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Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), the transcription template for all viral mRNAs, is highly stable and current treatment options cannot effectively induce its clearance. Previously, we established an HBV persistence mouse model based on a clinical isolate (termed BPS) and identified interleukin‐21 (IL‐21) as a potent inducer of HBV clearance. Lipid nanoparticle (LNP) mediated delivery of mRNA has proven to be a highly safe and effective delivery platform. This work explored the applicability and effectiveness of the mRNA‐LNP platform in IL‐21‐based HBV therapies. First, LNP‐encapsulated murine IL‐21 mRNA (LNP‐IL‐21) was prepared, characterized, and demonstrated to engender IL‐21 expression in vitro and in vivo. Next, LNP‐IL‐21 was shown to induce clearance of both serum and intrahepatic HBV antigen and DNA in two HBV persistence mouse models based on BPS and recombinant cccDNA (rcccDNA), respectively, which was associated with HBV‐specific humoral and cellular immune responses. Furthermore, peripheral blood mononuclear cells from BPS persistence mice treated ex vivo with LNP‐IL‐21 and HBV surface antigen (HBsAg) could induce similar HBV clearance upon infusion into recipient mice. These findings indicated that IL‐21 combined with mRNA‐LNP platform represents a valid and promising strategy for developing novel therapeutics against chronic HBV infection. [ABSTRACT FROM AUTHOR]

To ensure reasonable reactive power distribution and voltage standard, a large number of STATCOMs are integrated to wind farms and afflux stations. However, the issue of device tripping caused by the interaction between STATCOMs is emerging. This paper sets out to bring a clear understanding of the fault mechanism of single STATCOM tripping caused by the harmonic circulation between STATCOMs in a clustered wind‐farm afflux station in North‐China grid. The equivalent circuit of harmonic circulation between two paralleled STATCOMs based on cascaded H‐bridge topology is established first. Thereafter, the intrinsic relationship between high‐order harmonic circulation and inter‐converter harmonic voltage difference as well as the phase deviation of SPWM carriers are analysed. A generalized model is also built to estimate the higher‐order harmonics. The impact of non‐characteristic harmonics on DC voltage of each H‐bridge cell is investigated by calculating the difference of active power flowing through DC capacitors. It is pointed out that the harmonic circulation is one of the main reasons resulting in the DC overvoltage protection action of STATCOM. Finally, the correctness of theoretical analysis is verified by real‐time simulation and hardware experiments. [ABSTRACT FROM AUTHOR]

The interaction between the voltage source converter (VSC) and weak grid causes a negatively damped or diverging oscillation (DVO). The diverging oscillation generally evolves into a sustained oscillation (STO) when governed by the nonlinearities in the VSC's control system, such as the saturation of pulse width modulation (PWM). The conventional small‐signal impedance/admittance modelling (SSIM/SSAM) and stability analysis methods are not suitable for the characteristic analysis of STO. This paper presents a large‐signal impedance/admittance model (LSIM/LSAM)‐based quantitative analysis method to better understand the mechanism, characteristics, and occurrence conditions of STO. The LSAM extends the SSAM by incorporating the nonlinearity of PWM saturation using the describing function method. First, a unique time‐varying characteristic of the oscillation associated with nonlinearity is investigated. Then, two LSIM/LSAM‐based occurrence criteria for STO are established based on an equivalent RLC circuit model of the system. Three critical pieces of information, including the occurrence condition, frequency, and magnitude, associated with STO are revealed by the criteria. Finally, the LSAM‐based analysis method is applied to investigate the time‐varying admittance of the VSC and to assess the magnitude and frequency of STO. Both the criteria and LSAM‐based analysis results have been verified through time‐domain simulations on a typical grid‐connected VSC. [ABSTRACT FROM AUTHOR]

Recurrent hepatitis activity during chronic hepatitis B virus infection results in fibrosis and even hepatocellular carcinoma. It is still unclear what causes acute exacerbation. As platelets have recently been identified as a significant role in inflammation, we here investigated the role of platelets in mediating liver damage in patients with chronic hepatitis B virus infection. Platelet aggregation testing and flow cytometry were carried out to evaluate platelet activation status in 121 patients chronically infected with hepatitis B across different phases of the condition. The correlation between platelet aggregation rate and liver inflammation or liver fibrosis index was evaluated. To investigate the genesis of platelet activation, several serum cytokines were also assessed by MILLIPLEX microsphere‐based multiplex cytokine assay. Active hepatitis patients showed a higher aggregation rate than others. Levels of CD62p, a marker of platelet activation, were also increased in this group of patients. Positive correlations between platelet aggregation rate and liver inflammation or liver fibrosis were also noted, indicating a significant role of platelet in the progression of liver disease. The level of tumor necrosis factor‐alpha, which is known to trigger platelet activation, was markedly higher in the active hepatitis group (P <.005). Based on the findings in our study, platelet activation plays a vital role in the progression of chronic hepatitis B virus infection. Antiplatelet therapy may provide a new means of hepatitis B infection treatment. [ABSTRACT FROM AUTHOR]

The mainstream researches focus on the linearised impedance/admittance model and its related coupling effects or stability problems. However, since various non‐linear components exist in control loops, their non‐linear dynamics shall be described to improve the modelling accuracy. To fill in this gap, this study develops a large‐signal impedance/admittance model (LSIM/LSAM) to describe the dominant non‐linearity of modulation saturation in a grid‐connected voltage‐source converter (VSC). The LSAM represents the non‐linearity with the equivalent saturation gains based on the describing function theory and then incorporates the derived gains into conventional small‐signal AM (SSAM) to obtain a partially non‐linear admittance. The proposed LSAM distinguishes itself from SSAM by reflecting the improvement in the magnitude‐ and phase‐response of admittance during non‐linear oscillations. Case studies on a grid‐connected VSC containing saturation non‐linearity are conducted to validate the model's effectiveness in stability analysis. It is found that the frequency deviation and sustained oscillation caused by non‐linearity, which can hardly be assessed using SSAM, can be well captured by LSAM. The results of parameter analysis verify that the modulation saturation dominates the system non‐linearity. [ABSTRACT FROM AUTHOR]

A parallel static var generator (SVG) system based on cascaded H‐bridge topology in wind afflux station is analysed in this study to reveal the mechanism of harmonic current and DC voltage instability due to the phase difference between the PWM carriers. First, the inherent relation of harmonic current and low‐frequency disturbance is revealed by carrier‐phase‐shift pulse‐width‐modulation (CPS‐PWM) theory. Second, to identify the negative impact of low‐frequency disturbance, a small‐signal circuit model is built to research the electric coupling relation between SVGs and the grid, then pointing out the main factors which affect the harmonic circulation among the two‐paralleled SVGs. Third, the output impedance and the transfer function of SVG give an insight into the interaction between SVG and low‐frequency resonance characteristics, based on which a virtual resistance method is proposed to shape the resonant peak. Finally, theoretical analysis and system experiment prove that the proposed control strategy can rapidly attenuate low‐frequency resonant peaks of the system, avoiding the DC voltage instability in the SVG system when harmonic circulation occurs. [ABSTRACT FROM AUTHOR]

Under certain conditions, grid‐connected voltage source converter (VSC) may result in electromagnetic oscillations. Many coupling components with different frequencies could be observed in converter outputs when oscillation happens. The characteristics and mechanism of frequency coupling phenomenon in oscillations of VSC are studied. The magnitude relationship between first‐order components in the three‐phase domain is drawn by impedance model. The two first‐order components will result in higher‐order components due to the non‐linearity of VSC controller. There are mainly three coupling paths in a controller: phase‐locked loop, DC voltage fluctuation and overmodulation. The coupling mechanism and frequency distribution characteristics are investigated in this study. Theoretical results are validated by simulations with PSCAD/EMTDC. [ABSTRACT FROM AUTHOR]

Short‐term voltage stability (STVS) issue poses a significant threat to receiving‐end power systems with high penetration of induction motors. To improve STVS of a receiving‐end system in a limited geographic area, this study proposes a local‐area STVS control system (LVCS). LVCS consists of phasor measurement units (PMUs), a local‐area centralised controller (LCC), generator‐level actuators (GLAs) and high‐speed communication networks. The PMUs or GLAs are pre‐deployed according to the observability or controllability of STVS. LCC receives and processes voltage measurements from PMUs to generate supplementary excitation control signals (SECSs). The SECSs are next forwarded to and executed by GLAs. Simulation studies on a practical receiving‐end system in China Southern Power Grid demonstrate that: once the target system suffers a serious fault, LVCS can 'feel' the voltage sag at critical buses and enforce the excitation control of generators to inject more dynamic var into the receiving‐end system. As a result, the increasing var demand is met locally and STVS can be improved considerably. Time delay caused by synchrophasor transmission has also been considered in the design of LVCS to make it feasible in practice. Thus, the proposed LVCS offers a new and effective solution to the STVS problem. [ABSTRACT FROM AUTHOR]

Numerical oscillation is a fatal problem caused by the trapezoidal (TR) algorithm in nodal analysis‐based electromagnetic transient (EMT) programmes. Traditional techniques of suppressing numerical oscillation involve switching among different algorithms or adding damping elements, which would undermine the flexibility and accuracy of the overall algorithm. In this study, a new algorithm based on rational‐fraction approximations to exponential functions is proposed to address the issue. Furthermore, it is combined with TR algorithm to form a hybrid method (HM) for EMT simulation. Analytical as well as numerical analyses have been conducted to compare the HM with other popular methods in terms of stability, accuracy and efficiency. The results from either theoretical analysis or case studies on an RLC circuit and a practical power system have concluded that the proposed HM gains advantages over classical methods in suppressing numerical oscillation without sacrificing accuracy and efficiency. [ABSTRACT FROM AUTHOR]

Practical subsynchronous instability events have been observed in doubly fed induction generator‐based wind farms, which are radially connected to fixed series compensated transmission lines. As a special type of subsynchronous resonance, this phenomenon is described here as subsynchronous control interaction (SSCI). This study proposes a centralised SSCI mitigation scheme named as subsynchronous damper (SSD). In this scheme, an additional high‐power electronic voltage‐sourced converter is added to the collection bus of wind farms. It is designed to dissipate the electrical resonance power of SSCI. Thus, SSD provides positive damping for SSCI. Its basic principle is explained with equivalent electric circuit and the sufficient conditions for stabilisation are obtained mathematically. Controller design guidelines are given and have been verified first by eigenvalue analysis. Then a method to choose the capacity of power electronic converter is proposed. The effectiveness of SSD is finally demonstrated by extensive time‐domain simulations on a target system. [ABSTRACT FROM AUTHOR]