Iterative Antimicrobial Candidate Selection from Informed D‐/L‐Peptide Dimer Libraries

Growing resistance to antibiotics, as well as newly emerging pathogens, stimulate the investigation of antimicrobial peptides (AMPs) as therapeutic agents. Here, we report a new library design concept based on a stochastic distribution of natural AMP amino acid sequences onto half‐length synthetic peptides. For these compounds, a non‐natural motif of alternating D ‐ and L ‐backbone stereochemistry of the peptide chain predisposed for β‐helix formation was explored. Synthetic D ‐/L ‐peptides with permuted half‐length sequences were delineated from a full‐length starter sequence and covalently recombined to create two‐dimensional compound arrays for antibacterial screening. Using the natural AMP magainin as a seed sequence, we identified and iteratively optimized hit compounds showing high antimicrobial activity against Gram‐positive and Gram‐negative bacteria with low hemolytic activity. Cryo‐electron microscopy characterized the membrane‐associated mechanism of action of the new D ‐/L ‐peptide antibiotics.     

The TRAPS Apparatus: Enhancing Target Density of Nanoparticle Beams in Vacuum for X-ray and Optical Spectroscopy

We present an experimental setup that allows the injection of charged nanoparticles in a diameter range of 3–15 nm into a vacuum chamber and their storage there in an electrodynamic cage. The nanoparticle density in the trap is limited by space charge and can be several orders of magnitude higher than in a free nanoparticle beam. The setup provides for the first time a tool for the application of advanced techniques of spectroscopy to free nanoparticles in this size range. It consists of a combination of (1) a plasma discharge nanoparticle source that generates a high density of nanoparticles of various composition suspended in helium carrier gas at a pressure of about 10–150 mbar, (2) an aerodynamic lens optimized for small particles (diameter 3–15 nm) that forms a well-collimated beam of charged nanoparticles and focuses it into (3) an octopole ion trap operated at low frequencies and filled with helium buffer gas at 10^?2 mbar in order to moderate and store the nanoparticles at densities of more than 10⁷ cm^?3.     

High‐Temperature Creep Behavior of Dense SiOC‐Based Ceramic Nanocomposites: Microstructural and Phase Composition Effects

In this work, dense monolithic polymer‐derived ceramic nanocomposites (SiOC, SiZrOC, and SiHfOC) were synthesized via hot‐pressing techniques and were evaluated with respect to their compression creep behavior at temperatures beyond 1000°C. The creep rates, stress exponents as well as activation energies were determined. The high‐temperature creep in all materials has been shown to rely on viscous flow. In the quaternary materials (i.e., SiZrOC and SiHfOC), higher creep rates and activation energies were determined as compared to those of monolithic SiOC. The increase in the creep rates upon modification of SiOC with Zr/Hf relies on the significant decrease in the volume fraction of segregated carbon; whereas the increase of the activation energies corresponds to an increase of the size of the silica nanodomains upon Zr/Hf modification. Within this context, a model is proposed, which correlates the phase composition as well as network architecture of the investigated samples with their creep behavior and agrees well with the experimentally determined data.     

Field evaluation of a Portable Fine Particle Concentrator (PFPC) for ice nucleating particle measurements

The custom-built Portable Fine Particle Concentrator (PFPC) is evaluated for the measurement of ice nucleating particles (INPs) in the atmosphere. The concentrations of INPs in remote regions of the atmosphere are very low, often close to instrumental detection limits. The PFPC is a dual slit-nozzle virtual impactor where particles are concentrated from an input flow of 250 LPM (litres per minute) into an output flow of 10 LPM. The enrichment factors (EFs) for ambient particles with diameters between 0.4 and 2.5?µm were found to be 21?±?5 at sea level and 18?±?2 at a field station 3580 meters above sea level for the PFPC operated in horizontal configuration. Similar enhancement factors (16?±?5) in the concentrations of INPs measured by the Horizontal Ice Nucleation Chamber at the high-altitude station were observed when the air mass was characterized by high numbers of particles larger than 0.5?µm. When the number size distribution was dominated by particles smaller than 0.5?µm, the INP EF was considerably lower. Corroborating short-term measurements were provided by additional INP-measuring instruments, the Fast Ice Nucleus CHamber and the Frankfurt Ice Deposition Freezing Experiment. Results from two aerosol mass spectrometers also indicate significant particle enhancement using the PFPC. These results indicate that the PFPC can be usefully deployed to improve the detection efficiency of ambient INP measurements.

Copyright © 2019 American Association for Aerosol Research     

Artificial Antigen-Presenting Interfaces in the Service of Immunology

While the beneficial impact of modifying and/or targeting T lymphocytes is becoming increasingly accepted in the treatment of different diseases, the road towards cell-based immunotherapy is still long and winding. Major challenges that remain include, amongst others, the guidance and exquisite regulation of immune processes ex vivo. In part, this is due to the difficulties of simulating ex vivo the intimate cellular interactions that occur between T cells and antigen-presenting cells (APCs). The fate of T cells is not solely regulated by the presence of certain molecules on the surface of APCs but also by their density and spatial distribution on the micro- and nanometric scale. Moreover, mechanical properties of APCs and force-dependent conformational changes during the formation of an immunological synapse (IS; a highly organized supramolecular complex at the T cell APC interface), play a crucial role in T cell fate regulation. Various different technical means have been developed to create APC substitutes that are able to simulate ex vivo signals originating from naturally occurring APCs. Here, we review the performance of APC surrogates and discuss their contribution to understanding mechanisms underlying the ability of T cells to perform the “intelligent” mission of acquiring, processing and responding to environmental information.     

Development of a metallic/ceramic composite for the deposition of thin-film oxygen transport membrane

Asymmetric perovskite membranes have an attractive potential in the application of O₂/N₂ gas separation for future membrane-based power plants using oxyfuel technology. In this study – a metal-supported membrane structure with a thin-film perovskite layer and porous ceramic interlayers was developed. Porous NiCoCrAlY sintered at 1225 °C in H₂ was selected as the substrate based on a sufficient permeability and corrosion resistance in co-firing conditions. According to the oxidation behaviour of NiCoCrAlY, the temperature for co-firing of the substrate and the interlayers was defined as 1100 °C for 5 h in air. Two interlayers of La_0.58Sr_0.4Co_0.2Fe_0.8O_3?δ were applied by screen printing. The top layer was deposited by magnetron sputtering with a thickness of 3.8 μm. While gas-tightness was improved considerably, significant air-leakage was still detected. In summary, the successful development of a metal-perovskite-composite is shown, which acts as a basis for further development of a gas-tight metal-supported oxygen transport membrane structure.     

Strength degradation and failure limits of dense and porous ceramic membrane materials

Thin dense membrane layers, mechanically supported by porous substrates, are considered as the most efficient designs for oxygen supply units used in Oxy-fuel processes and membrane reactors. Based on the favorable permeation properties and chemical stability, several materials were suggested as promising membrane and substrate materials: Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3?δ, La_0.6?xSr_0.4Co_0.2Fe_0.8O_3?δ (x = 0, 0.02) and Ce_0.9Gd_0.1O_1.95?δ. Although membranes operate at elevated temperatures, the ends of tubes in certain three-end concepts remain almost at room temperature. The current work concentrates on the failure potential of these membrane parts, where in a complex device also the highest residual stresses should arise due to differences in thermal expansion. In particular, sensitivity of the materials to subcritical crack growth was assessed since the long-term reliability of the component does not only depend on its initial strength, but also on strength degradation effects. The results were subsequently used as a basis for a strength–probability–time lifetime prediction.     

Exchanging the substrate specificities of pyruvate decarboxylase from Zymomonas mobilis and benzoylformate decarboxylase from Pseudomonas putida

Pyruvate decarboxylase from Zymomonas mobilis (PDC) and benzoylformate decarboxylase from Pseudomonas putida (BFD) are thiamine diphosphate-dependent enzymes that decarboxylate 2-keto acids. Although they share a common homotetrameric structure they have relatively low sequence similarity and different substrate spectra. PDC prefers short aliphatic substrates whereas BFD favours aromatic 2-keto acids. These preferences are also reflected in their carboligation reactions. PDC catalyses the conversion of benzaldehyde and acetaldehyde to (R)-phenylacetylcarbinol and predominantly (S)-acetoin, whereas (R)-benzoin and mainly (S)-2-hydroxypropiophenone are the products of BFD catalysis. Comparison of the X-ray structures of both enzymes identified two residues in each that were likely to be involved in determining substrate specificity. Site-directed mutagenesis was used to interchange these residues in both BFD and PDC. The substrate range and kinetic parameters for the decarboxylation reaction were studied for each variant. The most successful variants, PDCI472A and BFDA460I, catalysed the decarboxylation of benzoylformate and pyruvate, respectively, although both variants now preferred the long-chain aliphatic substrates, 2-ketopentanoic and 2-ketohexanoic acid. With respect to the carboligase activity, PDCI472A proved to be a real chimera between PDC and BFD whereas BFDA460I/F464I provided the most interesting result with an almost complete reversal of the stereochemistry of its 2-hydroxypropiophenone product.     

Synthesis of Ultrahigh-Temperature Si–B–C–N Ceramic from Polymeric Waste Gas

A "green" route to ultrahigh-temperature Si–B–C–N ceramic from vacuum-degassing waste gas of polyborosilazane {B[C₂H₄Si(CH₃)NH]₃} _n (T2-1) has been developed. After gas-to-gel transformation, an amorphous ceramic Si_5.3B_1.0C₁₉N_3.7 was derived from the gel by dehydrocoupling and polymer-to-ceramic transformation. The ceramic started to form a nanostructure at 1700°C and resisted thermal degradation up to 2200°C in argon. This suggests that vacuum-degassing waste gases of polymer precursors may be perfect raw materials for various advanced ceramics.     

Filler Wetting in Miscible ESBR/SSBR Blends and Its Effect on Mechanical Properties

The selective wetting behavior of silica in emulsion styrene butadiene rubber (ESBR)/solution styrene butadiene rubber (SSBR) blends is characterized by the wetting concept, which is further developed for filled blends based on miscible rubbers. It is found that not only the chemical rubber–filler affinity but also the topology of the filler surface significantly influences the selective filler wetting in rubber blends. The nanopore structure of the silica surface has been recognized as the main reason for the difference in the wetting behavior of the branched ESBR molecules and linear SSBR molecules. However, the effect of nanopore structure becomes more significant in the presence of silane. It is discussed that the adsorption of silane on silica surface constricts the nanopore to some extent that hinders effectively the space filling of the nanopores by the branched ESBR molecules but not by the linear SSBR molecules. As a result, in silanized ESBR/SSBR blends the dominant wetting of silica surface by the tightly bonded layer of SSBR molecules causes a low‐energy dissipation in the rubber–filler interphase. That imparts the low rolling resistance to the blends similar to that of a silica‐filled SSBR compound, while the ESBR‐rich matrix warrants the good tensile behavior, i.e., good abrasion and wear resistance of the blends.