Zur Berechnung von Brettlagenholz mit starrem und nachgiebigem Verbund unter plattenartiger Belastung mit besonderer Berücksichtigung des Rollschubes und der Drillweichheit

Lischke führt grundlegende Überlegungen zum Trag- und Verformungsverhalten von Brettlagenholz durch und gewinnt dadurch Erkenntnisse über Brettlagenholz, die bis heute die Grundlage für viele ingenieurmäßige Betrachtungen von Brettlagenholz sind. Aufbauend auf den Erkenntnissen von Lischke gelingt es Bosl für Brettlagenholz mit starrem Verbund unter überwiegender scheibenartiger Beanspruchung einen Zusammenhang zwischen den Erkenntnissen von Lischke und der Mehrschichtentheorie herzustellen. In der vorliegenden Arbeit wird das Trag- und Verformungsverhalten von Brettlagenholz mit starrem und nachgiebigem Verbund unter plattenartiger Belastung mit besonderer Berücksichtigung des Rollschubes und der Drillweichheit untersucht. Es werden ingenieurmäßige Näherungslösungen zur Berechnung vorgestellt bzw. erarbeitet. Die Untersuchung umfasst bislang nicht veröffentlichte Überlegungen zum Rollschubmodul des Holzes, zum Rollschubmodul der Brettlage, zum nichtlinearen Schubkraft-Verschiebungsdiagramm für stiftförmige, nachgiebige Verbindungsmittel in Brettlagenholz. Zu den Überlegungen werden experimentelle Untersuchungen entworfen, durchgeführt und ausgewertet. Die ingenieurmäßigen Näherungslösungen zur Berechnung sind das Berechnungsmodell für Brettlagenholz mit starrem Verbund aufbauend auf die Theorie des Mehrschichtenverbundes mit Schubdeformation "MSV", das Berechnungsmodell für Brettlagenholz mit nachgiebigem Verbund unter Verwendung von Schalen- und Federelementen "Feder" und das Berechnungsmodell für Brettlagenholz mit starrem Verbund unter Verwendung von Schalen- und Federelementen "Kneidl" aufbauend auf Kneidl

SPH Simulation of an Air-Assisted Atomizer Operating at High Pressure : Influence of Non-Newtonian Effects

A twin-fluid atomizer configuration is predicted by means of the 2D weakly-compressible Smooth Particle Hydrodynamics (SPH) method and compared to experiments. The setup consists of an axial liquid jet fragmented by a co-flowing high-speed air stream (Ug ~ 60 m/s) in a pressurized atmosphere up to 11 bar (abs.). Two types of liquid are investigated: a viscous Newtonian liquid (µ = 200 mPa.s) obtained with a glycerol/water mixture and a viscous non-Newtonian liquid (µ ~ 150 mPa.s) obtained with a carboxymethyl cellulose (CMC) solution. 3D effects are taken into account in the 2D code by introducing (i) a surface tension term, (ii) a cylindrical viscosity operator and (iii) a modified velocity accounting for the divergence of the volume in the radial direction. The numerical results at high pressure show a good qualitative agreement with experiment, i.e. a correct transition of the atomization regimes with regard to the pressure, and similar dynamics and length scales of the generated ligaments. The predicted frequency of the Kelvin-Helmholtz instability needs a correction factor of 2 to be globally well recovered with the Newtonian liquid. The simulation of the non-Newtonian liquid at high pressure shows a similar breakup regime with finer droplets compared to Newtonian liquids while the simulation at atmospheric pressure shows an apparent viscosity similar to the experiment

The evolving small-molecule fluorescent-conjugate toolbox for Class A GPCRs

The past decade has witnessed fluorescently tagged drug molecules gaining significant attraction in their use as pharmacological tools with which to visualize and interrogate receptor targets at the single-cell level. Additionally, one can generate detailed pharmacological information, such as affinity measurements, down to almost single-molecule detection limits. The now accepted utilization of fluorescence-based readouts in high-throughput/high-content screening provides further evidence that fluorescent molecules offer a safer and more adaptable substitute to radioligands in molecular pharmacology and drug discovery. One such drug-target family that has received considerable attention are the GPCRs; this review therefore summarizes the most recent developments in the area of fluorescent ligand design for this important drug target. We assess recently reported fluorescent conjugates by adopting a receptor-family-based approach, highlighting some of the strengths and weaknesses of the individual molecules and their subsequent use. This review adds further strength to the arguments that fluorescent ligand design and synthesis requires careful planning and execution; providing examples illustrating that selection of the correct fluorescent dye, linker length/composition and geographic attachment point to the drug scaffold can all influence the ultimate selectivity and potency of the final conjugate when compared with its unlabelled precursor. When optimized appropriately, the resultant fluorescent conjugates have been successfully employed in an array of assay formats, including flow cytometry, fluorescence microscopy, FRET and scanning confocal microscopy. It is clear that fluorescently labelled GPCR ligands remain a developing and dynamic research arena

Fluorescence Nanoscopy in Whole Cells by Asynchronous Localization of Photoswitching Emitters

We demonstrate nanoscale resolution in far-field fluorescence microscopy using reversible photoswitching and localization of individual fluorophores at comparatively fast recording speeds and from the interior of intact cells. These advancements have become possible by asynchronously recording the photon bursts of individual molecular switching cycles. We present images from the microtubular network of an intact mammalian cell with a resolution of 40 nm

Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice

SARS-CoV-2 continues to circulate in the human population necessitating regular booster immunization for its long-term control. Ideally, vaccines should ideally not only protect against symptomatic disease, but also prevent transmission via asymptomatic shedding and cover existing and future variants of the virus. This may ultimately only be possible through induction of potent and long-lasting immune responses in the nasopharyngeal tract, the initial entry site of SARS-CoV-2. To this end, we have designed a vaccine based on recombinantly expressed receptor binding domain (RBD) of SARS-CoV-2, fused to the C-terminus of C. perfringens enterotoxin, which is known to target Claudin-4, a matrix molecule highly expressed on mucosal microfold (M) cells of the nasal and bronchial-associated lymphoid tissues. To further enhance immune responses, the vaccine was adjuvanted with a novel toll-like receptor 3/RIG-I agonist (Riboxxim™), consisting of synthetic short double stranded RNA. Intranasal prime-boost immunization of mice induced robust mucosal and systemic anti-SARS-CoV-2 neutralizing antibody responses against SARS-CoV-2 strains Wuhan-Hu-1, and several variants (B.1.351/beta, B.1.1.7/alpha, B.1.617.2/delta), as well as systemic T-cell responses. A combination vaccine with M-cell targeted recombinant HA1 from an H1N1 G4 influenza strain also induced mucosal and systemic antibodies against influenza. Taken together, the data show that development of an intranasal SARS-CoV-2 vaccine based on recombinant RBD adjuvanted with a TLR3 agonist is feasible, also as a combination vaccine against influenza