New insight into the structural, electrochemical and biological aspects of macrocylic Cu(II) complexes derived from S-substituted dithiocarbazate Schiff bases

Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7

Antibiotic Transport in Resistant Bacteria: Synchrotron UV Fluorescence Microscopy to Determine Antibiotic Accumulation with Single Cell Resolution

A molecular definition of the mechanism conferring bacterial multidrug resistance is clinically crucial and today methods for quantitative determination of the uptake of antimicrobial agents with single cell resolution are missing. Using the naturally occurring fluorescence of antibacterial agents after deep ultraviolet (DUV) excitation, we developed a method to non-invasively monitor the quinolones uptake in single bacteria. Our approach is based on a DUV fluorescence microscope coupled to a synchrotron beamline providing tuneable excitation from 200 to 600 nm. A full spectrum was acquired at each pixel of the image, to study the DUV excited fluorescence emitted from quinolones within single bacteria. Measuring spectra allowed us to separate the antibiotic fluorescence from the autofluorescence contribution. By performing spectroscopic analysis, the quantification of the antibiotic signal was possible. To our knowledge, this is the first time that the intracellular accumulation of a clinical antibitiotic could be determined and discussed in relation with the level of drug susceptibility for a multiresistant strain. This method is especially important to follow the behavior of quinolone molecules at individual cell level, to quantify the intracellular concentration of the antibiotic and develop new strategies to combat the dissemination of MDR-bacteria. In addition, this original approach also indicates the heterogeneity of bacterial population when the same strain is under environmental stress like antibiotic attack

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Simulation numérique de transferts de chaleur et d'impureté lors de la fusion d'un barreau métallique

Un modèle 2D transitoire des transferts de chaleur et d'impureté est proposé pour étudier la purification d'un barreau cylindrique par zone fondue. Ce modèle se base sur les équations d'énergie et de concentration locales en régime variable. L'ensemble des phases, liquide, solide et mélange sont considérées comme un seul domaine décrit par la fraction de la phase liquide locale. Dans ce modèle, l'hypothèse retenue est que la diffusion de la température n'est pas conditionnée par la diffusion de l'impureté alors que l'inverse est vrai. Cette hypothèse pourrait être acceptable pour de très faibles concentrations. Ainsi on résout à chaque pas de temps l'équation de l'énergie, on en déduit la fraction de la phase liquide locale, par la suite on résout l'équation de concentration. Notons que, ni la convection ni les effets SORET et DUFOUR ne sont pris en compte. Ces équations de transferts, aux dérivées partielles et non linéaires étaient résolues à l'aide du logiciel Castem 2000 en adoptant un schéma explicite. Une première étude a été faite pour le choix de la géométrie du barreau, une deuxième a porté sur la migration de l'impureté suivant l'importance des gradients radial et longitudinal de la température. L'influence du rapport des coefficients de diffusion massique (liquide-solide) sur le profil de concentration le long du barreau a été approfondie

Wood transverse fracture analysis at the mesoscopic scale

The present study is an analysis of wood fracture behavior at the mesoscopic scale (i.e. the scale of growth ring). Radial TR crack growth mechanisms are complex and involve several events such as secondary cracks creation while cracks extend from one growth ring to another. Crack tip strain field of radial TR crack is measured by digital image correlation in order to better understand these phenomena. A numerical model for wood fracture has been conducted and a transverse model of spruce wood has been implemented. The simulation is realized by Material Point Method, a meshless method that discretizes material bodies into a collection of material points or particles. This promising tool improves the understanding of transverse fracture in spruce wood and can easily be used in further studies

Numerical reconstruction of interfacial defects and interface thermal resistances using thermal measurements.

No abstract provide

Variation over time of excavated soil properties treated with surfactants

International audienceFoaming agents are frequently used to dig tunnels in soft ground. These additives are often considered to be biodegradable. However, the soil fine material of excavated treated soils is generally classified as waste, stored, and not used again. The foaming agent addition affects the hydromechanical property of the soil, and the resulting evolution of the soil remains poorly understood. This study evaluated the impact of surfactants on the potential of reuse of excavated soil. For this purpose, the degradation mechanisms of the treatment were first analyzed and quantified. Standard geotechnical tests were then used to characterize the evolution of hydromechanical properties of the treated soil. The foam state of surfactant was the driving force of the observed physical property changes. The half-life of this altered state was quite short on the order of days, and the material recovered its initial mechanical properties. On the other hand, the presence of surfactant in liquid form affected the hydraulic and viscous properties over longer time periods. Concerning the mechanical behavior variation, the compressibility index of the argillaceous soil passed from 0.12 to 0.24 after treatment; the friction angle of treated soil decreased to 19° and recovered the initial value of 23° after 20 days. The viscosity of more sandy soil was reduced by approximately 100-fold after treatment. This viscosity was recovered much longer after the mechanical one after about 2 months. The hydraulic permeability decreased with the introduction of the foam from 3.4 × 10−9 to 9.6 × 10−10 m/s. After 1 month, the total recovery had not yet occurred. The statistical analysis using PCA on mechanical, hydraulic, and rheological parameters measured as a function of time after the addition of the surfactant demonstrated that the surfactant was degraded over time and the initial conditions were approached

Behaviour of masonry lateral loaded walls made with sediment-based bricks from the Usumacinta river (Mexico)

A feasibility study on Usumacinta River sediment-based bricks for resilient housing adapted to both climate change and seismic risks is performed on laterally loaded reduced-scale walls. Mortar formulations with different volume ratios of lime and sand (2/1, 1/2, 1/4, 1/6) are prepared while different types of sediment-based bricks are thoroughly investigated, manufactured and strength characterized. Commercial fired bricks as reference bricks completed the set of bricks tested (FRS: Fired River Sediment-based brick (at 850 °C); LRS: Lime treated River Sediment-based unfired brick (1.5% of lime addition); NRS: Natural fiber Reinforced river Sediment-based unfired brick and FR: commercial Fired Reference brick made without sediment). Walls of different sizes were built with these types of bricks and mortars. Tests under lateral in-plane loads of walls i.e. pushover tests, were conducted. The most significant results are as follows: (1) the addition of lime increases the strength of the mortar; (2) the wall size effect is observed for wall built with reference bricks (FR) and mortar ratio (1/2), where, large walls (LW), intermediate walls (IW) and small walls (SW) exhibiting maximum load of about 1200 N, 440 N and 260 N respectively. Rocking failure mode is the most observed unlike shear and sliding mode which are rarer. (3) maximum load measured during a pushover test performed on walls with sediment-based bricks provides a satisfactory average of 130 N, which exceeds the strength recommended for light buildings; The failure mode is sliding for fired bricks and rocking for unfired bricks. (4) the sediment-based bricks walls give an interesting ductility to pushover test while (2.6-40). These results show promising perspectives on the possibility of using the Usumacinta River sediment-based bricks in walls for light constructions under seismic loading