一种基于神经网络的混沌控制方法

将神经网络(NN)与内模控制(IMC)相结合,提出了一种用基于BP神经网络的内模控制进行混沌抑制的方法,该方法既具有内模控制的特点,又引入了神经网络的在线自校正机制。应用所提出的方法,针对Duffing振荡器的混沌控制问题进行了仿真研究,仿真结果验证了该方法的有效性,同时还表明该方法具有很好的鲁棒性与自适应能力。     

基于自适应神经网络的边坡位移预测

通过对边坡位移历史数据序列进行特征分析 ,计算出饱和嵌入维数和最大 Lyapunov指数 ,给出了边坡位移的最大可预报时间尺度。在此基础上 ,确定了神经网络的输入节点数 ,建立了基于自适应神经网络的边坡位移预报方法 .通过对三峡升船机高边坡和新滩滑坡实际位移数据进行预测 ,结果令人满意 .这对于建立边坡位移的实时监测 -预警系统有重要意义.     

Evolution of neoplastic cell lineages in Barrett oesophagus.

It has been hypothesized that neoplastic progression develops as a consequence of an acquired genetic instability and the subsequent evolution of clonal populations with accumulated genetic errors. Accordingly, human cancers and some premalignant lesions contain multiple genetic abnormalities not present in the normal tissues from which the neoplasms arose. Barrett oesophagus (BE) is a premalignant condition which predisposes to oesophageal adenocarcinoma (EA) that can be biopsied prospectively over time because endoscopic surveillance is recommended for early detection of cancer. In addition, oesophagectomy specimens frequently contain the premalignant epithelium from which the cancer arose. Neoplastic progression in BE is associated with alterations in TP53 (also known as p53) and CDKN2A (also known as p16) and non-random losses of heterozygosity (LOH). Aneuploid or increased 4N populations occur in more than 90-95% of EAs, arise in premalignant epithelium and predict progression. We have previously shown in small numbers of patients that disruption of TP53 and CDKN2A typically occurs before aneuploidy and cancer. Here, we determine the evolutionary relationships of non-random LOH, TP53 and CDKN2A mutations, CDKN2A CpG-island methylation and ploidy during neoplastic progression. Diploid cell progenitors with somatic genetic or epigenetic abnormalities in TP53 and CDKN2A were capable of clonal expansion, spreading to large regions of oesophageal mucosa. The subsequent evolution of neoplastic progeny frequently involved bifurcations and LOH at 5q, 13q and 18q that occurred in no obligate order relative to each other, DNA-content aneuploidy or cancer. Our results indicate that clonal evolution is more complex than predicted by linear models.     

核筒悬挂结构的动力特性及参数优化

基于欧拉伯努利梁理论和层剪切模型,应用拉格朗日方程推导了单段核筒悬挂减振控制结构的运动方程.在此基础上通过时程分析评价了结构的减振性能,应用复模态叠加法对结构的响应进行了频域分析,以主体核筒顶点位移和悬挂楼面层间位移响应为优化目标,对悬挂楼面的侧移刚度、阻尼器的刚度和阻尼系数进行优化.分析结果表明,存在最优的侧移刚度和阻尼器刚度使得核筒位移响应最小,存在较优的阻尼器阻尼系数可同时有效抑制核筒和悬挂楼面的响应,所以通过合理设置结构参数能够显著减小核筒悬挂减振结构的动力响应.     

有机物分子量分布特点对BAF-O3-BAC净水工艺的评价

采用曝气生物滤池(BAF)、气浮和臭氧生物活性炭(BAC)联用技术对太湖原水进行试验.有机物分子量分布测定结果表明:曝气生物滤池单元对分子量小于0.5 kD(道尔顿)的有机物去除率最高,其次是分子量介于1～3 kD的有机物;气浮单元对分子量大于100 kD的有机物去除率最高;臭氧氧化单元对分子量大于3 kD的有机物去除率较高,而对于小于3 kD的有机物不但不能去除,反而有所增加;生物活性炭单元对分子量小于10 kD的有机物均能有效去除,分子量越小,去除率越高.综合评价认为:曝气生物滤池、气浮和臭氧生物活性炭联用技术处理微污染水源水的净水工艺是合理的.     

放电电流对热阴极等离子体化学气相沉积金刚石膜影响

建立了快速沉积高品质金刚石膜的热阴极辉光放电等离子体化学气相沉积新方法. 相对于常规冷阴极辉光放电而言,热阴极辉光放电是一种新型放电形式,具有许多新的特性,其中重要一点是具有较高的放电电流(6.0～10.0 A). 较高的放电电流既是热阴极辉光放电本身的突出特点,同时对于化学气相沉积金刚石膜工艺也产生重要影响. 实验研究了放电电流于金刚石膜沉积速率、表面形貌和热导率的影响,发现由于放电电流影响辉光放电的等离子体区和阳极区,进而对金刚石膜的沉积速率和品质有很大影响. 特别是通过放电电流的提高,可以有效地提高金刚石膜的品质,这对于制备优质金刚石膜产品有重大意义.     

Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r?/? mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC₃ PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.     

Cytochrome P450 2U1, a very peculiar member of the human P450s family

Cytochrome P450 2U1 (CYP2U1) exhibits several distinctive characteristics among the 57 human CYPs, such as its presence in almost all living organisms with a highly conserved sequence, its particular gene organization with only five exons, its major location in thymus and brain, and its protein sequence involving an unusually long N-terminal region containing 8 proline residues and an insert of about 20 amino acids containing 5 arginine residues after the transmembrane helix. Few substrates, including fatty acids, N-arachidonoylserotonin (AS), and some drugs, have been reported so far. However, its biological roles remain largely unknown, even though CYP2U1 mutations have been involved in some pathological situations, such as complicated forms of hereditary spastic paraplegia. These data together with its ability to hydroxylate some fatty acids and AS suggest its possible role in lipid metabolism.     

Toxin bioportides: exploring toxin biological activity and multifunctionality

Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides—a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity.     

Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin

Background

Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN.

Methods

Primary cultures of myotubes from DMD and control patients were treated or not by ApN after an inflammatory challenge. Myokines secreted in medium were identified by cytokine antibody-arrays and ELISAs. The early events of ApN signaling were assessed by abrogating selected genes.

Results

ApN retained its anti-inflammatory properties in both dystrophic and control myotubes. Profiling of secretory products revealed that ApN downregulated the secretion of two pro-inflammatory factors (TNFα and IL-17A), one soluble receptor (sTNFRII), and one chemokine (CCL28) in DMD myotubes, while upregulating IL-6 that exerts some anti-inflammatory effects. These changes were explained by pretranslational mechanisms. Earlier events of the ApN cascade involved AdipoR1, the main receptor for muscle, and the AMPK-SIRT1-PGC-1α axis leading, besides alteration of the myokine profile, to the upregulation of utrophin A (a dystrophin analog).

Conclusion

ApN retains its beneficial properties in dystrophic muscles by activating the AdipoR1-AMPK-SIRT1-PGC-1α pathway, thereby inducing a shift in the secretion of downstream myokines toward a less inflammatory profile while upregulating utrophin. ApN, the early events of the cascade and downstream myokines may be therapeutic targets for the management of DMD.