Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Flexible,Mechanically Stable,Porous Self-Standing Microfiber Network Membranes of Covalent Organic Frameworks: Preparation Method and Characterization

Covalent organic frameworks (COFs) show advantageous characteristics, such as an ordered pore structure and a large surface area for gas storage and separation, energy storage, catalysis, and molecular separation. However, COFs usually exist as difficult-to-process powders, and preparing continuous, robust, flexible, foldable, and rollable COF membranes is still a challenge. Herein, such COF membranes with fiber morphology for the first time prepared via a newly introduced template-assisted framework process are reported. This method uses electrospun porous polymer membranes as a sacrificial large dimension template for making self-standing COF membranes. The porous COF fiber membranes, besides having high crystallinity, also show a large surface area (1153 m² g⁻¹), good mechanical stability, excellent thermal stability, and flexibility. This study opens up the possibility of preparation of large dimension COF membranes and their derivatives in a simple way and hence shows promise in technical applications in separation, catalysis, and energy in the future.     

Trypsiligase-Catalyzed Labeling of Proteins on Living Cells

Fluorescent fusion proteins are powerful tools for studying biological processes in living cells, but universal application is limited due to the voluminous size of those tags, which might have an impact on the folding, localization or even the biological function of the target protein. The designed biocatalyst trypsiligase enables site-directed linkage of small-sized fluorescence dyes on the N terminus of integral target proteins located in the outer membrane of living cells through a stable native peptide bond. The function of the approach was tested by using the examples of covalent derivatization of the transmembrane proteins CD147 as well as the EGF receptor, both presented on human HeLa cells. Specific trypsiligase recognition of the site of linkage was mediated by the dipeptide sequence Arg-His added to the proteins’ native N termini, pointing outside the cell membrane. The labeling procedure takes only about 5 minutes, as demonstrated for couplings of the fluorescence dye tetramethyl rhodamine and the affinity label biotin as well.     

Phase locked loop-based clock synthesizer for reconfigurable analog-to-digital converters

Analog Integrated Circuits and Signal Processing - This paper presents the complete design of a phase locked loop-based clock synthesizer for reconfigurable analog-to-digital converters. The...     

A Survey on Advanced Multiple Access Techniques for 5G and Beyond Wireless Communications

Wireless Personal Communications - This paper summarizes the ongoing research initiatives based on the advanced multiple access techniques towards the fifth generation (5G) wireless communication...     

Hydraulic reactivity and cement formation of baghdadite

In this study, the hydraulic reactivity and cement formation of baghdadite (Ca₃ZrSi₂O₉) was investigated. The material was synthesized by sintering a mixture of CaCO₃, SiO₂, and ZrO₂ and then mechanically activated using a planetary mill. This leads to a decrease in particle and crystallite size and a partial amorphization of baghdadite as shown by X-ray powder diffraction (XRD) and laser diffraction measurements. Baghdadite cements were formed by the addition of water at a powder to liquid ratio of 2.0 g/ml. Maximum compressive strengths were found to be ~2 MPa after 3-day setting for a 24-h ground material. Inductively coupled plasma mass spectrometry (ICP-MS) measurements showed an incongruent dissolution profile of set cements with a preferred dissolution of calcium and only marginal release of zirconium ions. Cement formation occurs under alkaline conditions, whereas the unground raw powder leads to a pH of 11.9 during setting, while prolonged grinding increased pH values to approximately 12.3.     

Modeling of the Magnetization and Magnetocaloric Effect in Ni2MnGa Heusler Alloy with the Effective Field Theory

Journal of Low Temperature Physics - This study modeled and investigated the magnetocaloric effect in Ni2MnGa Heusler alloy characterized by its magnetic entropy change (ΔSm) and its...     

Personalized web service recommendation through mishmash technique and deep learning model

Multimedia Tools and Applications - Discovering the relevant web services for specific applications in the dynamically changing business world becomes very critical. Researchers have used many...     

Phase formation,structure and properties of light-weight aluminosilicate proppants based on clay-diabase and clay-granite binary mixes

One of the drawbacks of fusible clays is the narrow sintering interval due to a sharp increase in the amount of iron-silicate melt at a temperature of 1000–1100 °C, which hardens in the form of a glass phase upon cooling. This leads to a relatively low mechanical strength of the calcined samples and causes the danger of melting the granular material surface from such clays during the firing process. To increase the strength of samples of fusible clays, the influence of diabase and granitoid rocks was considered. It was found that the strengthening effect of diabase and granitoid rock additives in an amount of 20–50% in a mixture with fusible clay is due to an increase of total content of the crystalline phase (mullite, cristobalite and residual quartz) from 18–20% in clays without additives to 22–28 % - in mixtures with diabase and to 28–34% - with granitoid additives) at a temperature of 1050–1100 °C. This increase is due to the activation of synthesis processes of secondary mullite and crystallization from alkali-rich feldspar melt of amorphous silica, released from the structure of clay minerals. The established influence of the igneous rocks used made it possible to develop compositions and propose process flow sheet for producing aluminosilicate proppants based on fusible clays. The use of granitoid and diabase rocks in an amount of 20–70% with fusible clays produces lightweight aluminosilicate proppants with bulk density of 1.40–1.46 g/cm³ at temperature range of 1050–1100 °C, which can endure destructive pressures up to 34.5–52 MPa.