Computational fluid dynamic simulation of airfoils in unsteady low Reynolds number flows

Computational fluid dynamic simulation of airfoils in unsteady low Reynolds number flows

Computational fluid dynamic simulation of airfoils in unsteady low Reynolds number flows

Computational fluid dynamic simulation of airfoils in unsteady low Reynolds number flows

Rational antibody design for undruggable targets using kinetically controlled biomolecular probes

Several important drug targets, e.g., ion channels and G protein–coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics–sensitive druggability probes in native-state and disease-relevant proteins. By using low–Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal antibodies targeting the transient receptor potential vanilloid 1 (TRPV1) channel, a clinically validated pain target widely considered undruggable with antibodies, and apoptosis-inducing antibodies selectively mediating cytotoxicity in KRAS-mutated cells. It is our hope that this platform will widen the scope of antibody therapeutics for the benefit of patients.

D5.3 Report on theoretical work to allow the use of MLMC with adaptive mesh refinement

This documents describes several studies undertaken to assess the applicability of MultiLevel Monte Carlo (MLMC) methods to problems of interest; namely in turbulent fluid flow over civil engineering structures. Several numerical experiments are presented wherein the convergence of quantities of interest with mesh parameters are studied at different Reynolds’ numbers and geometries. It was found that MLMC methods could be used successfully for low Reynolds’ number flows when combined with appropriate Adaptive Mesh Refinement (AMR) strategies. However, the hypotheses for optimal MLMC performance were found to not be satisfied at higher turbulent Reynolds’ numbers despite the use of AMR strategies. Recommendations are made for future research directions based on these studies. A tentative outline for an MLMC algorithm with adapted meshes is made, as well as recommendations for alternatives to MLMC methods for cases where the underlying assumptions for optimal MLMC performance are not satisfied.

Applicability conditions of the Stokes formula

<abstract><p>In our research work on the microscopic properties of liquids in relation to biotechnical applications, we were led to use the Stokes formula to calculate the force exerted by a fluid on colloidal suspensions, and to look in the bibliography for the demonstration of this formula. The proofs that we have found are often partial and the applicability conditions not always explicit, which led us to resort to the initial demonstration made by Stokes ^{[<xref ref-type="bibr" rid="b1">1</xref>]} in 1850 with the mathematical formalism used in that time. Here we give the detailed demonstration by means of the vector analysis specific to this type of problem. We end the article with a brief discussion of low Reynolds number flows dominated by viscosity and where inertial effects are neglected.</p></abstract>