Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are system...Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.展开更多
N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR Gl...N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR GluN2A subunit） mutations in patients with epilepsy. Phenotypes of GRIN2 A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2 A mutation（c.1341 T[A, p.N447 K） from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizurefree with a combination of valproate and lamotrigine.Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447 K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293 T cells revealed that the N447 K mutation increased the NMDAR current density by;.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg;inhibition. These results indicated that N447 K is a gain-offunction mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue（N447 A and N447 E） did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447 K as a novel mutation associated with epilepsy and validated its functional consequences in vitro.Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.展开更多
Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite spec...Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay （ELISA）. Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus （Der p 1 ）, Blomia tropicalis （BIot ） and Tyrophagus putrescentia （Tyr p） were detected in dust samples. Dermatophagoides farinae （Der f 1 ）, Lepidoglyphus destructor （Lep d 2）, and Acarus siro （Aca s ） were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.展开更多
The optimal velocity model of traffc is extended to take the relative velocity into account. The traffcbehavior is investigated numerically and analytically with this model. It is shown that the car interaction with t...The optimal velocity model of traffc is extended to take the relative velocity into account. The traffcbehavior is investigated numerically and analytically with this model. It is shown that the car interaction with therelative velocity can effect the stability of the traffic flow and raise critical density. The jamming transition between thefreely moving and jamming phases is investigated with the linear stability analysis and nonlinear perturbation methods.The traffic jam is described by the kink solution of the modified Korteweg-de Vries equation. The theoretical result isin good agreement with the simulation.展开更多
Through the long-term plot studies on the precipitation distribution in the evergreen broad-leaved forest ecosystem in Hangzhou for two years, it was indicated that the pattern of precipitation distribution included l...Through the long-term plot studies on the precipitation distribution in the evergreen broad-leaved forest ecosystem in Hangzhou for two years, it was indicated that the pattern of precipitation distribution included larger amounts of penetration water and stemflow and a lower amount of interception water. The results revealed that the main factors to infulence the percentages of penetration and stemflow were the air temperature and the leaf area of the forest. The quantity of seepage through the litter layer was much larger than that through the soil layers which decreased sharply with soil depth. The output of water from the ecosystem by surface runoff and deep infiltration through the soil was much lower, only being 5.20 percent of the rainfall, while the water evapotranspiration loss was as large as more than 90 percent of it. The losses by the soil evaporation and plant evapotranspiration were the largest part of output in this forest ecosystem.展开更多
Through the long-term plot study on the litter and its decomposition in the evergreen broad-leaved forest ecosystem in Hangzhou for more than two years,it was resulted that the annual litter production was 5.85 t ha^-...Through the long-term plot study on the litter and its decomposition in the evergreen broad-leaved forest ecosystem in Hangzhou for more than two years,it was resulted that the annual litter production was 5.85 t ha^-1,most of which was the fallen leave (79.5 percent) and the withered branches and fruits were far less (7.1 and 13.4 percents respectively).The dynamics of the fallen litter was shown as a curve of two-peak pattern which appeared in April and September each year.The half-life of the litter was 1.59 years.The decay rate of the litter attenuted as an exponential function.The annual amount of the nutrient returned to the ground through the litter was as large as 223.69kg ha^-1.The total current amount of the litter on the ground was 7.47t ha^-1.The decay rate in the first half of a year was 45.18 percent.This ecosystem remained in the stage of litter increasing with time.展开更多
Taking two identical ions in a Paul trap,we solved the SchrÖdinger equation for one-,two-,and three-dimensional harmonically bound two-body Coulomb models,in which the eigenfunctions are written in a series form ...Taking two identical ions in a Paul trap,we solved the SchrÖdinger equation for one-,two-,and three-dimensional harmonically bound two-body Coulomb models,in which the eigenfunctions are written in a series form and the eigenenergies are obtained from a continued fraction.Numerical calculations are made for specific discussion of two-and three-dimensional case.The comparison with a former one-dimensional approximate work shows that our result is more general and accurate.展开更多
A novel trench insulated gate bipolar transistor(IGBT) with improved dynamic characteristics is proposed and investigated. The poly gate and poly emitter of the proposed IGBT are arranged alternately along the trench....A novel trench insulated gate bipolar transistor(IGBT) with improved dynamic characteristics is proposed and investigated. The poly gate and poly emitter of the proposed IGBT are arranged alternately along the trench. A self-biased p-MOSFET is formed on the emitter side. Owing to this unique three-dimensional(3D) trench architecture, both the turnoff characteristic and the turn-on characteristic can be greatly improved. At the turn-off moment, the maximum electric field and impact ionization rate of the proposed IGBT decrease and the dynamic avalanche(DA) is suppressed. Comparing with the carrier-stored trench gate bipolar transistor(CSTBT), the turn-off loss(E_(off)) of the proposed IGBT also decreases by 31% at the same ON-state voltage. At the turn-on moment, the built-in p-MOSFET reduces the reverse displacement current(I_(G_dis)), which is conducive to lowing dI_(C)/d_(t). As a result, compared with the CSTBT with the same turn-on loss(E_(on)), at I_(C) = 20 A/cm^(2), the proposed IGBT decreases by 35% of collector surge current(I_(surge)) and 52% of dI_(C)/d_(t).展开更多
基金supported by the National Natural Science Foundation of China (81571273,81571274,81501124,81271434,and 81301107)Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400)+5 种基金the Natural Science Foundation of Guangdong Province,China (2014A030313489)Science and Technology Planning Projects of Guangdong Province,China (2012B031800404 and 2013B051000084)the Department of Education of Guangdong Province,China (2013CXZDA022,2013KJCX0156,and 2012KJCX009)the Foundation for High-level Talents in Higher Education of Guangdong Province,China (2013-167)Yangcheng Scholar Research Projects of Guangzhou Municipal College (12A016S and 12A017G)Science and Technology Projects of Guangzhou,Guangdong Province,China (2014J4100069,201508020011,201604020161,and 201607010002)
文摘Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsyassociated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations（funotypes）, and phenotypes of these mutations. Eleven genes featured loss-offunction mutations and six had gain-of-function mutations.Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.
基金supported by the grants of the National Natural Science Foundation of China(81671162,81521062,81561168,and 81571273)the National Basic Research Development Program of China(2014CB910300 and 2013CB530904)Key Research Project of the Ministry of Science and Technology of China(2016YFC0904400)
文摘N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR GluN2A subunit） mutations in patients with epilepsy. Phenotypes of GRIN2 A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2 A mutation（c.1341 T[A, p.N447 K） from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizurefree with a combination of valproate and lamotrigine.Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447 K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293 T cells revealed that the N447 K mutation increased the NMDAR current density by;.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg;inhibition. These results indicated that N447 K is a gain-offunction mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue（N447 A and N447 E） did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447 K as a novel mutation associated with epilepsy and validated its functional consequences in vitro.Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.
基金The project was partly supported by a grant from Natural Science Foundation of Hainan Province, China （No. 808206）.
文摘Background Haikou locates in tropical island with unique mite allergens levels in Haikou, and to investigate the prevalence of between house dust mites. propagation. The aim of this stuy is to determine mite mite specific IgE-sensitization and IgE cross-reactivity Methods Allergen and antigen concentrations against six mite species were tested by enzyme-linked immunosorbent assay （ELISA）. Specific IgE concentrations and cross-inhibitions were measured with ADVIA Centaur . Results Allergen or antigen Dermatophagoides pteronyssinus （Der p 1 ）, Blomia tropicalis （BIot ） and Tyrophagus putrescentia （Tyr p） were detected in dust samples. Dermatophagoides farinae （Der f 1 ）, Lepidoglyphus destructor （Lep d 2）, and Acarus siro （Aca s ） were found in very few samples. Specific IgE tests showed high prevalence of sensitizations against all tested mites with high IgE levels to Der p, Der f, and BIot. Storage mites, BIo t, Tyr p, Lep d, and Aca s, could inhibit Der p from 0 to 50%. Storage mites could inhibit Der f between 30% and 100%. Der p IgE could be inhibited by Der f with up to 90%, and vice versa. Der p could inhibit BIot from 40% to 80%. BIot was able to fully inhibit IgE binding to Lep d, Tyr p, and Aca s compared to partial inhibition by Der p. Conclusions Der p is the dominating mite and has the highest specific IgE prevalence among asthmatic children. BIot represents an important source of storage mite sensitization and some patients may be independently sensitized to both Der p and BIot. High prevalence of sensitization to Der f may be due to IgE-mediated cross-reactivity with Der p and BIo t.
文摘The optimal velocity model of traffc is extended to take the relative velocity into account. The traffcbehavior is investigated numerically and analytically with this model. It is shown that the car interaction with therelative velocity can effect the stability of the traffic flow and raise critical density. The jamming transition between thefreely moving and jamming phases is investigated with the linear stability analysis and nonlinear perturbation methods.The traffic jam is described by the kink solution of the modified Korteweg-de Vries equation. The theoretical result isin good agreement with the simulation.
基金Project supported by the Laboratory of Material Cycling in Pedosphere, Institute of Soil Science, Chinese Academy of Sciences.
文摘Through the long-term plot studies on the precipitation distribution in the evergreen broad-leaved forest ecosystem in Hangzhou for two years, it was indicated that the pattern of precipitation distribution included larger amounts of penetration water and stemflow and a lower amount of interception water. The results revealed that the main factors to infulence the percentages of penetration and stemflow were the air temperature and the leaf area of the forest. The quantity of seepage through the litter layer was much larger than that through the soil layers which decreased sharply with soil depth. The output of water from the ecosystem by surface runoff and deep infiltration through the soil was much lower, only being 5.20 percent of the rainfall, while the water evapotranspiration loss was as large as more than 90 percent of it. The losses by the soil evaporation and plant evapotranspiration were the largest part of output in this forest ecosystem.
基金Project supported by the Laboratory of Material Cycling in Pedosphere, Insitute of Soil Science, Chinese Academy of Sciences.
文摘Through the long-term plot study on the litter and its decomposition in the evergreen broad-leaved forest ecosystem in Hangzhou for more than two years,it was resulted that the annual litter production was 5.85 t ha^-1,most of which was the fallen leave (79.5 percent) and the withered branches and fruits were far less (7.1 and 13.4 percents respectively).The dynamics of the fallen litter was shown as a curve of two-peak pattern which appeared in April and September each year.The half-life of the litter was 1.59 years.The decay rate of the litter attenuted as an exponential function.The annual amount of the nutrient returned to the ground through the litter was as large as 223.69kg ha^-1.The total current amount of the litter on the ground was 7.47t ha^-1.The decay rate in the first half of a year was 45.18 percent.This ecosystem remained in the stage of litter increasing with time.
基金Supported by the National Natural Science Foundation of China under Grant No.19404004。
文摘Taking two identical ions in a Paul trap,we solved the SchrÖdinger equation for one-,two-,and three-dimensional harmonically bound two-body Coulomb models,in which the eigenfunctions are written in a series form and the eigenenergies are obtained from a continued fraction.Numerical calculations are made for specific discussion of two-and three-dimensional case.The comparison with a former one-dimensional approximate work shows that our result is more general and accurate.
基金Project supported by the Natural Science Foundation of Hunan Province, China (Grant No. 2023JJ40161)the Natural Science Foundation of Changsha, China (Grant No. kq2202163)+1 种基金the National Natural Science Foundation of China (Grant No. U21A20499)the Fundamental Research Funds for the Central Universities, China (Grant No. 531118010735)。
文摘A novel trench insulated gate bipolar transistor(IGBT) with improved dynamic characteristics is proposed and investigated. The poly gate and poly emitter of the proposed IGBT are arranged alternately along the trench. A self-biased p-MOSFET is formed on the emitter side. Owing to this unique three-dimensional(3D) trench architecture, both the turnoff characteristic and the turn-on characteristic can be greatly improved. At the turn-off moment, the maximum electric field and impact ionization rate of the proposed IGBT decrease and the dynamic avalanche(DA) is suppressed. Comparing with the carrier-stored trench gate bipolar transistor(CSTBT), the turn-off loss(E_(off)) of the proposed IGBT also decreases by 31% at the same ON-state voltage. At the turn-on moment, the built-in p-MOSFET reduces the reverse displacement current(I_(G_dis)), which is conducive to lowing dI_(C)/d_(t). As a result, compared with the CSTBT with the same turn-on loss(E_(on)), at I_(C) = 20 A/cm^(2), the proposed IGBT decreases by 35% of collector surge current(I_(surge)) and 52% of dI_(C)/d_(t).
基金financially supported by the National Natural Science Foundation of China(52171164 and 51790484)the National Key Laboratory of Science and Technology on Materials under Shock and Impact(WDZC2022-13)+2 种基金the Natural Science Foundation of Liaoning Province(2021-MS-009)China Manned Space Engineering(YYMT1201EXP08)the Youth Innovation Promotion Association CAS(2021188)。
