Leonurine, an improved synthesis.

Leonurine (1) is the uterotonic principle of Leonurus artemisia. We have developed a simple, high-yield synthetic procedure of 1 that is adaptable to large scale preparation. The synthesis involves the condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of DDC using 1:1 HMPT-ether as solvent. The synthetic leonurine showed uterotonic activity in vivo and in vitro.     

A YAC-based physical map of the mouse genome.

A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.     

Late retroperitoneal recurrence of hepatocellular carcinoma 12 years after initial diagnosis

Hepatocellular carcinoma (HCC) is an aggressive tumor with poor long-term prognosis.Here,we present an unusual patient with a solitary recurrence of HCC in the right kidney 12 years after the initial diagnosis.This illustrates the importance of considering late recurrence in patients with a history of HCC and the management of these metastases.     

Structure of the insulin receptor ectodomain reveals a folded-over conformation

The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding.     

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.     

A new approach to forecasting intermittent demand based on the mixed zero-truncated Poisson model

This paper proposes a new approach to forecasting intermittent demand by considering the effects of external factors. We classify intermittent demand data into two parts—zero value and nonzero value—and fit nonzero values into a mixed zero-truncated Poisson model. All the parameters in this model are obtained by an EM algorithm, which regards external factors as independent variables of a logistic regression model and log-linear regression model. We then calculate the probability of occurrence of zero value at each period and predict demand occurrence by comparing it with critical value. When demand occurs, we use the weighted average of the mixed zero-truncated Poisson model as predicted nonzero demands, which are combined with predicted demand occurrences to form the final forecasting demand series. Two performance measures are developed to assess the forecasting methods. By presenting a case study of electric power material from the State Grid Shanghai Electric Power Company in China, we show that our approach provides greater accuracy in forecasting than the Poisson model, the hurdle shifted Poisson model, the hurdle Poisson model, and Croston's method.     

一种宽带光纤拉曼放大器数值模拟的新算法

以后向泵浦的宽带光纤拉曼放大器为模型,基于平均功率的思想,运用矩阵迭代法模拟信号光和泵浦光在光纤中的传输特性,数值计算出拉曼增益曲线.这种算法结合了平均功率法的快速和矩阵迭代法的简单易控制的优点,在保证计算精度的情况下能提高计算速度.理论分析结果和实验结果均显示该算法可以准确模拟拉曼放大过程.该算法可以为设计制作光纤拉曼放大器提供参考.