| 1. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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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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| 2. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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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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| 3. |
- Allan, Eric, et al.
(författare)
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Interannual variation in land-use intensity enhances grassland multidiversity
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:1, s. 308-313
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Tidskriftsartikel (refereegranskat)abstract
- Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
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| 4. |
- Demaziere, Christophe, 1973, et al.
(författare)
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Enhancing higher education through hybrid and flipped learning: Experiences from the GRE@T-PIONEeR project
- 2024
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Ingår i: Nuclear Engineering and Design. - 0029-5493. ; 421
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Tidskriftsartikel (refereegranskat)abstract
- GRE@T-PIONEeR is a Horizon 2020 project coordinated by Chalmers University of Technology, running over the period 2020–2024. 18 university teachers from 8 different universities located in 6 different countries gathered forces to develop and offer advanced courses in computational and experimental nuclear reactor physics and safety. All courses are flipped hybrid courses, i.e., students work on online preparatory activities at their own pace before attending a set of interactive sessions organized on five consecutive days. Those sessions can be attended either onsite or remotely. During the academic year 2022/2023, 8 different courses were offered, and 185 students successfully completed the courses, with a success rate of 87.7% for the students taking at least one activity during the interactive sessions. Student behaviour and performance were monitored via the Learning Management System (LMS) used in all courses. This paper presents an analysis of various metrics from the LMS and demonstrates a high level of engagement of the students committed to the courses and a high success rate for those students. Whereas all students are equally engaged in the online preparatory work and perform equally well, significant differences exist during the interactive sessions between the students who opted for onsite participation and those who attended the sessions online, with the onsite students outperforming the online students.
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| 5. |
- Dykin, Victor, 1985, et al.
(författare)
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Investigation of global and regional BWR instabilities with a four heated-channel Reduced Order Model
- 2013
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 53, s. 381-400
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Tidskriftsartikel (refereegranskat)abstract
- The development of an advanced Reduced Order Model (ROM) including four heated channels and meant to study global and regional Boiling Water Reactor (BWR) instabilities is described. The ROM contains three sub-models: a neutron-kinetic model (describing neutron transport), a thermal-hydraulic model (describing fluid transport) and a heat transfer model (describing heat transfer between the fuel and the coolant). All these three models are coupled to each other using two feedback mechanisms: the void feedback and the doppler feedback mechanisms. Each of the sub-models is described by a set of reduced ordinary differential equations, derived from the corresponding time- and space-dependent partial differential equations, by using different types of approximations and mathematical techniques that are explained in this paper.One of the novelties of the present ROM is that it takes the effect of the first three neutronic modes into account, namely the fundamental, first, and second azimuthal modes. In order to have a proper representation of both azimuthal modes and of their dependence on the thermal-hydraulic conditions in the heated channels, a four heated channel ROM was constructed. Another novelty of the present work is to develop a special methodology which guarantees the full consistency between the spatial discretization procedures used in the dynamical calculations and the ones implemented in the static case. Accordingly, a re-computation of the static solution based on the CORE SIM tool was embedded into the ROM in such a way that the balance equations expressing the conservation of neutron balance, heat generation, and mass, momentum, enthalpy for the flow, could be fulfilled for the steady-state solution of the coupled neutron-kinetic/thermal-hydraulic problem. Once the static problem is solved, the time-dependent solution in case of a perturbed system can be determined. Moreover, a non-uniform power profile representing different heat production rates in the one- and two-phase regions was introduced into the ROM. Careful attention was paid to the determination of the coupling coefficients for the reactivity effects related to both void fraction and fuel temperature, so that such coefficients correspond to the re-computed static solution. The evaluation of these coefficients was based on the cross-section perturbations estimated by the SIMULATE-3 code, and on the different neutronic eigenmodes of the heterogeneous core determined by the CORE SIM tool.
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| 6. |
- Dykin, Victor, 1985, et al.
(författare)
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Investigation of local BWR instabilities with a four heated-channel Reduced Order Model
- 2013
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Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 53, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- his paper deals with the modeling of Boiling Water Reactor (BWR) local instabilities via so-called Reduced Order Models (ROMs). More specifically, a four-heated channels ROM, which was earlier developed (Dykin et al., submitted for publication), was modified in such a way that the effect of local perturbations could also be accounted for.This model was thereafter used to analyze a local instability event that took place at the Swedish Forsmark-1 BWR in 1996/1997. Such a local instability was driven by unseated fuel assemblies. Comparisons between the results of ROM simulations and actual measurement data demonstrated that the developed ROM was able to correctly reproduce the main features of the event. The ROM has also the ability to give some further physical insights into the phenomena taking place in case of instabilities. For the particular instability event investigated, it was for instance demonstrated that the global and regional oscillation modes were stable, but were excited by the local oscillation acting as an external perturbation. When performing a modal decomposition of the measured neutron flux in case of an instability event driven by a local oscillation, each mode will apparently be excited, whereas in reality such modes might be stable. Such an apparent contradictory behavior is due to the inability of a modal decomposition to catch with only a few modes the spatial dependence of the neutron flux in case of a local oscillation.
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| 7. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 8. |
- Gorski, Mathias, et al.
(författare)
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Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
- 2021
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
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Tidskriftsartikel (refereegranskat)abstract
- Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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| 9. |
- Hursin, Mathieu, et al.
(författare)
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Modeling noise experiments performed at AKR-2 and CROCUS zero-power reactors
- 2023
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Ingår i: Annals of Nuclear Energy. - 0306-4549 .- 1873-2100. ; 194
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Tidskriftsartikel (refereegranskat)abstract
- CORTEX is a EU H2020 project (2017-2021) devoted to the analysis of ’reactor neutron noise’ in nuclear reactors, i.e. the small fluctuations occurring around the stationary state due to external or internal disturbances in the core. One important aspect of CORTEX is the development of neutron noise simulation codes capable of modeling the spatial variations of the noise distribution in a reactor. In this paper we illustrate the validation activities concerning the comparison of the simulation results obtained by several noise simulation codes with respect to experimental data produced at the zero-power reactors AKR-2 (operated at TUD, Germany) and CROCUS (operated at EPFL, Switzerland). Both research reactors are modeled in the time and frequency domains, using transport or diffusion theory. Overall, the noise simulators managed to capture the main features of the neutron noise behavior observed in the experimental campaigns carried out in CROCUS and AKR-2, even though computational biases exist close to the region where the noise-inducing mechanical vibration was located (the so-called ”noise source”). In some of the experiments, it was possible to observe the spatial variation of the relative neutron noise, even relatively far from the noise source. This was achieved through reduced uncertainties using long measurements, the installation of numerous, robust and efficient detectors at a variety of positions in the near vicinity or inside the core, as well as new post-processing methods. For the numerical simulation tools, modeling the spatial variations of the neutron noise behavior in zero-power research reactors is an extremely challenging problem, because of the small magnitude of the noise field; and because deviations from a point-kinetics behavior are most visible in portions of the core that are especially difficult to be precisely represented by simulation codes, such as experimental channels. Nonetheless the limitations of the simulation tools reported in the paper were not an issue for the CORTEX project, as most of the computational biases are found close to the noise source.
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| 10. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 11. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 12. |
- Lange, Carsten, et al.
(författare)
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Comments on local power oscillation phenomenon at BWRs
- 2012
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Ingår i: Progress in Nuclear Energy. - : Elsevier BV. - 0149-1970. ; 60, s. 73-88
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Tidskriftsartikel (refereegranskat)abstract
- Under the framework of BWR stability analysis, local neutron-flux oscillation events have attracted the attention of a number of researchers. In 1996, an unusual instability event occurred at Forsmark-1 in which an irregular oscillation pattern with highly localized, relatively large-amplitude oscillations were measured. Some authors assumed that this behaviour was caused by the superposition of stable spatial mode limit cycle oscillations, where the BWR core as a neutron kinetics/-thermal-hydraulic coupled system is unstable. Subsequent time-series analysis of the local power range monitor (LPRM) signals resulted in a space-dependent decay ratio, an inexplicable result. Furthermore, noise analysis-based localization techniques pointed towards the existence of two strong “perturbation sources” in one of the two halves of the core, one of them coinciding with the radial position of an unseated bundle. In the scope of theoretical work, the possibility of a space-dependent decay ratio was discussed but not comprehensively understood. Motivated by these findings, the effect of local neutron-flux oscillations on the stability behaviour of BWR is discussed, and one possible interpretation is proposed which is able to explain the space-dependent decay ratio as well as the long term oscillation pattern. The RAM–ROM method is applied to a Forsmark measurement case, where an irregular oscillation pattern was found and to an operational point (KKB-B8) of NPP Brunsbüttel, where a local neutron-flux oscillation is superimposed on an unstable global power oscillation. The effect of the local neutron flux oscillating sources on the space- and time-dependent neutron field is described by a rigorous application of the mode expansion approach. The consequences to signal analysis are then discussed. It will be pointed out in the paper that when a BWR system is stable with regards to power oscillations but is driven by local neutron-flux oscillating sources, the decay ratio does not indicate the real BWR stability behaviour.
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| 13. |
- Lauvset, Siv K., et al.
(författare)
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The annual update GLODAPv2.2023: the global interior ocean biogeochemical data product
- 2024
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Ingår i: Earth System Science Data. - 1866-3591. ; 16, s. 2047-2072
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Tidskriftsartikel (refereegranskat)abstract
- The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface to bottom ocean biogeochemical bottle data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of seawater samples. GLODAPv2.2023 is an update of the previous version, GLODAPv2.2022 (Lauvset et al., 2022). The major changes are as follows: data from 23 new cruises were added. In addition, a number of changes were made to the data included in GLODAPv2.2022. GLODAPv2.2023 includes measurements from more than 1.4 million water samples from the global oceans collected on 1108 cruises. The data for the now 13 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, chlorofluorocarbon-11 (CFC-11), CFC-12, CFC-113, CCl4, and SF6) have undergone extensive quality control with a focus on the systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but converted to World Ocean Circulation Experiment (WOCE) exchange format and (ii) as a merged data product with adjustments applied to minimize bias. For the present annual update, adjustments for the 23 new cruises were derived by comparing those data with the data from the 1085 quality-controlled cruises in the GLODAPv2.2022 data product using crossover analysis. SF6 data from all cruises were evaluated by comparison with CFC-12 data measured on the same cruises. For nutrients and ocean carbon dioxide (CO2), chemistry comparisons to estimates based on empirical algorithms provided additional context for adjustment decisions. The adjustments that we applied are intended to remove potential biases from errors related to measurement, calibration, and data-handling practices without removing known or likely time trends or variations in the variables evaluated. The compiled and adjusted data product is believed to be consistent to better than 0.005 in salinity, 1% in oxygen, 2% in nitrate, 2% in silicate, 2% in phosphate, 4µmolkg−1 in dissolved inorganic carbon, 4µmolkg−1 in total alkalinity, 0.01–0.02 in pH (depending on region), and 5% in the halogenated transient tracers. The other variables included in the compilation, such as isotopic tracers and discrete CO2 fugacity (fCO2), were not subjected to bias comparison or adjustments. The original data, their documentation, and DOI codes are available at the Ocean Carbon and Acidification Data System of NOAA National Centers for Environmental Information (NCEI), which also provides access to the merged data product. This is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/zyrq-ht66 (Lauvset et al., 2023). These bias-adjusted product files also include significant ancillary and approximated data, which were obtained by interpolation of, or calculation from, measured data. This living data update documents the GLODAPv2.2023 methods and provides a broad overview of the secondary quality control procedures and results.
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| 14. |
- Nordin, Angelica, et al.
(författare)
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Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation : a large multinational screening study
- 2017
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 18:3-4, s. 256-264
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Tidskriftsartikel (refereegranskat)abstract
- A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele. In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.
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| 15. |
- Viebach, Marco, et al.
(författare)
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A comparison between time domain and frequency domain calculations of stationary neutron fluctuations
- 2019
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Ingår i: International Conference on Mathematics and Computational Methods Applied to Nuclear Science and Engineering, M and C 2019. ; , s. 631-640
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Konferensbidrag (refereegranskat)abstract
- Unexplained neutron flux fluctuation patterns observed in some reactors were recently investigated by various European institutions. The time-domain code DYN3D is one of the tools used for simulating these fluctuations. Though, the applicability of time-domain codes for modelling small stationary fluctuations remains a discussed question. Aiming at a confirmation that these codes may be applied for neutron noise calculations, two special cases of neutron flux oscillations have been simulated with DYN3D and with CORE SIM, the latter one being validated for the context here. The comparison between the results of these two codes is the subject of this paper. This study demonstrates that time- and frequency-dependent calculations can give qualitatively equivalent results but substantial quantitative deviations may occur. Nevertheless, DYN3D may be considered as qualified for neutron-noise calculations as the deviations are smaller than 20 %. The optimization of the DYN3D setup is a matter of future research.
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| 16. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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