集结降阶方法及其在系统设计中的应用

本文提出能保证精确集结简化线性连续、离散系统模型的一种简便方法,而且被应用于系统简化设计,从而简化了控制器和状态观测器结构,而且减少了系统设计的计算量。     

Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

Genetic and molecular approaches to synthesis and action of the yeast killer toxin

Summary The K1 killer toxin ofSaccharomyces cerevisiae is a secreted, virally-coded protein lethal to sensitive yeasts. Killer yeasts are immune to the toxin they produce. This killer system has been extensively examined from genetic and molecular perspectives. Here we review the biology of killer yeasts, and examine the synthesis and action of the protein toxin and the immunity component. We summarise the structure of the toxin precursor gene and its protein products, outline the proteolytic processing of the toxin subunits from the precursor, and their passage through the yeast secretory pathway. We then discuss the mode of action of the toxin, its lectin-like interaction with a cell wall glucan, and its probable role in forming channels in the yeast plasma membrane. In addition we describe models of how a toxin precursor species functions as the immunity component, probably by interfering with channel formation. We conclude with a review of the functional domains of the toxin structural gene as determined by site-directed mutagenesis. This work has identified regions associated with glucan binding, toxin activity, and immunity.     

糖尿病肾病患者血脂异常与尿蛋白关系

探讨糖尿病肾病(DN)患者血脂异常与尿蛋白关系.选取122例住院的DN患者,年龄(62.26±12.67)岁,女性49例,男性73例,测定血脂代谢各指标,同时留取24h尿蛋白定量(24h pro),依据蛋白尿定量分为肾病和非肾病综合征组,比较两组相关血脂指标,并行相关性分析比较.肾病综合征组患者的TC(总胆固醇)、NHDL、Lpa和Apo-B水平均显著高于非肾病综合征组(P0.05);TC、NHDL、Apo-B和Apo-E均分别与24h尿蛋白定量和糖化血红蛋白(HbA1C)相关(P0.01),Lpa与24h尿蛋白定量及肾小球滤过率(eGFR)相关,LDL-C及TG仅与HbA1C相关(P0.01),Apo-A1仅与24hpro相关(P0.05);各血脂指标依据四分位法分组,TC、NHDL-C、TG、Apo-A1、Apo-B、Lpa及Apo-E随着数值升高,组内24h尿蛋白定量(≥3.5g)百分比例增高(P0.05),而LDL-C及HDL-C组内比较无统计学差异(P0.05).DN患者随着24h蛋白尿增多,血脂异常更为显著,尤其在肾病综合征患者以TC、NHDL、Lpa及Apo-B升高为主,而血脂异常进一步加重肾脏病进展,有效控制血脂有望改善肾脏病预后.     

颗粒群组方法中关键参数的选取

为了深入了解颗粒群组方法的特点,提出了修正最大群组数方法,研究了颗粒群组方法中的两个关键参数(体积增量和最大群组数)对数量密度和体积分数的影响.结果表明:传统最大群组数在计算颗粒数量密度时比较准确,修正最大群组数在计算颗粒体积分数时比较准确.随着颗粒体积增量的增加,传统最大群组数得到的颗粒数量密度的预测值降低,而颗粒体积分数的预测值增加.随着颗粒体积增量的增加,修正最大群组数得到的颗粒数量密度的预测值下降,而颗粒体积分数的预测值呈振荡趋势.     

结核分枝杆菌ClpX与人UBC9蛋白的相互作用抑制宿主细胞增殖

ClpX是原核生物中高度保守的基因,其编码丝氨酸蛋白酶ClpXP的ATP结合亚基,具有底物识别及ATP水解活性.ClpX参与调控细胞周期与应激反应,且为多种病原微生物致病所必需,但目前相关研究仍非常有限.为了探索结核分枝杆菌(Mycobacterium tuberculosis)ClpX在感染宿主细胞过程中的作用机制,本文首先通过酵母双杂交技术在人类淋巴细胞cDNA文库中筛选得到了一个新的与结核ClpX相互作用的蛋白UBC9,并利用GST pull-down和Co-IP技术证实了这两个蛋白在体外和体内相互作用的特异性.将ClpX转染HEK293T细胞过表达,RNA干扰与回复实验进一步证实了ClpX蛋白能够通过与UBC9的相互作用抑制宿主细胞的增殖.     

耐辐射菌Micrococcus luteus SC1204总蛋白双向电泳体系的建立

以耐辐射藤黄微球菌Micrococcus luteus SC1204为研究对象,建立总蛋白双向电泳体系.结果表明,采用液氮研磨-酚/超高速离心法提取总蛋白,裂解液Ⅱ(8 mol/L尿素、2mol/L硫脲、60mmol/L DTT、4%CHAPS、40mmol/L Tris、1%pH 3~10NL IPG buffer、0.002%BPB)溶解蛋白,使用24cm、pH 4~7的IPG胶条,上样量250μg及等电聚焦7h(56000Vh),可获得满意分辨率的双向电泳图谱,适用于后续的质谱及差异蛋白质组分析.     

Pin1的细胞定位调控Rb蛋白的磷酸化状态

为了研究Pin1和Rb蛋白的细胞定位、Pin1调控Rb磷酸化的相关机制,本研究构建了慢病毒载体pLVX-Flag-HA-Pin1和Plko.1-shRNA,包装病毒感染人非小细胞肺癌(H1299),免疫印迹检测Pin1蛋白表达水平,采用免疫荧光染色、免疫组化技术研究蛋白的定位.结果表明,沉默Pin1可降低Rb的磷酸化并抑制细胞的增殖;培养的肿瘤细胞和肿瘤组织中,Pin1可定位到细胞质中,而胞质定位的Pin1也可增加Rb的磷酸化.     

假色槭种子层积过程中储藏物质及淀粉酶活性变化

研究假色槭种子层积过程中内含物质及淀粉酶活性的变化情况,以揭示种子生理物质的变化规律,阐明种子休眠解除与种子层积过程中内含物质及淀粉酶活性变化的联系.结果表明:在自然层积过程中,假色槭种子中的可溶性糖、淀粉、可溶性蛋白的含量从整体来看变化趋势基本一致,均表现为逐渐减少;α淀粉酶活性均表现为先下降后上升,再下降,再上升的趋势;β淀粉酶活性先迅速下降,再变化比较平缓.由此说明,假色槭种子中的贮藏物质在层积过程中不断分解代谢,为种子萌发做物质和能量上的准备.