AUGMENTED LAGRANGIAN METHOD AND OPEN BOUNDARY CONDITIONS IN 2D SIMULATION OF POISEUILLE–BÉNARD CHANNEL FLOW

The main objective of this study is to compare the influence of different boundary conditions upon the incompressible Poiseuille –Bénard channel flow (PBCF) in a 2D rectangular duct heated from below. In a first technical part the algorithm used to carry out this work, based on the augmented Lagrangian method, is presented. The implementation details of the five different open boundary conditions (OBCs) and the periodic boundary conditions (PBCs) tested in the present paper are also given. The study is then carried out for 1800<Ra≤ 10,000, 0<Re≤10 and 0·67≤Pr≤6·4. The five selected OBCs, applied at the outlet of the computational domain, respectively express the following conditions: a square profile for the velocity (OBC1), mass conservation (OBC2), zero second derivative of the horizontal velocity component (OBC3), a mixed boundary condition combining Dirichlet and Neumann conditions (OBC4) and an Orlanski-type boundary condition (OBC5). A good estimation of the perturbation amplitude and of the length of the perturbed zone at the outlet boundary is proposed. It is shown that OBC5 causes very little perturbation in the recirculating flow compared with the other OBCs. © 1997 John Wiley & Sons, Ltd.     

Molecular Design in Practice: A Review of Selected Projects in a French Research Institute That Illustrates the Link between Chemical Biology and Medicinal Chemistry

Chemical biology and drug discovery are two scientific activities that pursue different goals but complement each other. The former is an interventional science that aims at understanding living systems through the modulation of its molecular components with compounds designed for this purpose. The latter is the art of designing drug candidates, i.e., molecules that act on selected molecular components of human beings and display, as a candidate treatment, the best reachable risk benefit ratio. In chemical biology, the compound is the means to understand biology, whereas in drug discovery, the compound is the goal. The toolbox they share includes biological and chemical analytic technologies, cell and whole-body imaging, and exploring the chemical space through state-of-the-art design and synthesis tools. In this article, we examine several tools shared by drug discovery and chemical biology through selected examples taken from research projects conducted in our institute in the last decade. These examples illustrate the design of chemical probes and tools to identify and validate new targets, to quantify target engagement in vitro and in vivo, to discover hits and to optimize pharmacokinetic properties with the control of compound concentration both spatially and temporally in the various biophases of a biological system.     

Space-Time Transfer Function-Noise Modelling of Rainfall-Runoff Process

An explanatory model class belonging to the family of Space-Time Transfer Function-Noise (STTFN) process is presented. The paper develops a three-stage iterative procedure for building STTFN models of the rainfall-runoff process. Four precipitation and runoff stations located in a watershed in southern Ontario, Canada, sampled at 15-day intervals are used for the numerical analysis. Three STTF models are identified. The model parameters are estimated by the polytope technique, a nonlinear optimization algorithm. Two of the developed space-time models proved adequate in describing the spatio-temporal characteristics of precipitation and runoff time series.     

Isoconversional Analysis of the Nonisothermal Crystallization of a Polymer Melt

The advanced isoconversional method can be used to determine effective activation energies of the nonisothermal crystallization of polymer melts. The application of this method to differential scanning calorimetric data on the crystallization of poly(ethylene terephthalate) yields an activation energy that increases with the extent of crystallization from –270 to 20 kJ·mol^–1. The variation is interpreted in terms of accepted crystallization models.     

Three of a Kind: Control of the Expression of Liver-Expressed Antimicrobial Peptide 2 (LEAP2) by the Endocannabinoidome and the Gut Microbiome

The endocannabinoidome (expanded endocannabinoid system, eCBome)-gut microbiome (mBIome) axis plays a fundamental role in the control of energy intake and processing. The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently identified molecule acting as an antagonist of the ghrelin receptor and hence a potential effector of energy metabolism, also at the level of the gastrointestinal system. Here we investigated the role of the eCBome-gut mBIome axis in the control of the expression of LEAP2 in the liver and, particularly, the intestine. We confirm that the small intestine is a strong contributor to the circulating levels of LEAP2 in mice, and show that: (1) intestinal Leap2 expression is profoundly altered in the liver and small intestine of 13 week-old germ-free (GF) male mice, which also exhibit strong alterations in eCBome signaling; fecal microbiota transfer (FMT) from conventionally raised to GF mice completely restored normal Leap2 expression after 7 days from this procedure; in 13 week-old female GF mice no significant change was observed; (2) Leap2 expression in organoids prepared from the mouse duodenum is elevated by the endocannabinoid noladin ether, whereas in human Caco-2/15 epithelial intestinal cells it is elevated by PPARγ activation by rosiglitazone; (3) Leap2 expression is elevated in the ileum of mice with either high-fat diet—or genetic leptin signaling deficiency—(i.e., ob/ob and db/db mice) induced obesity. Based on these results, we propose that LEAP2 originating from the small intestine may represent a player in eCBome- and/or gut mBIome-mediated effects on food intake and energy metabolism.