FK506 sensitizes mammalian cells to high osmolarity by modulating p38 MAP kinase activation

The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004     

Coulomb blockade and the Kondo effect in single-atom transistors

Using molecules as electronic components is a powerful new direction in the science and technology of nanometre-scale systems. Experiments to date have examined a multitude of molecules conducting in parallel, or, in some cases, transport through single molecules. The latter includes molecules probed in a two-terminal geometry using mechanically controlled break junctions or scanning probes as well as three-terminal single-molecule transistors made from carbon nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting molecular layer. The ultimate limit would be a device where electrons hop on to, and off from, a single atom between two contacts. Here we describe transistors incorporating a transition-metal complex designed so that electron transport occurs through well-defined charge states of a single atom. We examine two related molecules containing a Co ion bonded to polypyridyl ligands, attached to insulating tethers of different lengths. Changing the length of the insulating tether alters the coupling of the ion to the electrodes, enabling the fabrication of devices that exhibit either single-electron phenomena, such as Coulomb blockade, or the Kondo effect.     

Large Cretaceous sphenodontian from Patagonia provides insight into lepidosaur evolution in Gondwana

Sphenodontian reptiles successfully radiated during Triassic and Jurassic times, but were driven almost to extinction during the Cretaceous period. The sparse Early Cretaceous record of sphenodontians has been interpreted as reflecting the decline of the group in favour of lizards, their suspected ecological successors. However, recent discoveries in Late Cretaceous beds in Patagonia partially modify this interpretation. Numerous skeletons of a new sphenodontian, Priosphenodon avelasi gen. et sp. nov., were collected from a single locality in the Cenomanian-Turonian Candeleros Formation, where it is more abundant than any other tetrapod group recorded in the quarry (for example, Crocodyliformes, Serpentes, Dinosauria and Mammalia). Adult specimens of Priosphenodon reached one metre in length, larger than any previously known terrestrial sphenodontian. Here we propose, using available evidence, that sphenodontians were not a minor component of the Cretaceous terrestrial ecosystems of South America, and that their ecological replacement by squamates was delayed until the early Tertiary. The new discovery helps to bridge the considerable gap in the fossil record (around 120 million years) that separates the Early Cretaceous sphenodontians from their living relatives (Sphenodon).     

Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28

Linkage disequilibrium (LD), or the non-random association of alleles, is poorly understood in the human genome. Population genetic theory suggests that LD is determined by the age of the markers, population history, recombination rate, selection and genetic drift. Despite the uncertainties in determining the relative contributions of these factors, some groups have argued that LD is a simple function of distance between markers. Disease-gene mapping studies and a simulation study gave differing predictions on the degree of LD in isolated and general populations. In view of the discrepancies between theory and experimental observations, we constructed a high-density SNP map of the Xq25-Xq28 region and analysed the male genotypes and haplotypes across this region for LD in three populations. The populations included an outbred European sample (CEPH males) and isolated population samples from Finland and Sardinia. We found two extended regions of strong LD bracketed by regions with no evidence for LD in all three samples. Haplotype analysis showed a paucity of haplotypes in regions of strong LD. Our results suggest that, in this region of the X chromosome, LD is not a monotonic function of the distance between markers, but is more a property of the particular location in the human genome.     

植物谷胱甘肽-S-转移酶的分子生物学研究进展

谷胱甘肽-S-转移酶(GST),这种超家族酶系主要在解毒和对机体有害物质的防御方面发挥作用,是动物、植物和人体代谢过程中的重要酶.对植物中谷胱甘肽-S-转移酶催化机理、分类及其分子生物学研究进展进行了综述.     

基于室温模糊PID控制的供暖监控系统

基于模糊控制和PID控制理论，在经典PID控制结构中加入Fuzzy自调整结构，对集中供暖系统室温的控制策略进行深入探讨，从而改善室温的自动控制，使系统具有良好的控制效果和鲁棒性。该监控系统以计算机技术、智能仪器仪表技术、传感器技术、现代电子技术和通讯技术相结合，对集中供暖温度监控系统的现场监控软、硬件，及监控中心进行了设计和研究。使该系统实现了远程通讯控制，便于管理，调节直观，可以自动调节室温使其更加舒适，同时提高用户的节能意识，达到良好的节能效果，具有良好的经济效益和社会效益。     

海明威:异化世界中英雄神话的守望者

美国现代小说家厄内斯特.海明威以其海明威式英雄的塑造,成为英雄缺席的20世纪西方文学中英雄神话的精神守望者。置身于异己世界中的海明威式英雄,以超人的勇气和顽强的生命意志,激越地抗争异化,反叛死亡,所谓“打不败的精神”乃是海明威式英雄最好的哲学注脚。海明威式英雄于重压下仍保持优雅的风度,不仅给人以力量,而且给人以美感。     

数据仓库在成绩分析及教学决策中的应用

分析了学生成绩对学校教学进行分析决策的重要价值,提出了建立基于学生成绩的教学分析决策系统的策略,进一步确定了数据仓库的各个主题域.采用多维技术建立了数据仓库的逻辑模型,并且对事实表和各个维表的设计进行了研究.最后,提供了系统具体实现的过程和步骤.     

浅谈如何培养高职高专学生英语单词记忆能力

目前,高职高专院校学生英语水平成绩普遍较差,究其原因主要是由于单词量少所致。所以,争取在较短的时间内提高学生的单词记忆能力至关重要。在教学中,教师很有必要对学生单词记忆加以指导,以帮助学生树立信心,掌握有效方法,攻克单词难关。