Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the leading genetic cause of autosomal dominant familial Parkinson’s disease. We previously reported that two mutations within the ROC domain, n...Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the leading genetic cause of autosomal dominant familial Parkinson’s disease. We previously reported that two mutations within the ROC domain, namely R1441C and A1442P, exhibit increased protein degradation leading to lowered steady state LRRK2 protein levels in HEK293 cells. More recently, the common WD40 domain LRRK2 haplotype, Met2397, which is a risk factor for Crohn’s disease, has been shown to lower steady state protein levels in HEK293 cells. In view of recent evidence implicating LRRK2 and inflamemation in PD, we investigated the effects of Met2397 on LRRK2 expression, and compared them to the Thr2397 variant and other LRRK2 mutants. In this study, we transfected HEK293 cells with plasmid constructs encoding the different LRRK2 variants, and analyzed the resulting protein levels by Western blot and flow cytometry. Here we found that both the Met2397 and Thr2397 haplotypes yield similar levels of LRRK2 protein expression and do not appear to impact cell viability in HEK293 cells, compared to other LRRK mutants. Thus, we have concluded that the Met2397 haplotype is unlikely to play a role in LRRK2 mediated or idiopathic PD.展开更多
An effective rapid assessment technique, called ＂P25 Scoring Method＂, has been developed and tested on 26 different case studies recently, in order to predict the collapse vulnerability of the R/C buildings. After a...An effective rapid assessment technique, called ＂P25 Scoring Method＂, has been developed and tested on 26 different case studies recently, in order to predict the collapse vulnerability of the R/C buildings. After a short description of the approach, the study presents the sensitivity study of the method to the selected structural parameters by considering incremental deviation of the final scores from the base model. Further, the methodology was applied to an additional 100 damaged buildings in order to check the reliability of the method and some necessary modifications have been applied to the algorithm after considering this larger database. The evaluation of the results has been interpreted as a beneficial guidance for local authorities. The risk bands are defined according to the final scores and the effect of changing the band-width has also been studied through a safe but an economical procedure. A satisfactory correlation of the method with real damage states is obtained and a ready-to-use methodology has been introduced for future studies.展开更多
Foreword Since the foundation of P.R.C.,the China's power grid develops with a high rate.By now,grids in all provinces except Xinjiang,Tibet,Hainan and Taiwan are AC/DC interconnected together,forming the structur...Foreword Since the foundation of P.R.C.,the China's power grid develops with a high rate.By now,grids in all provinces except Xinjiang,Tibet,Hainan and Taiwan are AC/DC interconnected together,forming the structure of power grid interconnection in the whole country.展开更多
AIM To investigate the role of the complement 5a(C5a)/C5 a receptor(C5a R) pathway in the pathogenesis of acute liver failure(ALF) in a mouse model.METHODS BALB/c mice were randomly assigned to different groups, and i...AIM To investigate the role of the complement 5a(C5a)/C5 a receptor(C5a R) pathway in the pathogenesis of acute liver failure(ALF) in a mouse model.METHODS BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide(LPS)/D-galactosamine(D-Gal N)(600 mg/kg and 10 μg/kg) were used to induce ALF. The KaplanMeier method was used for survival analysis. Serum alanine aminotransferase(ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer. Pathological examination of liver tissue was performed 36 h after ALF induction. Serum complement 5(C5), C5 a, tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, high-mobility group protein B1(HMGB1) and sphingosine-1-phosphatelevels were detected by enzyme-linked immunosorbant assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of C5 a R, sphingosine kinase 1(Sph K1), p38-MAPK and p-p38-MAPK in liver tissue, peripheral blood mononuclear cells(PBMCs) and peritoneal exudative macrophages(PEMs) of mice or RAW 264.7 cells was analyzed by western blotting. C5 a R m RNA levels were detected by quantitative real-time PCR.RESULTS Activation of C5 and up-regulation of C5 a R were observed in liver tissue and PBMCs of mice with ALF. Blockade of C5 a R with a C5 a R antagonist(C5a Ra C5 a Ra) significantly reduced the levels of serum ALT, inflammatory cytokines(TNF-α, IL-1β and IL-6) and HMGB1, as well as the liver tissue damage, but increased the survival rates(P < 0.01 for all). Blockade of C5 a R decreased Sph K1 expression in both liver tissue and PBMCs significantly at 0.5 h after ALF induction. C5 a Ra pretreatment significantly downregulated the phosphorylation of p38-MAPK in liver tissues of ALF mice and C5 a stimulated PEMs or RAW 264.7 cells. Moreover, inhibition of p38-MAPK activity with SB203580 reduced Sph K1 protein production significantly in PEMs after C5 a stimulation.CONCLUSION The C5a/C5 a R pathway is essential for up-regulating Sph K1 expression through p38 MAPK activation in ALF in mice, which provides a potential immunotherapeutic strategy for ALF in patients.展开更多
Although pre-Northridge earthquake steel moment resisting frame buildings have been shown to be susceptible to brittle connection failures,they still represent a large fraction of the existing steel buildings in the U...Although pre-Northridge earthquake steel moment resisting frame buildings have been shown to be susceptible to brittle connection failures,they still represent a large fraction of the existing steel buildings in the United States of America.In this study,the performance of the 3-and 9-story Los Angeles pre-Northridge SAC buildings are analyzed considering ductile and brittle beam-column connection failures,and their uncertainty.This paper contributes to understanding the influence of uncertainty associated with connections brittle fracture on building interstory deformation capacity and its impact on bias and variability of fragility functions and loss assessment.The results show that considering brittle connections leads to significantly l arger d rift demands a nd t o h igher r epair costs,particularly under intense ground shaking.New fragility curve parameters are derived that account for the effect of the uncertainty of the strength and deformation capacity of brittle connections.展开更多
proach change of CGRP with time in periodontal ligaments of rats in magnetic field, maxillae of 28 Wistar rats of 6 7 weeks were placed in magnetic fields of permanent magnets Nd 2 Fe 4 B. Changes of CGRP w...proach change of CGRP with time in periodontal ligaments of rats in magnetic field, maxillae of 28 Wistar rats of 6 7 weeks were placed in magnetic fields of permanent magnets Nd 2 Fe 4 B. Changes of CGRP with t ime in maxillary periodontal ligaments of the rats were studied by immunohistochemistry. The result showed that: magnetic field had dynamic effect and some promotional effect on recove?E F F E C T O F M A G N E T I C F I E L D O N C A L C I T O N I N G E N E- R E L A T E D P E P T I D E I N P E R I O D O N T A L L I G A M E N T S O F R A T S X. Chang , K. Qin and Y. L. Lu Orthodontic Department of Stomatology College , China Medical University , Shenyang 110001 , China Manuscript received 24 June 1999 In order to approach change of C G R P with tim e in periodontal liga m ents of rats in m agneticfield , m axillae of 28 Wistar rats of 6 7 weeks w ere placed in m agnetic fields of per m anentm agnets Nd 2 Fe4 B. Changes of C G R P with tim e in m axillary periodontal liga ments of therats were stu died by i m m unohistoche mistry . The result sho wed that : m agnetic field had dy na m ic effect an d so m e pro motional effect on recovering and reconstruction of the periodontaltissues in it . This provided a better theoretical evidence for clinical use of per m anent m agnets .展开更多
Objective:To analyze the clinical and genetic characteristics of late-onset Charcot–Marie–Tooth(CMT)type 2A.Methods:A pedigree survey combined with clinical and genetic testing was used for integrated analyses.Resul...Objective:To analyze the clinical and genetic characteristics of late-onset Charcot–Marie–Tooth(CMT)type 2A.Methods:A pedigree survey combined with clinical and genetic testing was used for integrated analyses.Results:The proband showed muscle atrophy in both hips and thighs,obviously in the posterior sides of both legs.The serum creatine kinase(CK)value was 272U/L.EMG:the median nerve conduction velocity was normal and the nerves of both lower extremities showed neurogenic damage(mainly axonal).Genetic testing revealed a heterozygous variant in exon 9 of the MFN2 gene NM 014874:c.839G>A(p.R280H).The Father of the proband had similar symptoms of peripheral neuromuscular and the same heterozygous mutation,but the mother did not show similar clinical symptoms and the genetic mutation.Conclusion:Pedigree investigation combined with clinical and genetic analysis is a kind of reliable method for late-onset CMT2A diagnosing and helping to identify different neuromuscular diseases.展开更多
October 19,2007 Vice Premier Wu Yi,PRC On behalf of Chinese government,I would like to congratulate the 20th Foundation of World Federation of Acupuncture-Moxibustion Societies(WFAS)and International Acupuncture Congr...October 19,2007 Vice Premier Wu Yi,PRC On behalf of Chinese government,I would like to congratulate the 20th Foundation of World Federation of Acupuncture-Moxibustion Societies(WFAS)and International Acupuncture Congress which is to be held in Beijing,China.And also I give my warm welcome and regards to TCM/Acupuncture colleagues all over the world.展开更多
一论文集的一般P-C矩阵由论文数据和引文数据两部分组成。基于一般P-C矩阵并引入“等时性”概念，我们创建了关键变量Ck。Ck表示的是不同年份发表的论文在各自发表后第k年的引文数量的平均值。借助Ck可以构建R族科学发展节律指标，定义...一论文集的一般P-C矩阵由论文数据和引文数据两部分组成。基于一般P-C矩阵并引入“等时性”概念，我们创建了关键变量Ck。Ck表示的是不同年份发表的论文在各自发表后第k年的引文数量的平均值。借助Ck可以构建R族科学发展节律指标，定义为引文观察值和引文期望值的比值，用于反映科学发展的节律。R族指标包括4项指标：①指标R——被引年视角加三角形引文窗口；②指标R’——被引年视角加平行四边形引文窗口；③指标r——引用年视角加三角形引文窗121；④指标r’——引用年视角加平行四边形引文窗口。以Journal of Documentation为例，本文具体说明了R族序列的计算和R族指标的应用。展开更多
文摘Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the leading genetic cause of autosomal dominant familial Parkinson’s disease. We previously reported that two mutations within the ROC domain, namely R1441C and A1442P, exhibit increased protein degradation leading to lowered steady state LRRK2 protein levels in HEK293 cells. More recently, the common WD40 domain LRRK2 haplotype, Met2397, which is a risk factor for Crohn’s disease, has been shown to lower steady state protein levels in HEK293 cells. In view of recent evidence implicating LRRK2 and inflamemation in PD, we investigated the effects of Met2397 on LRRK2 expression, and compared them to the Thr2397 variant and other LRRK2 mutants. In this study, we transfected HEK293 cells with plasmid constructs encoding the different LRRK2 variants, and analyzed the resulting protein levels by Western blot and flow cytometry. Here we found that both the Met2397 and Thr2397 haplotypes yield similar levels of LRRK2 protein expression and do not appear to impact cell viability in HEK293 cells, compared to other LRRK mutants. Thus, we have concluded that the Met2397 haplotype is unlikely to play a role in LRRK2 mediated or idiopathic PD.
文摘An effective rapid assessment technique, called ＂P25 Scoring Method＂, has been developed and tested on 26 different case studies recently, in order to predict the collapse vulnerability of the R/C buildings. After a short description of the approach, the study presents the sensitivity study of the method to the selected structural parameters by considering incremental deviation of the final scores from the base model. Further, the methodology was applied to an additional 100 damaged buildings in order to check the reliability of the method and some necessary modifications have been applied to the algorithm after considering this larger database. The evaluation of the results has been interpreted as a beneficial guidance for local authorities. The risk bands are defined according to the final scores and the effect of changing the band-width has also been studied through a safe but an economical procedure. A satisfactory correlation of the method with real damage states is obtained and a ready-to-use methodology has been introduced for future studies.
文摘Foreword Since the foundation of P.R.C.,the China's power grid develops with a high rate.By now,grids in all provinces except Xinjiang,Tibet,Hainan and Taiwan are AC/DC interconnected together,forming the structure of power grid interconnection in the whole country.
基金Supported by the National Natural Science Foundation of China,No.81260455 and No.81160065
文摘AIM To investigate the role of the complement 5a(C5a)/C5 a receptor(C5a R) pathway in the pathogenesis of acute liver failure(ALF) in a mouse model.METHODS BALB/c mice were randomly assigned to different groups, and intraperitoneal injections of lipopolysaccharide(LPS)/D-galactosamine(D-Gal N)(600 mg/kg and 10 μg/kg) were used to induce ALF. The KaplanMeier method was used for survival analysis. Serum alanine aminotransferase(ALT) levels, at different time points within a 1-wk period, were detected with a biochemistry analyzer. Pathological examination of liver tissue was performed 36 h after ALF induction. Serum complement 5(C5), C5 a, tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, IL-6, high-mobility group protein B1(HMGB1) and sphingosine-1-phosphatelevels were detected by enzyme-linked immunosorbant assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of C5 a R, sphingosine kinase 1(Sph K1), p38-MAPK and p-p38-MAPK in liver tissue, peripheral blood mononuclear cells(PBMCs) and peritoneal exudative macrophages(PEMs) of mice or RAW 264.7 cells was analyzed by western blotting. C5 a R m RNA levels were detected by quantitative real-time PCR.RESULTS Activation of C5 and up-regulation of C5 a R were observed in liver tissue and PBMCs of mice with ALF. Blockade of C5 a R with a C5 a R antagonist(C5a Ra C5 a Ra) significantly reduced the levels of serum ALT, inflammatory cytokines(TNF-α, IL-1β and IL-6) and HMGB1, as well as the liver tissue damage, but increased the survival rates(P < 0.01 for all). Blockade of C5 a R decreased Sph K1 expression in both liver tissue and PBMCs significantly at 0.5 h after ALF induction. C5 a Ra pretreatment significantly downregulated the phosphorylation of p38-MAPK in liver tissues of ALF mice and C5 a stimulated PEMs or RAW 264.7 cells. Moreover, inhibition of p38-MAPK activity with SB203580 reduced Sph K1 protein production significantly in PEMs after C5 a stimulation.CONCLUSION The C5a/C5 a R pathway is essential for up-regulating Sph K1 expression through p38 MAPK activation in ALF in mice, which provides a potential immunotherapeutic strategy for ALF in patients.
文摘Although pre-Northridge earthquake steel moment resisting frame buildings have been shown to be susceptible to brittle connection failures,they still represent a large fraction of the existing steel buildings in the United States of America.In this study,the performance of the 3-and 9-story Los Angeles pre-Northridge SAC buildings are analyzed considering ductile and brittle beam-column connection failures,and their uncertainty.This paper contributes to understanding the influence of uncertainty associated with connections brittle fracture on building interstory deformation capacity and its impact on bias and variability of fragility functions and loss assessment.The results show that considering brittle connections leads to significantly l arger d rift demands a nd t o h igher r epair costs,particularly under intense ground shaking.New fragility curve parameters are derived that account for the effect of the uncertainty of the strength and deformation capacity of brittle connections.
文摘proach change of CGRP with time in periodontal ligaments of rats in magnetic field, maxillae of 28 Wistar rats of 6 7 weeks were placed in magnetic fields of permanent magnets Nd 2 Fe 4 B. Changes of CGRP with t ime in maxillary periodontal ligaments of the rats were studied by immunohistochemistry. The result showed that: magnetic field had dynamic effect and some promotional effect on recove?E F F E C T O F M A G N E T I C F I E L D O N C A L C I T O N I N G E N E- R E L A T E D P E P T I D E I N P E R I O D O N T A L L I G A M E N T S O F R A T S X. Chang , K. Qin and Y. L. Lu Orthodontic Department of Stomatology College , China Medical University , Shenyang 110001 , China Manuscript received 24 June 1999 In order to approach change of C G R P with tim e in periodontal liga m ents of rats in m agneticfield , m axillae of 28 Wistar rats of 6 7 weeks w ere placed in m agnetic fields of per m anentm agnets Nd 2 Fe4 B. Changes of C G R P with tim e in m axillary periodontal liga ments of therats were stu died by i m m unohistoche mistry . The result sho wed that : m agnetic field had dy na m ic effect an d so m e pro motional effect on recovering and reconstruction of the periodontaltissues in it . This provided a better theoretical evidence for clinical use of per m anent m agnets .
基金Fundamental research general project of local undergraduate universities(part)in Yunnan Province(No.2018FH001-082)Key project of Applied Basic Research Plan of Yunnan Province(No.2018FA010)+2 种基金National Natural Science Foundation of China(No.31571304)Yunnan Training Programme for the advanced Talents of Health and Medical Technology(No.D-2018013)the Scientific and technological talents and platform plan,high-level scientific and technological talents and innovative team selection project-Young and middle-aged academic and technical leaders reserve talent project(No.202005AC160011)。
文摘Objective:To analyze the clinical and genetic characteristics of late-onset Charcot–Marie–Tooth(CMT)type 2A.Methods:A pedigree survey combined with clinical and genetic testing was used for integrated analyses.Results:The proband showed muscle atrophy in both hips and thighs,obviously in the posterior sides of both legs.The serum creatine kinase(CK)value was 272U/L.EMG:the median nerve conduction velocity was normal and the nerves of both lower extremities showed neurogenic damage(mainly axonal).Genetic testing revealed a heterozygous variant in exon 9 of the MFN2 gene NM 014874:c.839G>A(p.R280H).The Father of the proband had similar symptoms of peripheral neuromuscular and the same heterozygous mutation,but the mother did not show similar clinical symptoms and the genetic mutation.Conclusion:Pedigree investigation combined with clinical and genetic analysis is a kind of reliable method for late-onset CMT2A diagnosing and helping to identify different neuromuscular diseases.
文摘October 19,2007 Vice Premier Wu Yi,PRC On behalf of Chinese government,I would like to congratulate the 20th Foundation of World Federation of Acupuncture-Moxibustion Societies(WFAS)and International Acupuncture Congress which is to be held in Beijing,China.And also I give my warm welcome and regards to TCM/Acupuncture colleagues all over the world.
文摘一论文集的一般P-C矩阵由论文数据和引文数据两部分组成。基于一般P-C矩阵并引入“等时性”概念，我们创建了关键变量Ck。Ck表示的是不同年份发表的论文在各自发表后第k年的引文数量的平均值。借助Ck可以构建R族科学发展节律指标，定义为引文观察值和引文期望值的比值，用于反映科学发展的节律。R族指标包括4项指标：①指标R——被引年视角加三角形引文窗口；②指标R’——被引年视角加平行四边形引文窗口；③指标r——引用年视角加三角形引文窗121；④指标r’——引用年视角加平行四边形引文窗口。以Journal of Documentation为例，本文具体说明了R族序列的计算和R族指标的应用。
