| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Gilbert, M. R., et al.
(författare)
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Perspectives on multiscale modelling and experiments to accelerate materials development for fusion
- 2021
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115 .- 1873-4820. ; 554
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Forskningsöversikt (refereegranskat)abstract
- Prediction of material performance in fusion reactor environments relies on computational modelling, and will continue to do so until the first generation of fusion power plants come on line and allow long-term behaviour to be observed. In the meantime, the modelling is supported by experiments that attempt to replicate some aspects of the eventual operational conditions. In 2019, a group of leading experts met under the umbrella of the IEA to discuss the current position and ongoing challenges in modelling of fusion materials and how advanced experimental characterisation is aiding model improvement. This review draws from the discussions held during that workshop. Topics covering modelling of irradiation-induced defect production and fundamental properties, gas behaviour, clustering and segregation, defect evolution and interactions are discussed, as well as new and novel multiscale simulation approaches, and the latest effort s to link modelling to experiments through advanced observation and characterisation techniques.
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| 4. |
- Adriani, O., et al.
(författare)
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The gamma-400 space observatory : Status and perspectives
- 2014
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Ingår i: Proceedings of Science. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- The present design of the new space observatory GAMMA-400 is presented in this paper. The instrument has been designed for the optimal detection of gamma rays in a broad energy range (from ∼100 MeV up to 3 TeV), with excellent angular and energy resolution. The observatory will also allow precise and high statistic studies of the electron component in the cosmic rays up to the multi TeV region, as well as protons and nuclei spectra up to the knee region. The GAMMA-400 observatory will allow to address a broad range of science topics, like search for signatures of dark matter, studies of Galactic and extragalactic gamma-ray sources, Galactic and extragalactic diffuse emission, gamma-ray bursts and charged cosmic rays acceleration and diffusion mechanism up to the knee.
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| 5. |
- Axelsson, A, et al.
(författare)
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Excited superdeformed band in Eu-143
- 1999
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 6:2, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- A new superdeformed band has been discovered in a EUROBALL experiment and assigned to Eu-143. It has a maximum intensity of 35% of the Eu-143 yrast superdeformed band and the transition energies of the two bands are very similar. Based on comparison with cranked shell model calculations the new band is tentatively assigned the high-N intruder configuration pi 6(2)nu 7(0) and the parity and signature quantum numbers (pi, alpha) = (-1, +1/2). In addition to the already known high-energy transition at 3361 keV another discrete line at 2715 keV was found to be in coincidence with the yrast superdeformed band. However, it was not possible to connect the decay out of either of the superdeformed bands to, known normally deformed states.
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| 6. |
- Bark, R A, et al.
(författare)
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Coexistence of triaxial and prolate shapes in Ir-171
- 1999
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Ingår i: Nuclear Physics A. - 0375-9474 .- 1873-1554. ; 657:2, s. 113-133
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in Ir-171 have been observed for the first time. Gamma-rays were assigned to the nucleus by the recoil-decay tagging method, The ground-state band has a structure consistent with an h(11/2) proton coupled to a core of large triaxial deformation. At high spins, a bandcrossing occurs which is interpreted as a change in shape to a prolate deformation, Band-mixing calculations are performed for Ir171-175. These show that shape-coexistence between triaxial and prolate states in these nuclei follows the same systematics found in their Pt and Os neighbours. The systematics are also compared with deformations calculated for Ir171-179 using the code "Ultimate Cranker". Dipole bands were also observed, but tilted axis cranking calculations suggest that they are associated with a collective rotation.
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| 7. |
- Leonov, A. A., et al.
(författare)
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The GAMMA-400 gamma-ray telescope characteristics. Angular resolution and electrons/protons separation
- 2014
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Ingår i: Proceedings of Science. - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- The measurements of gamma-ray fluxes and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV, which will be realized by the specially designed GAMMA-400 gamma-ray telescope, concern with the following broad range of scientific topics. Search for signatures of dark matter, surveying the celestial sphere in order to study point and extended sources of gamma-rays, measuring the energy spectra of Galactic and extragalactic diffuse gamma-ray emission, study of gamma-ray bursts and gamma-ray emission from the Sun, as well as high precision measurements of spectra of high-energy electrons and positrons, protons and nuclei up to the knee. To clarify these scientific problems with the new experimental data the GAMMA-400 gamma-ray telescope possesses unique physical characteristics comparing with previous and present experiments. For gamma-ray energies more than 100 GeV GAMMA-400 provides the energy resolution ~1% and angular resolution better than 0.02 deg. The methods, developed to reconstruct the direction of incident gamma photon, are presented in this paper, as well as, the capability of the GAMMA-400 gamma-ray telescope to distinguish electrons and positrons from protons in cosmic rays is investigated. The first point concerns with the space topology of high-energy gamma photon interaction in the matter of GAMMA-400. Multiple secondary particles, generated inside gamma-ray telescope, produce significant problems to restore the direction of initial gamma photon. Also back-splash particles, i.e., charged particles and gamma photons generated in calorimeter and moved upward, mask the initial tracks of electron/positron pair from conversion of incident gamma photon. The processed methods allow us to reconstruct the direction of electromagnetic shower axis and extract the electron/positron trace. As a result, the direction of incident gamma photon with the energy of 100 GeV is calculated with an accuracy of better than 0.02 deg. The main components of cosmic rays are protons and helium nuclei, whereas the part of lepton component in the total flux is ~10 -3 for high energies. The separate contribution in proton rejection is studied for each detector system of the GAMMA-400 gamma-ray telescope. Using combined information from all detector systems allow us to provide the rejection from protons with a factor of ~4 10 5 for vertical incident particles and ~3 10 5 for particle with initial inclination of 30 deg. Science with the New Generation of High Energy Gamma-ray experiments, 10th Workshop (Scineghe2014) 04-06 June 2014 Lisbon - Portugal.
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| 8. |
- Topchiev, N. P., et al.
(författare)
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GAMMA-400 gamma-ray observatory
- 2015
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Ingår i: Proceedings of Science. - : Proceedings of Science (PoS).
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Konferensbidrag (refereegranskat)abstract
- The GAMMA-400 gamma-ray telescope with excellent angular and energy resolutions is designed to search for signatures of dark matter in the fluxes of gamma-ray emission and electrons+ positrons.Precision investigations of gamma-ray emission fromGalactic Center, Crab, Vela, Cygnus, Geminga, and other regions will be performed, as well asdiffuse gamma-rayemission,along with measurements of high-energy electron + positron and nuclei fluxes. Furthermore, it will studygamma-ray bursts and gamma-ray emission from the Sun during periods of solar activity. The energy range of GAMMA-400 is expected to be from ∼20 MeV up to TeV energies for gamma rays, up to 10 TeV for electrons + positrons, and up to 1015eV for cosmic-ray nuclei. For high-energy gamma rays with energy from 10 to 100 GeV, the GAMMA-400 angular resolution improves from 0.1° to ∼0.01° and energy resolution from 3% to ∼1%; the proton rejection factor is ∼5x105. GAMMA-400 will be installed onboardthe Russian space observatory.
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| 9. |
- Topchiev, N. P., et al.
(författare)
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The GAMMA-400 experiment : Status and prospects
- 2015
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Ingår i: Bulletin of the Russian Academy of Sciences: Physics. - 1062-8738. ; 79:3, s. 417-420
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Tidskriftsartikel (refereegranskat)abstract
- The development of the GAMMA-400 γ-ray telescope continues. The GAMMA-400 is designed to measure fluxes of γ-rays and the electron-positron cosmic-ray component possibly associated with annihilation or decay of dark matter particles; and to search for and study in detail discrete γ-ray sources, to measure the energy spectra of Galactic and extragalactic diffuse γ-rays, and to study γ-ray bursts and γ-rays from the active Sun. The energy range for measuring γ-rays and electrons (positrons) is from 100 MeV to 3000 GeV. For 100-GeV γ-rays, the γ-ray telescope has an angular resolution of ∼0.01°, an energy resolution of ∼1%, and a proton rejection factor of ∼5 × 105. The GAMMA-400 will be installed onboard the Russian Space Observatory.
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| 10. |
- Liu, Y. Q., et al.
(författare)
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Eddy-current computations using adaptive grids and edge elements
- 2002
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Ingår i: IEEE transactions on magnetics. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9464 .- 1941-0069. ; 38:2, s. 449-452
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Tidskriftsartikel (refereegranskat)abstract
- Results are presented from eddy-current computations using adaptive techniques, based on rigorous a posteriori error estimates. The adaptivity restores the quadratic convergence with grid size of the magnetic energy, despite singularities occurring at corners. A new procedure is introduced to satisfy the solvability condition for the curl-curl equation. The methods are applied to a model of a hydrogenerator, with anisotropic conductivity and permeability. The ungauged formulation with both vector and scalar potentials gives very significant improvements in rate of convergence for this problem. Reasons for the improved convergence are discussed.
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