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.     

Recycling of multilayer packaging using a reversible cross-linking adhesive

Plastic-based multilayer packaging has an important function on the packaging market, but is currently not recyclable as the polymer layers used are usually thermodynamically immiscible. This work therefore follows the approach to prepare separable multilayer packaging using a packaging adhesive modified with thermally unstable adducts, and proposes a corresponding recycling process. For this purpose, typical multilayer structures (polyethylene (PE)// polyethylene terephtalate (PET), PET//aluminum, and PE//aluminum) were prepared by curing furan-/maleimide-functionalized polyurethane (PU)-prepolymers with a three-functional cross-linking agent. Adhesions of up to over 3N per 15 mm test specimen were measured or substrate failures of PET films were observed. However, heating in dimethylsulfoxide, the retro-Diels–Alder reaction takes place and the cross-linked adhesive turns thermoplastic and dissolves in the solvent. Thus, the laminate separates and the pure PE, PET, and aluminum foils can be recovered without any PU residue.     

Lecture capture with real‐time rearrangement of visual elements: impact on student performance

The primary goal of this study is to create and test a lecture‐capture system that can rearrange visual elements while recording is still taking place, in such a way that student performance can be positively influenced. The system we have devised is capable of integrating and rearranging multimedia sources, including learning content, the instructor and students' images, into lecture videos that are embedded in a website for students to review after school. The present study employed a two‐group experimental design, with 153 participants (145 females and 8 males) making up an experimental group in which lecture courses were recorded using the new lecture‐capture system, and 149 participants (140 females and 9 males) forming a control group whose lectures were recorded by traditional means. All participants were in the freshman college and studying Introduction to Computer and Information Science in one of six classes, and were randomly assigned to one of the two groups. The participants' midterm examination and final examination scores were collected as indicators of their academic performance, with their mathematics entrance scores used as a pre‐test. The findings obtained from analysis of covariance (ANCOVA) suggest that appropriate rearrangement of visual elements in lecture videos can significantly impact students' learning performance.     

Masking the Peroxidase-Like Activity of the Molybdenum Disulfide Nanozyme Enables Label-Free Lipase Detection

Two-dimensional MoS₂ nanoparticles (2D-nps) exhibit artificial enzyme properties that can be regulated at bio-nanointerfaces. We discovered that protein lipase is able to tune the peroxidase-like activity of MoS₂ 2D-nps, offering low-nanomolar, label-free detection and identification in samples with unknown identity. The inhibition of the peroxidase-like activity of the MoS₂ 2D-nps was demonstrated to be concentration dependent, and as low as 5 nm lipase was detected with this approach. The results were compared with those obtained with several other proteins that did not display any significant interference with the nanozyme behavior of the MoS₂ 2D-nps. This unique response of lipase was characterized and exploited for the successful identification of lipase in six unknown samples by using qualitative visual inspection and a quantitative statistical analysis method. The developed methodology in this approach is noteworthy for many aspects; MoS₂ 2D-nps are neither labeled with a signaling moiety nor modified with any ligands for signal readout. Only the intrinsic nanozyme activity of the MoS₂ 2D-nps is exploited for this detection approach. No analytical equipment is necessary for the visual detection of lipase. The synthesis of the water-soluble MoS₂ 2D-nps is low costing and can be performed in bulk scale. Exploring the properties of 2D-nps and their interactions with biological materials reveals highly interesting yet instrumental features that offer the development of novel bioanalytical approaches.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Photovoltaic Power Supply Unit for the Basic Stations of Cellular Companies

The data on the use of solar photovoltaic plants (PVPs) for providing a reliable and guaranteed power supply to telecommunication systems and cellular communication systems in the conditions prevalent in Uzbekistan are given. The research-based structures developed by OOO MIR SOLAR and the selection of PVP elements ensuring their reliable operation are described. The main influencing factors are discussed, and the use of effective combinations of different types of panels (from monocrystalline and polycrystalline silicon) and a specially developed controller are considered.     

Modeling the Motion of a Saw Ginning Machine

The dynamic characteristics of a saw gin as a subsystem with lumped and distributed parameters are considered in the paper. On the basis of investigation of the machine assembly, graphs are drawn that allow establishing the maximum values of the angle of relative rotation and the angle of rotation of the saw cylinder shaft under torsion.     

Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

Carbon supported bimetallic Ru‐Co catalysts for H2 production through NaBH4 and NH3BH3 hydrolysis

This work investigates the effect of the addition of small amounts of Ru (0.5‐1 wt%) to carbon supported Co (10 wt%) catalysts towards both NaBH₄ and NH₃BH₃ hydrolysis for H₂ production. In the sodium borohydride hydrolysis, the activity of Ru‐Co/carbon catalysts was sensibly higher than the sum of the activities of corresponding monometallic samples, whereas for the ammonia borane hydrolysis, the positive effect of Ru‐Co systems with regard to catalytic activity was less evident. The performances of Ru‐Co bimetallic catalysts correlated with the occurrence of an interaction between Ru and Co species resulting in the formation of smaller ruthenium and cobalt oxide particles with a more homogeneous dispersion on the carbon support. It was proposed that Ru^°, formed during the reduction step of the Ru‐Co catalysts, favors the H₂ activation, thus enhancing the reduction degree of the cobalt precursor and the number of Co nucleation centers. A subsequent reduction of cobalt and ruthenium species also occurs in the hydride reaction medium, and therefore the state of the catalyst before the catalytic experiment determines the state of the active phase formed in situ. The different relative reactivity of the Ru and Co active species towards the two investigated reactions accounted for the different behavior towards NaBH₄ and NH₃BH₃ hydrolysis.