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.     

A 223- $$\mu W$$ μ W single-to-differential RF mixer with 8.6dBm IIP3 using current-bleeding and body-effect for sub-6 GHz 5G applications

Analog Integrated Circuits and Signal Processing - As the 5G era beckons in the world of communication and information technology, there is a surge in demand for battery-operated, mobile wireless...     

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Evaluating the Possibility of Using Ionic Liquids in the Synthesis and Separation of Cyclohexanone

Theoretical Foundations of Chemical Engineering - Using gas–liquid chromatography, the activity coefficients upon the infinite dilution of the components of the reaction mixture for obtaining...     

Characterization of the structure and properties of processed alumina-graphene and alumina-zirconia composites

The onset of hybrid alumina-based composites, which combines two or more nano-particles within the alumina matrix has already shown promising improvements in the matrix material. However, variations in mechanical properties including the optimum compositions that give improved properties faced with the development of alumina-based composites require further studies to understand the underlying mechanisms and synergistic effects of the nano-particle additions on the alumina matrix. In the current study, the structure and properties of Al?O?-graphene (0.5 wt%) and Al?O?–ZrO? (4 wt% and 10 wt%) composites fabricated via hot-pressing was studied as a baseline for multiple combinations. Even though the addition of 10 wt%ZrO? resulted in a 23% reduction in the grain size of the alumina matrix, the 4 wt%ZrO? addition resulted in a 14% increase in grain size as compared to the parent alumina matrix. X-ray diffraction analysis revealed that there was approximately 85% monoclinic (m-ZrO₂) vs. 15% tetragonal (t-ZrO₂) crystal structures in the A4ZrO? sample whilst the A₁₀ZrO? had approximately 93% m-ZrO₂ vs. 7% t-ZrO₂. The high-volume fraction of the monoclinic crystal structures in the A₁₀ZrO? accounts for the induced microcracks in the sample since the transition from the ductile-tetragonal to brittle-monoclinic is associated with the exertion of compressive stresses on the alumina matrix by the associated elastic volume expansion of m-ZrO₂. Also, the addition of 0.5 wt%graphene resulted in about 37% reduction in the grain size of the alumina matrix, and approximately 10% increase in hardness as a result of the distribution of graphene along the grain boundaries of the parent alumina matrix, which restricts grain coalescence and growth during processing. Furthermore, an increase up to 115% and 164% were observed in the fracture toughness (K_IC) with the inclusion of 0.5 wt%graphene and 10 wt%ZrO? respectively, which was primarily ascribed to the fine-grained microstructures and toughening mechanisms of the intergranular graphene and ZrO? particles.     

Interfacial microstructure and mechanical properties of Ti3SiC2 ceramic and TC11 alloy joint diffusion bonded with a Cu interlayer

Reliable joints of Ti₃SiC₂ ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti₂Cu + TiCu/Ti₅Si₄ + TiSiCu/Cu(s, s)/Ti₃SiC₂. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti₃SiC₂/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti₅Si₄ and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti₃SiC₂ substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti₃SiC₂ ceramic.     

Reusable and Efficient Polystyrene Immobilized Ionic Liquid Catalyst for Batch and Flow Methylation of Hydroquinone

Catalysis Letters - An environmentally benign process for synthesizing 4-methoxyphenol through methylation of hydroquinone using polystyrene immobilized Bronsted acidic ionic liquid is presented....     

Description of the thermodynamic properties and fluid-phase behavior of aqueous solutions of linear,branched, and cyclic amines

The SAFT-γ Mie group-contribution equation of state is used to represent the fluid-phase behavior of aqueous solutions of a variety of linear, branched, and cyclic amines. New group interactions are developed in order to model the mixtures of interest, including the like and unlike interactions between alkyl primary, secondary, and tertiary amine groups (NH₂, NH, N), cyclic secondary and tertiary amine groups (cNH, cN), and cyclic methine-amine groups (cCHNH, cCHN) with water (H₂O). The group-interaction parameters are estimated from appropriate experimental thermodynamic data for pure amines and selected mixtures. By taking advantage of the group-contribution nature of the method, one can describe the fluid-phase behavior of mixtures of molecules comprising those groups over broad ranges of temperature, pressure, and composition. A number of aqueous solutions of amines are studied including linear, branched aliphatic, and cyclic amines. Liquid–liquid equilibria (LLE) bounded by lower critical solution temperatures (LCSTs) have been reported experimentally and are reproduced here with the SAFT-γ Mie approach. The main feature of the approach is the ability not only to represent accurately the experimental data employed in the parameter estimation, but also to predict the vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria, and LCSTs with the same set of parameters. Pure compound and binary phase diagrams of diverse types of amines and their aqueous solutions are assessed in order to demonstrate the main features of the thermodynamic and fluid-phase behavior.     

Alumina-Periclase-Carbon Refractories Produced by OOO Ogneupor

Refractories and Industrial Ceramics - Technology for producing alumina-periclase-carbon refractories of the brands APUK-D and APU-D is developed and implemented. Use of complex antioxidant and...     

A novel ceramic matrix composite based on YNbO4–TiO2 for microwave applications

This work presents the dielectric properties of YNbO₄ (YNO)–TiO₂ composites in the microwave range. X-ray diffraction analysis demonstrates that the addition of TiO₂ to YNO results in the formation of a Y(Nb_0.5Ti_0.5)₂O₆ phase. In the microwave range, the values of permittivity and dielectric loss did not present major changes with the increment of TiO₂. Moreover, the addition of TiO₂ results in an improvement in the thermal stability of YNO, with YNO63 demonstrating a resonant frequency of ?8.96 ppm.°C^?1. We utilised numerical simulations to evaluate the behaviour of these materials as dielectric resonator antennae and it is found that they exhibit a reflection coefficient below ?10 dB at the resonant frequency, with a realised gain of 4.94 – 5.76 dBi, a bandwidth of 665–1050 MHz and a radiation efficiency above 84%. Our results indicate that YNO–TiO₂ composites are interesting candidates for microwave operating devices.