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Abstract: Nanocrystalline barium strontium titanate (Ba x Sr1− x Ti1.02O3) thin films with a barium content of x =0.8, 0.9 and 1 have been fabricated in a metal–insulator–metal configuration on glass-planarized alumina substrates. Cost-effective processing measures have been utilized by using poly-crystalline alumina substrates, wet-chemical processing of the dielectric, and by a small physical area of the ferroelectric capacitors (as low as 50µm2 for radio frequencies measurements). Glass-planarization on alumina ceramic substrates enables barium strontium titanate films with high quality and homogeneity. We mainly focus on fine-tuning the electrical performance in the low gigahertz range (<10GHz). Extensive micro-structural and electrical characterization has been performed. Micro-structural information is obtained by: Transmission Electron Microscopy, Scanning Electron Microscopy and X-ray diffraction. The dielectric response is investigated as a function of temperature, frequency and electric field for each sample. We measured a relatively constant permittivity for typical operating temperatures of applications. The quality factor Q is between 21 and 27 at 1GHz at zero DC bias and the tuning ratio η between 1.8 and 2.2 at |E|=0.4MV/cm. [Copyright &y& Elsevier]

Background and Purpose: Ligand-receptor binding kinetics is receiving increasing attention in the drug research community. The Motulsky and Mahan model, a one-state model, offers a method for measuring the binding kinetics of an unlabelled ligand, with the assumption that the labelled ligand has no preference while binding to distinct states or conformations of a drug target. As such, the one-state model is not applicable if the radioligand displays biphasic binding kinetics to the receptor., Experimental Approach: We extended the Motulsky and Mahan model to a two-state model, in which the kinetics of the unlabelled competitor binding to different receptor states (R 1 and R 2 ) can be measured. With this extended model, we determined the binding kinetics of unlabelled N-5'-ethylcarboxamidoadenosine (NECA), a representative agonist for the adenosine A 1 receptor. Subsequently, an application of the model was exemplified by measuring the binding kinetics of other A 1 receptor ligands. In addition, limitations of the model were investigated as well., Key Results: The kinetic rate constants of unlabelled NECA were comparable with the results of kinetic radioligand binding assays in which [ 3 H]-NECA was used. The model was further validated by good correlation between simulated results and the experimental data., Conclusion: The two-state model is sufficient to analyse the binding kinetics of an unlabelled ligand, when a radioligand shows biphasic association characteristics. We expect this two-state model to have general applicability for other targets as well., (© 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The duration of action of adenosine A 2A receptor (A2A) agonists is critical for their clinical efficacy, and we sought to better understand how this can be optimized. The in vitro temporal response profiles of a panel of A2A agonists were studied using cAMP assays in recombinantly (CHO) and endogenously (SH-SY5Y) expressing cells. Some agonists (e.g., 3cd; UK-432,097) but not others (e.g., 3ac; CGS-21680) demonstrated sustained wash-resistant agonism, where residual receptor activation continued after washout. The ability of an antagonist to reverse pre-established agonist responses was used as a surrogate read-out for agonist dissociation kinetics, and together with radioligand binding studies suggested a role for slow off-rate in driving sustained effects. One compound, 3ch, showed particularly marked sustained effects, with a reversal t 1/2 > 6 hours and close to maximal effects that remained for at least 5 hours after washing. Based on the structure-activity relationship of these compounds, we suggest that lipophilic N6 and bulky C2 substituents can promote stable and long-lived binding events leading to sustained agonist responses, although a high compound logD is not necessary. This provides new insight into the binding interactions of these ligands and we anticipate that this information could facilitate the rational design of novel long-acting A2A agonists with improved clinical efficacy., (Copyright © 2016 by The Author(s).)

Thin-film ferroelectric capacitors have been integrated with resistors and active functions such as ESD protection into small, miniaturized modules, which enable a board space saving of up to 80%. With the optimum materials and processes, integrated capacitors with capacitance densities of up to 100 nF/mm2 for stacked capacitors combined with breakdown voltages of 90 V have been achieved. The integration of these high-density capacitors with extremely high breakdown voltage is a major accomplishment in the world of passive components and has not yet been reported for any other passive integration technology. Furthermore, thin-film tunable capacitors based on barium strontium titanate with high tuning range and high quality factor at 1 GHz have been demonstrated. Finally, piezoelectric thin films for piezoelectric switches with high switching speed have been realized.