Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations.Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized.Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h−1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL.Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia

Research on Frequency Adaptability of Permanent Magnet Synchronous Generator

In this paper, a study on frequency adaptability of permanent magnet synchronous generator (PMSG) is carried out, the influence mechanism of the frequency changes on PMSG is revealed. It is proposed that setting the converter protection setting value and PLL parameters reasonably can ensure that the grid frequency change has little effect on the PMSG. The simulation of frequency adaptability of PMSG is realized on Matlab/Simulink, and the simulation results verify the correctness of the conclusion

Small-Signal Stability Analysis for Power System Frequency Regulation with Renewable Energy Participation

With the improvement of the permeability of wind and photovoltaic (PV) energy, it has become one of the key problems to maintain the small-signal stability of the power system. Therefore, this paper analyzes the small-signal stability in a power system integrated with wind and solar energy. First, a mathematical model for small-signal stability analysis of power systems including the wind farm and PV station is established. And the characteristic roots of the New England power system integrated with wind energy and PV energy are obtained to study their small-signal stability. In addition, the validity of the theory is verified by the voltage drop of different nodes, which proves that power system integrated with wind-solar renewable energy participating in the frequency regulation can restore the system to the rated frequency in the shortest time and, at the same time, can enhance the robustness of each unit

Research on Frequency Adaptability of Photovoltaic Power Generation

In this paper, photovoltaic power generation(PV) and the asynchronously grid-connected power grid are taken as the research objects, and the frequency adaptability of PV to power grid is studied. The influence mechanism of grid frequency variation on PV is revealed, and it is proposed that the frequency tolerance range of PV is mainly determined by the setting value of inverter protection and PLL parameters. The whole process simulation of wind turbine adaptability under frequency change is realized on Matlab/Simulink, and the simulation results verify the correctness of the conclusion

Biobjective Optimization-Based Frequency Regulation of Power Grids with High-Participated Renewable Energy and Energy Storage Systems

Large-scale renewable energy sources connected to the grid bring new problems and challenges to the automatic generation control (AGC) of the power system. In order to improve the dynamic response performance of AGC, a biobjective of complementary control (BOCC) with high-participation of energy storage resources (ESRs) is established, with the minimization of total power deviation and the minimization of regulation mileage payment. To address this problem, the strength Pareto evolutionary algorithm is employed to quickly acquire a high-quality Pareto front for BOCC. Based on the entropy weight method (EWM), grey target decision-making theory is designed to choose a compromise dispatch scheme that takes both of the operating economy and power quality into account. At last, an extended two-area load frequency control (LFC) model with seven AGC units is taken to verify the effectiveness and the performance of the proposed method

Nonlinear Observer-Based Robust Passive Control of Doubly-Fed Induction Generators for Power System Stability Enhancement via Energy Reshaping

The large-scale penetration of wind power might lead to degradation of the power system stability due to its inherent feature of randomness. Hence, proper control designs which can effectively handle various uncertainties become very crucial. This paper designs a novel robust passive control (RPC) scheme of a doubly-fed induction generator (DFIG) for power system stability enhancement. The combinatorial effect of generator nonlinearities and parameter uncertainties, unmodelled dynamics, wind speed randomness, is aggregated into a perturbation, which is rapidly estimated by a nonlinear extended state observer (ESO) in real-time. Then, the perturbation estimate is fully compensated by a robust passive controller to realize a globally consistent control performance, in which the energy of the closed-loop system is carefully reshaped through output feedback passification, such that a considerable system damping can be injected to improve the transient responses of DFIG in various operation conditions of power systems. Six case studies are carried out while simulation results verify that RPC can rapidly stabilize the disturbed DFIG system much faster with less overshoot, as well as supress power oscillations more effectively compared to that of linear proportional-integral-derivative (PID) control and nonlinear feedback linearization control (FLC)

Boosted Surface‐Redox Pseudocapacitance in 2D Mesoporous TiN for High‐Power Sodium‐Ion Capacitors

Pseudocapacitive materials with surface‐redox reactions are capable of realizing high capacities at ultrahigh rates; however, it remains a challenge in the synthesis of active components with high surface area to boost surface‐redox sodiation but restrain side reactions. Herein, a two‐step, topochemical synthesis of 2D mesoporous TiN (2D‐meso‐TiN) with high surface area and rich mesoporosities is presented. It is demonstrated that the sodium‐ion storage mechanism of TiN anode is based on the existence of surficial titanium oxides via redox reactions between Ti4+ and Ti3+. The interconnected, highly conductive 2D‐meso‐TiN with high surface area largely increases the pseudocapacitive capacities, leading to a high capacity of 160/93 mAh g−1 at 0.1/10 A g−1, which is much higher than 2D‐TiN (120/72 mAh g−1) and commercial TiN nanoparticles (57/30 mAh g−1). The surface‐redox (de)sodiation undergoes no destruction of crystalline TiN, which enables high initial coulombic efficiency and long‐term cycles. Furthermore, a novel hybrid sodium‐ion capacitor consisting of 2D‐meso‐TiN anode and Na3V2(PO4)3 cathode is assembled without any presodiation treatments. The hybrid capacitor delivers both high energy density (94 Wh kg−1 at 64 W kg−1) and high power density (38 Wh kg−1 at 4.4 kW kg−1), as well as long cycling stability

Efficient CRISPR–Cas9 mediated multiplex genome editing in yeasts

Abstract Background The thermotolerant methylotrophic yeast Ogataea polymorpha has been regarded as an important organism for basic research and biotechnological applications. It is generally recognized as an efficient and safe cell factory in fermentative productions of chemicals, biofuels and other bio-products. However, it is difficult to genetically engineer for the deficiency of an efficient and versatile genome editing technology. Results In this study, we developed a CRISPR–Cas9-assisted multiplex genome editing (CMGE) approach including multiplex genes knock-outs, multi-locus (ML) and multi-copy (MC) integration methods in yeasts. Based on CMGE, various genome modifications, including gene deletion, integration, and precise point mutation, were performed in O. polymorpha. Using the CMGE-ML integration method, three genes TAL from Herpetosiphon aurantiacus, 4CL from Arabidopsis thaliana and STS from Vitis vinifera of resveratrol biosynthetic pathway were simultaneously integrated at three different loci, firstly achieving the biosynthesis of resveratrol in O. polymorpha. Using the CMGE-MC method, ∼ 10 copies of the fusion expression cassette P ScTEF1 -TAL-P ScTPI1 -4CL-P ScTEF2 -STS were integrated into the genome. Resveratrol production was increased ~ 20 fold compared to the one copy integrant and reached 97.23 ± 4.84 mg/L. Moreover, the biosynthesis of human serum albumin and cadaverine were achieved in O. polymorpha using CMGE-MC to integrate genes HSA and cadA, respectively. In addition, the CMGE-MC method was successfully developed in Saccharomyces cerevisiae. Conclusions An efficient and versatile multiplex genome editing method was developed in yeasts. The method would provide an efficient toolkit for genetic engineering and synthetic biology researches of O. polymorpha and other yeast species