Strapdown inertial navigation system(SINS)/celestial navigation system(CNS)integrated navigation is widely used to achieve long-time and high-precision autonomous navigation for aircraft.In general,SINS/CNS integrated...Strapdown inertial navigation system(SINS)/celestial navigation system(CNS)integrated navigation is widely used to achieve long-time and high-precision autonomous navigation for aircraft.In general,SINS/CNS integrated navigation can be divided into two integrated modes:loosely coupled integrated navigation and tightly coupled integrated navigation.Because the loosely coupled SINS/CNS integrated system is only available in the condition of at least three stars,the latter one is becoming a research hotspot.One major challenge of SINS/CNS integrated navigation is obtaining a high-precision horizon reference.To solve this problem,an innovative tightly coupled rotational SINS/CNS integrated navigation method is proposed.In this method,the rotational SINS error equation in the navigation frame is used as the state model,and the starlight vector and star altitude are used as measurements.Semi-physical simulations are conducted to test the performance of this integrated method.Results show that this tightly coupled rotational SINS/CNS method has the best navigation accuracy compared with SINS,rotational SINS,and traditional tightly coupled SINS/CNS integrated navigation method.展开更多
In order to improve the autonomous navigation capability of satellite,a pulsar/CNS（celestial navigation system） integrated navigation method based on federated unscented Kalman filter（UKF） is proposed.The celestia...In order to improve the autonomous navigation capability of satellite,a pulsar/CNS（celestial navigation system） integrated navigation method based on federated unscented Kalman filter（UKF） is proposed.The celestial navigation is a mature and stable navigation method.However,its position determination performance is not satisfied due to the low accuracy of horizon sensor.Single pulsar navigation is a new navigation method,which can provide highly accurate range measurements.The major drawback of single pulsar navigation is that the system is completely unobservable.As two methods are complementary to each other,the federated UKF is used here for fusing the navigation data from single pulsar navigation and CNS.Compared to the traditional celestial navigation method and single pulsar navigation,the integrated navigation method can provide better navigation performance.The simulation results demonstrate the feasibility and effectiveness of the navigation method.展开更多
Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly re...Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.展开更多
Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders.Recurrent mutations,including c.5A>G,p.D2G;c.1367C>T,p.S456L;c.1535G>A,p.R512Q an...Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders.Recurrent mutations,including c.5A>G,p.D2G;c.1367C>T,p.S456L;c.1535G>A,p.R512Q and c.1846_1847del,p.Y616Lfs*6 of RARS1 gene,which encodes two forms of human cytoplasmic arginyl-tRNA synthetase(hArgRS),are linked to Pelizaeus-Merzbacher-like disease(PMLD)with unclear pathogenesis.Among these mutations,c.5A>G is the most extensively reported mutation,leading to a p.D2G mutation in the N-terminal extension of the long-form hArgRS.Here,we showed the detrimental effects of R512Q substitution andΔC mutations on the structure and function of hArgRS,while the most frequent mutation c.5A>G,p.D2G acted in a different manner without impairing hArgRS activity.The nucleotide substitution c.5A>G reduced translation of hArgRS mRNA,and an upstream open reading frame contributed to the suppressed translation of the downstream main ORF.Taken together,our results elucidated distinct pathogenic mechanisms of various RARS1 mutations in PMLD.展开更多
Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin in...Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin inhibition (Fischer, 2012). Even in the PNS, which has the principle ability to regenerate injured axons, functional recovery remains limited, particularly in cases where the nerve target has become unreceptive to re-innervation over time due to an insufficient axonal growth rate (Diekmann and Fischer, 2015). Progress towards robust neuroregenerative therapies depends upon an understanding of the relevant signaling and cytoskeletal proteins that drive and control axon extension. Muscle LIM protein (MLP), also known as cysteine and glycine-rich protein 3, was recently discovered to be one such protein that is expressed in regenerating rat neurons and whose overexpression can promote the axon regeneration of adult central, and peripheral neurons of different species (Levin et al., 2019).展开更多
Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biolo...Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.展开更多
As a serine hydrolase,monoacylglycerol lipase(MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol(2-AG) in the central nervous system(CNS),leading to the formation of arachidonic acid(AA).Dys...As a serine hydrolase,monoacylglycerol lipase(MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol(2-AG) in the central nervous system(CNS),leading to the formation of arachidonic acid(AA).Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms,including neuroinflammation,cognitive impairment,epileptogenesis,nociception and neurodegenerative diseases.Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions,and a MAGL positron emission tomography(PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors.Herein,we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates.Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound,which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[^(18)F]fluoropyridine scaffold.Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [^(18)F]14(also named as [^(18)F]MAGL-1902).This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers.展开更多
基金supported by the National Natural Science Foundation of China(61722301)
文摘Strapdown inertial navigation system(SINS)/celestial navigation system(CNS)integrated navigation is widely used to achieve long-time and high-precision autonomous navigation for aircraft.In general,SINS/CNS integrated navigation can be divided into two integrated modes:loosely coupled integrated navigation and tightly coupled integrated navigation.Because the loosely coupled SINS/CNS integrated system is only available in the condition of at least three stars,the latter one is becoming a research hotspot.One major challenge of SINS/CNS integrated navigation is obtaining a high-precision horizon reference.To solve this problem,an innovative tightly coupled rotational SINS/CNS integrated navigation method is proposed.In this method,the rotational SINS error equation in the navigation frame is used as the state model,and the starlight vector and star altitude are used as measurements.Semi-physical simulations are conducted to test the performance of this integrated method.Results show that this tightly coupled rotational SINS/CNS method has the best navigation accuracy compared with SINS,rotational SINS,and traditional tightly coupled SINS/CNS integrated navigation method.
基金supported by the National High Technology Research and Development Program of China(2006AAJ109)Aviation Science Fund(20070818001)
文摘In order to improve the autonomous navigation capability of satellite,a pulsar/CNS（celestial navigation system） integrated navigation method based on federated unscented Kalman filter（UKF） is proposed.The celestial navigation is a mature and stable navigation method.However,its position determination performance is not satisfied due to the low accuracy of horizon sensor.Single pulsar navigation is a new navigation method,which can provide highly accurate range measurements.The major drawback of single pulsar navigation is that the system is completely unobservable.As two methods are complementary to each other,the federated UKF is used here for fusing the navigation data from single pulsar navigation and CNS.Compared to the traditional celestial navigation method and single pulsar navigation,the integrated navigation method can provide better navigation performance.The simulation results demonstrate the feasibility and effectiveness of the navigation method.
基金Japan Leukemia Research FundGrant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science,Grant/Award Number:No.24500493
文摘Adult T-cell leukemia( ATL) is a mature T-cell malignancy caused by human T-cell leukemia virus type I infection, and 10%-25% of patients show central nervous system( CNS) involvement. CNS involvement significantly reduces survival and there are no effective treatments for CNS involvement. Therefore, an appropriate animal model is required to evaluate the inhibitory effects of novel drugs on the progression of ATL with CNS involvement. Here, we established a mouse model of ATL with CNS involvement using NOD.Cg-Prkdc~ (scid) Il2 rg ^(tm1Wjl)/SzJ mice inoculated with ATL cells intramuscularly in the postauricular region, and these mice showed paraparesis. Of the 10 mice inoculated with ATL cells intramuscularly(I.M.) at 5 weeks of age, 8(80%) showed paraparesis, whereas none of the 10 mice inoculated with ATL cells subcutaneously(S.C.) showed paraparesis. In the I.M. group, PCR detected HTLV-1-specific genes in the thoracic and lumbar vertebrae; however, in the S.C. group, the vertebrae were negative for HTLV-1 genes. Histological analysis revealed a particularly high incidence of tumors, characterized by accumulation of the injected cells, in the thoracic vertebrae of mice in the I.M. group. Tumor cell infiltration was relatively high in the bone marrow. Spinal cord compression caused by invasion of the tumor mass outside the pia mater was observed in the thoracic vertebrae of the spinal cord. In conclusion, we have reported a mouse model of tumor growth with paraparesis that may be used to assess novel therapeutic agents for ATL with CNS involvement.
基金supported by the National Key Research and Development Program of China(2017YFA0504000)the Natural Science Foundation of China(91940302,31500644,31570792,31822015,81870896,31670801,31870811)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19010203)Key Laboratory of Reproductive Genetics(Zhejiang University),Ministry of Education,P.R.China(ZDFY2020-RG-0003)Shanghai Key Laboratory of Embryo Original Diseases(Shelab201904).
文摘Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders.Recurrent mutations,including c.5A>G,p.D2G;c.1367C>T,p.S456L;c.1535G>A,p.R512Q and c.1846_1847del,p.Y616Lfs*6 of RARS1 gene,which encodes two forms of human cytoplasmic arginyl-tRNA synthetase(hArgRS),are linked to Pelizaeus-Merzbacher-like disease(PMLD)with unclear pathogenesis.Among these mutations,c.5A>G is the most extensively reported mutation,leading to a p.D2G mutation in the N-terminal extension of the long-form hArgRS.Here,we showed the detrimental effects of R512Q substitution andΔC mutations on the structure and function of hArgRS,while the most frequent mutation c.5A>G,p.D2G acted in a different manner without impairing hArgRS activity.The nucleotide substitution c.5A>G reduced translation of hArgRS mRNA,and an upstream open reading frame contributed to the suppressed translation of the downstream main ORF.Taken together,our results elucidated distinct pathogenic mechanisms of various RARS1 mutations in PMLD.
基金supported by the German Research Foundation(FI 867/12,to DF)
文摘Unlike the peripheral nervous system (PNS), the central nervous system (CNS) has a low intrinsic regenerative capacity and has mechanisms that actively suppress axon regrowth, for example, glial scarring and myelin inhibition (Fischer, 2012). Even in the PNS, which has the principle ability to regenerate injured axons, functional recovery remains limited, particularly in cases where the nerve target has become unreceptive to re-innervation over time due to an insufficient axonal growth rate (Diekmann and Fischer, 2015). Progress towards robust neuroregenerative therapies depends upon an understanding of the relevant signaling and cytoskeletal proteins that drive and control axon extension. Muscle LIM protein (MLP), also known as cysteine and glycine-rich protein 3, was recently discovered to be one such protein that is expressed in regenerating rat neurons and whose overexpression can promote the axon regeneration of adult central, and peripheral neurons of different species (Levin et al., 2019).
文摘Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.
基金the financial support from the NIH grants (DA038000 and DA043507 to S. H. L. and DA033760 to B. F. C.)the Swiss National Science Foundation for a postdoctoral fellowship to Michael A. Schafroth (Grant No. P2EZP3_175137, Switzerland)。
文摘As a serine hydrolase,monoacylglycerol lipase(MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol(2-AG) in the central nervous system(CNS),leading to the formation of arachidonic acid(AA).Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms,including neuroinflammation,cognitive impairment,epileptogenesis,nociception and neurodegenerative diseases.Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions,and a MAGL positron emission tomography(PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors.Herein,we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates.Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound,which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[^(18)F]fluoropyridine scaffold.Good blood-brain barrier permeability and high in vivo specific binding was demonstrated for radioligand [^(18)F]14(also named as [^(18)F]MAGL-1902).This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers.
