non-Gaussianity, as measured by the skewness and kurtosis of the 21-cm probability distribution functions. Images of the 21-cm signal with resolution around 11 arcmin still show fluctuations well above the expected noise for deep integrations with the SKA1-Low, indicating that direct imaging of the X-ray heating epoch could be feasible.
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| 23. |
- Singh, Vinayak, et al.
(författare)
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Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria.
- 2017
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 103:1, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need to discover new anti-tubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that has potent, bactericidal activity against M. tuberculosis. Mutations in APYS1-resistant M. tuberculosis mapped exclusively to wag31, a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to APYS1, however, neither overexpression nor conditional depletion of wag31 impacted M. tuberculosis susceptibility to this compound. In contrast, expression of the wildtype allele of wag31 in APYS1-resistant M. tuberculosis was dominant and restored susceptibility to APYS1 to wildtype levels. Time-lapse imaging and scanning electron microscopy revealed that APYS1 caused gross malformation of the old pole of M. tuberculosis, with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of wag31 in M. tuberculosis. These data show that Wag31 is likely not the direct target of APYS1, but the striking phenotypic similarity between APYS1 exposure and genetic depletion of Wag31 in M. tuberculosis suggests that APYS1 might indirectly affect Wag31 through an as yet unknown mechanism.
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| 24. |
- Watkinson, Catherine A., et al.
(författare)
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The 21-cm bispectrum as a probe of non-Gaussianities due to X-ray heating
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 482:2, s. 2653-2669
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Tidskriftsartikel (refereegranskat)abstract
- We present analysis of the normalized 21-cm bispectrum from fully-numerical simulations of intergalactic-medium heating by stellar sources and high-mass X-ray binaries (HMXBs) during the cosmic dawn. Ly-alpha coupling is assumed to be saturated, we therefore probe the nature of non-Gaussianities produced by X-ray heating processes. We find the evolution of the normalized bispectrum to be very different from that of the power spectrum. It exhibits a turnover whose peak moves from large to small scales with decreasing redshift, and corresponds to the typical separation of emission regions. This characteristic scale reduces as more and more regions move into emission with time. Ultimately, small-scale fluctuations within heated regions come to dominate the normalized bispectrum, which at the end of the simulation is almost entirely driven by fluctuations in the density field. To establish how generic the qualitative evolution of the normalized bispectrum we see in the stellar + HMXB simulation is, we examine several other simulations - two fully numerical simulations that include quasi-stellar object (QSO) sources, and two with contrasting source properties produced with the semi-numerical simulation 21CMFAST. We find the qualitative evolution of the normalized bispectrum during X-ray heating to be generic, unless the sources of X-rays are, as with QSOs, less numerous and so exhibit more distinct isolated heated profiles. Assuming mitigation of foreground and instrumental effects are ultimately effective, we find that we should be sensitive to the normalized bispectrum during the epoch of heating, so long as the spin temperature has not saturated by z approximate to 19.
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| 25. |
- Yoneyama, Sachiko, et al.
(författare)
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Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:9, s. 2498-2510
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Tidskriftsartikel (refereegranskat)abstract
- Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P 2.4 10(6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 0.046 0.01, P 2.2 10(6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.
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