Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

TAF-ID: An international thermodynamic database for nuclear fuels applications

The Thermodynamics of Advanced Fuels – International Database (TAF-ID) was developed using the Calphad method to provide a computational tool to perform thermodynamic calculations on nuclear fuel materials under normal and off-normal conditions. Different kinds of fuels are considered: oxide, metallic, carbide and nitride fuels. Many fission products are introduced as well as structural materials (e.g., zirconium, steel, concrete, SiC) and absorbers (e.g., B4C), in order to investigate the thermochemistry of irradiated fuels and to predict their chemical interaction with the surrounding materials. The approach to develop the database and the models implemented in the database are described. Examples of models for key chemical systems are presented. Finally, a few examples of application calculations on severe accidents with UO2 fuels, irradiated fuel chemistry of MOX and metallic fuels and metallic fuel/cladding interaction show how this tool can be used. To validate the database, the calculations are compared to the available experimental data. A good agreement is obtained which gives confidence in the maturity degree and quality of the TAF-ID database. The working version is only accessible to the participants of the TAF-ID project (Canada, France, Japan, the Netherlands, Republic of Korea, United Kingdom, USA). A public version is accessible by all the NEA countries. The current version contains models on the Am–Fe, Am–Np, Am-O-Pu, Am–U, Am–Zr, C–O–U-Pu, Cr–U, Np–U, Np–Zr, O–U–Zr, Re–U, Ru–U, Si–U, Ti–U, U-Pu-Zr, U–W systems. It is progressively extended with our published assessments. Information on how to join the project is available on the website: https://www.oecd-nea.org/science/taf-id/.Accepted Author ManuscriptRST/Reactor Physics and Nuclear Material

Oxide Transformation in Cr-Mn-Prealloyed Sintered Steels: Thermodynamic and Kinetic Aspects

The main obstacle for utilization of Cr and Mn as alloying elements in powder metallurgy is their high oxygen affinity leading to oxidation risk during powder manufacturing, handling, and especially during further consolidation. Despite the high purity of the commercially available Cr- and Mn-prealloyed iron powder grades, the risk of stable oxide formation during the sintering process remains. Thermodynamic and kinetic simulation of the oxide formation/transformation on the former powder surface during heating and sintering stages using thermodynamic modeling tools (Thermo-Calc and HSC Chemistry) was performed. Simulation is based on the results from the analysis of amount, morphology, and composition of the oxide phases inside the inter-particle necks in the specimens from interrupted sintering trials utilizing advanced analysis tools (HRSEM + EDX and XPS). The effect of the processing parameters, such as sintering atmosphere composition, temperature profile as well as graphite addition on the possible scenarios of oxide reduction/formation/transformation for Fe-Cr-Mn-C powder systems, was evaluated. Results indicate that oxide transformation occurs in accordance with the thermodynamic stability of oxides as follows: Fe2O3 -> FeO -> Fe2MnO4 -> Cr2FeO4 -> Cr2O3 -> MnCr2O4 -> MnO/MnSiO (x) -> SiO2. Spinel MnCr2O4 was identified as the most stable oxide phase at applied sintering conditions up to 1393 K (1120 A degrees C). Controlled conditions during the heating stage minimize the formation of stable oxide products and produce oxide-free sintered parts