Common variants at CD40 and other loci confer risk of rheumatoid arthritis

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).     

New developments in enzymatic peptide synthesis

This review article describes new enzymatic methods developed for the efficient and irreversible synthesis of peptides based on native and modified proteases, and for the synthesis of polypeptides containing D- and/or unnatural amino acids. Potential opportunities for future developments in the field based on new enzymes, tailormade catalytic antibodies, and on the technique of in vitro mutagenesis are also described.     

Potential aldose reductase inhibitors: 1,2,4-triazolidine-3,5-diones and 2-(3,4,5-trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione .

1,2,4-Triazolidine-3,5-diones and the 3,5-isoxazolidinedione were observed to be potent inhibitors of rat lens aldose reductase activity. In vivo in streptozotocin-diabetic rats, selected agents at 20 mg/kg/day, orally for 21 days reduced significantly the sorbitol levels of rbc, lens and sciatic nerves, suggesting that these derivatives may have some usefulness to treat clinical complications of diabetes mellitus.     

Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation

Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation.     

人工神经网络及其在金融预报中的应用

讨论了人工神经网络在金融汇率预报中的应用。其中介绍了广义交互验证(Generalized Cross Validation)法如何应用于确定神经网络中隐层的个数,并用实例说明了该方法甚至对复杂的非线性函数也可以得到很好的逼近。详细地介绍了运用人工神经网络作两周向前汇率预报的计算步骤。其平均相对误差(APE)为10*E-3的数量级,而国际上通用的状态空间模型及Box-Jenkins的ARIMA模型的预报误差都在10*E-2的数量级。     

不同饰面材料高强混凝土柱的耐火性能

通过对8根装饰有不同饰面材料的高强混凝土柱式构件进行ISO834标准升温条件下的明火试验,考察了饰面材料对构件表面混凝土爆裂的影响,分析了不同饰面材料高强混凝土构件的内部温度场,并与试验结果进行了对比.研究结果表明:饰面材料的引入虽然延缓了构件表面混凝土的起爆时刻,却加重了其爆裂程度;双层防火板可较好地抑制构件表面混凝土的高温爆裂;将饰面材料折算为等效混凝土的做法,总体上可较好地反映饰面材料对构件截面温度场的影响.     

Inhibition of in vitro RNA synthesis by hycanthone, oxamniquine and praziquantel.

The schistosomicides, hycanthone, oxamniquine and praziquantel, were found to inhibit the in vitro RNA synthesis using isolated hamster liver nuclei. Preincubation of the nuclei with these drugs revealed that the inhibitory effect of oxamniquine was irreversible and progressed with time, whereas that of hycanthone and praziquantel was reversible. On the other hand, hycanthone and praziquantel have a high affinity for DNA but oxamniquine does not. The data indicate that the mechanism of inhibition by oxamniquine is different from that of hycanthone and praziquantel.     

灌浆对地下连续墙及邻近土体变形的影响

在地下连续墙深基坑开挖工程中,开挖前常用灌浆的方法来加固将被挖去的软土,从而减少地下连续墙的变形,增加开挖稳定性,保证工程安全,但是,在灌浆过程中,灌浆的作用机制以及对地下连续墙及邻近土体变形的影响原理还没有得到很好的研究,以新加坡艺术中心地下连续墙深基坑开挖工程为背景。实测了灌浆施工过程中,地下连续墙的变形、超孔隙水压力以及地下水位的变化;再结合有限元的理论分析方法,研究了灌浆施工对地下连续墙及     

SCHEDULING TWO GROUPS OF JOBS WITH INCOMPLETE INFORMATION

In real world situations, most scheduling problems occur neither as complete off-line nor ascomplete on-line models. Most likely a problem arises as an on-line model with some partialinformation. In this article, we consider such a model. We study the scheduling problem P(n_1,n_2),where two groups of jobs are to be scheduled. The first job group is available beforehand. As soon asall jobs in the first group are assigned, the second job group appears. The objective is to minimize thelongest job completion time(makespan). We show a lower bound of 3/2 even for very special cases.Best possible algorithms are presented for a number of cases. Furthermore, a heuristic is proposed forthe general case. The main contribution of this paper is to discuss the impact of the quantity ofavailable information in designing an on-line algorithm. It is interesting to note that the absence ofeven a little bit information may significantly affect the performance of an algorithm.