A frameshift mutation in the gamma E-crystallin gene of the Elo mouse.

The murine Elo (eye lens obsolescence) mutation confers a dominant phenotype characterized by malformation of the eye lens. The mutation maps to chromosome 1, in close proximity to the gamma E-crystallin gene which is the 3'-most member of the gamma-crystallin gene cluster. We have analysed the sequence of this gene from the Elo mouse and identified a single nucleotide deletion which destroys the fourth and last "Greek key" motif of the protein. This mutation is tightly associated with the phenotype, as no recombination was detected in 274 meioses. In addition, the mutant mRNA is present in the affected lens, providing further support for our hypothesis that the deletion is responsible for the dominant Elo phenotype.     

颗粒增强聚合物复合材料损伤模型

研究了颗粒增强聚合物复合材料的力学行为,研究得知:材料屈服、裂纹形核、扩展与贯通直至最终断裂是一逐渐劣化过程,而损伤理论正是这一劣化过程的良好描述.通过假设自由能和耗散势函数,导出了损伤演化规律,与实验比较,模型和试验结果基本符合.进一步采用改进的Dugdale模型,重点研究损伤对GB/PPO复合材料宏观裂纹起裂的影响,通过建立损伤模型来描述材料的劣化行为和裂纹扩展,结果表明,损伤区域严重影响裂尖的性能,材料损伤对宏观裂纹起裂影响不可忽略.     

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

最小阶线性函数观测器设计的最好理论结果(英文)

最小阶线性函数观测器直接估测Kx(t)信号,其中K是任意给定的.这个观测器的极点在设计时也是任意给定的.1986年发表的一个设计程序所要解的公式是将这一设计问题简化成的一组线性方程组,保证设计出来的观测器阶数的上下限也是至今为止最低的.自1986年以来,上述的这一线性方程组已被宣称定性为这一设计问题的最可能简单的公式,上述的观测器阶数的上下限也已被宣称定性为最可能低的上下限.本文进一步证明和宣称定性这一1986年的结果是这一设计问题的最可能好的理论结果.这一宣称定性的重大意义可由以下两个事实来说明.首先这一明确而决定性的宣称定性是该结果发表26年后才作出的.其次相比最近发表的一篇相关论文,该文只是将整个设计问题推导成复杂得多的公式,没能提出真正系统地计算该复杂公式的解的计算程序,却宣称只有该文才得到了整个设计问题的解!     

MRPⅡ中物料清单树型结构的分析与实现

针对ＭＲＰⅡ物料清单的树状特点,提出了以物料结构与单据相结合的程序开发模式,以及相应的数据库设计方法。并且采用Ｖｉｓｕａｌ Ｐｏｘｐｒｏ５．０对物料清单管理进行了编程实现,得到了较为直观,方便,灵活的实用效果。另外,也与Ｇｏｚｉｎｔｏｇｒａｐｈ设计形式比较分析说明了物料清单树状结构设计实现的优势。     

A cluster of cystic fibrosis mutations in the first nucleotide-binding fold of the cystic fibrosis conductance regulator protein.

The gene responsible for cystic fibrosis (CF) has recently been identified and is predicted to encode a protein of 1,480 amino acids called the CF transmembrane conductance regulator (CFTR). Several functional regions are thought to exist in the CFTR protein, including two areas for ATP-binding, termed nucleotide-binding folds (NBFs), a regulatory (R) region that has many possible sites for phosphorylation by protein kinases A and C, and two hydrophobic regions that probably interact with cell membranes. The most common CF gene mutation leads to omission of phenylalanine residue 508 in the putative first NBF, indicating that this region is functionally important. To determine whether other mutations occur in the NBFs of CFTR, we determined the nucleotide sequences of exons 9, 10, 11 and 12 (encoding the first NBF) and exons 20, 21 and 22 (encoding most of the second NBF) from 20 Caucasian and 18 American-black CF patients. One cluster of four mutations was discovered in a 30-base-pair region of exon 11. Three of these mutations cause amino-acid substitutions at residues that are highly conserved among the CFTR protein, the multiple-drug-resistance proteins and ATP-binding membrane-associated transport proteins. The fourth mutation creates a premature termination signal. These mutations reveal a functionally important region in the CFTR protein and provide further evidence that CFTR is a member of the family of ATP-dependent transport proteins.     

Macroeconomic forecasting with mixed data sampling frequencies: Evidence from a small open economy

The aim of this study was to forecast the Singapore gross domestic product (GDP) growth rate by employing the mixed‐data sampling (MIDAS) approach using mixed and high‐frequency financial market data from Singapore, and to examine whether the high‐frequency financial variables could better predict the macroeconomic variables. We adopt different time‐aggregating methods to handle the high‐frequency data in order to match the sampling rate of lower‐frequency data in our regression models. Our results showed that MIDAS regression using high‐frequency stock return data produced a better forecast of GDP growth rate than the other models, and the best forecasting performance was achieved by using weekly stock returns. The forecasting result was further improved by performing intra‐period forecasting.     

Dynamic resource allocation for efficient patient scheduling: A data-driven approach

Efficient staff rostering and patient scheduling to meet outpatient demand is a very complex and dynamic task. Due to fluctuations in demand and specialist availability, specialist allocation must be very flexible and non-myopic. Medical specialists are typically restricted in sub-specialization, serve several patient groups and are the key resource in a chain of patient visits to the clinic and operating room (OR). To overcome a myopic view of once-off appointment scheduling, we address the patient flow through a chain of patient appointments when allocating key resources to different patient groups. We present a new, data-driven algorithmic approach to automatic allocation of specialists to roster activities and patient groups. By their very nature, simplified mathematical models cannot capture the complexity that is characteristic to the system being modeled. In our approach, the allocation of specialists to their day-to-day activities is flexible and responsive to past and present key resource availability, as well as to past resource allocation. Variability in roster activities is actively minimized, in order to enhance the supply chain flow. With discrete-event simulation of the application case using empirical data, we illustrate how our approach improves patient Service Level (SL, percentage of patients served on-time) as well as Wait Time (days), without change in resource capacity.