Synthesis and evaluation of new phosphonated δ-lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

An efficient synthesis of new γ,δ-insaturated δ-lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two-step procedure involving the preparation of phosphonated-1,5-ketoester and −1,5-diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base-promoted intramolecular amidation-cyclization sequence with primary amines, which accounts for the construction of δ-lactams and glutarimide skeletons. We performed the evaluation of angiotensin I-converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC₅₀ values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity.     

Forest fire modelling using cellular automata: application to the watershed Oued Laou (Morocco)

ABSTRACT

In this work, we consider the problem of modelling the phenomenon of forest fires using the cellular automata approach. The proposed model takes into account the main parameters that affect this phenomenon like nature and density of vegetation, humidity, wind, and altitude. We developed a decision-aided tool with JAVA which allows to analyse and format several hybrid collected data (satellite images, Digital Terrain Model) relatively to each studied area. The generated scenarios of forest fire spread in the study area will be considered as a guide for strategies in control and prevention of forest fires. As an application, we consider the watershed Oued Laou (Morocco).     

Discrepancy of Fractions with Divisibility Constraints

We provide bounds for the absolute discrepancy of sequences of fractions with denominators streaming in a given arithmetic progression and satisfying divisibility constraints. Supported by the CERES Program 4-147/2004 of the Romanian Ministry of Education and Research.     

Strongly essential coalitions and the nucleolus of peer group games

Most of the known efficient algorithms designed to compute the nucleolus for special classes of balanced games are based on two facts: (i) in any balanced game, the coalitions which actually determine the nucleolus are essential; and (ii) all essential coalitions in any of the games in the class belong to a prespecified collection of size polynomial in the number of players. We consider a subclass of essential coalitions, called strongly essential coalitions, and show that in any game, the collection of strongly essential coalitions contains all the coalitions which actually determine the core, and in case the core is not empty, the nucleolus and the kernelcore. As an application, we consider peer group games, and show that they admit at most 2n−1 strongly essential coalitions, whereas the number of essential coalitions could be as much as 2ⁿ⁻¹. We propose an algorithm that computes the nucleolus of an n-player peer group game in time directly from the data of the underlying peer group situation.Research supported in part by OTKA grant T030945. The authors thank a referee and the editor for their suggestions on how to improve the presentation     

Connecting a population dynamic model with a multi-period location-allocation problem for post-disaster relief operations

In this study, we propose a mathematical model and heuristics for solving a multi-period location-allocation problem in post-disaster operations, which takes into account the impact of distribution over the population. Logistics restrictions such as human and financial resources are considered. In addition, a brief review on resilience system models is provided, as well as their connection with quantitative models for post-disaster relief operations. In particular, we highlight how one can improve resilience by means of OR/MS strategies. Then, a simpler resilience schema is proposed, which better reflects an active system for providing humanitarian aid in post-disaster operations, similar to the model focused in this work. The proposed model is non-linear and solved by a decomposition approach: the master level problem is addressed by a non-linear solver, while the slave subproblem is treated as a black-box coupling heuristics and a Variable Neighborhood Descent local search. Computational experiments have been done using several scenarios, and real data from Belo Horizonte city in Brazil.     

A posteriori error analysis for nonconforming approximations of an anisotropic elliptic problem

We develop in this article an a posteriori error estimator for the P₁‐nonconforming finite element approximation, for a diffusion‐reaction equation. We adopt the error in a constitutive law approach in two and three dimensional space, for not necessary piecewise constant data of problems. The efficiency and the reliability of our estimators are proved, neither Helmholtz decomposition of the error nor saturation assumption. The constants are explicitly given, which prove the robustness of these estimators. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 950–976, 2015