Novel measurement system for respiratory aerosols and droplets in indoor environments

The SARS-CoV-2 pandemic has created a great demand for a better understanding of the spread of viruses in indoor environments. A novel measurement system consisting of one portable aerosol-emitting mannequin (emitter) and a number of portable aerosol-absorbing mannequins (recipients) was developed that can measure the spread of aerosols and droplets that potentially contain infectious viruses. The emission of the virus from a human is simulated by using tracer particles solved in water. The recipients inhale the aerosols and droplets and quantify the level of solved tracer particles in their artificial lungs simultaneously over time. The mobile system can be arranged in a large variety of spreading scenarios in indoor environments and allows for quantification of the infection probability due to airborne virus spreading. This study shows the accuracy of the new measurement system and its ability to compare aerosol reduction measures such as regular ventilation or the use of a room air purifier.     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Role of Perceived Importance in Intergroup Contact.

Furthering G. W. Allport's (1954) contentions for optimal contact, the authors introduce a new construct: the perceived importance of contact. They propose that perceived importance is the best proximal predictor of contact's reduction of prejudice. If individuals have opportunities for contact at work or in the neighborhood, their chances to have intergroup acquaintances and friends increase. Intergroup contact among acquaintances and friends can be perceived as more or less important, which in turn determines intergroup evaluations. A 1st study shows that the new measure of perceived importance is indeed distinct from established quantity and quality indicators. The results are cross-validated in a 2nd study that also sheds light on the meaning of importance. In 3rd and 4th studies, structural equation analyses and a meta-analysis support the hypotheses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Screening mixtures for biological activity by NMR

Development of the new drugs often involves the screening of compound libraries for biological activity. Currently, the biologically active component can only be identified if either a pure compound is being tested or if the components of a mixture are spatially separated, for example, on beads. Here, we present an NMR technique based on the transferred nuclear Overhauser effect (transfer NOE) that allows identification and structural characterization of biologically active molecules from a mixture. As an example we demonstrate that from mixtures of oligosaccharides only alpha-L-Fuc-(1-->6)-beta-D-GlcNAc-OMe binds to Aleuria aurantia agglutinin. The sign of transferred NOEs is opposite to NOEs of small molecules that do not bind to the protein and, thus, an unequivocal identification of molecules with binding activity is possible. Normally, the selection of bound ligands is further facilitated in that the absolute intensity of transfer NOEs is much greater than that of NOEs of non-binding molecules. In addition, transfer NOEs provide information on the three-dimensional structure of the ligands in the bound state. Therefore, measuring transfer NOEs of mixtures of small molecules in the presence of large molecules, like proteins, should significantly enhance the options for screening mixtures of compounds for biological activity.     

Electromagnetic scattering by a straight thin wire

The traveling-wave energy, which multiply diffracts on a straight thin wire, is represented as a sum of terms, each with a distinct physical meaning, that can be individually examined in the time domain. Expressions for each scattering mechanism on a straight thin wire are cast in the form of four basic electromagnetic wave concepts: diffraction, attachment, launch, and reflection. Using the basic mechanisms from P.Ya. Ufimtsev (1962), each of the scattering mechanisms is included into the total scattered field for the straight thin wire. Scattering as a function of angle and frequency is then compared to the moment-method solution. These analytic expressions are then extended to a lossy wire with a simple approximate modification using the propagation velocity on the wire as derived from the Sommerfeld wave on a straight lossy wire. Both the perfectly conducting and lossy wire solutions are compared to moment-method results, and excellent agreement is found. As is common with asymptotic solutions, when the electrical length of wire is smaller than 0.2 λ the results lose accuracy. The expressions modified to approximate the scattering for the lossy thin wire yield excellent agreement even for lossy wires where the wire radius is on the order of skin depth     

Choice With Initial and Terminal Link Reinforcement: An Alternative Self-Control Paradigm.

Self-control is demonstrated when a less desirable immediate outcome is chosen to ensure a substantially better future. In a novel animal analogue of this situation, primary reinforcement was delivered in both the initial and terminal links of a concurrent chain schedule. Rats made initial link choices between equal amounts of ethanol-free or ethanol-containing milk. Choosing the ethanol-free reinforcer resulted in delivery of the larger terminal link reinforcer and was thus analogous to self-control. Self-control decreased as the delay between initial and terminal links increased. The results have implications for human choice situations where decisions are made between two immediately available reinforcement alternatives each associated with a different delayed outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)