Refractory Alkali-Free Cristobalite Glass-Ceramics: Activated Reaction Sinter-Crystallization Synthesis and Properties

A new approach for the synthesis of chemically stabilized β-cristobalite-like glass-ceramic materials is developed. It is based on an activated reaction sinter-crystallization process of compacted powder mixtures at relatively low temperatures (1400–1450°C) and short heat treatment times. To facilitate homogeneous dopant distribution and thus the formation of a high content of β_x-cristobalite-like phases, possessing a very low thermal expansion coefficient, the batch components are introduced in a chemically, mechanically, or thermally preactivated form. In this way, the high-temperature glass premelting usually employed in the “classical” synthesis of glass-ceramics is avoided. Using different, mutually complementary techniques of analysis it is revealed that optimal refractory properties are achieved with glass-ceramics containing α_x- and β_x-cristobalite solid solutions with close values of the lattice parameters. In this case, the transformation between these two cristobalite-like solid solutions proceeds instead by a first-order displacive transition, by a process exhibiting features characteristic for both a suppressed first-order phase change and a second-order λ-type phase transitions. The refractory properties of the glass-ceramic materials thus synthesized and the possibility to use various forming techniques open many fields for their application.     

Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses

Medical research is changing into direction of precision therapy, thus, sophisticated preclinical models are urgently needed. In human pathogenic virus research, the major technical hurdle is not only to translate discoveries from animals to treatments of humans, but also to overcome the problem of interspecies differences with regard to productive infections and comparable disease development. Transgenic mice provide a basis for research of disease pathogenesis after infection with human-specific viruses. Today, humanized mice can be found at the very heart of this forefront of medical research allowing for recapitulation of disease pathogenesis and drug mechanisms in humans. This review discusses progress in the development and use of transgenic mice for the study of virus-induced human diseases towards identification of new drug innovations to treat and control human pathogenic infectious diseases.     

Characterization of C–S–H and C–A–S–H phases by electron microscopy imaging,diffraction, and energy dispersive X‐ray spectroscopy

Improving concrete sustainability by increasing durability requires a detailed knowledge about microstructural properties. Due to the nanoscale nature of hydrate phases that determine concrete properties, microstructural characterization remains a challenge. Analytical electron microscopy offers promising techniques to characterize cement hydrates. In this study, electron microscopy imaging, diffraction, and energy dispersive X‐ray spectroscopic information are combined in order to compare the structural properties of calcium silicate hydrate (C–S–H) and calcium aluminum silicate hydrate (C–A–S–H) phases. Results are shown for 28 days hydrated C–(A)–S–H of portland cement and cement containing ground granulated blast‐furnace slag (GGFBS). Electron diffraction patterns of single fibrous C–S–H and foil‐like C–A–S–H phases reveal a nanocrystalline structure. Also, it is shown by electron diffraction pattern that the crystal structures of C–S–H and C–A–S–H phases are similar. It is confirmed that the crystal structure of 14 Å tobermorite serves as good base for the structure of C–S–H. The electron diffraction patterns of fibrous C–S–H show streaks which indicate stacking faults, proofing that polymerization of silicate chains in C–S–H is limited. Here, we demonstrate for the first time that the dreierketten silicate chains contained in the C–S–H structure are oriented in parallel to the long axis of C–S–H fibers. This finding should be implemented in modeling of crystal growth of C–S–H.     

Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity.     

Sorption and diffusion of gold and silver nanoparticles in solution through nitrile rubber membrane

Mechanical and physical properties of the rubber material may be affected by swelling when brought into contact with solutions of engineered nanoparticles (ENP). As the rubber swells in the liquid carrier of the ENP, the polymeric chains of the network expand and the ENP can penetrate the structure being carried by the diffusion of the liquid. The aim of this work is to assess the influence of ENP and evaluate the effect of additives present in the solutions on the diffusion process through a rubbery structure. Swelling of membrane material specimens was evaluated by measuring mass gain and liquid diffusion was then deduced. The present study focuses on the contact of nitrile rubber membranes with commercial gold ENP (5 and 50 nm in diameter) and silver ENP (50 nm) in MilliQ water. Swelling tests were also conducted with MilliQ water and filtrates (the solutions from which the ENP were extracted). Results show that the diffusion coefficients of all the solutions of ENP are slightly different and are around 1.2 × 10^?10 cm² s^?1. However, it should be noted that these coefficients are notably higher for the filtrates and reach 2.4 × 10^?10 cm² s^?1 for the filtrate of the silver ENP. This result underscores the effect of the ENP on the liquid penetration process. We also found that the ENP has a noticeable effect on the Fickian diffusion mechanism of the penetrant; it was noticed that the presence of these nanoparticles lowers the diffusion mechanism index. Moreover, the size of the nanoparticles was found to have an impact on the diffusion coefficient of the solutions as well as their solubility. These findings help to better understand the diffusion phenomenon of the ENP through nitrile membrane materials. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45350.     

Improvement of Aglycone π-Stacking Yields Nanomolar to Sub-nanomolar FimH Antagonists

Antimicrobial resistance has become a serious concern for the treatment of urinary tract infections. In this context, an anti-adhesive approach targeting FimH, a bacterial lectin enabling the attachment of E. coli to host cells, has attracted considerable interest. FimH can adopt a low/medium-affinity state in the absence and a high-affinity state in the presence of shear forces. Until recently, mostly the high-affinity state has been investigated, despite the fact that a therapeutic antagonist should bind predominantly to the low-affinity state. In this communication, we demonstrate that fluorination of biphenyl α-d -mannosides leads to compounds with perfect π–π stacking interactions with the tyrosine gate of FimH, yielding low nanomolar to sub-nanomolar K_D values for the low- and high-affinity states, respectively. The face-to-face alignment of the perfluorinated biphenyl group of FimH ligands and Tyr48 was confirmed by crystal structures as well as ¹H,¹⁵N-HSQC NMR analysis. Finally, fluorination improves pharmacokinetic parameters predictive for oral availability.     

Lytic Polysaccharide Monooxygenase from Talaromyces amestolkiae with an Enigmatic Linker-like Region: The Role of This Enzyme on Cellulose Saccharification

The first lytic polysaccharide monooxygenase (LPMO) detected in the genome of the widespread ascomycete Talaromyces amestolkiae (TamAA9A) has been successfully expressed in Pichia pastoris and characterized. Molecular modeling of TamAA9A showed a structure similar to those from other AA9 LPMOs. Although fungal LPMOs belonging to the genera Penicillium or Talaromyces have not been analyzed in terms of regioselectivity, phylogenetic analyses suggested C1/C4 oxidation which was confirmed by HPAEC. To ascertain the function of a C-terminal linker-like region present in the wild-type sequence of the LPMO, two variants of the wild-type enzyme, one without this sequence and one with an additional C-terminal carbohydrate binding domain (CBM), were designed. The three enzymes (native, without linker and chimeric variant with a CBM) were purified in two chromatographic steps and were thermostable and active in the presence of H₂O₂. The transition midpoint temperature of the wild-type LPMO (Tm = 67.7 °C) and its variant with only the catalytic domain (Tm = 67.6 °C) showed the highest thermostability, whereas the presence of a CBM reduced it (Tm = 57.8 °C) and indicates an adverse effect on the enzyme structure. Besides, the potential of the different T. amestolkiae LPMO variants for their application in the saccharification of cellulosic and lignocellulosic materials was corroborated.     

Evaluation of solvent accessibility epitopes for different dehydrogenase inhibitors

Knowledge about the orientation of ligands or inhibitors bound to a protein is vital for the development of new drugs. It was recently shown that solvent accessibility epitopes for protein ligands can be mapped by transferring magnetization from water molecules to the ligand to derive the ligand orientation. This is based on the fact that NMR signals of ligands arising from magnetization transferred from solvent molecules via the protein have a different sign from those arising from direct magnetization transfer from bulk water. Herein we critically evaluate the applicability of solvent accessibility mapping to derive binding orientations for ligands of two dehydrogenases (AKR1C3 and HSD17beta1) with very different binding pockets, including complexes in which the ligand is buried more deeply inside the protein. We also evaluate the possibility of using co-solvents, such as DMSO, for magnetization transfer.     

Experimental Phase Diagram Study and Thermodynamic Optimization of the Ag-Bi-O System

The Ag-Bi-O system has been experimentally studied using differential thermal analysis (DTA) and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX), and thermodynamically optimized. The temperatures of the eutectic, monotectic, and Bi₂O₃ allotropic transformations have been measured in N₂, in air, and in O₂ by DTA. There are no ternary phases stable at ambient pressure. Presently measured transformation temperatures have been combined with existing oxygen activity measurements in the metal liquid to optimize thermodynamic parameters describing the liquid phase. The resulting fit is excellent. EDX measurements of the composition in the oxide liquid have a rather low precision but confirm the thermodynamic optimization. However, some uncertainties remain concerning the liquid composition at the eutectic transformation and the shape of the miscibility gap at higher temperatures.