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.     

Digital self-control interventions for distracting media multitasking - A systematic review

Digital distractions can interfere with goal attainment and lead to undesirable habits that are hard to get red rid of. Various digital self-control interventions promise support to alleviate the negative impact of digital distractions. These interventions use different approaches, such as the blocking of apps and websites, goal setting, or visualizations of device usage statistics. While many apps and browser extensions make use of these features, little is known about their effectiveness. This systematic review synthesizes the current research to provide insights into the effectiveness of the different kinds of interventions. From a search of the ‘ACM’, ‘Springer Link’, ‘Web of Science’, ’IEEE Xplore’ and ‘Pubmed’ databases, we identified 28 digital self-control interventions. We categorized these interventions according to their features and their outcomes. The interventions showed varying degrees of effectiveness, and especially interventions that relied purely on increasing the participants' awareness were barely effective. For those interventions that sanctioned the use of distractions, the current literature indicates that the sanctions have to be sufficiently difficult to overcome, as they will otherwise be quickly dismissed. The overall confidence in the results is low, with small sample sizes, short study duration, and unclear study contexts. From these insights, we highlight research gaps and close with suggestions for future research.     

Evaluation of the effect of processing on cocoa polyphenols: antiradical activity,anthocyanins and procyanidins profiling from raw beans to chocolate

The content and composition of anthocyanins and procyanidins in fermented cocoa beans (from different geographic origins: Ecuador, Cameroon, Ivory Coast, Ghana and Nigeria), roasted nibs, cocoa mass and chocolate were determined, beside the determination of the total antiradical capacity. Concerning geographic origin, cocoa beans and processed products from Ecuador showed the highest levels of anthocyanins, followed by Nigeria and Cameroon. Generally, as cocoa beans were further processed, the levels of anthocyanins and flavan‐3‐ols decreased. The largest observed losses of phenolics occurred during roasting. A progressive decreasing trend in polyphenol concentration was observed in the other processed samples as well. Despite the original content of polyphenols in raw cocoa beans, technological processes imply a significant impact on cocoa quality, confirming the need of specific optimisation to obtain high value chocolate.     

The Spatial LASSO With Applications to Unmixing Hyperspectral Biomedical Images

Hyperspectral imaging (HSI) is a spectroscopic method that uses densely sampled measurements along the electromagnetic spectrum to identify the unique molecular composition of an object. Traditionally HSI has been associated with remote sensing-type applications, but recently has found increased use in biomedicine, from investigations at the cellular to the tissue level. One of the main challenges in the analysis of HSI is estimating the proportions, also called abundance fractions of each of the molecular signatures. While there is great promise for HSI in the area of biomedicine, large variability in the measurements and artifacts related to the instrumentation has slow adoption into more widespread practice. In this article, we propose a novel regularization and variable selection method called the spatial LASSO (SPLASSO). The SPLASSO incorporates spatial information via a graph Laplacian-based penalty to help improve the model estimation process for multivariate response data. We show the strong performance of this approach on a benchmark HSI dataset with considerable improvement in predictive accuracy over the standard LASSO. Supplementary materials for this article are available online.     

Real-Time Duplex Applications of Loop-Mediated AMPlification (LAMP) by Assimilating Probes

Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other functionality based on the LAMP reaction has been intense. Here, we report on the development of duplexed LAMP assays for pathogen detection using spectrally unique Assimilating Probes. As proof of principle, we used a reaction for Salmonella enterica as a model coupled with a reaction for λ-phage DNA as an internal control, as well as a duplexed assay to sub-type specific quarantine strains of the bacterial wilt pathogen Ralstonia solanacearum. Detection limits for bacterial DNA analyzed in individual reactions was less than 100 genomic equivalents in all cases, and increased by one to two orders of magnitude when reactions were coupled in duplexed formats. Even so, due to the more robust activity of newly available strand-displacing polymerases, the duplexed assays reported here were more powerful than analogous individual reactions reported only a few years ago, and represent a significant advance for incorporation of internal controls to validate assay results in the field.     

Application of chitosan–alginate microspheres for the sustained release of bacteriophage in simulated gastrointestinal conditions

This study was designed to evaluate the acid stability, release property and antimicrobial efficacy of Escherichia coli O157:H7 bacteriophages encapsulated in chitosan–alginate microspheres under the simulated gastrointestinal conditions. The bacteriophages belonging to Myoviridae family were stable at the pH above 4 in trypticase soy broth. The chitosan–alginate microspheres exhibited protective effect on the viability of bacteriophages in the simulated gastric conditions at pH 2.0 and pH 2.5, showing 4.8 and 5.6 log PFU mL^‐1, respectively, after 1 h of incubation at 37 °C. The release per cent of bacteriophages from microspheres gradually increased up to 65% in the simulated intestinal condition (pH 7.5) at 37 °C for 6 h. The lytic efficacy of chitosan‐ and alginate‐encapsulated bacteriophages against E. coli O157:H7 was significantly maintained in the simulated intestinal conditions to 10 h of incubation (1.3 log reduction). The results suggest that the chitosan–alginate microspheres can be used as a reliable delivery system for bacteriophages.