Nitroarenes as Antitubercular Agents: Stereoelectronic Modulation to Mitigate Mutagenicity

Nitroarenes are less preferred in drug discovery due to their potential to be mutagenic. However, several nitroarenes were shown to be promising antitubercular agents with specific modes of action, namely, nitroimidazoles and benzothiazinones. The nitro group in these compounds is activated through different mechanisms, both enzymatic and non‐enzymatic, in mycobacteria prior to binding to the target of interest. From a whole‐cell screening program, we identified a novel lead nitrobenzothiazole (BT) series that acts by inhibition of decaprenylphosphoryl‐β‐d ‐ribose 2′‐epimerase (DprE1) of Mycobacterium tuberculosis (Mtb). The lead was found to be mutagenic to start with. Our efforts to mitigate mutagenicity resulted in the identification of 6‐methyl‐7‐nitro‐5‐(trifluoromethyl)‐1,3‐benzothiazoles (cBTs), a novel class of antitubercular agents that are non‐mutagenic and exhibit an improved safety profile. The methyl group ortho to the nitro group decreases the electron affinity of the series, and is hence responsible for the non‐mutagenic nature of these compounds. Additionally, the co‐crystal structure of cBT in complex with Mtb DprE1 established the mode of binding. This investigation led to a new non‐mutagenic antitubercular agent and demonstrates that the mutagenic nature of nitroarenes can be solved by modulation of stereoelectronic properties.     

New alginate foams: Box‐Behnken design of their manufacturing; fire retardant and thermal insulating properties

A new method for preparing alginate foams with progressive release of copper in the presence of sodium lauryl sulfate (SLS, foaming agent) has been designed. Copper acts as the ionotropic gelling agent through the reaction of copper carbonate with gluconolactone. The process does not require freeze‐drying contrarily to the conventional method used for preparing macroporous alginate foams. The new materials investigated in this study have remarkable thermal properties, including thermal conductivity lower than 0.041 W m^?1 K^?1 and low heat release (below 2 kJ g^?1), which allows labeling these foams self‐extinguishing materials. An experimental design methodology, based on a Box‐Behnken plan with three parameters and three levels, is successfully used for evaluating the impact of the amounts of alginate, SLS, and copper carbonate on the productivity, apparent density, and shrinking at air‐drying. It yielded an optimization of the process for the manufacturing of light, and stable/rigid insulating and thermally stable materials. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45868.     

Barrier effect of flame retardant systems in poly(methyl methacrylate): Study of the efficiency of the surface treatment by octylsilane of silica nanoparticles in combination with phosphorous fire retardant additives

In this work, flame retardant systems comprising ammonium polyphosphate (AP423) and hydrophilic (A200) or hydrophobic (R805) nanometric silica were incorporated into PMMA. The following techniques were performed to detail the fire behaviour of the composites: mass loss cone calorimetry, pyrolysis‐combustion flow calorimetry, pyrolysis‐gas chromatography–mass spectrometry, thermogravimetric analysis, X‐ray diffraction analysis, Fourier transform infrared spectroscopy and microscopic observations. The best fire behaviour was obtained with the surface‐treated silica in the presence of AP423. The formation of a new crystalline phase from the interactions between AP423 and R805 silica and a strong barrier effect due to a layered residue were the main modes of action of this system. Moreover, we have shown that the difference between the AP423 + R805 and AP423 + A200 systems was due to poor dispersion of the silica into the PMMA matrix in the latter formulation. Copyright © 2011 John Wiley & Sons, Ltd.     

Modelling and measurements of the velocity gradient and local flow direction at the pore scale of a packed bed

In a packed bed with single phase liquid flow, velocity gradient and local flow direction are measured at the pore scale using tri-segmented microelectrodes flush mounted at the surface of a sphere equator area. The experimental measurements are compared to numerical predictions deduced from the solution of a 3D model based on continuity and momentum balance equations.     

Mass Spectrometry-Based Proteomics Reveal Alcohol Dehydrogenase 1B as a Blood Biomarker Candidate to Monitor Acetaminophen-Induced Liver Injury

Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI.     

Hydroxytelechelic hydrocarbon copolymers with high aging resistance for elastomeric materials

Dihydroxytelechelic copolyalkenamers were prepared via metathetical polymerization of cyclic olefins (cyclooctadiene, cyclooctene and cyclododecene) in presence of first generation Grubbs catalyst and butene diacetate as functionalizing chain transfer agent in order to study their aging resistance. The influence of compositions and molar masses of the copolyalkenamers were investigated in terms of thermo‐mechanical properties. Increasing chains length or the proportion of polycyclooctadiene allow to get non‐cristalline polymers. Low T_g materials (between ?78°C and ?108°C) were prepared. The resistance towards oxidation of the different copolyalkenamers was carried out using a viscosity measurement method. A critical time, corresponding to a brutal increase of the apparent viscosity, was related to degradation of the polymers and was shown to be dependent on the Csp² proportion in the structure. The absence of vinylic units and the decrease of the double bonds content within the copolymers were proved to enhance the stability of the copolyalkenamers towards aging resistance. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Dietary intakes and food sources of fat and fatty acids in Guatemalan schoolchildren: A cross-sectional study

Background  

Consumption of healthy diets that contribute with adequate amounts of fat and fatty acids is needed for children. Among Guatemalan children, there is little information about fat intakes. Therefore, the present study sought to assess intakes of dietary fats and examine food sources of those fats in Guatemalan children.     

Investigations of silica scaling on reverse osmosis membranes

In reverse osmosis systems with high silica water severe and irreversible membrane scaling can be observed. But suitable test methods to find an appropriate antiscalant agent and the optimal dosage are missing. Usually only the silicate concentration in the feed water is regarded.In this paper the results of laboratory experiments about the influence of Ca²⁺- and Mg²⁺-ions on the behaviour of supersaturated solutions of silica in different test waters are discussed first. After that the new developed membrane-based test method to determine the effectiveness of antiscalants is presented.The applied different methods of analysis enabled the differentiation of three groups of silicates: ‘monomeric’, ‘polymeric’ and ‘filterable’.With the test method the strong impact of silicate scaling was proven, even if only small amounts of scale had been formed. It could be shown, that the ‘polymeric silica’ is mainly responsible for the membrane scaling. The kinetic of the formation of ‘polymeric silica’ is strongly influenced by the cations and the pH-value. It could be demonstrated that the use of a suitable antiscalant makes it possible to operate the plant at significantly higher recovery rates.