This paper presents a novel cooperative value iteration(VI)-based adaptive dynamic programming method for multi-player differential game models with a convergence proof.The players are divided into two groups in the l...This paper presents a novel cooperative value iteration(VI)-based adaptive dynamic programming method for multi-player differential game models with a convergence proof.The players are divided into two groups in the learning process and adapt their policies sequentially.Our method removes the dependence of admissible initial policies,which is one of the main drawbacks of the PI-based frameworks.Furthermore,this algorithm enables the players to adapt their control policies without full knowledge of others’ system parameters or control laws.The efficacy of our method is illustrated by three examples.展开更多
To determine the optimal or near optimal parameters of PID controller with incomplete derivation, a novel design method based on differential evolution （DE） algorithm is presented. The controller is called DE-PID co...To determine the optimal or near optimal parameters of PID controller with incomplete derivation, a novel design method based on differential evolution （DE） algorithm is presented. The controller is called DE-PID controller. To overcome the disadvantages of the integral performance criteria in the frequency domain such as IAE, ISE, and ITSE, a new performance criterion in the time domain is proposed. The optimization procedures employing the DE algorithm to search the optimal or near optimal PID controller parameters of a control system are demonstrated in detail. Three typical control systems are chosen to test and evaluate the adaptation and robustness of the proposed DE-PID controller. The simulation results show that the proposed approach has superior features of easy implementation, stable convergence characteristic, and good computational efficiency. Compared with the ZN, GA, and ASA, the proposed design method is indeed more efficient and robust in improving the step response of a control system.展开更多
Progression,relapse,and therapy resistance are the most challenging features of cancer therapy that have been postulated to be driven by Cancer Stem Cell(CSC)population.This enigmatic subpopulation of cancer cells has...Progression,relapse,and therapy resistance are the most challenging features of cancer therapy that have been postulated to be driven by Cancer Stem Cell(CSC)population.This enigmatic subpopulation of cancer cells has therefore emerged as promising therapeutic candidate.We earlier reported enrichment of CSC-like side population(SP)with increasing resistance towards Cisplatin and Paclitaxel either alone or in combination in epithelial ovarian cancer(EOC)cells.This SP population is a small proportion of the total population of cancer cells characterised with high expression of drug transporters,a unique feature of stem cells and thereby can be isolated through their efflux properties of DNA binding dyes.While the bulk non-SP(NSP)population of the cancer cells lack overexpression of the drug transporters and thus can be identified as the dye containing population.In this study,we show that increased expression of Runt related transcription factor 1(RUNX1)maintains undifferentiated state of CSC-like SP cells through upregulation of inhibitors of DNA binding/differentiation genes(ID1 and ID3)in late cisplatinpaclitaxel resistant cells.Higher RUNX1 expression was found to correlate with decreased median overall survival and disease-free survival in The Cancer Genome Atlas(TCGA)data set of high grade serous ovarian cancer(HGSOC)patients.The protein-protein interaction network analysis of 397 upregulated genes in RUNX1-high samples of TCGA data show significant enrichment of pathways known to negatively regulate CSC differentiation.Intriguingly RUNX1 inhibition not only induces CSC differentiation but also downregulates anti-apoptotic protein BCL2 in both SP and NSP cells and potentiates cytotoxic effects of Cisplatin-Paclitaxel in chemoresistant EOC cells.Inhibition of BCL2 through Venetoclax treatment,a small molecule BH3 mimic,sensitized these cells to platinum taxol treatment.Altogether,our data reveal new regulatory roles by RUNX1 to modulate CSC differentiation via ID1 and ID3 and to promote chemoresistance through BCL2 upregulation.展开更多
目的:探索分化抑制因子(inhibitor of differentiation,ID)家族在慢性髓系白血病(chronic myeloid leukemia,CML)中的表达和启动子甲基化水平,并分析其临床意义。方法:应用定量PCR及定量甲基化特异性PCR的方法检测2010年1月至2017年12...目的:探索分化抑制因子(inhibitor of differentiation,ID)家族在慢性髓系白血病(chronic myeloid leukemia,CML)中的表达和启动子甲基化水平,并分析其临床意义。方法:应用定量PCR及定量甲基化特异性PCR的方法检测2010年1月至2017年12月期间江苏大学附属人民医院就诊的非恶性血液病患者(对照组)和CML患者骨髓单个核细胞中ID2/ID3/ID4表达及ID4启动子甲基化水平,通过分组分析ID家族异常的临床意义。结果:ID2及ID3表达在CML患者中均呈现显著上调(P<0.001,P<0.05),而ID4表达在CML患者中呈现显著下调(P<0.01)。其中,接受者操作特征曲线分析揭示ID2表达可作为CML鉴别的潜在分子标志物(AUC=0.895,P<0.001)。CML患者中ID4启动子高甲基化概率显著高于对照组患者(P=0.001),且ID4启动子甲基化与ID4表达呈现负相关(r=-0.424,P=0.002)。通过分组分析发现ID2高表达较易发生于男性患者中(P=0.040);ID4低表达/高甲基化较易发生于加速/急变期患者(P=0.003,P<0.001)。此外,CML加速/急变期患者ID4表达水平低于慢性期患者(P<0.001),而ID4甲基化水平高于慢性期患者(P<0.001)。通过单因素及多因素Logistic回归分析发现ID4高甲基化是CML患者疾病进展的独立危险因素(P=0.007)。结论:ID家族在CML患者中表达态势不同,其中ID2/ID3表达上调;而ID4表达下调,与ID4启动子高甲基化相关。ID4表达/甲基化与CML疾病进展相关,其中ID4甲基化可能是CML疾病进展的独立危险因素。展开更多
基金supported by the Industry-University-Research Cooperation Fund Project of the Eighth Research Institute of China Aerospace Science and Technology Corporation (USCAST2022-11)Aeronautical Science Foundation of China (20220001057001)。
文摘This paper presents a novel cooperative value iteration(VI)-based adaptive dynamic programming method for multi-player differential game models with a convergence proof.The players are divided into two groups in the learning process and adapt their policies sequentially.Our method removes the dependence of admissible initial policies,which is one of the main drawbacks of the PI-based frameworks.Furthermore,this algorithm enables the players to adapt their control policies without full knowledge of others’ system parameters or control laws.The efficacy of our method is illustrated by three examples.
基金the National Natural Science Foundation of China (60375001)the Scientific Research Foundation of Hunan Provincial Education Department (05B016).
文摘To determine the optimal or near optimal parameters of PID controller with incomplete derivation, a novel design method based on differential evolution （DE） algorithm is presented. The controller is called DE-PID controller. To overcome the disadvantages of the integral performance criteria in the frequency domain such as IAE, ISE, and ITSE, a new performance criterion in the time domain is proposed. The optimization procedures employing the DE algorithm to search the optimal or near optimal PID controller parameters of a control system are demonstrated in detail. Three typical control systems are chosen to test and evaluate the adaptation and robustness of the proposed DE-PID controller. The simulation results show that the proposed approach has superior features of easy implementation, stable convergence characteristic, and good computational efficiency. Compared with the ZN, GA, and ASA, the proposed design method is indeed more efficient and robust in improving the step response of a control system.
文摘Progression,relapse,and therapy resistance are the most challenging features of cancer therapy that have been postulated to be driven by Cancer Stem Cell(CSC)population.This enigmatic subpopulation of cancer cells has therefore emerged as promising therapeutic candidate.We earlier reported enrichment of CSC-like side population(SP)with increasing resistance towards Cisplatin and Paclitaxel either alone or in combination in epithelial ovarian cancer(EOC)cells.This SP population is a small proportion of the total population of cancer cells characterised with high expression of drug transporters,a unique feature of stem cells and thereby can be isolated through their efflux properties of DNA binding dyes.While the bulk non-SP(NSP)population of the cancer cells lack overexpression of the drug transporters and thus can be identified as the dye containing population.In this study,we show that increased expression of Runt related transcription factor 1(RUNX1)maintains undifferentiated state of CSC-like SP cells through upregulation of inhibitors of DNA binding/differentiation genes(ID1 and ID3)in late cisplatinpaclitaxel resistant cells.Higher RUNX1 expression was found to correlate with decreased median overall survival and disease-free survival in The Cancer Genome Atlas(TCGA)data set of high grade serous ovarian cancer(HGSOC)patients.The protein-protein interaction network analysis of 397 upregulated genes in RUNX1-high samples of TCGA data show significant enrichment of pathways known to negatively regulate CSC differentiation.Intriguingly RUNX1 inhibition not only induces CSC differentiation but also downregulates anti-apoptotic protein BCL2 in both SP and NSP cells and potentiates cytotoxic effects of Cisplatin-Paclitaxel in chemoresistant EOC cells.Inhibition of BCL2 through Venetoclax treatment,a small molecule BH3 mimic,sensitized these cells to platinum taxol treatment.Altogether,our data reveal new regulatory roles by RUNX1 to modulate CSC differentiation via ID1 and ID3 and to promote chemoresistance through BCL2 upregulation.
文摘目的:探索分化抑制因子(inhibitor of differentiation,ID)家族在慢性髓系白血病(chronic myeloid leukemia,CML)中的表达和启动子甲基化水平,并分析其临床意义。方法:应用定量PCR及定量甲基化特异性PCR的方法检测2010年1月至2017年12月期间江苏大学附属人民医院就诊的非恶性血液病患者(对照组)和CML患者骨髓单个核细胞中ID2/ID3/ID4表达及ID4启动子甲基化水平,通过分组分析ID家族异常的临床意义。结果:ID2及ID3表达在CML患者中均呈现显著上调(P<0.001,P<0.05),而ID4表达在CML患者中呈现显著下调(P<0.01)。其中,接受者操作特征曲线分析揭示ID2表达可作为CML鉴别的潜在分子标志物(AUC=0.895,P<0.001)。CML患者中ID4启动子高甲基化概率显著高于对照组患者(P=0.001),且ID4启动子甲基化与ID4表达呈现负相关(r=-0.424,P=0.002)。通过分组分析发现ID2高表达较易发生于男性患者中(P=0.040);ID4低表达/高甲基化较易发生于加速/急变期患者(P=0.003,P<0.001)。此外,CML加速/急变期患者ID4表达水平低于慢性期患者(P<0.001),而ID4甲基化水平高于慢性期患者(P<0.001)。通过单因素及多因素Logistic回归分析发现ID4高甲基化是CML患者疾病进展的独立危险因素(P=0.007)。结论:ID家族在CML患者中表达态势不同,其中ID2/ID3表达上调;而ID4表达下调,与ID4启动子高甲基化相关。ID4表达/甲基化与CML疾病进展相关,其中ID4甲基化可能是CML疾病进展的独立危险因素。
