Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology

Neurofibromatosis type 2 is an autosomal dominant disorder characterized by tumors, predominantly schwannomas, in the nervous system. It is caused by mutations in the gene NF2, encoding the growth regulator schwannomin (also known as merlin). Mutations occur throughout the 17-exon gene, with most resulting in protein truncation and undetectable amounts of schwannomin protein. Pathogenic mutations that result in production of defective schwannomin include in-frame deletions of exon 2 and three independent missense mutations within this same exon. Mice with conditional deletion of exon 2 in Schwann cells develop schwannomas, which confirms the crucial nature of exon 2 for growth control. Here we report that the molecular adaptor paxillin binds directly to schwannomin at residues 50-70, which are encoded by exon 2. This interaction mediates the membrane localization of schwannomin to the plasma membrane, where it associates with beta 1 integrin and erbB2. It defines a pathogenic mechanism for the development of NF2 in humans with mutations in exon 2 of NF2.     

Axisymmetric fundamental solutions for a finite layer with impeded boundaries

Axisymmetrie fundamental solutions that are applied in the consolidation calculations of a finite clay layer with impeded boundaries were derived. Laplace and Hankel integral transforms were utilized with respect to time and radial coordinates, respectively in the analysis. The derivation of fundamental solutions considers two boundary-value problems involving unit point loading and ring loading in the vertical. The solut-ions are extended to circular distributed and strip distributed normal load. The computation and analysis of set-tlements, vertical total stress and excess pore pressure in the consolidation layer subject to circular loading are presented.     

Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.     

Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification

The genetic analysis of congenital skull malformations provides insight into normal mechanisms of calvarial osteogenesis. Enlarged parietal foramina (PFM) are oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM are usually asymptomatic, but may be associated with headache, scalp defects and structural or vascular malformations of the brain. Inheritance is frequently autosomal dominant, but no causative mutations have been identified in non-syndromic cases. We describe here heterozygous mutations of the homeobox gene MSX2 (located on 5q34-q35) in three unrelated families with PFM. One is a deletion of approximately 206 kb including the entire gene and the others are intragenic mutations of the DNA-binding homeodomain (RK159-160del and R172H) that predict disruption of critical intramolecular and DNA contacts. Mouse Msx2 protein with either of the homeodomain mutations exhibited more than 85% reduction in binding to an optimal Msx2 DNA-binding site. Our findings contrast with the only described MSX2 homeodomain mutation (P148H), associated with craniosynostosis, that binds with enhanced affinity to the same target. This demonstrates that MSX2 dosage is critical for human skull development and suggests that PFM and craniosynostosis result, respectively, from loss and gain of activity in an MSX2-mediated pathway of calvarial osteogenic differentiation.     

西藏芒康县盐井化探异常分布规律及找矿标志

盐井属于藏东昌都地区芒康县,地处于著名的三江成矿区;藏东地质构造复杂,成矿条件优越,具备形成铜、金、铅、锌、银矿的地质背景,是中国重要的多金属成矿带。根据1∶20万区域化探异常特征优选了芒康县盐井开展1∶5万地球化学测量,Au、Cu、Ag、Pb元素套叠好,异常强度大,属于典型的矿致异常,找矿前景十分广阔,是该区重要找矿靶区。     

基于响应面法的海上油藏注气参数设计方法

针对海上低渗油藏注气方案设计受平台环境、油藏特征和工艺条件等众多因素影响而复杂烦琐的问题,将响
应面方法引入水气交替驱方案的设计中。在确定了少量但具有代表性的气驱方案的基础上,通过对其结果的统计分
析,形成了采收率指标与注气时机、水气比、周期注入段塞3 个因素之间的预测模型与响应曲面,并在此基础上开展了
注气参数优化设计。通过该方法可以对研究范围内的气驱方案进行高效地设计、预测和优化,简洁、直观地确定最佳
气驱方案,科学、高效地实现设计目标,提高了海上低渗油藏气驱设计工作的效率和质量。     

西昌市月城广场设计思路

月城广场是西昌市政府的形象工程。该广场应设计成能够突出西昌特色,具有生态效益、社会效益、经济效益及以人为本的可游可憩的城市广场。本文论述了设计者设计的月城广场方案的立意构思、分区布局、设计特点与手法等。     

铜川地区油页岩地层电性断面特征及勘查

为了研究电阻率测深方法在油页岩地区的适用性及分辨率,在鄂尔多斯盆地南缘铜川地区开展了电阻率测深
工作。结合钻孔录井和见矿情况,分析了油页岩地段两种勘查方法获得的电阻率断面特征,在电性断面上圈定了油页
岩层的特定部位。油页岩层厚度相对埋深而言属薄层、高阻目标体,其厚度与埋深纵向比小,在获得的电阻率测深断
面上,高阻电性的油页岩层在电阻率测深断面上分辨率不清晰,其层位与电阻率等值线梯度变化带对应较好,从而间
接指示了油页岩层位置。同时,通过岩性与测井参数综合分析,认为测深断面上这种电阻率值随深度的渐变特征,从
电性角度描述了油页岩层由浅湖沉积环境到半深湖环境的变迁过程,提出电阻率测深方法可以达到勘查油页岩层之
目的。     

简论水淹略阳县城的山洪灾害

陕西南部的略阳县城,在1981～1990年间三次被淹,频度之高,危害之大是本县历史上所没有的。本文认为这是自然因素和人为因素共同作用的结果,建议在嘉陵江主要支流上修建具有蓄水、发电、灌溉综合效益的控水工程,配合生物措施和加强河道管理,根治水淹县城的山洪灾害,减轻生命财产的损失。     

Study on the Reliability Evaluation of Qualitative Indices in Multi-Objective Decision

Qualitative indices in multi-objective decision can usually be evaluated and measured by mathematical methods or models, but the obtained results are sometimes inaccurate because of fuzziness of indices. To improve the accuracy and reliability of the evaluation results, set-value statistic principle is applied, and accordingly four evaluation methods are obtained. Meanwhile, these methods are compared briefly.