Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Single Cell Bioprinting with Ultrashort Laser Pulses

Tissue engineering requires the precise positioning of mammalian cells and biomaterials on substrate surfaces or in preprocessed scaffolds. Although the development of 2D and 3D bioprinting technologies has made substantial progress in recent years, precise, cell-friendly, easy to use, and fast technologies for selecting and positioning mammalian cells with single cell precision are still in need. A new laser-based bioprinting approach is therefore presented, which allows the selection of individual cells from complex cell mixtures based on morphology or fluorescence and their transfer onto a 2D target substrate or a preprocessed 3D scaffold with single cell precision and high cell viability (93–99% cell survival, depending on cell type and substrate). In addition to precise cell positioning, this approach can also be used for the generation of 3D structures by transferring and depositing multiple hydrogel droplets. By further automating and combining this approach with other 3D printing technologies, such as two-photon stereolithography, it has a high potential of becoming a fast and versatile technology for the 2D and 3D bioprinting of mammalian cells with single cell resolution.     

Life time prediction of self-supporting flame-sprayed alumina-rich coatings

Main objective of the presented research is the life time prediction of self-supporting flame-sprayed Al₂O₃- and Al₂O₃ -ZrO₂ -TiO₂-materials under constant load. The characteristic life time and its scatter were derived from stable crack growth tests and Weibull-statistics including the four-point-bending and ball-on-three-balls method. The potential life time was estimated in order to assess room-temperature handling and long term storage of self-supporting flame-sprayed alumina components. In terms of flexural strength, energy release, and subcritical crack growth parameters, distinct differences between both materials were shown. In turn, the characteristic life times only barely deviated from each other. From that the conclusion was drawn that life time performance under constant load application is governed by the characteristic flame-spray microstructure. However, advantages in the flame-spray processing of Al₂O₃ - ZrO₂ -TiO₂ are still given, attributed to its lower melting temperature.     

Polar Lipids Reduce In Vitro Duodenal Lipolysis Rate of Oat Oil and Liquid Oat Base Products

Alternative ways for increased appetite control are today widely sought for due to the growing global health issues connected to obesity. In in vivo studies, oat has been proven an attractive candidate for inducing satiety. Oat is rich in polar lipids, of which the galactolipids are especially interesting, and a hypothesis is that these lipids play an important role for the ileal brake mechanism. In this study, the aim is to investigate the role of polar oat lipids on pancreatic lipolysis rate, using a pH-stat based in vitro digestion model of the duodenum. Lipolysis of oat oil, a mix of oat oil/rapeseed oil (RSO), as well as a liquid oat base (OB) simulating an oat drink with different polar lipid content are investigated, and compared with RSO as control. Increasing the polar lipid content of the product digested leads to a significantly decreased lipolysis rate, and this effect is even observed when mixing RSO with a low amount of oat oil (10%). The results support the hypothesis that polar lipids can delay lipolysis also in a complex, natural system like the liquid OB, and even a minor amount of oat lipids can have large effect on lipolysis rates. Practical applications: The number of studies connecting galactolipids with a decreasing effect on duodenal lipolysis is growing; however, the mechanism behind this phenomenon is still not clarified. Here, the same effect is seen in a complex, natural food system. These findings open up for interesting future food products, where inclusion of oat oil, even at low concentrations, can have a prolonging effect on satiety. Oat for human consumption is an increasing market, thanks to the positive health benefits oat has been connected to, in combination with the current trend toward climate-friendly plant-based options for meat and dairy products. It is believed that oat oil can be attractive as an ingredient in various food products, for example, protein bars and spreads. More studies are needed to confirm the results in vivo. However, a great potential is seen for the use of oat oil to enhance appetite control.     

Spurenstoffabtrennung mit keramischen Nanofiltrationsmembranen als Rotationsscheibenfilter

Reducing micropollutant pollution of water bodies is an important objective of water management and an integral part of environmental policy. Ceramic nanofiltration membranes were developed as multichannel membranes of increased membrane area and rotating disk filters. The membranes developed show retention of over 80 % for PEG 400. The membranes are currently being tested for the separation of micropollutants from wastewater contaminated with pharmaceuticals. With the help of a downstream oxidative process, the trace substances remaining in the permeate are degraded.     

Nucleation and crystallization of Ba2Si3O8 spherulites in a barium aluminum silicate glass,and mechanical properties of the obtained glass-ceramics

The effect of spherulitic crystallization on the elastic moduli and fracture toughness of a barium aluminum silicate glass was investigated. The crystallization process results in Ba₂Si₃O₈ phase and is initiated from Ba rich nuclei. Nucleation is optimal in the 690-720 °C interval. Young’s modulus is increased by 12.5% when the glass-ceramic conversion is nearly complete. Nevertheless, as the size and the volume fraction of crystals are increased, some microcracking shows up upon cooling from the crystallization temperature. An optimal improvement of the fracture toughness (SEPB method) by 27 % is observed for a 49 % volume fraction of 5 to 10 μm large spherulites.     

Influence of microwave heating and time on functional,pasting and thermal properties of cassava starch

The effect microwaving power and time on the functional, pasting and thermal properties of cassava starch was investigated. Cassava starch at a moisture content of 30% was microwaved at 600 and 700 W for 0, 5, 15, 30 and 60 s following a preliminary study. Microwaving power and time did not alter the crystalline pattern of the starch, but there were obvious changes in the starch morphology. Starch colour was significantly (P ≤ 0.05) altered by microwave heating, with the total colour difference increasing from 4.85 to 43.01. Microwave treatment increased starch gelatinisation temperatures but decreased the swelling power, water absorption capacity and the relative crystallinity. These changes were influenced by microwave heating power and time. The results further revealed that the peak viscosity (3714.00–1947.00 cP) and setback ratio (1.70–1.49) decreased with increasing microwave heating time. However, breakdown viscosity (322.67–897.63 cP) and pasting temperature (1947.00–3714.00 °C) increased.     

Vanadium promoted Ni(Mg,Al)O hydrotalcite-derived catalysts for CO2 methanation

A series of V-promoted hydrotalcite-derived nickel catalysts (1.0, 2.0, and 4.0 wt%) were tested in CO₂ methanation. Ni–I–V2.0 with 2.0 wt% vanadium loading showed the highest catalytic activity, achieving 74.7% of CO₂ conversion and 100% of CH₄ selectivity at 300 °C. XRD and XANES analyses showed that the smallest Ni⁰ particles in Ni–I–V2.0 were consistent with the improved textural features observed for this catalyst. Moreover, CO₂-TPD revealed the highest sum of weak and medium basic sites in Ni–I–V2.0 that can positively influence catalytic behavior. For the studied catalysts, a clear correlation was demonstrated between the catalytic activity and specific surface area, as well as the basic properties.