本文研究并比较了基于MMAe赋权的模型平均下,Wald置信区间,MATA置信区间,及Bootstrap置信区间的覆盖率、区间长度、左右错误率等各方面的表现性能。不同信噪比水平下的模拟显示,Wald置信区间在低信噪比时有更好的覆盖率,高信噪比下,三...本文研究并比较了基于MMAe赋权的模型平均下,Wald置信区间,MATA置信区间,及Bootstrap置信区间的覆盖率、区间长度、左右错误率等各方面的表现性能。不同信噪比水平下的模拟显示,Wald置信区间在低信噪比时有更好的覆盖率,高信噪比下,三者覆盖率相近,MATA置信区间相对长度更短。在与MMA等其他模型平均方法的横向比较中,MMAe的赋权在Wald、MATA及Bootstrap三种置信区间的构建下,均比其他赋权方式在更低的样本量下更早达到名义覆盖率。最后在实例中考察MMAe在不同置信区间下的表现,与模拟表现一致。This article studies and compares the performance of models based on MMAe weighting in terms of coverage, interval length, left and right error rates under average, Wald confidence interval, MATA confidence interval, and Bootstrap confidence interval. Simulations at different levels of signal show that the Wald confidence interval has better coverage at low signal, while at high signal, the three’s confidence interval has similar coverage, and the MATA confidence interval is relatively shorter in length. In the horizontal comparison with other model averaging methods such as MMA, the weighting of MMAe reached nominal coverage earlier than other weighting methods at lower sample sizes under the construction of Wald, MATA, and Bootstrap confidence intervals. Finally, the performance of MMAe at different confidence intervals was examined in the example, which was consistent with the simulation results.展开更多
For the case that two pursuers intercept an evasive target,the cooperative strategies and state estimation methods taken by pursuers can seriously affect the guidance accuracy for the target,which performs a bang For ...For the case that two pursuers intercept an evasive target,the cooperative strategies and state estimation methods taken by pursuers can seriously affect the guidance accuracy for the target,which performs a bang For the case that two pursuers intercept an evasive target,the cooperative strategies and state estimation methods taken by pursuers can seriously affect the guidance accuracy for the target,which performs a bang-bang evasive maneuver with a random switching time.Combined Fast multiple model adaptive estimation(Fast MMAE)algorithm,the cooperative guidance law takes detection configuration affecting the accuracy of interception into consideration.Introduced the detection error model related to the line-of-sight(LOS)separation angle of two interceptors,an optimal cooperative guidance law solving the optimization problem is designed to modulate the LOS separation angle to reduce the estimation error and improve the interception performance.Due to the uncertainty of the target bang-bang maneuver switching time and the effective fitting of its multi-modal motion,Fast MMAE is introduced to identify its maneuver switching time and estimate the acceleration of the target to track and intercept the target accurately.The designed cooperative optimal guidance law with Fast MMAE has better estimation ability and interception performance than the traditional guidance law and estimation method via Monte Carlo simulation.展开更多
Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for ...Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for modification with payload,but the relatively low molecular weight of this construction simultaneously results in short half-life time which hinders its application in cancer therapy.In this work,we prepared a nanomedicine self-assembled from the conjugate of affibody(ZPDGFRβ:09591,PDGFRβ:platelet-derived growth factor receptorβ)with monomethyl auristatin E(MMAE)through cathepsin B cleavable dipeptide linker for targeted colorectal cancer therapy.The nanoscale characteristics of ZPDGFRβ:09591-MMAE affibody-drug conjugate nanomedicine(ZPDGFRβ:09591-M ADCN)resulted in enhanced pharmacokinetics,improved drug accumulation,and promoted biosecurity performance than those of free drugs.As a result,ZPDGFRβ:09591-M ADCN exhibited excellent antitumor efficacy with tumor inhibition rates(TIR)over 99.0%in PDGFRβ-positive tumor models with small solid tumors(~150 mm^(3))or large established tumors(~500 mm^(3)),indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.展开更多
文摘本文研究并比较了基于MMAe赋权的模型平均下,Wald置信区间,MATA置信区间,及Bootstrap置信区间的覆盖率、区间长度、左右错误率等各方面的表现性能。不同信噪比水平下的模拟显示,Wald置信区间在低信噪比时有更好的覆盖率,高信噪比下,三者覆盖率相近,MATA置信区间相对长度更短。在与MMA等其他模型平均方法的横向比较中,MMAe的赋权在Wald、MATA及Bootstrap三种置信区间的构建下,均比其他赋权方式在更低的样本量下更早达到名义覆盖率。最后在实例中考察MMAe在不同置信区间下的表现,与模拟表现一致。This article studies and compares the performance of models based on MMAe weighting in terms of coverage, interval length, left and right error rates under average, Wald confidence interval, MATA confidence interval, and Bootstrap confidence interval. Simulations at different levels of signal show that the Wald confidence interval has better coverage at low signal, while at high signal, the three’s confidence interval has similar coverage, and the MATA confidence interval is relatively shorter in length. In the horizontal comparison with other model averaging methods such as MMA, the weighting of MMAe reached nominal coverage earlier than other weighting methods at lower sample sizes under the construction of Wald, MATA, and Bootstrap confidence intervals. Finally, the performance of MMAe at different confidence intervals was examined in the example, which was consistent with the simulation results.
基金This work was supported by the National Natural Science Foundation(NNSF)of China under grant no.61673386,62073335the China Postdoctoral Science Foundation(2017M613201,2019T120944).
文摘For the case that two pursuers intercept an evasive target,the cooperative strategies and state estimation methods taken by pursuers can seriously affect the guidance accuracy for the target,which performs a bang For the case that two pursuers intercept an evasive target,the cooperative strategies and state estimation methods taken by pursuers can seriously affect the guidance accuracy for the target,which performs a bang-bang evasive maneuver with a random switching time.Combined Fast multiple model adaptive estimation(Fast MMAE)algorithm,the cooperative guidance law takes detection configuration affecting the accuracy of interception into consideration.Introduced the detection error model related to the line-of-sight(LOS)separation angle of two interceptors,an optimal cooperative guidance law solving the optimization problem is designed to modulate the LOS separation angle to reduce the estimation error and improve the interception performance.Due to the uncertainty of the target bang-bang maneuver switching time and the effective fitting of its multi-modal motion,Fast MMAE is introduced to identify its maneuver switching time and estimate the acceleration of the target to track and intercept the target accurately.The designed cooperative optimal guidance law with Fast MMAE has better estimation ability and interception performance than the traditional guidance law and estimation method via Monte Carlo simulation.
基金supported by the National Key Research and Development Plan of China(No.2020YFA0907702)the National Facility for Translational Medicine(Shanghai)(No.TMST-2020-001).
文摘Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for modification with payload,but the relatively low molecular weight of this construction simultaneously results in short half-life time which hinders its application in cancer therapy.In this work,we prepared a nanomedicine self-assembled from the conjugate of affibody(ZPDGFRβ:09591,PDGFRβ:platelet-derived growth factor receptorβ)with monomethyl auristatin E(MMAE)through cathepsin B cleavable dipeptide linker for targeted colorectal cancer therapy.The nanoscale characteristics of ZPDGFRβ:09591-MMAE affibody-drug conjugate nanomedicine(ZPDGFRβ:09591-M ADCN)resulted in enhanced pharmacokinetics,improved drug accumulation,and promoted biosecurity performance than those of free drugs.As a result,ZPDGFRβ:09591-M ADCN exhibited excellent antitumor efficacy with tumor inhibition rates(TIR)over 99.0%in PDGFRβ-positive tumor models with small solid tumors(~150 mm^(3))or large established tumors(~500 mm^(3)),indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.
