Pure inertial navigation system(INS) has divergent localization errors after a long time. In order to compensate the disadvantage, wireless sensor network(WSN) associated with the INS was applied to estimate the mobil...Pure inertial navigation system(INS) has divergent localization errors after a long time. In order to compensate the disadvantage, wireless sensor network(WSN) associated with the INS was applied to estimate the mobile target positioning. Taking traditional Kalman filter(KF) as the framework, the system equation of KF was established by the INS and the observation equation of position errors was built by the WSN. Meanwhile, the observation equation of velocity errors was established by the velocity difference between the INS and WSN, then the covariance matrix of Kalman filter measurement noise was adjusted with fuzzy inference system(FIS), and the fuzzy adaptive Kalman filter(FAKF) based on the INS/WSN was proposed. The simulation results show that the FAKF method has better accuracy and robustness than KF and EKF methods and shows good adaptive capacity with time-varying system noise. Finally, experimental results further prove that FAKF has the fast convergence error, in comparison with KF and EKF methods.展开更多
AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-)mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice s...AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-)mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study.The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described.The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long)of the Rosa26 gene locus.Mice were injected with 2.1×108 VP of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR)via the tail vein.Mice in the control group were injected with 2.1×108 VP of a similar vector but missing the homologous arms(r AAV8-TTR.Fah).Primary hepatocytes from Fah-/-recipient mice,treated with our vectors,were isolated and 1×106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen.Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice.RESULTS Here,we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the"safe harbour locus"Rosa26 by recombinant AAV8.Both groups of mice showed long-term survival,weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment.In the group of C57 BL/6 Fah?exon5 mice,which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before,6 out of 6 mice showed long-term survival,weight gain and FAH positive clusters without need for NTBC treatment.In contrast only 1 out 5 mice,who received hepatocytes from r AAV8-TTR.Fah treated mice,survived and showed few and smaller FAH positive clusters.These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice)and is long lasting in a proliferating state of the liver as shown by withdrawal of NTBC treatment and serial transplantation of isolated hepatocytes from primary Fah-/-recipient mice into secondary Fah-/-recipient mice.This long term therapeutic efficacy is clearly superior to our control mice treated with episomal r AAV8 gene therapy approach.CONCLUSION HR-mediated r AAV8 gene therapy provides targeted transgene integration and phenotypic correction in Fah-/-mice with superior long-term efficacy compared to episomal r AAV8 therapy in proliferating livers.展开更多
基金Project(2013AA06A411)supported by the National High Technology Research and Development Program of ChinaProject(CXZZ14_1374)supported by the Graduate Education Innovation Program of Jiangsu Province,ChinaProject supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Pure inertial navigation system(INS) has divergent localization errors after a long time. In order to compensate the disadvantage, wireless sensor network(WSN) associated with the INS was applied to estimate the mobile target positioning. Taking traditional Kalman filter(KF) as the framework, the system equation of KF was established by the INS and the observation equation of position errors was built by the WSN. Meanwhile, the observation equation of velocity errors was established by the velocity difference between the INS and WSN, then the covariance matrix of Kalman filter measurement noise was adjusted with fuzzy inference system(FIS), and the fuzzy adaptive Kalman filter(FAKF) based on the INS/WSN was proposed. The simulation results show that the FAKF method has better accuracy and robustness than KF and EKF methods and shows good adaptive capacity with time-varying system noise. Finally, experimental results further prove that FAKF has the fast convergence error, in comparison with KF and EKF methods.
基金SFB 738the"Deutsche Forschungsgemeinschaft"(Gerok-Grant)for financial support
文摘AIM To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout(Fah-/-)mice by homologous-recombination-mediated targeted addition of the Fah gene.METHODS C57 BL/6 Fah?exon5 mice served as an animal model for human tyrosinaemia type 1 in our study.The vector was created by amplifying human Fah c DNA including the TTR promoter from a lentivirus plasmid as described.The Fah expression cassette was flanked by homologous arms(620 bp and 749 bp long)of the Rosa26 gene locus.Mice were injected with 2.1×108 VP of this vector(r AAV8-ROSA26.HAL-TTR.FahROSA26.HAR)via the tail vein.Mice in the control group were injected with 2.1×108 VP of a similar vector but missing the homologous arms(r AAV8-TTR.Fah).Primary hepatocytes from Fah-/-recipient mice,treated with our vectors,were isolated and 1×106 hepatocytes were transplanted into secondary Fah-/-recipient mice by injection into the spleen.Upon either vector application or hepatocyte transplantation NTBC treatment was stopped in recipient mice.RESULTS Here,we report successful HR-mediated genome editing by integration of a Fah gene expression cassette into the"safe harbour locus"Rosa26 by recombinant AAV8.Both groups of mice showed long-term survival,weight gain and FAH positive clusters as determined by immunohistochemistry analysis of liver sections in the absence of NTBC treatment.In the group of C57 BL/6 Fah?exon5 mice,which have been transplanted with hepatocytes from a mouse injected with r AAV8-ROSA26.HAL-TTR.Fah-ROSA26.HAR 156 d before,6 out of 6 mice showed long-term survival,weight gain and FAH positive clusters without need for NTBC treatment.In contrast only 1 out 5 mice,who received hepatocytes from r AAV8-TTR.Fah treated mice,survived and showed few and smaller FAH positive clusters.These results demonstrate that homologous recombinationmediated Fah gene transfer corrects the phenotype in a mouse model of human tyrosinaemia type 1(Fah-/-mice)and is long lasting in a proliferating state of the liver as shown by withdrawal of NTBC treatment and serial transplantation of isolated hepatocytes from primary Fah-/-recipient mice into secondary Fah-/-recipient mice.This long term therapeutic efficacy is clearly superior to our control mice treated with episomal r AAV8 gene therapy approach.CONCLUSION HR-mediated r AAV8 gene therapy provides targeted transgene integration and phenotypic correction in Fah-/-mice with superior long-term efficacy compared to episomal r AAV8 therapy in proliferating livers.
