Strategies To Design Selective Histone Deacetylase Inhibitors

This review classifies drug-design strategies successfully implemented in the development of histone deacetylase (HDAC) inhibitors, which have many applications including cancer treatment. Our focus is on especially demanded selective HDAC inhibitors and their structure-activity relationships in relation to corresponding protein structures. The main part of the paper is divided into six subsections each narrating how optimization of one of six structural features can influence inhibitor selectivity. It starts with the impact of the zinc binding group on selectivity, continues with the optimization of the linker placed in the substrate binding tunnel as well as the adjustment of the cap group interacting with the surface of the protein, and ends with the addition of groups targeting class-specific sub-pockets: the side-pocket-, lower-pocket- and foot-pocket-targeting groups. The review is rounded off with a conclusion and an outlook on the future of HDAC inhibitor design.     

Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Investigation on the effectiveness of the repair method 8.3 “Corrosion protection by increasing the electrical resistivity” in chloride-containing concrete Part 2: Chloride redistribution in concrete after application of a system sealing surface protective coating

This DFG-funded research project aimed to gain a better understanding of the mechanisms of the W-Cl repair principle within the framework of fundamental investigations, to contribute to the creation of the necessary basis for a broader application of the repair principle in practice. The focus was on the development of a model to describe the chloride redistribution after the application of a system sealing surface protective coating. On the basis of Fick's second law of diffusion, a mathematical model with a self-contained analytical solution was developed, with the help of which the chloride redistribution after application of a system sealing surface protective coating can be calculated under the idealized assumption of complete water saturation of the concrete. Furthermore, the influence of the dehydration of the concrete, expected as a result of the application of the repair principle W-Cl, on the chloride redistribution was investigated. On the basis of laboratory tests and numerical simulations, material-specific reduction functions were developed to quantify the relationship between the chloride diffusion coefficient and the ambient humidity.     

Spatially Resolved Characterization of the Gas Propagator in Monolithic Structured Catalysts Using NMR Diffusiometry

Gas diffusivity measurements in opaque porous media were performed using nuclear magnetic resonance. An optimized pulsed‐field gradient stimulated echo method with free volume selection was used to investigate the propagator of thermally polarized methane gas within commercial monolithic catalyst supports. Since signal losses due to T₂ relaxation were minimized by using a short echo time, diffusion processes could be characterized by the measured propagator functions and effective diffusion coefficients were determined for a broad range of observation times and in different spatial directions. The study of this noninvasive characterization of gas diffusion found a clear effect of the monolith type and its pore size and coating on the effective gas diffusion coefficient and the apparent tortuosity for a given observation time.     

Yttrium doping of Ba0.5Sr0.5Co0.8Fe0.2O3-δ part II: Influence on oxygen transport and phase stability

Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3-δ (BSCF) in its cubic perovskite phase has attracted much interest for potential use as oxygen transport membrane (OTM) due to its very high oxygen permeability at high temperatures. However, performance degradation due to a sluggish phase decomposition occurs when BSCF is operated below 840?°C. Partial B-site substitution of the transition metal cations in BSCF by larger and redox-stable cations has emerged as a potential strategy to improve the structural stability of cubic BSCF. In this study, the influence of yttrium doping (0…10?mol-%) on oxygen transport properties and stability of the cubic BSCF phase is assessed by in situ electrical conductivity relaxation (ECR) and electrical conductivity measurements during long-term thermal annealing both at 700?°C and 800?°C. Detailed phase analysis is performed by scanning electron microscopy (SEM) after long-term annealing of the samples in air at different temperatures.     

Analysis of the Processing-Pressure Dependent Refractive Index of Polycarbonate by Transmission Measurements of Glass-Filled Specimen

In this study, the influence of pressure during processing on the refractive index (RI) of polycarbonate (PC) was investigated by transmission measurements on glass-filled samples with a spectrometer. In order to isolate the pressure dependence of the RI from other influencing parameters such as cooling rate, orientation and stress states, the samples were prepared in a pressure-specific volume-Temperature (pvT) instrument under constant cooling rate and temperature history and without shear effects. Subsequently, the RI was determined at the intersection of the dispersion curves of the glass and the polymer by evaluating the wavelength of the maximal transmission of the samples. The mean RI over the entire cross section of the sample is determined by the transmission measurements without complex sample preparation. The investigations show that the RI of PC increases by 3.26 E-6 per bar with increasing pressure. POLYM. ENG. SCI., 60:512–516, 2020. © 2019 The Authors. Polymer Engineering & Science published by Wiley Periodicals, Inc. on behalf of Society of Plastics Engineers.     

Primary energy demand and energy costs of fixed-bed drying using the example of chamomile flowers

Abstract

Energy use efficiency in the drying of medicinal and aromatic plants is largely determined by weather conditions and process parameters. While the former are beyond control, the latter can be optimized. In order to achieve such optimization, different energy supply variants, based on typical operating conditions of batch-type grate drying in Thuringia, Germany, were analyzed. It was found that partial air recirculation and integration of heat pumps allow substantial savings in primary energy. However, under the constraint of German energy prices, significant savings in energy costs can only be achieved if combined heat and power generation systems are applied at the same time.     

Selective Analysis of Sulfur-Containing Species in a Heavy Crude Oil by Deuterium Labeling Reactions and Ultrahigh Resolution Mass Spectrometry

A heavy crude oil has been treated with deuterated alkylating reagents (CD₃I and C₂D₅I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) using electrospray ionization (ESI). The reaction of a polycyclic aromatic sulfur heterocycles (PASHs) dibenzothiophene (DBT), in the presence of silver tetrafluoroborate (AgBF₄) with ethyl iodide (C₂H₅I) in anhydrous dichloroethane (DCE) was optimized as a sample reaction to study heavy crude oil mixtures, and the reaction yield was monitored and determined by proton nuclear magnetic resonance spectroscopy (¹H-NMR). The obtained conditions were then applied to a mixture of standard aromatic CH-, N-, O- and S-containing compounds and then a heavy crude oil, and only sulfur-containing compounds were selectively alkylated. The deuterium labeled alkylating reagents, iodomethane-d₃ (CD₃I) and iodoethane-d₅ (C₂D₅I), were employed to the alkylation of heavy crude oil to selectively differentiate the tagged sulfur species from the original crude oil.     

Enhancing the temperature stability of PLA by compounding strategies

The low thermal stability of polylactid acid (PLA) limits its use for various applications such as microwave‐ready dishes or hot beverage packaging. Furthermore, contained items might be damaged by occurring temperature peaks during transport (e.g., shipping container internal temperature exceeds 80°C) or other usage (e.g., car dashboard heated by sun). The aim of this study was the development of a PLA compound with an operating temperature above 100°C. Therefore, different formulations (e.g., stereocomplex of PLLA and PDLA, cross‐linking of PLA or use of commercial additives) were identified and compounds with varying conditions produced and tested regarding their thermal and mechanical properties. The results showed clearly possible routes for improving the thermal properties of PLA. Using such compounds respectively processing routes and additives helps to overcome one of the most significant problems when using PLA. The higher operating temperature of this biopolymer will lead to a wider field of application and will avoid shipping hazards. POLYM. ENG. SCI., 55:2849–2858, 2015. © 2015 Society of Plastics Engineers