The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated that ZEL-H16 behaved as a partial agonist on the inhibition of forskolin-stimulated cAMP accumulation (the efficacy was 60% of that of histamine) and activation of ERK1/2 signaling (the efficacy was 50% of that of histamine) at H3 receptors, but acted as a full agonist just like histamin in the guinea-pig ileum contraction assay. These effects were blocked by pertussis toxin and H3 receptor specific antagonist thioperamide. ZEL-H16 showed no agonist or antagonist activities at the cloned human histamine H1, H2, and H4 receptors and other biogenic amine GPCRs in the CRE-driven reporter assay. Furthermore, our present data demonstrated that treatment of ZEL-H16 resulted in intensive H3 receptor internalization and delayed recycling to the cell surface as compared to that of control with treatment of histamine. Thus, ZEL-H16 is a novel and potent nonimidazole agonist of H3R, which might serve as a pharmacological tool for future investigations or as possible therapeutic agent of H3R.
Transient excitation boosting control (TEBC) is a cost-effective emergency control technique to improve the power system transient stability. However, it is found in this study that the conventional TEBCs have some drawbacks and may be ineffective or even worsen the system stability in some cases. To overcome these problems, a novel widearea measurement system (WAMS)-based TEBC (WTEBC) is proposed in this study. The proposed control law is as follows: boosting the excitation of the critical machines (CMs) in the critical swing and stopping their excitation boosting as the rotor angles of the CMs drop below a threshold after the critical swing. The implementations of the above control law in the special protection system are also provided. The simulation results from the 4-machine system and the China Southern power grid prove the superiority of the WTEBC over the conventional TEBCs. Furthermore, it also indicates that the stabilising effect is quite significant as long as the round-trip WAMS delay is <0.3 s, which further confirms the feasibility of the WTEBC in the practical engineering.
Stability is the fundamental demand to the system. Considering the stability and dynamic response of the system, we suggest an approach to select PI values. The ranges of PI parameters are attained based on the Bode plot criteria taking account of the systems' stability. Synthetic performance indexes to measure system's dynamic response are adopted, and the proper PI parameters corresponding to the minimal ITAE (Integral of Time multiplied by the Absolute value of the Error) performance index are searched and selected. The test of Cigre HVDC Benchmark model shows the validity of the proposed approach.
The histamine H3 receptor (H3R) has been recognized as a promising target for the treatment of various central and peripheral nervous system diseases. In this study, a non-imidazole compound, ZEL-H16, was identified as a novel histamine H3 receptor agonist. ZEL-H16 was found to bind to human H3R with a Ki value of approximately 2.07 nM and 4.36 nM to rat H3R. Further characterization indicated that ZEL-H16 behaved as a partial agonist on the inhibition of forskolin-stimulated cAMP accumulation (the efficacy was 60% of that of histamine) and activation of ERK1/2 signaling (the efficacy was 50% of that of histamine) at H3 receptors, but acted as a full agonist just like histamin in the guinea-pig ileum contraction assay. These effects were blocked by pertussis toxin and H3 receptor specific antagonist thioperamide. ZEL-H16 showed no agonist or antagonist activities at the cloned human histamine H1, H2, and H4 receptors and other biogenic amine GPCRs in the CRE-driven reporter assay. Furthermore, our present data demonstrated that treatment of ZEL-H16 resulted in intensive H3 receptor internalization and delayed recycling to the cell surface as compared to that of control with treatment of histamine. Thus, ZEL-H16 is a novel and potent nonimidazole agonist of H3R, which might serve as a pharmacological tool for future investigations or as possible therapeutic agent of H3R.
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