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31.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
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. 相似文献
32.
Claudia Paredes Francisco J. Martínez-Vázquez Hamada Elsayed Paolo Colombo Antonia Pajares Pedro Miranda 《Journal of the European Ceramic Society》2021,41(1):892-900
Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds. 相似文献
33.
Gladson S. Chrisben Prasad P. Siva Manickam Bhaskar 《Analog Integrated Circuits and Signal Processing》2021,109(3):571-583
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... 相似文献
34.
Dr. Thomas Le Bihan Dr. Cathryn H. S. Driver Dr. Thomas Ebenhan Dr. Nathalie Le Bris Dr. Jan Rijn Zeevaart Prof. Dr. Raphaël Tripier 《ChemMedChem》2021,16(5):809-821
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. 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-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal 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-2Mal. 相似文献
35.
Chenhui Ding Marion Breunig Jana Timm Roland Marschall Jürgen Senker Seema Agarwal 《Advanced functional materials》2021,31(49):2106507
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. 相似文献
36.
Zhuchkov V. I. Nazansky S. L. Frolkova A. K. Ganina K. D. 《Theoretical Foundations of Chemical Engineering》2021,55(4):786-791
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... 相似文献
37.
During the service life of structural sealant glazing (SSG) facades, the load-bearing capacity of the silicone bonds needs to be guaranteed. Laboratory tests can assess the durability of SSG-systems based on mechanical characteristics of the bond after simultaneous exposure to both climatic and mechanical loads. This article studies how the material characteristics of two common structural sealants are affected by laboratory and field exposure. Dynamic mechanical analysis (DMA) confirms a reduction in the dynamic modulus of exposed silicone samples. Results from thermogravimetric analysis, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and small-angle X-ray scattering/wide-angle X-ray scattering show differences between the two sealants and indicate no/minor changes in the composition and morphology of the laboratory and field exposed sealants. Mechanical characterization methods, such as DMA, and tensile and shear testing of the structural bond, are shown to be sensitive toward the combined climatic and mechanical loadings, and are hence suitable for studying degradation mechanisms of structural sealants. 相似文献
38.
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. 相似文献
39.
Catalysis Letters - An environmentally benign process for synthesizing 4-methoxyphenol through methylation of hydroquinone using polystyrene immobilized Bronsted acidic ionic liquid is presented.... 相似文献
40.
Bokyung Kim Young Ho Ko Massimiliano Runfola Simona Rapposelli Gabriella Ortore Grazia Chiellini Jin Hae Kim 《International journal of molecular sciences》2021,22(7)
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases. 相似文献