Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.     

A functional switch from lung cancer resistance to susceptibility at the Pas1 locus in Kras2LA2 mice

Pulmonary adenoma susceptibility 1 (Pas1) is the major mouse lung cancer susceptibility locus on chromosome 6 (ref. 1). Kras2 is a common target of somatic mutation in chemically induced mouse lung tumors and is a candidate Pas1 gene. M. spretus mice (SPRET/Ei) carry a Pas1 resistance haplotype for chemically induced lung tumors. We demonstrate that the SPRET/Ei Pas1 allele is switched from resistance to susceptibility by fixation of the parental origin of the mutant Kras2 allele. This switch correlates with low expression of endogenous Kras2 in SPRET/Ei. We propose that the Pas1 modifier effect is due to Kras2, and that a sensitive balance between the expression levels of wild-type and mutant alleles determines lung tumor susceptibility. These data demonstrate that cancer predisposition should also be considered in the context of somatic events and could have major implications for the design of human association studies to identify cancer susceptibility genes.     

Model algorithm control using neural networks for input delayed nonlinear control system

The performance of the model algorithm control method is partially based on the accuracy of the system’s model. It is difficult to obtain a good model of a nonlinear system, especially when the nonlinearity is high. Neural networks have the ability to "learn"the characteristics of a system through nonlinear mapping to represent nonlinear functions as well as their inverse functions. This paper presents a model algorithm control method using neural networks for nonlinear time delay systems. Two neural networks are used in the control scheme. One neural network is trained as the model of the nonlinear time delay system, and the other one produces the control inputs. The neural networks are combined with the model algorithm control method to control the nonlinear time delay systems. Three examples are used to illustrate the proposed control method. The simulation results show that the proposed control method has a good control performance for nonlinear time delay systems.     

矢量分析新论

E.B.Wilson对J.W.Gibbs创立的矢量分析作了修改，其     

急性肝功能衰竭的猪动物模型

目的：建立一个比较接近人类条件的急性肝衰竭模型。用于人工肝脏治疗的疗效和安全性的测试。方法：以右旋半乳糖来制造猪肝衰竭的大型动物模型,分组３组给药,剂量分别为０．５、１和０．７５g/kg。观察其临床表现、生理生化指标和病理改变。结果：３组实验都能引出与人的临床和生化指标变化相伫的肝功能衰竭的表现,以０．７５g/kg组最为理想。结论：以０．７５g/kg的半乳糖胺制造的急性肝功能衰竭的猪动物模型,符合人工肘脏研究对动物模型的要求。     

Kras regulatory elements and exon 4A determine mutation specificity in lung cancer

Kras is the most frequently mutated ras family member in lung carcinomas, whereas Hras mutations are common in tumors from stratified epithelia such as the skin. Using a Hras knock-in mouse model, we demonstrate that specificity for Kras mutations in lung and Hras mutations in skin tumors is determined by local regulatory elements in the target ras genes. Although the Kras 4A isoform is dispensable for mouse development, it is the most important isoform for lung carcinogenesis in vivo and for the inhibitory effect of wild-type (WT) Kras on the mutant allele. Kras 4A expression is detected in a subpopulation of normal lung epithelial cells, but at very low levels in lung tumors, suggesting that it may not be required for tumor progression. The two Kras isoforms undergo different post-translational modifications; therefore, these findings can have implications for the design of therapeutic strategies for inhibiting oncogenic Kras activity in human cancers.     

广义牛顿程序

本文提出了一种广义牛顿迭代程序,作为特例,它包含了通常的车贝谢夫程序、切双曲线程序和最速下降程序。     

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.