Prenatal exclusion of haemophilia a and carrier testing by direct detection of a disease lesion

A novel mutation was detected in the Factor VIII gene of a sporadic case of severe haemophilia A. The lesion, a CGA → TGA transition, converts Arg 795 to Term and adequately accounts for the severe phenotype observed. PCR/direct sequencing was used to confirm the carrier status in the mother. Exclusion of haemophilia A in an at-risk pregnancy was then achieved by demonstration of the absence of this lesion in fetal DNA from a chorionic villus sample. The mutation was also detectable by chemical cleavage of mismatch (CCM), which both confirmed the prenatal diagnosis and established the carrier status of the proband's sister. This example therefore serves to illustrate the potential of direct gene analysis in sporadic cases of haemophilia A and/or in families uninformative for known RFLPs.     

全球人口与粮食的空间错位演变及影响因素分析

基于重心模型和空间错位指数方法,系统分析了1990—2017年全球人口与粮食的时空格局、空间错位特征及影响因素等。结果表明：（1）近30年来,全球人口与粮食均呈增长态势,两者的时序变化特征存在明显差异,全球人均粮食产量的区域差异特征显著,多数国家的“人粮关系”矛盾突出。（2）在全球尺度,人口与粮食重心存在显著的空间错位特征,两者在空间分布上呈现反向错位发展的态势。（3）在国家尺度,人口与粮食的空间错位格局呈现由南至北依次为“正错位区—负错位区—正错位区”。负向高错位区稳定在印度、日本等国家,正向高错位区稳定在美国、加拿大等国家。（4）全球各大洲人口与粮食的空间错位格局基本稳定,空间错位指数发生转向的国家分布在亚洲、欧洲、南美洲和非洲。（5）自然环境、国际环境、农业发展、社会环境等多种因素综合作用致使人口规模和粮食产量在空间分布上存在区域差异,促成全球人口与粮食的空间错位格局。政策启示：中国有必要加快农业供给侧结构性改革,增强农业竞争力和粮食自给率,合理统筹配置两种资源和处理两个市场之间的关系,建立规避世界粮食贸易波动和不确定性风险的应对策略,构建中国农业生态安全和粮食安全的保障体系。     

长江经济带国土空间纠错实施机制——以江苏省仪征市和张家港市为例

国土空间纠错是自然资源管理部门落实“统一行使所有国土空间用途管制职责”的重要手段,是国土空间管控和治理的重要内容。以江苏省仪征市和张家港市为例,探究国土空间错配类型、表现形式及成因,尝试构建国土空间纠错实施机制,以期为长江经济带国土空间用途管制制度构建提供理论和实践参考。研究结果表明：（1）国土空间错配类型主要有：因规划欠合理、规划缺乏、规划冲突引起的错配,城镇、农业、生态三大空间现状用途错配,因劳动力、资本、土地错配及环境规制要求引起的行业错配,因资源过度利用或低效利用引起的强度错配。（2）针对不同错配类型,可从建立“三线”协调机制、构建“全流程、多主体、多路径”分类纠错机制、完善国土空间用途管制制度、建立国土综合整治和生态修复保障机制及动态监管机制等角度入手,构建国土空间纠错机制体系。研究结果可为长江经济带国土空间纠错、国土空间用途管制、国土空间优化提供理论和实践参考。     

用自动电位滴定仪测定水的总硬度实验

水的总硬度测定采用EDTA进行络合滴定。实验中用自动电位滴定仪代替人工进行样品分析,由颜色突变判断滴定终点改为电位突变,具有高硬度样品预判断、滴定干扰小、准确度高、节省人力、便于数据记录统计比较等优点。     

基于Mann-Kendall法的湖泊稳态转换突变分析

采用变化趋势与倾向率、Mann-Kendall趋势检验法和突变点分析法对1981~2008年间太湖湖泊稳态转换关键因子总氮(TN)、总磷(TP)和叶绿素a(Chla)进行突变识别,结果表明,(1)TN、TP和Chla分别在0.05、0.10和0.05水平上呈显著增加趋势;(2)TN浓度在1990~1991年间和1994~1995年间发生了两次突变;TP浓度突变点发生在1987~1988年;Chla浓度历史变化存在三个阶段,1981~1989年为第一阶段,尚未产生突变阶段,第二阶段为1990~1996年,突变过渡阶段,第三阶段为1997~2008年,属于突变后的状态;(3)综合TN、TP和Chla浓度历史变化存在不同阶段,结合各因子的历史变化序列,太湖湖泊稳态转换突变点为1988年和1997年,并把太湖划分为三个阶段,第一阶段为1981~1987年, TP浓度为0.025mg/L,属于草藻共存,接近于清水稳态阶段;第二阶段为1988~1996年, TP浓度为0.086mg/L,属于藻草共存阶段;第三阶段为1997到2008年, TP浓度为0.103mg/L,属于藻型浊水稳态.研究结果表明Mann-Kendall法在湖泊稳态转换突变分析中具有一定的适用性.     

近60年黄河流域典型区域气温突变与变暖停滞研究

以黄河流域典型区域-黄河流域内蒙古段为研究区,采用1951~2012年62年气温区域平均数据,应用M-K检验等方法对研究区区域平均最高气温、平均气温、平均最低气温突变前后变化及气温突变后变暖停滞特征进行了分析.结果表明：年（季）平均最低气温首先发生突变（1977~1987年）,平均气温次之（1978~1993年）,平均最高气温最晚（1978~1994年）,平均最高气温与平均气温秋、冬季发生突变时间一样;年内突变早晚顺序为冬季最早（1977~1978）,夏季最晚（1987~1994）.冬季比夏季、平均最高气温比平均最低气温变化更剧烈.平均最低气温（0.231~0.604℃/10a）对升温贡献较大.各类气温年（季）突变后在1997~2007年间先后发生变暖停滞现象,春季和冬季首先发生变暖停滞,秋季较晚,夏季未停滞,年气温最晚（2007年）,大部分年（季）气温要素变暖停滞晚于全球变暖停滞时间（1998年）.年际气温突变后到停滞前平均最高气温的升温速率相对最慢,而其停滞后降温速率反而最快,平均最低气温与其相反,初步说明平均最低气温对升温反应较为明显,平均最高气温对降温反应较为明显.季节中,突变后到气温停滞前,春季平均最高气温增长速率最快;气温停滞后,春季最低气温下降速率最快（-0.324℃/a¹）.     

Prenatal analysis of the insulin receptor gene in a family with leprechaunism

We report on the prenatal diagnosis of a fetus at risk of leprechaunism. We had previously determined the nature of the causative mutation in the insulin receptor gene in this family. The mutation removes a restriction site for the enzyme Mbo II. Genomic DNA was extracted from a chorionic villus sample and the 3′ half of exon 2 was amplified by the polymerase chain reaction (PCR) followed by restriction digest. Using this method, we correctly predicted an unaffected child.     

复合诱变菌处理氨氮废水

采用诱变技术对微生物菌种进行了诱变处理，分别研究了紫外线诱变菌、硫酸二乙酯（DES）诱变菌和复合诱变菌对含氨废水的降解性能。结果表明，复合诱变后获得的变异菌株Z5对含氨废水中NH4^ -N的去除率比单独采用紫外线或DES诱变后获得的菌株有明显的提高。混合菌种对化肥行业废水中COD的NH4^ -N的去除率可以达到95%～98%，出水能达到行业一级排放标准。     

古蔺河流域径流特性分析与研究

为能充分掌握宜宾市古蔺河流域径流量的演变规律,基于1960—2009年古蔺河流域径流量统计资料,采用线性趋势法、滑动平均法、改进的Mann-Kendall(M-K)趋势法分析古蔺河径流量的年季变化趋势,运用Mann-Kendall(M-K)突变检验法、改进的Mann-Kendall(M-K)突变检验法、滑动t检验法对古蔺河径流量的年季突变特征进行综合分析。结果表明:古蔺河径流量序列的年季变化趋势均不显著,年均径流量总体呈上升趋势;春、夏两季呈上升趋势,秋、冬两季呈下降趋势;古蔺河年季径流时间序列均有突变出现,年均径流量的突变点发生在1985年附近;春季径流量的突变点发生在1982年;夏季径流量的突变点发生在1988,2001年;秋季径流量的突变点发生在1983,1993年;冬季径流量的突变点发生在2004年。     

Prenatal diagnosis of a lethal form of Netherton syndrome by SPINK5 mutation analysis

Netherton syndrome (NS) is a severe autosomal recessive ichthyosis with no specific treatment or prenatal diagnosis available at present. The recent identification of SPINK5, which encodes a serine protease inhibitor, as the defective gene enables DNA-based prenatal diagnosis to be carried out. Here we report the first direct molecular prenatal diagnosis of a lethal form due to a recurrent SPINK5 mutation in three consanguineous Turkish families. XmnI restriction enzyme digestion and DNA sequencing demonstrated that each deceased affected child was homozygous for mutation 153delT inherited from each parent. Analysis of fetal DNA from amniotic fluid cells in Family 1 and from a chorionic villus sampling in Family 3 showed that the fetus was heterozygous for 153delT in both cases. The pregnancies were carried to term and the newborns were unaffected. In Family 2, fetal DNA analysis from chorionic villus biopsy showed in a first pregnancy that the fetus was homozygous for 153delT. The pregnancy was terminated at 13 weeks and DNA analysis of fetal keratinocytes confirmed the prenatal prediction. In a second pregnancy in Family 2, fetal DNA analysis showed heterozygosity for 153delT, and the pregnancy was continued. Direct SPINK5 mutation analysis in families at risk for NS represents the first early, rapid and reliable method for prenatal diagnosis of this life-threatening form of ichthyosis. Copyright © 2002 John Wiley & Sons, Ltd.     

紫外诱变优势菌处理含氯废水

采用紫外诱变技术选育高效降解菌，对未诱变菌和６株诱变菌进行含氯废水的降解性能实验。结果表明：紫外诱变的最佳时间是４０ｓ；变异优势菌４＾＃菌株对含氯废水的ＣＯＤＣｒ和ＴＣ１（总氯）的去除率比未诱变优势菌０＾＃菌株分别提高１０％和２０％；变异菌菌株生长速度快，抗有机氯毒性大大提高。     

Prenatal diagnosis of Crigler–Najjar syndrome type I by single-strand conformation polymorphism (SSCP)

Crigler–Najjar syndrome type I (CN-I) is a rare and severe inherited disorder of bilirubin metabolism, caused by the total deficiency of bilirubin-UDP-glucuronosyltransferase (UGT) activity. Enzymatic diagnosis cannot be performed in chorionic villi or amniocytes as UGT is not active in these tissues. The cloning of the UGT1 gene and the identification of disease-causing mutations have led to the possibility of performing DNA-based diagnosis. Here we report DNA-based prenatal diagnosis of CN-I in two Tunisian families in whom CN-I patients were diagnosed. As we had previously shown that CN-I was, in Tunisia, associated with homozygosity for the Q357R mutation within the UGT1 gene, we were able to detect this mutation in both families and to show that it was easily recognized by single-strand conformation polymorphism (SSCP) analysis. In both cases, SSCP analysis of fetal DNA showed that the fetus was heterozygous for the Q357R mutation. In one family, the pregnancy was carried to term and a healthy baby was born, whereas, in the other family, the pregnancy is still continuing. Thus the prenatal diagnosis of CN-I is possible, provided disease-causing mutations have been identified. SSCP analysis of DNA prepared either from amniocytes or from chorionic villi is a simple, reliable and fast method for prenatal diagnosis. Copyright © 2002 John Wiley & Sons, Ltd.     

机载光电吊舱隔振系统研究综述

主要从振动对光电设备成像的影响和无角位移隔振设计两个方面,综述了近年来国内外学术界对机载光电设备的隔振设计方法和技术。提出角振动较线振动对光电吊舱成像质量的影响大,光电吊舱隔振设计需重点考虑降低角振动问题。引起设备角振动的重要因素为光电设备的质心与隔振系统的刚度中心相偏离,以及各隔振器之间的刚度和阻尼不匹配,隔振系统设计时应予以关注。     

Design and manufacturing of femoral stems for the Indian population

Several researchers have stressed the need for a proper implant-patient match in hip joint replacements, in particular, for cementless femoral stems. Some of the complications of mismatch are aseptic loosening, improper load distribution, and discomfort. In this study, the differences in dimensions between femurs of elderly Indians and those of populations from other regions are compared in order to solve the problem of a possible geometric mismatch between a selected implant and the femurs of an Indian patients are concerned. This paper also describes a methodology for implant designing from measured anthropometric data, fit evaluation, finite element (FE) stress analysis and subsequently implant manufacturing using the CAM (Computer Aided Manufacturing) technique. The machining of the Titanium alloy femoral stem is usually performed on a 5 Axis CNC (Computer Numerical Control) machining center. However, in this study the machining of the femoral stem was effectively performed on a 3 Axis CNC machining center to emphasize on economical benefits for low cost manufacturing strategy.     

1951~2014年中国北方地区气温突变与变暖停滞的时空变异性

基于1951~2014年中国北方及周边地区357个气象站点平均最低气温、平均气温和平均最高气温年（月）数据,采用M~K检验等方法,分析了中国北方地区3类气温突变和变暖停滞特征的时空变异性.结果表明：研究区3类气温整体突变年（1978~1999年、1981~2002年、1981~2005年）、分布广泛的普遍突变年（1988年、1989年、1997年）及范围（3a）均依次变晚.整体上,突变年随纬度降低变晚,东北突变早于西北和华北地区.变暖停滞集中于1998和2007年及其前后,3类气温亦依次变晚（1994~2007年、1995~2009年、1998~2010年）,由黄河流域中段向其他方向越来越晚.突变至变暖停滞周期整体随纬度降低缩短（3~30a）,突变越早周期越长.西北地区突变与变暖停滞前后各时段均值温差最大（2.4℃）,温差在1℃左右站点分布最广泛.各时段升（降）温速率整体依次在0.01℃/10a、0.05℃/10a、-0.03℃/10a左右站点分布最广泛,突变后升温最快（0.02~0.16℃/10a）,且西北地区对升温贡献最大,变暖停滞后东北地区对降温贡献最大,2时段按平均最低气温、平均最高气温、平均气温顺序升（降）温速率递减.3类气温波动程度减弱,整体随纬度降低.高纬度、高海拔和山地地区突变和变暖停滞较周边地区偏早或偏晚,特征值较大.整个北方地区3类气温突变、变暖停滞、突变与变暖停滞时间及各时段特征值各自具有自身一致性的普遍规律.     

二种除草剂遗传毒性的研究

以黄鳝为试验材料,研究了艾割和使它隆二种除草剂对鱼类的致突变性。对经腹腔注射染毒上述二种除草剂的受试黄鳝,通过对其活体肾细胞染色体数目和形态的观察,分析其突变率。研究结果(经t检验)显示:艾割和使它隆二种除草剂分别在其试验最低受试剂量50mg/kg和8.0mg/kg即可引起黄鳝的染色体畸变。采用SOS/Umu显色试验研究,在SOS/Umu试验中,使它隆和艾割2个受试除草剂可以诱发SOS阳性反应,且呈明显的剂量-效应关系。试验表明这二种除草剂具有遗传毒性,应对这二种除草剂严加管控,避免其对环境的影响。     

The amplification refractory mutation system (ARMS): A rapid and direct prenatal diagnostic technique for β-thalassaemia in Singapore

β-Thalassaemia major patients have chronic anaemia and since 3–4 per cent of Singaporeans carry the β-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of β-major. Six mutations along the β-gene were studied—41–42 (-TCTT), IVSII #654 (C-T), 17β (A-T), – 28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54·6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the β-trait carrying the 41–42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the β-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at − 29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our β-thalassaemia prenatal diagnosis programme in Singapore.     

水资源与社会经济发展要素时空匹配特征——以张家口为例

水资源短缺已成为制约区域经济社会发展的重要因素,协调水资源与社会经济关系是水资源可持续利用的关键。以张家口为例,采用洛伦兹基尼系数和不均衡指数模型对水资源与社会经济发展要素的时空匹配特征进行研究,结果表明：2004—2015年张家口水资源与人口、耕地面积分布处于“匹配比较合理”和“相对匹配”状态,水资源与经济布局匹配呈现出由“完全不匹配”状态逐渐转变为“相对不匹配”状态。在空间匹配演化方面,水资源与人口、耕地面积的匹配度变化不大。水资源与经济匹配结果表明在水资源禀赋越差的地区,经济增速越快,水资源与经济的空间匹配状况越差。张家口水资源与社会经济发展要素时空匹配特征研究,对于指导区域水资源合理开发利用具有重要的现实意义。     

Mid–trimester hyperechogenic bowel in a fetus of Japanese origin carrying a new mutation of CFTR gene (L548Q)

We present a case of a fetus with hyperechogenic bowel, in which the L548Q mutation was detected in the mother of Japanese origin and the ΔF508 mutation in the father of Caucasian origin. The fetus proved to be compound heterozygous. Research into cystic fibrosis transmembrane conductance regulator (CFTR) mutations in this case was triggered by the fact that the fetus had a characteristic hyperechogenic bowel image with normal karyotype and no indications of intrauterine infections. Hyperechogenic bowel is highly indicative of a CFTR gene mutation. The incidence of cystic fibrosis (CF) in fetuses with mid-trimester hyperechogenic bowel is 5%, but once the most frequent mutations have been accounted for, rarer mutations must be investigated. Copyright © 2006 John Wiley & Sons, Ltd.     

Non-invasive prenatal detection of achondroplasia in size-fractionated cell-free DNA by MALDI-TOF MS assay

Achondroplasia is the most common form of short-limbed dwarfism in humans and is caused by mutations in the FGFR3 gene. Currently, prenatal diagnosis of this disorder relies on invasive procedures. Recent studies have shown that fetal single gene point mutations could be detected in cell-free DNA (cf-DNA) from maternal plasma by either the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single allele base extension reaction (SABER) approach or the size fractionation of cf-DNA in maternal plasma. Here, we combined the two approaches to non-invasively examine the fetal G1138A mutation in maternal plasma. cf-DNA was extracted from maternal plasma samples obtained from two pregnant women at risk for achondroplasia. The fetal G1138A mutation was determined by the analysis of size-fractionated cf-DNA in maternal plasma using MALDI-TOF MS with SABER approach and homogenous MassEXTEND (hME) assay, respectively. The fetal G1138A mutation was detectable in the two achondroplasia-affected pregnancies by the analysis of cf-DNA in maternal plasma using MALDI-TOF MS. However, the size-fractionation approach led to a more precise detection of the fetal mutation in both analyses. This analysis would be suitable for non-invasive prenatal diagnosis of diseases caused by fetal single gene point mutations. Copyright © 2007 John Wiley & Sons, Ltd.