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- Acharyya, A., et al.
(author)
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Monte Carlo studies for the optimisation of the Cherenkov Telescope Array layout
- 2019
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 111, s. 35-53
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Journal article (peer-reviewed)abstract
- The Cherenkov Telescope Array (CTA) is the major next-generation observatory for ground-based veryhigh-energy gamma-ray astronomy. It will improve the sensitivity of current ground-based instruments by a factor of five to twenty, depending on the energy, greatly improving both their angular and energy resolutions over four decades in energy (from 20 GeV to 300 TeV). This achievement will be possible by using tens of imaging Cherenkov telescopes of three successive sizes. They will be arranged into two arrays, one per hemisphere, located on the La Palma island (Spain) and in Paranal (Chile). We present here the optimised and final telescope arrays for both CTA sites, as well as their foreseen performance, resulting from the analysis of three different large-scale Monte Carlo productions.
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- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)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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- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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- Willer, Cristen J., et al.
(author)
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Discovery and refinement of loci associated with lipid levels
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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- Wain, Louise V., et al.
(author)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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In: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Journal article (peer-reviewed)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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- Shungin, Dmitry, et al.
(author)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Journal article (peer-reviewed)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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- Caamano, M, et al.
(author)
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Isomers in neutron-rich A approximate to 190 nuclides from Pb-208 fragmentation
- 2005
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 23:2, s. 201-215
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Journal article (peer-reviewed)abstract
- Relativistic projectile fragmentation of Pb-208 has been used to produce isomers in neutron-rich, A approximate to 190 nuclides. A forward-focusing spectrometer provided ion-by-ion mass and charge identification. The detection of gamma-rays emitted by stopped ions has led to the assignment of isomers in Ta-188, W-190, Re-192, Re-193, Os-195, Ir-197, Ir-198, Pt-200, Pt-201, Pt-202 and Au-203, with half-lives ranging from approximately 10 ns to 1 ms. Tentative isomer information has been found also for Er-174, Er-175, Hf-185, Re-191, Re-194 and Ir-199. In most cases, time-correlated, singles gamma-ray events provided the first spectroscopic data on excited states for each nuclide. In Pt-200 and Pt-201. the assignments are supported by gamma-gamma coincidences. Isomeric ratios provide additional information, such as half-life and transition energy constraints in particular cases. The level structures of the platinum isotopes are discussed, and comparisons are made with isomer systematics.
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- Field, Christopher B., et al.
(author)
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Summary for Policymakers
- 2014
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In: Climate Change 2014: Impacts, Adaptation, and Vulnerability. Part A: Global and SectoralAspects.. - 9781107415379 ; , s. 1-32
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Book chapter (peer-reviewed)
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- Mach, Henryk, et al.
(author)
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Ultrafast-timing lifetime measurements in Ru-94 and Pd-96 : Breakdown of the seniority scheme in N=50 isotones
- 2017
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In: PHYSICAL REVIEW C. - : American Physical Society. - 2469-9985. ; 95:1
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Journal article (peer-reviewed)abstract
- The advanced time-delayed gamma gamma(t) method has been applied to determine half-lives of low-lying states in the N = 50 isotones Ru-94 and Pd-96. The inferred experimental E2 strengths for the 4(+) -> 2(+) transitions in the two nuclei show a dramatic deviation with respect to the shell model predictions in the (f(5/2), p, g(9/2)) proton hole space in Sn-100. The anomalous behavior can be ascribed to a breakdown of the seniority quantum number in the pi g(9/2)(n) configuration due to particle-hole excitations across the N = Z = 50 shell as confirmed by large-scale shell model calculations.
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