An efficient ‘a priori’ model reduction for boundary element models

The Boundary Element Method (BEM) is a discretisation technique for solving partial differential equations, which offers, for certain problems, important advantages over domain techniques. Despite the high CPU time reduction that can be achieved, some 3D problems remain today untreatable because the extremely large number of degrees of freedom—dof—involved in the boundary description. Model reduction seems to be an appealing choice for both, accurate and efficient numerical simulations. However, in the BEM the reduction in the number of degrees of freedom does not imply a significant reduction in the CPU time, because in this technique the more important part of the computing time is spent in the construction of the discrete system of equations. In this way, a reduction also in the number of weighting functions, seems to be a key point to render efficient boundary element simulations

Using droplet-based microfluidics to improve the catalytic properties of RNA under multiple-turnover conditions.

In vitro evolution methodologies are powerful approaches to identify RNA with new functionalities. While Systematic Evolution of Ligands by Exponential enrichment (SELEX) is an efficient approach to generate new RNA aptamers, it is less suited for the isolation of efficient ribozymes as it does not select directly for the catalysis. In vitro compartmentalization (IVC) in aqueous droplets in emulsions allows catalytic RNAs to be selected under multiple-turnover conditions but suffers severe limitations that can be overcome using the droplet-based microfluidics workflow described in this paper. Using microfluidics, millions of genes in a library can be individually compartmentalized in highly monodisperse aqueous droplets and serial operations performed on them. This allows the different steps of the evolution process (gene amplification, transcription, and phenotypic assay) to be uncoupled, making the method highly flexible, applicable to the selection and evolution of a variety of RNAs, and easily adaptable for evolution of DNA or proteins. To demonstrate the method, we performed cycles of random mutagenesis and selection to evolve the X-motif, a ribozyme which, like many ribozymes selected using SELEX, has limited multiple-turnover activity. This led to the selection of variants, likely to be the optimal ribozymes that can be generated using point mutagenesis alone, with a turnover number under multiple-turnover conditions, kss cat, ∼28-fold higher than the original X-motif, primarily due to an increase in the rate of product release, the rate-limiting step in the multiple-turnover reaction

Dissection of a QTL Hotspot on Mouse Distal Chromosome 1 that Modulates Neurobehavioral Phenotypes and Gene Expression

A remarkably diverse set of traits maps to a region on mouse distal chromosome 1 (Chr 1) that corresponds to human Chr 1q21–q23. This region is highly enriched in quantitative trait loci (QTLs) that control neural and behavioral phenotypes, including motor behavior, escape latency, emotionality, seizure susceptibility (Szs1), and responses to ethanol, caffeine, pentobarbital, and haloperidol. This region also controls the expression of a remarkably large number of genes, including genes that are associated with some of the classical traits that map to distal Chr 1 (e.g., seizure susceptibility). Here, we ask whether this QTL-rich region on Chr 1 (Qrr1) consists of a single master locus or a mixture of linked, but functionally unrelated, QTLs. To answer this question and to evaluate candidate genes, we generated and analyzed several gene expression, haplotype, and sequence datasets. We exploited six complementary mouse crosses, and combed through 18 expression datasets to determine class membership of genes modulated by Qrr1. Qrr1 can be broadly divided into a proximal part (Qrr1p) and a distal part (Qrr1d), each associated with the expression of distinct subsets of genes. Qrr1d controls RNA metabolism and protein synthesis, including the expression of ∼20 aminoacyl-tRNA synthetases. Qrr1d contains a tRNA cluster, and this is a functionally pertinent candidate for the tRNA synthetases. Rgs7 and Fmn2 are other strong candidates in Qrr1d. FMN2 protein has pronounced expression in neurons, including in the dendrites, and deletion of Fmn2 had a strong effect on the expression of few genes modulated by Qrr1d. Our analysis revealed a highly complex gene expression regulatory interval in Qrr1, composed of multiple loci modulating the expression of functionally cognate sets of genes

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Development and Applications of Fluorogen/Light-Up RNA Aptamer Pairs for RNA Detection and More.

The central role of RNA in living systems made it highly desirable to have noninvasive and sensitive technologies allowing for imaging the synthesis and the location of these molecules in living cells. This need motivated the development of small pro-fluorescent molecules called "fluorogens" that become fluorescent upon binding to genetically encodable RNAs called "light-up aptamers." Yet, the development of these fluorogen/light-up RNA pairs is a long and thorough process starting with the careful design of the fluorogen and pursued by the selection of a specific and efficient synthetic aptamer. This chapter summarizes the main design and the selection strategies used up to now prior to introducing the main pairs. Then, the vast application potential of these molecules for live-cell RNA imaging and other applications is presented and discussed.journal article2020importe

Mathematical and numerical study on the parametric sensitivity of a structural dynamic hyper-reduction

We consider the Hyper-reduction technique [1], in the framework of parametric structural dynamic problems. Efficient parametric models in hyper-reduction of structural design allow to act towards real time computations. The reduced coordinates are solutions of equations restricted to a subdomain, named the reduced integration domain (RID). Then one significant question is: Can we control the accuracy of the reduced-basis and the RID so they can be used online to reproduce dynamic solutions, which are different than the ones computed to generate the reduced-basis? Concerning the mathematical formulation of the Hyper-reduction, we propose a time-continuous Petrov-Galerkin one. This formulation is more general than the Galerkin projection one [2], since we are able to write our hyper-reduced order model through a reduced basis which is not necessarily orthogonal. We attest the following assumption on the Hyper-reduction of a structural dynamic problem, in this case: While dynamic solutions are regular via parametric evolution and no bifurcation occurs, then the parametric online error relative to the Hyper-reduction by reference reduced elements is also regular with respect to parametric evolution. In particular, a reference hyper-reduction is justified when variations occur within a viscoelastic dynamic problem, for the viscosity parameter. So to answer the preceding question, we show a mathematical and sharp a priori upper bound of the parametric online error relative to a reference hyper-reduction. We show mathematically that the parametric accuracy of the Hyper-reduction is improved when considering enriched reduced elements in association with the reference snapshots expanded by the ones of the parametric derivative of the viscoelastic dynamic solution at the same reference viscosity value [3, 4]. All these findings are generalisations to hyperbolic equations of the ones developed in [4] for parabolic equations in the context of fluid mechanics. Numerical validations of these theoretical results will be shown during the conference for academic applications in structural design

Efficient Hyper-Reduction of contact problems treated by Lagrange multipliers

International audienc

Efficient Hyper-Reduction of contact problems treated by Lagrange multipliers

International audienc