Maroteaux-Lamy综合征的ARSB基因分析及新突变的致病性鉴定

【目的】对7家拟诊为Maroteaux_Lamy综合征(MPSⅥ)的患儿及其父母进行ARSB基因的突变检测和新突变的致病性鉴定,以揭示其分子发病机制,为将来的产前/植入前基因诊断等创造前提条件。【方法】在临床初诊及GAG尿检和MPS酶检的基础上,抽取患儿及其父母EDTA抗凝血,进行ARSB基因的PCR扩增和Sanger测序。对所发现的新突变,在经HGMD、1000G和ExAC等数据库核实排查后,首先用SWISS-MODEL软件分析、比对突变蛋白和正常蛋白的空间构象,然后用Clustal X软件分析跨物种氨基酸的保守性,用PROVEAN、SIFT、PolyPhen-2软件预测新突变的致病性,最后用ACMG标准对新突变的致病性进行综合分析鉴定。【结果】1)7个家系先证者的基因检测结果分别为:No1:c.574T> C,p.C192R纯合错义突变;No2:c.160G> A/p.D54N(来自其母)和c.1197C> G/p.F399L(来自其父)的复合杂合子;No3:仅检出c.1072G> A/p.V358M和IVS5 as(-27)A>C变异,但酶检和临床表型符合Ⅵ型;No4:为c.281C> T,p.S94L(新突变,来自其母)和IVS5 as(-27)A> C(来自其父)的复合杂合子;No5:为c.1197 C> G,p.F399L纯合错义突变;No6:为c.1197 C> G,p.F399L(来自其母)和c.1379 C> T,p.S460F(新突变,来自其父)的复合杂合子;No7:为c.499 G> A,p.G167R(来自其父)和c.1325C>T,p.T442M(来自其母)的复合杂合子。2)新突变鉴定结果:对正常ARSB酶蛋白和p.S94L突变酶蛋白的空间构象的预测比对结果显示,两者有明显区别;跨物种保守性分析结果显示,p.94突变点所在氨基酸(S)在物种进化过程中具有高度保守性;PROVEAN、SIFT和PolyPhen-2软件对p.S94L预测结果分别为:Deleterious、Damaging和Probably damaging。用上述方法对p.S460F的预测结果及ACMG的综合分析结果也显示该突变可能是致病性的。【结论】1)家系4的p.S94L和家系6的p.S460F新突变可能都是新的致病性突变,有可能都是引起患儿发病的内在原因之一。2)家系1,2,5,6,7可以确诊为MPS Ⅵ型,其基因型和表现型具有显著的相关性,家系3虽经酶检确诊,临床症状和尿检结果也都与MPS Ⅵ型符合,但却未能在DNA水平查到明确的突变类型,其表现型与基因型的相关性还有待进一步证实。国家自然科学基金(30772069);;闽粤合作科研基金(71010025和71020010

Fast detection of thanatophoric dysplasia type I p.R248C mutation hot spots and rapid prenatal diagnosis of three TD type I high-risk fetuses

目的针对致死性侏儒症I型（thanatophoric dysplasia typeⅠ,TD-Ⅰ）FGFR3基因的突变热点＂p.R248C＂,建立快速特异的酶切鉴定法（restriction endonuelease testing,RE）和扩增受阻突变系统（amplification refractory mutation system,ARMS）/RE法,并应用于后续3例疑似TD-I高危胎儿的快速产前诊断,以及时防止患胎出生,同时为今后的胚胎植入前遗传学诊断（preimplantation genetic diagnosis,PGD）打下良好基础。方法首先,针对突变热点p.R248C突变前后的序列特点,选择合适的内切酶＂Afe I＂,建立酶切鉴定法。其次,设计双错配碱基特异引物结合Apa LI酶切,建立ARMS/RE双重特异鉴定法。对阴性和阳性结果均再用普通引物扩、测的结果进行验证。结果用Afe I酶切FGFR3基因exons（6-7）普通引物的PCR产物（535 bp）,正常对照及非p.R248C突变的TD病例均能被切成255 bp和280 bp 2个片段,而胎1~胎3均切出255 bp、280 bp和535 bp 3个片段。用特异引物E7（p.R248C）扩增,正常对照和非p.R248C突变的TD病例均扩增阴性,无法进一步做酶切鉴定;而p.R248C突变均扩增阳性,当再用Apa LI酶切PCR产物（365 bp）时,胎1~胎3均切出22 bp和343 bp 2个片段。通过引物扩、测结果显示：胎1~胎3均是p.R248C杂合突变。结论该法快速特异、准确可靠,可用于p.R248C突变热点的快速检测及含该突变高危胎儿的快速产前诊断。该法还可用于含p.R248C突变TD-I型家系的PGD。胎1~胎3都是TD-I患胎,建议尽早终止妊娠。Objective To build up the specific rapid methods of RE and ARMS/RE for mutation hotspot＂p.R248C＂in the FGFR3 gene of thanatophoric dysplasia type I（TD-I）,then use the method for rapid prenatal diagnosis of 3 follow-up high-risk fetuses of TD-I to stop the birth of suffering fetuses,at the same time,lay a good foundation of preimplantation genetic diagnosis（PGD） for the future.Methods First,according to the characteristics of the sequence of the mutation hot spot p.248 C before and after mutation,the appropriate enzyme＂Afe I＂was selected to establish the identification method of enzyme digestion.After that,specific primers of double mismatch bases were devised,combining the method of digestion of Apa LI（ARMS/RE） to achieve the double identification.In the end,the sequences obtained by common primers were used to verify the negative and positive results through DNA sequencing.Results For the normal control and the patient without p.R248 C mutation of TD-I,PCR products（535 bp） of exons（6-7） of FGFR3 gene,amplified by common primers,could be digested into 2 fragments（255 bp and 280 bp） by Afe I.However,for fetuses 1~3,the PCR products could be digested into 3 fragments（255 bp,280 bp and 535 bp）.The normal control and the patient without p.R248 C mutation of TD-I were negative using the specific primers E7（p.R248C）,which could not be further identified by enzyme digestion.For the fetuses with p.R248 C mutation of TD-I,PCR products（365 bp） of exon 7 of FGFR3 gene,amplified by specific primers,could be digested by Apa LI and all the digested products were 22 bp and 343 bp.Sequencing results of common primers＇ products indicated：fetuses 1~3 were p.R248 C heterozygous mutation.Conclusions The method is fast,accurate and reliable,which can be available for the fast detection of mutation hot spot p.R248 C and the rapid prenatal diagnosis of high-risk fetus with p.R248 C mutation.This method can also be applied to PGD of high-risk fetus of TD-I with the mutation＂p.R248C＂.Fo闽粤合作科研基金（71010025

Fast leakage detector for overpressure resistant cabin

本实用新型公开一种通过使用真空装置快速检验耐压舱密封效果的耐压舱快速检漏装置。它由气管接头,耐压舱端盖,密封圈组以及耐压舱舱体组成,在端盖内法兰外圆柱面上设有密封槽,密封圈组放置在密封槽内,端盖内法兰外圆柱面上还设有孔,密封圈组中间,与气管接头相通。它可大幅度减小对承受外压的耐压舱进行气密性检验的时间,降低试验场地要求,省去进行气密性检验时对大型真空设备的需求,节约试验的时间和经费

Procedural Justice,Legitimacy,and Public Cooperation with Police：Whether Western Wisdom Applicable to China

研究目标：本研究的首要目的是检验汤姆·泰勒（Tom Tyler）基于程序的警务模型在中国的适用性,第二目的则是研究泰勒模型关键复合结构中的内部一致性和区分效度。研究方法：利用一个中国城市约1000名居民的调查数据,采用普通最小二乘回归法,评估程序正义、特定分配正义和警察效能对与警察合作意愿的直接和（通过合法性的）间接影响。研究结果：泰勒原始模型中关键复合结构的内部一致性和区分效度在中国数据中存在问题。来自西方的程序正义,就像西方本身一样,在预测中国人对警察合法性和与警察合作的意愿方面起着重要作用。与此同时,中国警察合法性的最有力预测因素是警察效能。分配正义和效能对中国人合作意愿的影响主要是通过警察的合法性来间接实现的。研究结论：泰勒模型的关键论点在很大程度上得到了中国数据的支持。未来需要进行特定文化的测量,以进一步完善泰勒基于程序的警务模型。Objectives： The principal objective of the study is to test the applicability of Tom Tyler＇s process-based model of policing in China. The secondary objective is to examine the internal consistency and discriminant validity of key composite constructs in Tyler＇s model. Methods： Using survey data collected from approximately 1,000 residents in a Chinese city,ordinary least squares regression was employed to assess the direct and indirect（ through legitimacy） effects of procedural justice,specific distributive justice,and police effectiveness on willingness to cooperate with the police. Results： The internal consistency and discriminant validity of key composites in Tyler＇s original model appear questionable with the Chinese data. Procedural justice,just like in the West,plays a significant role in predicting Chinese views on police legitimacy and willingness to cooperate with the police. Meanwhile,the strongest predictor of Chinese perceptions of police legitimacy is police effectiveness. The impact of both distributive justice and effectiveness on Chinese willingness to cooperate is mainly indirect through police legitimacy. Conclusions： Key arguments of Tyler＇s model are largely supported by the Chinese data. Future research needs to develop culture-specific measures to further elaborate Tyler＇s process-based model of policing

Pesticide Degrading Microorganisms and Mechanism in Soil

化学农药在土壤中残留造成的环境污染和给人类健康带来的危害日益严重,土壤微生物在土壤残留农药降解中起着关键作用,利用微生物来降解农药可以保障土壤的健康发展。本文从土壤残留农药的种类、降解农药的微生物类群、微生物降解农药的机理、微生物降解的影响因素等方面进行了综述,并且对土壤农药微生物降解的研究趋势提出了自己的观点。Pesticides have played an important role on the aspects of preventing crops from disaster of diseases,pests,weeds,and so on.However, the subsequent problem was that pesticide residue brought serious harm to the health of human beings and environment.In order to change the status quo,a mass of scientific researches have been made by scientists at present,including degrading pesticide residue by microorganism.Pesticides in soil,degrading microorganisms of pesticide in nature,degradation mechanism of pesticide and factors affecting on pesticide's degradation were reviewed in this paper.At the same time,own opinions on pesticide biodegradation were put forward.国家支撑计划项目课题(2008BADA7B09); 国家自然科学基金(40771116

外延晶体硅薄膜太阳电池的量子效率和特性研究

为了澄清限制所制备的颗粒硅带上的晶体硅薄膜太阳电池效率的主要因素, 对制备在颗粒硅带、经区熔(ZMR)后的颗粒硅带和单晶硅衬底上的外延晶体硅薄膜太阳电池进行了QE和Suns-Voc研究. 结果表明, 颗粒硅带上沉积的外延层的表面有一定的粗糙度, 它不但增加了电池表面的漫反射, 也使氮化硅减反射膜的结构变得疏松, 最终影响了减反射膜的陷光效果; 沉积在颗粒硅带上的硅活性层的晶体质量也较差, 较重的晶界复合限制了少子扩散长度, 使得制备在颗粒硅带上的硅薄膜太阳电池在长波方向上的光谱响应明显变坏. 所制备的晶体硅薄膜太阳电池的暗特性参数值均不理想, 电池性能尤其受到过高的暗饱和电流I02值和过低的并联电阻Rsh值的严重影响. 高的I02值是由于结区硅活性层较差的晶体质量所导致的严重的晶界复合造成的, 低的Rsh值被归结为电池经激光切割后未经钝化的裸露的PN结及电池边缘的漏电造成的

奇善宝对世玛除草剂药害小麦的恢复效应研究

在冬前麦田化学除草过程中,除草剂药害经常发生,以世玛等除草剂产生的药害较多,研究其缓解技术十分必要。针对世玛除草剂药害麦田,通过叶面喷施海洋寡糖生物制剂奇善宝,研究其对受害小麦恢复效应;受除草剂药害小麦叶面喷施奇善宝后7天,小麦植株开始有别于对照,25天后处理株高、绿叶数量、次生根显著高于对照,处理产量增加了549.30 kg/hm2,增产9.7%。同时喷施奇善宝在一定程度上改善籽粒品质,稳定时间增加15.7%,吸水率较对照降低1.4%,硬度、沉降值、出粉率和拉伸参数差异不显著;奇善宝可显著缓解除草剂对小麦的危害程度,有显著的增产效应,并在一定程度上改善籽粒品质

身份·语境·性别·历史及其他——李安电影研讨沙龙

市场的全球化与文化的自我意识日益强化相交汇的今天,文化的疆界日渐暧昧、含混,在此一视角下通过电影作品探视李安的文化身份、性别意识、家国情节,是本次研讨沙龙的主题。透过李安,我们隐约可以发现一个华语电影与世界电影,传统与现代,历史与现实,家国宏大叙事与个体微观选择共同构筑、交叉而成的十字路口,以此为坐标,我们似乎可以相对清晰地从不同向度标明边界,最后尝试性地去破解李安电影作品中潜藏的文化密码

乌鲁木齐环境容载力与城市污染控制对策

三年时间课题组进行了大量的调查、典型监测、取样分析,从乌鲁木齐环境保护和经济建设要求的生态环境研究入手,以指导乌鲁木齐区域环境保护和生态建设实践为落脚点,以市政府决策部门为用户,结合生态学、环境学、地理学、地质学、气象学、水文学、生物学等,建立了环境容载力研究的理论方法框架、提出了环境容载力评价的指标体系和计算的模型方法、设计了环境容载力的判据模型和环境生态位的计算模型、确定了乌鲁木齐环境容载力总量及其控制目标的生态位、提出了乌鲁木齐市可持续发展城市战略模式