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111.
Dr. Remya Rajan Dr. Dirk Schepmann Ruben Steigerwald Dr. Julian A. Schreiber Dr. Ehab El-Awaad Prof. Joachim Jose Prof. Guiscard Seebohm Prof. Bernhard Wünsch 《ChemMedChem》2021,16(20):3201-3209
Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site. 相似文献
112.
Thermal and Electrical Conductivity of Amorphous and Graphitized Carbide‐Derived Carbon Monoliths
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Andreas M. Kern Bodo Zierath Joachim Haertlé Tobias Fey Bastian J. M. Etzold 《化学工程与技术》2016,39(6):1121-1129
The influence of graphitization and composition of carbide‐derived carbon (CDC) monoliths on the electrical and thermal conductivity was investigated. Carbon monoliths with varying porosities were synthesized employing biomorphous macroporous TiC and SiC as precursors. Graphitization was carried out in situ during high‐temperature chlorination with and without addition of nickel, iron, and cobalt chloride to the carbide. The graphitized monoliths showed improved properties. The results demonstrate that despite graphitic carbon also glass‐like carbon, stemming from the carbide synthesis, increases the thermal and electrical conductivity significantly. 相似文献
113.
In lightweight walls and floors, the load‐bearing timber members are protected by cladding on the sides to form a divider between two fire compartments or to provide appropriate fire protection to the load‐bearing members. The spaces between the timber members can be void or filled with insulation materials. Although a huge number of different insulation materials exist, the most commonly used material is mineral wool insulation. The existing design model for glass wool‐insulated timber‐frame constructions, given in European standard 1995‐1‐2, assumes collapse of the glass wool after failure of the cladding. However, a new form of glass wool insulation, suitable for use at high maximum service temperatures, is now available in the market. The charring phase after the cladding's failure is known as the post‐protection phase. The behaviour of the new heat‐resistant glass wool in the post‐protection phase is similar to that of stone wool and considerably better than that of traditional glass wool. The protective properties of stone wool have changed over the last decades. Charring is one of the main parameters needed to calculate the resistance of a structure to fire. Based on experimental investigations, this paper describes the analysis of the effect of the insulation with regard to its ability to protect timber members against charring during the post‐protection phase. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
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Hadas Schwartz-Chassidim Joachim Meyer Yisrael Parmet Efrat Rogatka Ohad Amzaleg 《Applied ergonomics》2014
Maps should be designed so that users can comprehend and use the information. Display decisions, such as choosing the scale at which an area is shown, depend on properties of the displayed information such as the perceived density (PD) of the information. Taking a psychophysical approach we suggest that the PD of information in a road map is related to the scale and properties of the mapped area. 54 participants rated the PD of 60 maps from different regions. We provide a simple model that predicts the PD of electronic road map displays, using the logarithm of the number of roads, the logarithm of the number of junctions and the length of the shown roads. The PD model was cross-validated using a different set of 60 maps (n = 44). The model can be used for automatically adjusting display scales and for evaluating map designs, considering the required PD to perform a map-related task. 相似文献
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Emil Meng-Lund Jette Jacobsen Morten B. Andersen Mads L. Jespersen Jens-Jacob Karlsson Mats Garmer 《Drug development and industrial pharmacy》2014,40(5):604-610
The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55?±?5 and 35?±?5?min) were significantly different to the buccal anaesthetised groups (120?±?0 and 165?±?15?min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7?±?4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets. 相似文献
119.
In this contribution the problem of maximizing the efficiency of a hybrid power unit at a specified output power level by optimizing the generator current trajectory as well as the design variables that can be chosen during the machine design process is investigated. The concept is demonstrated based on a hybrid single-cylinder diesel engine that is coupled to an electric generator. By developing a model of the system and using open-loop optimal control the optimal operating strategy and the optimal machine design are determined. Besides that, the problems occurring in the application of this strategy to a test rig are discussed. For this purpose, a model-free real-time optimization concept based on extremum seeking control is presented. The effectiveness of both the model-based and the model-free concept are demonstrated by simulation and experimental results. 相似文献
120.
Benjamin Papendorf Emanuel Ionescu Hans‐Joachim Kleebe Christoph Linck Olivier Guillon Katharina Nonnenmacher Ralf Riedel 《Journal of the American Ceramic Society》2013,96(1):272-280
In this work, dense monolithic polymer‐derived ceramic nanocomposites (SiOC, SiZrOC, and SiHfOC) were synthesized via hot‐pressing techniques and were evaluated with respect to their compression creep behavior at temperatures beyond 1000°C. The creep rates, stress exponents as well as activation energies were determined. The high‐temperature creep in all materials has been shown to rely on viscous flow. In the quaternary materials (i.e., SiZrOC and SiHfOC), higher creep rates and activation energies were determined as compared to those of monolithic SiOC. The increase in the creep rates upon modification of SiOC with Zr/Hf relies on the significant decrease in the volume fraction of segregated carbon; whereas the increase of the activation energies corresponds to an increase of the size of the silica nanodomains upon Zr/Hf modification. Within this context, a model is proposed, which correlates the phase composition as well as network architecture of the investigated samples with their creep behavior and agrees well with the experimentally determined data. 相似文献