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.     

Proton-Detected Solid-State NMR of the Cell-Free Synthesized α-Helical Transmembrane Protein NS4B from Hepatitis C Virus

Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D ¹H-detected ¹H,¹⁵N and 3D ¹H,¹³C,¹⁵N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies.     

Influence of compaction on the interfacial transition zone and the permeability of concrete

The interfacial transition zone (ITZ) is regarded as a key feature for the transport properties and the durability of concrete. In this study one self-compacting concrete (SCC) mixture and two conventionally vibrated concrete (CVC) mixtures are studied in order to determine the influence of compaction on the porosity of the ITZ. Additionally oxygen permeability and water conductivity were measured in vertical and horizontal direction. The quantitative analysis of images made with an optical microscope and an environmental scanning electron microscope shows a significantly increased porosity and width of the ITZ in CVC compared to SCC. At the same time oxygen permeability and water conductivity of CVC are increased in comparison to SCC. Moreover, considerable differences in the porosity of the lower, lateral and upper ITZ are observed in both types of concrete. The anisotropic distribution of pores in the ITZ does not necessarily cause anisotropy in oxygen permeability and water conductivity though.     

Steady-state O<Subscript>2</Subscript> and CO<Subscript>2</Subscript> diffusion in carbonated mortars produced with blended cements

The diffusion coefficient \(D_{{{\text{O}}_{2} }}\), the porosity and the pore structure of mortars produced with a Portland cement and a range of blended cements containing limestone powder, microsilica, portlandite or slag were measured in the non-carbonated and the carbonated state. Additionally, the setup for measuring O₂ diffusion was adapted to measure also the CO₂ diffusion of the carbonated mortars. The diffusion coefficient \(D_{{{\text{O}}_{2} }}\) and the total porosity were increased in the mortars containing microsilica and slag, while they were decreased in the other mortars due to carbonation. Invariably, the pore structure became coarser in all samples. The relationship between diffusion coefficients \(D_{{{\text{O}}_{2} }}\) and \(D_{{{\text{CO}}_{2} }}\) in the carbonated mortars was always linear, with \(D_{{{\text{O}}_{2} }}\) systematically higher by factor of 1.37. As this factor broadly agrees with what was found in the scant literature about CO₂ diffusion, it could be used for estimating \(D_{{{\text{CO}}_{2} }}\) of carbonated mortar and concrete based on measurements of O₂ diffusion.     

Interactive Paper as a Mobile Client for a Multi-channel Web Information System

We describe how interactive paper can be used together with a multi-channel web information system to build a platform for experimenting with multi-modal context-aware mobile information services. As an application, we present a tourist guide for visitors to an international festival that was developed to investigate alternative modes of information delivery and interaction in mobile environments. The guide is based around a set of interactive paper documents—an event brochure, map and bookmark. The brochure and map are augmented with digital services by using a digital pen to activate links and a text-to-speech engine for information delivery. The digital pen is also used for data capture of event ratings and reviews. The bookmark provides access to advanced searches and ticket reservations. We describe the architecture and operation of the system, highlighting the challenges of extending a web information system to support both the generation of the paper documents and the interaction from these documents, alongside more traditional access channels. Finally, we discuss the range of context-aware interactions that is supported by our platform.     

Influence of cement type on ITZ porosity and chloride resistance of self-compacting concrete

With the increasing use of self-compacting concrete (SCC) its durability has come into focus. Concerning the microstructure of concrete, the porosity in the interfacial transition zone (ITZ) is regarded as a key feature for permeability and durability. Generally, a combination of cement and mineral admixtures is used for the production of SCC. In the present study, ITZ porosity of four SCC mixtures produced with ordinary Portland cement, Portland limestone cement, slag cement and ordinary Portland cement combined with fly ash is analyzed. Additionally, the chloride migration coefficient is determined. ITZ porosity and width of the SCC mixtures are similar. The substantial differences in the chloride migration coefficients show that the binder type has a stronger influence on permeability than the pore volume in the ITZ.     

Short communication: Genomic prediction using imputed whole-genome sequence variants in Brown Swiss Cattle

The accuracy of genomic prediction determines response to selection. It has been hypothesized that accuracy of genomic breeding values can be increased by a higher density of variants. We used imputed whole-genome sequence data and various single nucleotide polymorphism (SNP) selection criteria to estimate genomic breeding values in Brown Swiss cattle. The extreme scenarios were 50K SNP chip data and whole-genome sequence data with intermediate scenarios using linkage disequilibrium-pruned whole-genome sequence variants, only variants predicted to be missense, or the top 50K variants from genome-wide association studies. We estimated genomic breeding values for 3 traits (somatic cell score, nonreturn rate in heifers, and stature) and found differences in accuracy levels between traits. However, among different SNP sets, accuracy was very similar. In our analyses, sequence data led to a marginal increase in accuracy for 1 trait and was lower than 50K for the other traits. We concluded that the inclusion of imputed whole-genome sequence data does not lead to increased accuracy of genomic prediction with the methods.     

Swiss Industrial Biocatalysis Consortium (SIBC)

Taking up the common challenges in biocatalysis, a group of industrialists decided to react with a bottom-up solution, and created the Swiss Industrial Biocatalysis Consortium (SIBC). The Swiss Industrial Biocatalysis Consortium is a pre-competitive working group to better implement and utilize existing know-how and resources in biocatalysis, and to influence and shape the economic and educational political environment. Recent examples of activities are outlined.     

Modelling crosstalk through common semiconductor layers in AMOLED displays

High pixel density displays are demanded for active matrix organic light‐emitting diode displays (AMOLED) in applications such as virtual reality headsets, micro‐displays, and high‐end smartphones. Parasitic emission from non‐addressed neighboring pixels (crosstalk) is a common problem in such high pixel density AMOLED, and this crosstalk becomes more severe as the pixel density and fill ratio of the display increases. One of the causes of crosstalk is parasitic currents that travel through common organic semiconductor layers. In this paper, we model and quantify the pixel crosstalk using a 2 + 1D finite element model that is based on the conductivity of the common layer and the luminance–current–voltage curves of the subpixels as measured input parameters. We assess the effect of crosstalk on the pixel current, observed color, and luminance. The 2 + 1D model limits the number of degrees of freedom so that calculations on a standard personal computer are feasible.