Mechanisms of valence selectivity in biological ion channels

Transmembrane ion channels play a crucial role in the existence of all living organisms. They partition the exterior from the interior of the cell, maintain the proper ionic gradient across the cell membrane and facilitate signaling between cells. To perform these functions, ion channels must be highly selective, allowing some types of ions to pass while blocking the passage of others. Here we review a number of studies that have helped to elucidate the mechanisms by which ion channels discriminate between ions of differing charge, focusing on four channel families as examples: gramicidin, ClC chloride, voltage-gated calcium and potassium channels. The recent availability of high-resolution structural data has meant that the specific inter-atomic interactions responsible for valence selectivity can be pinpointed. Not surprisingly, electrostatic considerations have been shown to play an important role in ion specificity, although many details of the origins of this discrimination remain to be determined. Received 4 September 2005; received after revision 17 October 2005; accepted 2 November 2005     

Two independent alleles at 6q23 associated with risk of rheumatoid arthritis

To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study. After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 (rs10499194, approximately 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association (GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium (WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 (rs6920220; P = 5 x 10(-6) in WTCCC). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.     

Phytochrome signalling is mediated through nucleoside diphosphate kinase 2.

Because plants are sessile, they have developed intricate strategies to adapt to changing environmental variables, including light. Their growth and development, from germination to flowering, is critically influenced by light, particularly at red (660 nm) and far-red (730 nm) wavelengths. Higher plants perceive red and far-red light by means of specific light sensors called phytochromes(A-E). However, very little is known about how light signals are transduced to elicit responses in plants. Here we report that nucleoside diphosphate kinase 2 (NDPK2) is an upstream component in the phytochrome signalling pathway in the plant Arabidopsis thaliana. In animal and human cells, NDPK acts as a tumour suppressor. We show that recombinant NDPK2 in Arabidopsis preferentially binds to the red-light-activated form of phytochrome in vitro and that this interaction increases the activity of recombinant NDPK2. Furthermore, a mutant lacking NDPK2 showed a partial defect in responses to both red and farred light, including cotyledon opening and greening. These results indicate that NDPK2 is a positive signalling component of the phytochrome-mediated light-signal-transduction pathway in Arabidopsis.     

Cloning and functional research of renal cell carcinoma related novel gene—— GYLZ-RCC18

After the renal cell carcinoma related novel gene fragmentGYLZ-RCC18 was cloned by using suppression subtractive hybridization (SSH), we used the SMART RACE technology to clone the full length ofGYLZ-RCC18 and performed chromosome location by the FISH method. RT-PCR was used to detect the expression of the first reading frame ofGYLZ-RCC18 in different stages and grades of renal cell carcinoma tissue and other tissues. Also we transfected the antisense oligonucleotide ofGYLZ-RCC18 to renal cell carcinoma cell line GRC-1, and analyzed the proliferation activity, growth speed, apoptosis and mortality changes in GRC-1. The results show that the full length ofGYLZ-RCC18 (GenBank accession No.: BE825133) cDNA is about 3.5 kb long which is located at No. 14 chromosome.GYLZ-RCC18 has a higher expression in higher grades and stages of renal cell carcinoma than in the lower ones. The expression ofGYLZ-RCC18 in renal cell carcinoma was much higher than that in normal kidney and other tissues. After transfection ofGYLZ-RCC18 antisense oligonucleotide, the mortality of GRC-1 increases evidently, the proliferation activity and growth speed were inhibited remarkably at the same time. Also the antisense oligonucleotide can induce the apoptosis of GRC-1 all through the observation time. Our results indicated thatGYLZ-RCC18 is an important novel gene related to renal cell carcinoma. Its overexpression would stimulate the growth and proliferation activity and plays an antidead and antiapoptosis effect in renal cell carcinoma. Transfection of antisense oligonucleotide could inhibit the generation and development of renal cell carcinoma. The study provides a new clue for the research of renal cell carcinoma, and also provides an instruction for special genetic diagnosis and the therapy of renal cell carcinoma.     

An integration model for manpower forecasting

Manpower forecasting has made significant contributions to human resource management. Due to difficulties in collecting the required data for making appropriate analysis, most studies in the literature concentrate on forecasts of individual firms. This paper presents a regression model which utilizes the data of large firms to draw inferences to the demands of other firms. More specifically, a regression model showing the negative relationship between the rank of a firm and its associated demand is fitted to the data of a number of large manufacturing firms. The area under the regression line delineated by the y-axis is then an estimate of the total demand of the whole industry. Confidence intervals for the estimate can also be constructed. As an illustration, the demand for the industrial management manpower in Taiwan is forecasted by applying the proposed model.     

多功能化纳米材料络合物体外特异性结合和调控结肠癌细胞的研究

 循环肿瘤细胞(CTCs)因携带原发肿瘤的一些生物特性以及自身独特的生物学功能,在癌症的诊断、治疗和转移预防方面发挥着重要作用.但外周血中CTCs 的低含量使其检测、分离和富集有一定技术难度.本文选取结肠癌HT29 细胞为CTCs 模型,以表面高表达的EpCAM 为生物标记物,选取纳米级高分子聚合物G6 PAMAM dendrimers 为基质,多价络合针对EpCAM的抗体来构建络合物,实现体外对HT29 细胞的特异性捕获及活性调控.应用红外、动态光散射、紫外和荧光等方法表征络合物的理化特性,荧光分析法考察络合物对HT29 细胞的识别和捕获,MTT、荧光拍照、流式分析法显示络合物对捕获的HT29 细胞的活性调控.结果表明,制备的络合物可以高特异性地识别和结合贴壁的和悬浮的HT29 细胞,从而对捕获的细胞产生一定的活性下调作用,但不产生严重的细胞毒效应.可见,利用具有多价络合效应的纳米材料来共价连接针对CTCs 表面标记物的靶向抗体,有望实现在病人血中对CTCs 的特异性捕获和活性调控.     

地下圆形衬砌洞室对SV及Rayleigh波的动应力集中(Ⅰ):3-D级数解

为了研究地下圆形衬砌洞室在入射平面SV波和Rayleigh波作用下的动应力集中问题,利用波函数展开法,求解出三维条件下的级数解。当衬砌与半空间介质相同时,级数解将退化为无衬砌时的结果。级数解为进一步定量分析衬砌洞室对入射平面SV波和Rayleigh波的动力集中提供了理论基础。     

DESIGN SAMPLING AND REPLICATION ASSIGNMENT UNDER FIXED COMPUTING BUDGET

1. Introduction The essence of any decision problem is an optimization problem. Whether it is a decision on the production schedule of a manufacturing plant, a decision on the routing rules of networking, or a decision on the make-up of investment portfolios, the problem always revolves around making a choice from a population of alternatives (either finite or infinite) so as to optimize certain targeted objective. Without loss of generality, the objective can be represented by Mθ ∈iΘn J(…     

火电单元机组智能控制系统

提出了一个实现大范围负荷跟踪的火电单元机组智能控制系统．该系统包括设定值调节器、神经网络模糊前馈控制器、模糊反馈控制器和单元机组．设定值调节器根据机组负荷指令提供设定值．前馈控制器采用神经网络模糊控制逼近单元机组的逆稳态特性而得到前馈控制信号，以实现单元机组的大范围运行．反馈控制器则采用模糊控制补偿负荷扰动所引起的单元机组的实际值与设定值的偏差．前馈控制信号与反馈控制信号相加后发出指令到单元机组完成负荷跟踪任务．仿真结果表明，该系统有较好的动态特性，能适应于机组大范围的负荷跟踪．