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After the underground coal gasification is completed, a hyperbolic shaped coal pillar is formed between the two cavities to support the overlying rock and ensure the safety and stability of the gasification area. The work aimed to study the bearing mechanical characteristics of hyperbolic shaped coal pillar. Based on the acoustic emission (AE) monitoring system and the XTDIC 3D full-field strain measure system, 6 sets of “hyperbolic” coal samples with different lateral arch heights (h=0, 3 mm, 7 mm, 10 mm, 13 mm, 17 mm) were tested for uniaxial compression. The influence of h on peak load, deformation damage, and AE characteristics of coal samples were analyzed to reveal the bearing failure mechanism. The results are as follows. ① The “hyperbolic” coal sample can be divided into rectangular structure (main load-bearing body) and lateral arch structure, and its load-bearing failure mechanism is related to the force form and lateral arch structure. As h increases, the bearing capacity of the coal sample decreases. Compared with h=0 mm coal samples, the peak load was reduced by 7.66, 13.56, 26.83, 35.28, and 62.75%. ② The overall force form of coal samples changed from pressure-based to pressure-bending with increased h. Stress concentration occurs in the middle region of the coal sample, forming a weak area. The corresponding horizontal displacement field migrates towards the middle and finally at the edge of the middle. The vertical displacement field changed from a horizontal strip to an inclined strip, and ultimately concentrated at the upper end of the lateral arch structure of the coal sample. ③ Under axial load, the lateral arch structure of the coal sample exerts an equivalent force on the middle area of its rectangular structure, and is affected by the heterogeneity of the coal sample, which exacerbates the damage degree of the weak area in the middle. The effect increases with the increase of h, the coal sample undergoes shear failure when the load does not exceed its tensile strength. The failure mode of the coal samples shifted from tensile-shear mixed failure to shear failure, and all typical coal samples have experienced varying degrees of peeling and local ejection failure. ④ The evolution of the cumulative count-time curve of coal AE can be divided into three types. When h is 0 mm and 3 mm, it can be divided into four stages: “upward convex” growth, relatively rapid growth, rapid growth, and “sudden” growth, and its evolutionary characteristics are consistent with conventional rock samples. When h is 7 mm and 10 mm, it can be divided into three stages: relatively rapid growth, rapid growth, and “sudden” growth. When h is 13 mm and 17 mm, it can be divided into two stages: rapid growth and “sudden” growth. The post-peak stage shows a “sudden” growth pattern, while the inconsistent growth pattern in the pre-peak stage is caused by the stable expansion of coal sample cracks and continuous damage in the central region.

Background and objectives: Perineural invasion (PNI) refers to the invasion, encasement, or penetration of tumor cells around or through nerves. Various malignant tumors, including pancreatic cancer, head and neck tumors, and bile duct cancer, exhibit the characteristic of PNI. Particularly, in head and neck-skull base tumors such as adenoid cystic carcinoma (ACC), PNI is a significant factor leading to incomplete surgical resection and postoperative recurrence. Methods: Spatial transcriptomic and single-cell transcriptomic sequencing were conducted on a case of ACC tissue with PNI to identify potential probes targeting PNI. The efficacy of the probes was validated through in vivo and in vitro experiments. Results: Spatial transcriptomic and single-cell RNA sequencing revealed phenotypic changes in Schwann cells within the PNI region of ACC. Peptide probes were designed based on the antigen-presenting characteristics of Schwann cells in the PNI region, which are dependent on Major Histocompatibility Complex II (MHC-II) molecules. Successful validation in vitro and in vivo experiments confirmed that these probes can label viable Schwann cells in the PNI region, serving as a tool for dynamic in vivo marking of tumor invasion into nerves. Conclusions: Peptide probes targeting Schwann cells' MHC-II molecules have the potential to demonstrate the occurrence of PNI in patients with ACC

Abstract This paper proposes three‐phase steady‐state models for distributed generators (DGs) with different negative control strategies. An augmented rectangular load flow method is used for three‐phase distribution systems. For two types of DGs with power electronic devices: photovoltaic power generators and doubly fed induction generators, the nodal voltage equations and output power equations are derived. Moreover, under unbalanced conditions, the strategies for mitigating the effects caused by negative sequence components are formulated as functions of the nodal voltage and the injected current. Furthermore, the models are incorporated into an augmented rectangular load flow method with nodal voltage and injected current as state variables in three‐phase systems. Case studies are conducted to verify the correctness and accuracy of the proposed models by comparing the results obtained from MATLAB and PSCAD.

This paper proposes a coordinated frequency regulation strategy for grid-forming (GFM) type-4 wind turbine (WT) and energy storage system (ESS) controlled by DC voltage synchronous control (DVSC), where the ESS consists of a battery array, enabling the power balance of WT and ESS hybrid system in both grid-connected (GC) and stand-alone (SA) modes. The newly developed GFM framework, i.e., DVSC, is adopted in both WT and ESS, which utilizes DC voltage dynamics for synchronization purposes. In this paper, the GC mode and SA mode are transferred by changing the status of the series-connected switch, and it is necessary to meet the grid connection conditions when the system is transferred to the GC mode, namely, voltage, frequency, and phase sequence. For the GC mode, the inertia response from WT can be realized using the reserved energy of the DC capacitor, while the ESS serves to eliminate the steady-state frequency deviation and reduce the DC voltage fluctuation of WT using the designed secondary frequency regulation scheme. For the SA mode, the proposed strategy can keep the power balance without external power sources. The small-signal model of the WT and ESS hybrid system is derived. The stability analysis in both GC and SA modes is fully conducted utilizing the modal analysis method, where the impacts of control parameters on stability are assessed. The performance of the proposed strategy in a weak system is evaluated. Simulation studies are carried out under various power system contingencies to verify the effectiveness of the proposed strategy and validate the correctness of the theoretical analysis.

Abstract Converter interfaced generation (CIG) may switch into different control modes under different fault scenarios, which poses a significant challenge to the fault calculation of modern power systems. This paper first establishes a reduced fault analysis model of CIG considering control mode switching. By neglecting the fast dynamic processes of the converter controller, CIG with each control mode can be expressed by equality and inequality constraints. Then, an alternative iteration algorithm is proposed to determine the control mode of each grid‐tied converter after fault, which mainly contains the estimation and discrimination steps. In the estimation step, the voltage of the point of common coupling (PCC) and output current of CIG are obtained by simultaneously solving the equality constraints of CIG and the reduced network equation. In the discrimination step, the inequality constraints of CIG are utilized to judge and revise the control mode of each converter. With alternative execution of the estimation and discrimination steps, the fault network can be solved. Simulation studies based on PSCAD/EMTP validate that the proposed method has high accuracy in fault calculation of the CIG embedded system under various fault locations and fault resistances.

Abstract This paper expands the damping torque coefficient analysis (DTCA) for studying the small‐signal stability of permanent magnet synchronous generator (PMSG)‐based wind turbine (WT) under virtual synchronous generator (VSG) control with consideration of WT dynamics. Firstly, the typical VSG is implemented in the grid‐side voltage source converter (GSVSC), which enables selfsynchronization without phase‐locked loop (PLL). The maximum power point track (MPPT) algorithms are utilized to give the power reference for VSG. Then, the corresponding inertia and damping support can be provided by the kinetic energy of PMSG. Based on the established model, the DTCA is analytically conducted to not only reveal the key factors that influence the WT stability but also provide guidance for parameter tuning. As a result, it is important to find that the WT dynamics impair the damping and even lead to system instability. Moreover, the minimum value of VSG damping control parameter is analytically given to ensure the system stability under any load below the rated wind speed. Finally, the case studies considering one single PMSG connected to a large grid with and without inclusion of WT dynamics are performed and compared to demonstrate the accuracy of the proposed model and evaluate the applications of DTCA.

Abstract Background Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea. Methods 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea. Results In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway. Conclusions SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.

Background: Spatial transcriptome (ST) provides molecular profiles of tumor cells at the spatial level, which brings new progress to the research of tumors and the tumor microenvironment. This study summarizes the experiences and lessons learned in the spatial section preparation of two different pathological types of nose and skull base tumors at our institution, with the aim of offering guidelines to researchers to avoid wasting precious samples and provide a basis for the application of ST in clinical practice. Methods: Frozen tissue blocks from patients with squamous cell carcinoma and adenocarcinoma of the nose and skull base diagnosed at our institution were prepared. The effects of different procedures and pathological tissue types on slide quality were explored and evaluated using RNA integrity number (RIN) and HE scores as criteria. The effects of different RIN values on ST sequencing data were explored. Results: A total of 43 samples were obtained from 26 patients, including 22 with squamous carcinomas and 21 with adenocarcinomas. Thirteen samples with satisfactory RNA quality control and good histological morphology were sequenced for ST. Sample isolation time 7 in ST sequencing results was found, indicating that RIN ≥6 can be used as a criterion for qualified RNA quality control. Therefore, fresh tissues washed as soon as possible with cold PBS and then dried using OCT for snap freezing are currently the best method for preparing spatial sections of nose and skull base tumor tissues of different pathological types. Conclusion: This study is the first to investigate the feasibility of applying ST to different pathological types of nose and skull base tumors and to demonstrate the widespread application of ST in tumors. Rational optimization of spatial slide preparation procedures and exploration of individualized pre-sequencing protocols are used as the first stage to ensure the quality of spatial sequencing and lay the foundation for subsequent spatial analysis.

Abstract Background The ETS transcription factor GABPA has long been thought of as an oncogenic factor and recently suggested as a target for cancer therapy due to its critical effect on telomerase activation, but the role of GABPA in clear cell renal cell carcinoma (ccRCC) is unclear. In addition, ccRCC is characterized by metabolic reprograming with aberrant accumulation of L-2-hydroxyglurate (L-2HG), an oncometabolite that has been shown to promote ccRCC development and progression by inducing DNA methylation, however, its downstream effectors remain poorly defined. Methods siRNAs and expression vectors were used to manipulate the expression of GABPA and other factors and to determine cellular/molecular and phenotypic alterations. RNA sequencing and ChIP assays were performed to identify GABPA target genes. A human ccRCC xenograft model in mice was used to evaluate the effect of GABPA overexpression on in vivo tumorigenesis and metastasis. ccRCC cells were incubated with L-2-HG to analyze GABPA expression and methylation. We carried out immunohistochemistry on patient specimens and TCGA dataset analyses to assess the effect of GABPA on ccRCC survival. Results GABPA depletion, although inhibiting telomerase expression, robustly enhanced proliferation, invasion and stemness of ccRCC cells, whereas GABPA overexpression exhibited opposite effects, strongly inhibiting in vivo metastasis and carcinogenesis. TGFBR2 was identified as the GABPA target gene through which GABPA governed the TGFβ signaling to dictate ccRCC phenotypes. GABPA and TGFBR2 phenocopies each other in ccRCC cells. Higher GABPA or TGFBR2 expression predicted longer survival in patients with ccRCC. Incubation of ccRCC cells with L-2-HG mimics GABPA-knockdown-mediated phenotypic alterations. L-2-HG silenced the expression of GABPA in ccRCC cells by increasing its methylation. Conclusions GABPA acts as a tumor suppressor by stimulating TGFBR2 expression and TGFβ signaling, while L-2-HG epigenetically inhibits GABPA expression, disrupting the GABPA-TGFβ loop to drive ccRCC aggressiveness. These results exemplify how oncometabolites erase tumor suppressive function for cancer development/progression. Restoring GABPA expression using DNA methylation inhibitors or other approaches, rather than targeting it, may be a novel strategy for ccRCC therapy.

Human activities modulate the impact of environmental forcing in general and of climate in particular. Information on the spatial and temporal patterns of human activities is in high demand, but scarce in sparsely populated and data-poor regions such as Northern Africa. The intensity and spatial distribution of nighttime lights provide useful information on human activities and can be observed by space-borne imaging radiometers. Our study helps to bridge the gap between the DMSP – OLS data available until 2013 and the NPP – VIIRS data available since 2013. The approach to calibrate the OLS data includes three steps: a) inter-calibrate the OLS DN data acquired by different sensors in 1992–2013; b) calibrate the OLS DN data using VIIRS data in 2013; c) generate synthetic OLS radiance data by degrading the VIIRS data in 2013–2020. We generated a) a time series of calibrated OLS nighttime light radiance data (1992–2013); b) mean annual VIIRS radiance on stable lights at the OLS spatial resolution for 2013–2020; c) synthetic OLS radiance data generated using VIIRS radiance data degraded to match the radiometric specifications of OLS for 2013–2020. The evaluation of these data products in 2013 documented their accuracy and consistency.

Abstract This paper introduces a novel cascading frequency regulation scheme (CFRS) for VSC‐HVDC to provide strong support for the connected weak AC grid without phase‐locked loop and remote‐communication considering the cost‐effective property. The proposed CFRS utilises a DC voltage synchronisation control to enable the self‐synchronisation of VSC‐HVDC without phase‐locked loop, while the corresponding inertia response can be exerted via utilising the stored HVDC capacitor energy. Meanwhile, the DC voltage acts as the reflection of system frequency, enabling the coordination between two‐end VSC stations without communication. More importantly, to fully utilise the VSC‐HVDC potentials, the CFRS that sequentially activates HVDC capacitor and primary frequency control is implemented so that the energy loss and the detrimental control impacts on the sending‐end systems can be minimised while making sure the requirement of system frequency support. Analytical derivations have been done to evaluate the contribution of the proposed CFRS to system frequency regulation. Furthermore, the effectiveness of the proposed scheme has been well validated in PSCAD/EMTDC under several power system contingencies by fully comparing with existing control schemes. The proposed CFRS stands out by the reduced complexity of the control structure, the robustness for connecting the very weak AC grid and the fast frequency regulation ability with consideration of cost‐effective property.

Abstract Background Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co‐factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes. Methods The genomic alterations of the TERT loci including TERT promoter's gain‐of‐function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow‐up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC‐featured telomere/telomerase biology and discuss underlying implications in TC precision medicine. Conclusion Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression‐based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT‐based system and 2022 WHO TC classification may be combined to improve TC care.

Abstract FKBP4 belongs to the family of immunophilins, which serve as a regulator for steroid receptor activity. Thus, FKBP4 has been recognized to play a critical role in several hormone-dependent cancers, including breast and prostate cancer. However, there is still no research to address the role of FKBP4 on lung adenocarcinoma (LUAD) progression. We found that FKBP4 expression was elevated in LUAD samples and predicted significantly shorter overall survival based on TCGA and our cohort of LUAD patients. Furthermore, FKBP4 robustly increased the proliferation, metastasis, and invasion of LUAD in vitro and vivo. Mechanistic studies revealed the interaction between FKBP4 and IKK kinase complex. We found that FKBP4 potentiated IKK kinase activity by interacting with Hsp90 and IKK subunits and promoting Hsp90/IKK association. Also, FKBP4 promotes the binding of IKKγ to IKKβ, which supported the facilitation role in IKK complex assembly. We further identified that FKBP4 TPR domains are essential for FKBP4/IKK interaction since its association with Hsp90 is required. In addition, FKBP4 PPIase domains are involved in FKBP4/IKKγ interaction. Interestingly, the association between FKBP4 and Hsp70/RelA favors the transport of RelA toward the nucleus. Collectively, FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to potentiate the transcriptional activity and nuclear translocation of NF-κB, thereby promoting LUAD progression. Our findings suggest that FKBP4 may function as a prognostic biomarker of LUAD and provide a newly mechanistic insight into modulating IKK/NF-κB signaling.

Abstract Traditional permanent magnet synchronous generator (PMSG)‐based wind turbine (WT) normally utilises phase lock loop (PLL) for obtaining accurate phase angle of AC grid to make sure of maximum power point tracking (MPPT). However, a weak AC system with a low short circuit ratio (SCR) and high control bandwidth of PLL might have impaired effects on the stability of the system. To overcome these, a novel power synchronous control of PMSG‐based WT with grid forming ability of PMSG for integrating very weak AC system is first proposed in this study. Grid‐side converter (GSC) of PMSG emulates the inertia response of synchronous generator (SG) by artificially coupling the DC‐link voltage with the grid frequency based on the certain droop property, while the converter voltage magnitude is regulated according to DC‐link voltage deviation by controlling the modulation index of GSC. This novel scheme can realise the grid synchronisation without PLL by mimicking the natural characteristic of SG. Small‐signal analysis of the proposed scheme indicates the DC‐link capacitor energy can be exerted for system inertia support during system disturbances, while the system damping can be provided by spontaneously alternating converter voltage magnitude. More importantly, MPPT property of PMSG is not compromised while providing inertia and damping for the system, and the related inertia and damping coefficient of WT with the proposed control can be easily tuned for satisfying the system requirement. Non‐linear simulations of one PMSG connected with one large SG considering a sudden change of active power reference and variable wind speeds have been studied to verify the effectiveness of the proposed grid‐forming control.

BackgroundAdvanced recurrent nasopharyngeal carcinoma (NPC) is a relatively common nasopharyngeal skull base disease for which there is no uniform treatment modality. Not all patients are satisfied with the efficacy of immunotherapy with or without chemotherapy.MethodsThis study included patients who underwent salvage endoscopic skull base nasopharyngectomy after immunotherapy between February 2017 and June 2021. Patient survival information was analyzed. Relevant publications were retrieved from five databases from December 1, 2011 to December 1, 2021. The outcomes of patients with advanced recurrent NPC who received programmed death 1 (PD-1) immunotherapy were collected and analyzed.ResultsNine patients who underwent skull base surgery, all of whom had previously undergone PD-1 immunotherapy, were included in this study. The 2-year overall survival (OS) and progression-free survival (PFS) rates of these patients were 25% and 29.2%, respectively. Eight publications involving 688 patients with advanced recurrent NPC were also included in this study. The combined complete response (CR), partial response (PR), and stable disease (SD) values were 2%, 23%, and 29%, respectively. The combined DCR included the three disease conditions, CR, PR, and SD, with a value of 53%. PD-1 monotherapy was more effective than PD-1 combination chemotherapy.ConclusionsPD-1 immunotherapy may improve the remission rate in patients with recurrent NPC. Salvage endoscopic skull base nasopharyngectomy may be another option for patients with poor immunotherapeutic outcomes. For patients with advanced recurrent NPC, better evidence-based medical data are needed to determine whether they should receive immunotherapy before or after surgery.

Ursolic acid (UA), a natural pentacyclic triterpenoid, possesses widespread biological and pharmacological activities. However, drawbacks such as low bioavailability, poor targeting and rapid metabolism greatly hinder its further clinical application. Recently, with the development of nanotechnology, various UA nanosystems have emerged as promising strategies for effective cancer therapy. This article reviews various types of UA-based nano-delivery systems, primarily with emphasis placed on novel UA-based carrier-free nano-drugs, which are considered to be innovative methods for cancer therapy. Moreover, this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance. Finally, the article also describes the development and challenges of UA nanosystems for future research in this field. Overall, the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.

Subsynchronous oscillations (SSOs) induced by the interaction between wind farms based on direct-drive permanent magnet synchronous generators (D-PMSGs) and weak grids have attracted extensive attention. To better understand this SSO phenomenon, this paper derives multi-input multi-output (MIMO) transfer functions between the references of the current controller and the current of a grid-connected converter in the d-q frame, where the dynamic of PLL is considered. The dynamic of PLL lead to positive feedback in the MIMO transfer function, which impairs the stability of the overall system and induces the SSO phenomenon. Using the classical root locus method, the influence of correlated control parameters and different operation conditions on the system stability is substantially analysed. It is found that heavy load, low short circuit ratio (SCR) will intensify the SSO instability of system. Nonlinear electromagnetic transient simulations of a D-PMSG-based weak-grid-connected wind-farm system using PSCAD/EMTDC software effectively verify the correctness of the model proposed in the SSO analysis.

Multimodal sub-synchronous resonance (SSR) induced by the interactions between the generator shafts and the fixed series capacitors has become a serious threat for the power system. To overcome this, a voltage source converter (VSC) based controller for multimodal SSR suppression, named sub-synchronous resonance dynamic suppressor (SSRDS), is presented and analyzed in this paper. The controller is placed at the point of common coupling (PCC) of the power plant for multi-generator SSR suppression purpose so that the investment costs can be minimized while making sure the requirements of the SSR damping. To quantify the contribution of SSRDS to the SSR damping, the damping torque analysis is carried out, which can reveal the influences of the operating conditions and the correlated control parameters on the damping performance. Furthermore, to avoid the negative affects between the different TMs in close range as well as maximize the damping ability of SSRDS, the parameters tuning method of the mode filters and the gain and phase shifters are proposed. A detailed nonlinear simulation model is established in PSCAD/EMTDC based on the Jinjie series compensated transmission system located in China. The damping torque analysis, the eigenvalues analysis and the simulation results have fully demonstrated the effectiveness and the robustness of the proposed SSRDS for multi-generator and multimodal SSR suppression under both small and large disturbances in various operating conditions.

This study presents a comprehensive analysis of the impact that a supplementary damping controller of the permanent magnet synchronous generator (PMSG)-based wind turbine (WT) has on low-frequency oscillation (LFO) damping. A reduced mathematical model of an interarea system is first established. Then, an auxiliary damping controller is designed using the PMSG active power control loop, enabling the WT to actively support the interarea LFO mitigation. Based on this, the damping torque analysis (DTA) method is applied to explore the contribution of the PMSG-based WT with an auxiliary damping controller to LFO damping enhancement, whose analytical expressions of the damping torque coefficients reveal the impacts of the control parameters and the operation conditions on the system damping characteristics. It is evident that the installation location of the wind power plant (WPP) plays a leading role in determining whether the damping provided by the PMSG controller is positive or negative. Also, the contribution of damping from the PMSG can be improved by tuning the droop coefficient of the PMSG controller properly. The results indicate that the proposed damping control is always helpful in improving the system damping when the wind power penetration increases. Accordingly, analytical conclusions can serve as guidelines for the control design. Case studies of a two-area test system integrated with a PMSG-based wind farm have been conducted to verify the theoretical analysis.

Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC) development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3–H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC. Higher levels of ASF1A expression predicted significantly shorter patient overall survival in colorectal cancer (P = 0.0012). The further analyses of the GEO dataset validate higher ASF1A expression as a prognostic factor for CRC patients. Mechanistically, ASF1A interacted with β-catenin and promoted the transcription of β-catenin target genes including c-MYC, cyclin D1, ZEB1 and LGR5, thereby stimulating proliferation, stemness and migration/invasion of GIC cells. β-Catenin inhibition abolished these effects of ASF1A. Moreover, the ASF1A-β-catenin-ZEB1 axis down-regulated E-Cadherin expression, thereby contributing to enhanced migration/invasion of GIC cells. ASF1A over-expression and depletion facilitated and inhibited in vivo tumor growth and/or metastasis in mouse xenograft models, respectively. Taken together, ASF1A is aberrantly over-expressed in GIC tumors and plays key roles in GIC development and progression by stimulating the transcription of β-catenin target genes. ASF1A may thus be a novel target for GIC therapy and a potential prognostic marker.

Subsynchronous oscillation (SSO) is a critical issue for the direct-drive permanent magnet synchronous generator (D-PMSG) based wind farm integrated to a weak onshore AC grid. To analyze the mechanism of the SSO phenomenon of D-PMSG based wind farm, widely used impedance-based stability analysis method is utilized in this paper. First, the impedance model based on the harmonic linearization theory of grid-connected D-PMSG is proposed, and the mechanism of sub/supsynchronous currents coupling is analyzed quantitatively for the first time. Then, based on the impedance model and relative stability criterion, the influence of wind farm operating parameters and grid impedance on stability is discussed. Simulations are carried out to verify the correctness of theoretical analysis.