Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.

Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.     

A natural allele of Nxf1 suppresses retrovirus insertional mutations

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements.     

泰国华人社会的文化复兴运动——同姓团体的大宗祠建设

在泰国 ,从 2 0世纪 6 0年代到 80年代中期 ,同姓团体的一种类型———宗亲总会持续不断地产生。创立宗亲总会目的在于一是为华人的族群认同提供依据。二是宗亲总会所建的大宗祠是象征华人民族群体的具有纪念碑意义的建筑物。同姓团体其大宗祠的建设标志着泰国华人社会的文化复兴运动的兴起。     

ELAM-1 is an adhesion molecule for skin-homing T cells.

Endothelial cell leukocyte adhesion molecule-1 (ELAM-1) has been described as an inducible endothelial cell-adhesion molecule for neutrophils, and is believed to have a key role in the extravasation of these cells at sites of acute inflammation. Here we report that ELAM-1-transfected COS cells also bind a unique skin-associated subset of circulating memory T cells defined by the expression of the cutaneous lymphocyte-associated antigen. T cells expressing this antigen bind at least as well as neutrophils to expressed ELAM-1, whereas other lymphocytes in the peripheral blood bind poorly, or not at all. Immunohistological survey of chronically inflamed tissue specimens revealed that vascular expression of ELAM-1 occurs at cutaneous sites in preference to noncutaneous sites. We conclude that at sites of chronic inflammation, ELAM-1 may function as a skin vascular addressin, a tissue-selective endothelial cell-adhesion molecule for skin-homing memory T lymphocytes.     

Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor

Changes in membrane potential affect ion channels and transporters, which then alter intracellular chemical conditions. Other signalling pathways coupled to membrane potential have been suggested but their underlying mechanisms are unknown. Here we describe a novel protein from the ascidian Ciona intestinalis that has a transmembrane voltage-sensing domain homologous to the S1-S4 segments of voltage-gated channels and a cytoplasmic domain similar to phosphatase and tensin homologue. This protein, named C. intestinalis voltage-sensor-containing phosphatase (Ci-VSP), displays channel-like 'gating' currents and directly translates changes in membrane potential into the turnover of phosphoinositides. The activity of the phosphoinositide phosphatase in Ci-VSP is tuned within a physiological range of membrane potential. Immunocytochemical studies show that Ci-VSP is expressed in Ciona sperm tail membranes, indicating a possible role in sperm function or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously realized.     

A record of Permian subaqueous vent activity in southeastern Brazil

The remarkable occurrence of more than 4,500 conical siliceous mounds in an area of less than 1.5 square kilometres has been reported in the Paraná basin, near Anhembi, S?o Paulo, in southeastern Brazil. These structures, which are up to two metres high, are thought to have been formed at the margin of a very shallow, broad but waning internal sea, and it was originally suggested that they are stromatolites. Yet their restricted occurrence, unusual abundance and nearly pure siliceous composition have never been satisfactorily explained by this hypothesis. Here we report field and laboratory observations on their shape, construction, composition and mineralogy. On the basis of our data we suggest that the conical mounds are the result of subaqueous Late Permian vent activity in southwestern Gondwana. The present siliceous cone field differs considerably from other Palaeozoic siliceous hot spring deposits, such as those at Rhynie, Scotland, and the Drummond basin, Australia, and therefore represents an unusual occurrence of vent activity.     

Development of Simulation System for the Disaster Evacuation Based on Multi-Agent Model Using

This paper presents a simulation system for the disaster evacuation based on multi-agent model considering geographical information. This system consists of three parts, the modeling for the land and buildings using GIS data, the analysis of disaster evacuation using multi-agent model, and the visualization for the numerical results using the virtual reality technique. By introducing the numerical solver of the natural disaster to the present system, it is possible to evaluate not only the damage of structure but also the damage of human being. Furthermore, it is possible to investigate the appropriate evacuation route by the simulation. The Dijkstra algorithm is used to obtain shortest route to the refuge. In addition, the visualization using virtual reality technique is curried out to understand the feeling of refugee. The present system is applied to the evacuation analysis by the flood flow in urban area and is shown to be a useful tool to investigate the damage by natural disasters.     

Large Scale Finite Element Modeling,Simulation and Visualization for Wind Flows in Urban Area Using Virtual Reality

A large-scale finite element modeling, simulation and visualization for wind flows are presented. The modeling method using GIS/CAD data is employed. The stabilized parallel finite element method based on SUPG/PSPG method is employed for the analysis of wind flows. The present method is applied to the simulation of wind flow and contaminant spread in urban area. The visualization based on virtual reality is employed to evaluate the mesh quality and computational results. The computed results are qualitatively in agreement with the experimental results and actual phenomena. The present method is shown to be a useful tool to simulate the wind flows in urban area.     

领悟社会支持对社交焦虑网络认知行为干预的效果

通过两个研究考察领悟社会支持和客观社会支持与社交焦虑的关系, 并探索领悟社会支持对社交焦虑个体网络认知行为治疗(ICBT)干预的效果。研究1: 对122名大学生被试进行两个时间点的社会支持与社交焦虑的测量, 结果发现领悟社会支持与社交焦虑相互影响, 领悟社会支持在客观社会支持与社交焦虑之间起中介作用, 中介效应的95%置信区间为[–1.47, –0.09]。研究2: 对比64名不同领悟社会支持水平的被试接受社会支持网络认知行为治疗与自助网络认知行为治疗的疗效, 结果发现社会支持组和自助组的被试在接受干预后社交焦虑得分都有显著下降, 领悟社会支持得分都有显著提高(社会支持组的得分显著高于自助组)。被试的领悟社会支持得分与有无社会支持被试的 ICBT 干预效果存在交互作用, 有支持小组的ICBT对低领悟社会支持个体干预效果更好, 而无支持小组的ICBT对高领悟社会支持个体干预效果更好。研究结果进一步理解并澄清了社会支持在社交焦虑中的作用, 可为未来临床工作的实践与应用提供了依据和方向。