Amythiamicin D and Related Thiopeptides as Inhibitors of the Bacterial Elongation Factor EF‐Tu: Modification of the Amino Acid at Carbon Atom C2 of Ring C Dramatically Influences Activity

Three analogues of amythiamicin D, which differ in the substitution pattern at the methine group adjacent to C2 of the thiazole ring C, were prepared by de novo total synthesis. In amythiamicin D, this carbon atom is (S)‐isopropyl substituted. Two of the new analogues carry a hydroxymethyl in place of the isopropyl group, one at an S‐ (compound 3 a ) and the other at an R‐configured stereogenic center ( 3 b ). The third analogue, 3 c , contains a benzyloxymethyl group at an S‐configured stereogenic center. Compounds 3 b and 3 c showed no inhibitory effect toward various bacterial strains, nor did they influence the translation of firefly luciferase. In stark contrast, compound 3 a inhibited the growth of Gram‐positive bacteria Staphylococcus aureus (strains NCTC and Mu50) and Listeria monocytogenes EGD. In the firefly luciferase assay it proved more potent than amythiamicin D, and rescue experiments provided evidence that translation inhibition is due to binding to the bacterial elongation factor Tu (EF‐Tu). The results were rationalized by structural investigations and by molecular dynamics simulations of the free compounds in solution and bound to the EF‐Tu binding site. The low affinity of compound 3 b was attributed to the absence of a critical hydrogen bond, which stabilizes the conformation required for binding to EF‐Tu. Compound 3 c was shown not to comply with the binding properties of the binding site.     

Bioconversion of the antihistaminc drug loratadine by tobacco cell suspension cultures expressing human cytochrome P450 3A4

In this study we have expanded the metabolic potential of plant cell suspension cultures by introducing active human cytochrome P450 monooxygenase 3A4 into tobacco cells. Exogenously supplied loratadine was metabolized in a 3A4-specific manner, showing the capacity of this system for the generation of metabolites.     

Quenched solid density functional theory method for characterization of mesoporous carbons by nitrogen adsorption

Quenched solid density functional theory (QSDFT) model for characterization of mesoporous carbons using nitrogen adsorption is extended to cylindrical and spherical pore geometries. The kernels of theoretical isotherms in the range from 0.4 to 50 nm are constructed accounting for different possible variations of the pore shapes in micropore and mesopore regions. The results of QSDFT method are illustrated with experimental data on adsorption on novel CMK-3 and 3DOm carbons. The proposed method is recommended for pore size distribution calculations for micro–mesoporous carbons obtained through various templating mechanisms.     

Thermal precipitation or gelling behaviour of dissolved methylcellulose (MC) derivatives—Behaviour in water and influence on the extrusion of ceramic pastes. Part 1: Fundamentals of MC-derivatives

Methylcelluloses dissolved in water show a temperature dependent gelling behaviour. The gel temperatures depend mainly on the degree of substitution with methyl groups. The behaviour of methylcellulose containing pastes is of high importance in various applications. The paper describes the influence of the degree of substitution on the thermal characteristics of methylcelluloses in water and in ceramic pastes. The gelation temperature of the methylcellulose in both systems is increasing with decreasing degree of substitution. This enables a broader temperature window in the ceramic extrusion process. Extrusion near the gelation temperature normally leads to many defects in the extrudate. However, close to the gelation temperature the extruded profiles show more defects with methylcelluloses having a higher degree of substitution. Methylcelluloses having a low degree of substitution also enable a paste extrusion above the gelation temperature (up to 90 °C). This is not possible with currently commercially available methylcelluloses.     

On the role of turbulence and compositional fluctuations in rapid compression machines: Autoignition of syngas mixtures

With the increasing interest in utilizing syngas in gas turbine applications, the characterization of H₂/CO combustion and reaction chemistry under high-pressure and moderate-temperature operating conditions has been the focus of recent investigations. Different chemical-kinetics and hydrodynamic processes have been identified as being responsible for the discrepancies between experimental measurements and kinetic predictions of syngas ignition delay times. This contribution complements previous studies, and provides improved understanding about the role of turbulence and fluctuations in temperature and mixture composition on the syngas combustion process in rapid compression machines (RCMs). To this end, a self-contained model is developed that describes the ignition and combustion process by considering the interaction between turbulence, detailed reaction chemistry, and wall heat loss effects. Different mechanisms can be identified as being responsible for the generation of inhomogeneities in flow-field, temperature, and mixture composition, including turbulence-generation during the filling process, corner vortices, wall-generated turbulence, and mixing between fluid in the core region and the boundary layer. In the present model, these contributions are parametrically represented in terms of initial turbulence levels, and the mean-strain amplification of these perturbations during the compression phase is described using rapid distortion theory. The model is applied to different syngas mixtures and operating conditions, including pressures up to 20 atm and temperatures between 600 and 1300 K. Parametric studies show that the model captures experimentally observed trends of reduced ignition delay and prolonged reaction progress during the ignition phase. A Damköhler criterion is proposed in order to characterize the sensitivity of the induction chemistry to turbulence fluctuations. Results suggest that syngas mixtures with Damköhler numbers below 50 exhibit increasing sensitivity to turbulence and mixture fluctuations. This parametric study indicates that the turbulence/chemistry interaction can play an equally important role in affecting the syngas ignition chemistry, and requires consideration in addition to chemical-kinetics and hydrodynamic processes previously identified as leading mechanisms for the observed discrepancy in syngas ignition.     

Quantile regression of indoor air concentrations of volatile organic compounds (VOC)

There are many factors determining the concentration of volatile organic compounds (VOCs) in indoor air. On the basis of 601 population-based measurements we develop an explicit exposure model that includes factors, such as renovation, furniture, flat size, smoking, and education level of the occupants.As a novel method for the evaluation of concentrations of indoor air pollutants we use quantile regression, which has the advantages of robustness against non-Gaussian distributions (and outliers) and can adjust for unbalanced frequencies of observations. The applied bi- and multivariate quantile regressions provide (1) the VOC burden that is representative for the population of Leipzig, Germany, and (2) an inter-comparison of the effects of the studied factors and their levels.As a result, we find strong evidence for factors of general impact on most VOC components, such as the season, flooring, the type of the room, and the size of the apartment. Other impact factors are very specific to the VOC components. For example, wooden flooring (parquet) and new furniture increase the concentration of terpenes as well as the modifying factors high education and sampling in the child's room. Smokers ventilate their flats in an extent that in general reduces the VOC concentrations, except for benzene (contained in tobacco smoke), which is still higher in smoking than in non-smoking flats. Very often dampness is associated with an increased VOC burden in indoor air.An investigation of mixtures emphasises a high burden of co-occurring terpenes in very small and very large apartments.     

Continuous polymerization of methyl methacrylate in a taylor‐couette reactor. II. influence of fluid dynamics on polymer properties

In this work, the free radical continuous polymerization of methyl methacrylate (MMA) with the solvent xylene and 2,2‐Azoisobutyronitrile (AIBN) as initiator was studied in a laboratory Taylor‐Couette reactor. It was found that the property of the polymerized product (molecular weight distribution) is affected by the fluid dynamic conditions (mean residence time, rotational speed, diameter of the inner cylinder, and gap width). The weight average molecular weight decreases with an increase of the mean residence time, is strongly dependent on the geometry of the reactor, and was found to be independent on the shear rate in the gap. The width of the molecular weight distribution decreases weakly with increasing residence time, increases with increasing shear rate, and weakly depends on the diameter of the inner cylinder. A correlation was developed to describe the weight‐average molecular weight as a function of the Taylor number and the Damköhler number. This correlation is dimensionless and may be used for scaling‐up purposes. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

Plastic deformation mechanism of ultra-fine-grained AA6063 processed by equal-channel angular pressing

Equal-channel angular pressing (ECAP) is an established method to produce ultra-fine-grained (UFG) materials with extraordinary mechanical properties. However, different methods to characterize the complex microstructure give contradictory results. Therefore an ECAP-processed UFG aluminum alloy AA6063 was characterized by various electron-microscopy-based methods such as backscattered electron contrast, electron backscatter diffraction, transmission electron microscopy and low-voltage scanning transmission electron microscopy. Only a skilful combination of all methods reveals the complete information about the microstructure which is needed to understand the results of the mechanical testing by nanoindentation, tensile tests and strain-rate jump test. The main difference is the amount of low-angle grain boundaries and high-angle grain boundaries which determine hardness, tensile and yield strength and strain-rate sensitivity of ECAP materials produced by different numbers of passes and routes. This is explained by the interaction of dislocations with the different grain boundaries.