A mouse model for spinal muscular atrophy

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.     

CpG methylation is maintained in human cancer cells lacking DNMT1

Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16INK4a, remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome.     

Origins of sulphate in Antarctic dry-valley soils as deduced from anomalous 17O compositions

The dry valleys of Antarctica are some of the oldest terrestrial surfaces on the Earth. Despite much study of soil weathering and development, ecosystem dynamics and the occurrence of life in these extreme environments, the reasons behind the exceptionally high salt content of the dry-valley soils have remained uncertain. In particular, the origins of sulphate are still controversial; proposed sources include wind-blown sea salt, chemical weatherings, marine incursion, hydrothermal processes and oxidation of biogenic sulphur in the atmosphere. Here we report measurements of delta18O and delta17O values of sulphates from a range of dry-valley soils. These sulphates all have a large positive anomaly of 17O, of up to 3.4/1000. This suggests that Antarctic sulphate comes not just from sea salt (which has no anomaly of 17O) but also from the atmospheric oxidation of reduced gaseous sulphur compounds, the only known process that can generate the observed 17O anomaly. This source is more prominent in high inland soils, suggesting that the distributions of sulphate are largely explained by differences in particle size and transport mode which exist between sea-salt aerosols and aerosols formed from biogenic sulphur emission.     

铝型材挤压模具导流孔结构优化

基于MATLAB平台,将BP人工神经网络、遗传算法和数值模拟技术应用于铝型材挤压模具的导流孔形状优化设计。由正交实验法安排模拟实验组合,采用SuperForge软件对进行型材挤压过程进行数值模拟,并以挤压时金属流出模口平面的z向质点流速的均方差作为模型目标值;将模拟结果作为人工神经网络的输入样本对进行网络训练并建立网络知识源;通过遗传算法求得模型的全局优化解;最后通过有限体积法数值模拟技术验证并比较优化所得导流孔形状与经验法确定的导流孔形状对金属流动均匀性的影响。分析结果表明,通过调整导流孔形状能使金属流出模口的速度分布更均匀,表明对挤压模具导流孔形状的优化是有效的。     

自动转换开关电器的设计应用

自动转换开关电器主要用在重要场所的紧急供电系统,将负载电路从一个电源自动转换至另一个电源的电器,以确保重要负荷连续、可靠运行。     

简单树结构存储系统数据分块标准及其证明

为解决传统磁盘阵列技术受系统总线与设备通道制约的问题,采用树结构和单元控制器构建了新型的存储系统.在树结构存储系统的基础上,通过对简单树结构存储系统数据分块方式的定义、推论,以及冲突系数的证明,给出了简单树结构存储系统的数据分块标准.结果证明:简单树结构存储系统数据分块标准能最大程度降低存储系统有效冲突系数,提升存储系统性能.