<div style="text-align:justify;"> Due to the influence of processing technology and environmental factors, there are errors in attitude measurement with the three-axis magnetometer, and the change of p...<div style="text-align:justify;"> Due to the influence of processing technology and environmental factors, there are errors in attitude measurement with the three-axis magnetometer, and the change of parameters during the operation of the magnetometer in orbit will have a great impact on the measurement accuracy. This paper studies the calibration method of magnetometer based on BP neural network, which reduces the influence of model error on calibration accuracy. Firstly, the error model of the magnetometer and the structural characteristics of the BP neural network are analyzed. Secondly, the number of hidden layers and hidden nodes is optimized. To avoid the problem of slow convergence and low accuracy of basic BP algorithm, this paper uses the Levenberg Marquardt backpropagation training method to improve the training speed and prediction accuracy and realizes the on-orbit calibration of magnetometer through online training of the neural network. Finally, the effectiveness of the method is verified by numerical simulation. The results show that the neural network designed in this paper can effectively reduce the measurement error of magnetometer, while the online training can effectively reduce the error caused by the change of magnetometer parameters, and reduce the measurement error of magnetometer to less than 10 nT. </div>展开更多
The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to f...The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.展开更多
The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyc...The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1neo/neo and K14cre:SmoM2YFP). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis.展开更多
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is st...Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.展开更多
文摘<div style="text-align:justify;"> Due to the influence of processing technology and environmental factors, there are errors in attitude measurement with the three-axis magnetometer, and the change of parameters during the operation of the magnetometer in orbit will have a great impact on the measurement accuracy. This paper studies the calibration method of magnetometer based on BP neural network, which reduces the influence of model error on calibration accuracy. Firstly, the error model of the magnetometer and the structural characteristics of the BP neural network are analyzed. Secondly, the number of hidden layers and hidden nodes is optimized. To avoid the problem of slow convergence and low accuracy of basic BP algorithm, this paper uses the Levenberg Marquardt backpropagation training method to improve the training speed and prediction accuracy and realizes the on-orbit calibration of magnetometer through online training of the neural network. Finally, the effectiveness of the method is verified by numerical simulation. The results show that the neural network designed in this paper can effectively reduce the measurement error of magnetometer, while the online training can effectively reduce the error caused by the change of magnetometer parameters, and reduce the measurement error of magnetometer to less than 10 nT. </div>
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘The long-term enhancement in glutamate receptor mediated excitatory responses has been observed in stroke model. This pathological form of plasticity, termed post-ischemic long-term potentiation （i-LTP）, points to functional reorganization after stroke. Little is known, however, about whether and how this i-LTP would affect subsequent induction of synaptic plasticity. Here, we first directly confirmed that i-LTP was induced in the endothelin-l-induced ischemia model as in other in vitro models. We also demonstrated increased expression of NR2B, CaMKII and p-CaMKII, which are reminiscent of i-LTP. We further induced LTP of field excitatory post- synaptic potentials （fEPSPs） on CA1 hippocampal neurons in peri-infarct regions of the endothelin-l-induced mini-stroke model. We found that LTP of fEPSPs, induced by high-frequency stimulation, displayed a progressive impairment at 12 and 24 hours after ischemia. Moreover, using in vivo multi-channel recording, we found that the local field potential, which represents electrical property of cell ensembles in more restricted regions, was also dam- pened at these two time points. These results suggest that i-LTP elevates the induction threshold of subsequent synap- tic plasticity. Our data helps to deepen the knowledge of meta-synaptic regulation of plasticity after focal ischemia.
基金supported by a grant from the National Institute of Health, USA (No. R01-CA94160)
文摘The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hh pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hh antagonists prevent the clinical development of Cyc as a therapeutic agent. Here, we report properties of cyclopamine tartrate salt (CycT) and its activities in Hh signaling-mediated cancer in vitro and in vivo. Unlike Cyc, CycT is water soluble (5-10 mg/mL). The median lethal dose (LD50) of CycT was 62.5 mg/kg body weight compared to 43.5 mg/kg for Cyc, and the plasma half-life (T1/2) of CycT was not significantly different from that of Cyc. We showed that CycT had a higher inhibitory activity for Hh signaling-dependent motor neuron differentiation than did Cyc (IC50 = 50 nmol/L for CycT vs. 300 nmol/L for Cyc). We also tested the antitumor effectiveness of these Hh inhibitors using two mouse models of basal cell carcinomas (K14cre:Ptch1neo/neo and K14cre:SmoM2YFP). After topical application of CycT or Cyc daily for 21 days, we found that all CycT-treated mice had tumor shrinkage and decreased expression of Hh target genes. Taken together, we found that CycT is an effective inhibitor of Hh signaling-mediated carcinogenesis.
基金supported by Major State Basic Research Program of China(Grant No.2013CB733801)
文摘Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 （ET-1） into the dorsal hippo- campus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also elimi- nated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1- induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.
