Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

From linear temporal logic and limit-deterministic Büchi automata to deterministic parity automata

Controller synthesis for general linear temporal logic (LTL) objectives is a challenging task. The standard approach involves translating the LTL objective into a deterministic parity automaton (DPA) by means of the Safra-Piterman construction. One of the challenges is the size of the DPA, which often grows very fast in practice, and can reach double exponential size in the length of the LTL formula. In this paper, we describe a single exponential translation from limit-deterministic Büchi automata (LDBA) to DPA and show that it can be concatenated with a recent efficient translations from LTL to LDBA to yield a double exponential, ‘Safraless’ LTL-to-DPA construction. We also report on an implementation and a comparison with other LTL-to-DPA translations on several sets of formulas from the literature.

     

Selecting a battery of bioassays for ecotoxicological characterization of wastes

This study was conducted in France within the context of waste classification (Hazardous Waste Council Directive 91/689/EEC), and focused on "ecotoxic" property (H14). In 1998, an experimental test strategy was developed to assess ecotoxicological properties of wastes using a battery of six standardized bioassays. This combined direct and indirect approaches integrating two solid-phase tests: emergence and growth inhibition of Lactuca sativa (14 days), mortality of Eisenia fetida (14 days) and four standardized tests performed on water extracts from wastes: growth inhibition of Pseudokirchneriella subcapitata (3 days), inhibition of mobility of Daphnia magna (48 h), inhibition of reproduction of Ceriodaphnia dubia (7 days), inhibition of light emission of Vibrio fischeri (30 min). This study aimed to set up preliminary conclusions on relevancy of this experimental test strategy, based on data obtained since 1998. Results were analyzed from the combined use of Hierarchical Cluster Analysis, Principal Component Analysis and Nonlinear Mapping. These multivariate analyses clearly showed that it was possible to reduce this number of tests without changing the typology of the wastes. A battery of bioassays including one solid phase test and two tests performed on water extracts (L. sativa, V. fischeri and C. dubia) was found as an optimal solution for characterizing the toxicity of the studied wastes. This optimal battery represents a good basis for determining the H14 property.     

Solid-Phase Synthesis of Substrate-Based Dipeptides and Heterocyclic Pseudo-dipeptides as Potential NO Synthase Inhibitors

More than 160 arginine analogues modified on the C-terminus via either an amide bond or a heterocyclic moiety (1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,4-triazole) were prepared as potential inhibitors of NO synthases (NOS). A methodology involving formation of a thiocitrulline intermediate linked through its side-chain on a solid support followed by modification of its carboxylate group was developed. Finally, the side-chain thiourea group was either let unchanged, S-alkylated (Me, Et) or guanidinylated (Me, Et) to yield respectively after TFA treatment the corresponding thiocitrulline, S-Me/Et-isothiocitrulline and N-Me/Et-arginine substrate analogues. They all were tested against three recombinant NOS isoforms. Several compounds containing a S-Et- or a S-Me-Itc moiety and mainly belonging to both the dipeptide-like and 1,2,4-oxadiazole series were shown to inhibit nNOS and iNOS with IC₅₀ in the 1–50 μM range. Spectral studies confirmed that these new compounds interacted at the heme active site. The more active compounds were found to inhibit intra-cellular iNOS expressed in RAW264.7 and INS-1 cells with similar efficiency than the reference compounds L-NIL and SEIT.     

Image-based truss recognition for density-based topology optimization approach

Structural and Multidisciplinary Optimization - Topology optimization is a tool that supports the creativity of structural-designers and is used in various industries, from automotive to...     

Computing the lowest equilibrium pose of a cable-suspended rigid body

We solve the problem of finding the lowest stable-equilibrium pose of a rigid body subjected to gravity and suspended in space by an arbitrary number of cables. Besides representing a contribution to fundamental rigid-body mechanics, this solution finds application in two areas of robotics research: underconstrained cable-driven parallel robots and cooperative towing. The proposed approach consists in globally minimizing the rigid-body potential energy. This is done by applying a branch-and-bound algorithm over the group of rotations, which is partitioned into boxes in the space of Euler-Rodrigues parameters. The lower bound on the objective is obtained through a semidefinite relaxation of the optimization problem, whereas the upper bound is obtained by solving the same problem for a fixed orientation. The resulting algorithm is applied to several examples drawn from the literature. The reported Matlab implementation converges to the lowest stable equilibrium pose generally in a few seconds for cable-robot applications. Interestingly, the proposed method is only mildly sensitive to the number of suspending cables, which is shown by solving an example with 1000 cables in two hours.