Grauwasserreinigung mit einer Sumpfpflanzenmatte unter Praxisbedingungen

There is increasing interest worldwide in the decentralized treatment of gray water. Since ground‐level areas are generally costly, gray‐water treatment can also be carried out using helophyte mats on the roofs of buildings as an alternative. Alongside the water treatment itself, this process also has a positive effect on the indoor climate in the building. In a test carried out under realistic conditions, it was shown that a helophyte mat with a root‐layer depth of 0.1 m and with hydraulic loads per unit up to 15 L m^?2d^?1 is suitable for treating typical gray water from a residential building.     

Biocatalytic Asymmetric Phosphorylation Catalyzed by Recombinant Glycerate‐2‐Kinase

The efficient synthesis of pure d ‐glycerate‐2‐phosphate is of great interest due to its importance as an enzyme substrate and metabolite. Therefore, we investigated a straightforward one‐step biocatalytic phosphorylation of glyceric acid. Glycerate‐2‐kinase from Thermotoga maritima was expressed in Escherichia coli, allowing easy purification. The selective glycerate‐2‐kinase‐catalyzed phosphorylation was followed by ³¹P NMR and showed excellent enantioselectivity towards phosphorylation of the d ‐enantiomer of glyceric acid. This straightforward phosphorylation reaction and subsequent product isolation enabled the preparation of enantiomerically pure d ‐glycerate 2‐phosphate. This phosphorylation reaction, using recombinant glycerate‐2‐kinase, yielded d ‐glycerate 2‐phosphate in fewer reaction steps and with higher purity than chemical routes.     

A Conjugate of an Anti‐Epidermal Growth Factor Receptor (EGFR) VHH and a Cell‐Penetrating Peptide Drives Receptor Internalization and Blocks EGFR Activation

Overexpression of (mutated) receptor tyrosine kinases is a characteristic of many aggressive tumors, and induction of receptor uptake has long been recognized as a therapeutic modality. A conjugate of a synthetically produced cell‐penetrating peptide (CPP), corresponding to amino acids 38–59 of human lactoferrin, and the recombinant llama single‐domain antibody (VHH) 7D12, which binds the human epidermal growth factor receptor (EGFR), was generated by sortase A mediated transpeptidation. The conjugate blocks EGF‐mediated EGFR activation with higher efficacy than that of both modalities alone; a phenomenon that is caused by both effective receptor blockade and internalization. Thus, the VHH–CPP conjugate shows a combination of activities that implement a highly powerful new design principle to block receptor activation by its clearance from the cell surface.     

Effect of solvent type on preparation of ethyl cellulose microparticles by solvent evaporation method with double emulsion system using focused beam reflectance measurement

The purpose of this study was to investigate the effect of solvent type on the solidification rate of ethyl cellulose (EC) microparticles and particle size/distribution of emulsion droplets/hardened microparticles during the solvent evaporation process using focused beam reflectance measurement (FBRM). EC microparticles were prepared with a water‐in‐oil‐in‐water solvent evaporation method using various solvents, including dichloromethane, dichloromethane–methanol (1:1), ethyl acetate and chloroform. The particle size/distribution of the emulsion droplets/hardened microparticles was monitored using FBRM. The morphology of EC microparticles was characterized using scanning electron microscopy (SEM). The transformation of the emulsion droplets into solid microparticles for all solvents occurred within the first 10–90 min. The square weighted mean chord length of EC microparticles prepared using chloroform was smallest, but the chord count was not the highest. The chord length distribution (CLD) measured by FBRM showed that a larger mean particle size gave longer CLD and a lower peak of particle number. SEM data revealed that the morphology of microparticles was influenced by the type of solvent. FBRM can be employed for online monitoring of the shift in the microparticle CLD and detect transformation of emulsion droplets into solid microparticles during the solvent evaporation process. The microparticle CLD and transformation process were strongly influenced by solvent type. © 2017 Society of Chemical Industry     

Rational Structure-Based Design of Fluorescent Probes for Amyloid Folds

Amyloid fibrils are pathological hallmarks of various human diseases, including Parkinson's, Alzheimer's, amyotrophic lateral sclerosis (ALS or motor neurone disease), and prion diseases. Treatment of the amyloid diseases are hindered, among other factors, by timely detection and therefore, early detection of the amyloid fibrils would be beneficial for treatment against these disorders. Here, a small molecular fluorescent probe is reported that selectively recognize the fibrillar form of amyloid beta(1–42), α-synuclein, and HET-s(218–289) protein over their monomeric conformation. The rational design of the reporters relies on the well-known cross-β-sheet repetition motif, the key structural feature of amyloids.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Development of Biarylalkyl Carboxylic Acid Amides with Improved Anti-schistosomal Activity

The parasitic disease schistosomiasis is the cause of more than 200 000 human deaths per year. Although the disease is treatable, there is one major shortcoming: praziquantel has been the only drug used to combat these parasites since 1977. The risk of the emergence of resistant schistosomes is known to be increasing, as a reduced sensitivity of these parasites toward praziquantel has been observed. We developed a new class of substances, which are derived from inhibitors of human aldose reductase, and which showed promising activity against Schistosoma mansoni couples in vitro. Further optimisation of the compounds led to an increase in anti-schistosomal activity with observed phenotypes such as reduced egg production, vitality, and motility as well as tegumental damage and gut dilatation. Here, we performed structure–activity relationship studies on the carboxylic acid moiety of biarylalkyl carboxylic acids. Out of 82 carboxylic acid amides, we identified 10 compounds that are active against S. mansoni at 25 μm . The best five compounds showed an anti-schistosomal activity up to 10 μm and induced severe phenotypes. Cytotoxicity tests in human cell lines showed that two derivatives had no cytotoxicity at 50 or 100 μm . These compounds are promising candidates for further optimisation toward the new anti-schistosomal agents.     

A Complementarity Problem–Based Solution Procedure for 2D Steady-State Rolling Contacts with Dry Friction

The problem of steady-state rolling contact between two cylinders with dry friction was formulated into standard linear complementarity problems (LCPs) using the explicit physical definition. For normal contacts, the complementarity variables are the normal pressure and the gap. For the tangential contact, the traction distribution and relative slip are the variables obtained by solving the LCP. The frictional behavior is assumed to be governed by the Coulomb friction law, and LCP formulations of both similar elastic (Carter problem) and dissimilar elastic rolling contacts are presented in this work. Good agreement was found between the current LCP approach and publicly available software for both the rolling contact of similar elastic and dissimilar elastic cylinders. Moreover, the surface roughness was taken into account in this article by the verified approach. The results show the initial slope of the traction-relative creepage curve decreases as the surface roughness increases.     

Linear Complementarity Framework for 3D Steady-State Rolling Contact Problems Including Creepages with Isotropic and Anisotropic Friction for Circular Hertzian Contact

In this article, the problem of 3D steady-state rolling contacts with dry friction for circular Hertzian contacts is formulated mathematically as a linear complementarity problem (LCP). The complementarity variables are the traction and the relative slip of contact regions, in which a polyhedral friction law is employed. The present work uses the general expressions describing the surface deformations due to uniform traction over a rectangular area on an elastic half-space to derive the influence coefficient matrix for rolling contact problems. Three possible creepage types—that is, longitudinal, lateral, and spin creepage—are considered in this work. Firstly, the numerical results are verified against the existing numerical solutions and good agreement has been found. Secondly, the anisotropic friction is studied by the verified approach. Some numerical examples are provided to illustrate the current LCP method for both isotropic and anisotropic friction in which the combined effects of the three kinds of creepage on the traction distribution are shown.