Screening and metamodeling of computer experiments with functional outputs. Application to thermal-hydraulic computations

To perform uncertainty, sensitivity or optimization analysis on scalar variables calculated by a cpu time expensive computer code, a widely accepted methodology consists in first identifying the most influential uncertain inputs (by screening techniques), and then in replacing the cpu time expensive model by a cpu inexpensive mathematical function, called a metamodel. This paper extends this methodology to the functional output case, for instance when the model output variables are curves. The screening approach is based on the analysis of variance and principal component analysis of output curves. The functional metamodeling consists in a curve classification step, a dimension reduction step, then a classical metamodeling step. An industrial nuclear reactor application (dealing with uncertainties in the pressurized thermal shock analysis) illustrates all these steps

Main Results of the OECD BEMUSE Programme

The BEMUSE (Best Estimate Methods Uncertainty and Sensitivity Evaluation) Programme promoted by the Working Group on Analysis and Management of Accidents (WGAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI) represents an important step towards reliable application of high-quality best-estimate and uncertainty and sensitivity evaluation methods. The methods used in this activity are considered to be mature for application, including licensing processes. Skill, experience and knowledge of the users about the applied suitable computer code as well as the used uncertainty method are important for the quality of the results

Global translational impacts of the loss of the tRNA modification t(6)A in yeast

Artículo de publicación ISIThe universal tRNA modification t(6)A is found at position 37 of nearly all tRNAs decoding ANN codons. The absence of t(6)A(37) leads to severe growth defects in baker's yeast, phenotypes similar to those caused by defects in mcm(5)s(2)U(34) synthesis. Mutants in mcm(5)s(2)U(34) can be suppressed by overexpression of tRNA(UUU)(Lys), but we show t(6)A phenotypes could not be suppressed by expressing any individual ANN decoding tRNA, and t(6)A and mcm(5)s(2)U are not determinants for each other's formation. Our results suggest that t(6)A deficiency, like mcm(5)s(2)U deficiency, leads to protein folding defects, and show that the absence of t(6)A led to stress sensitivities (heat, ethanol, salt) and sensitivity to TOR pathway inhibitors. Additionally, L-homoserine suppressed the slow growth phenotype seen in t(6)A-deficient strains, and proteins aggregates and Advanced Glycation End-products (AGEs) were increased in the mutants. The global consequences on translation caused by t(6)A absence were examined by ribosome profiling. Interestingly, the absence of t(6)A did not lead to global translation defects, but did increase translation initiation at upstream non-AUG codons and increased frame-shifting in specific genes. Analysis of codon occupancy rates suggests that one of the major roles of t(6)A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I-34:C-3 pairs while increasing the elongation rate of rare tRNAs and G(34):U-3 pairs. This work reveals that the consequences of t(6)A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes