Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer

The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2 60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate. Received 25 August 2006; received after revision 20 November 2006; accepted 20 December 2006     

Starch-binding domains in the post-genome era

Starch belongs to the most abundant biopolymers on Earth. As a source of energy, starch is degraded by a large number of various amylolytic enzymes. However, only about 10% of them are capable of binding and degrading raw starch. These enzymes usually possess a distinct sequence-structural module, the so-called starchbinding domain (SBD). In general, all carbohydrate-binding modules (CBMs) have been classified into the CBM families. In this sequence-based classification the individual types of SBDs have been placed into seven CBM families: CBM20, CBM21, CBM25, CBM26, CBM34, CBM41 and CBM45. The family CBM20, known also as a classical C-terminal SBD of microbial amylases, is the most thoroughly studied. The three-dimensional structures have already been determined by X-ray crystallography or nuclear magnetic resonance for SBDs from five CBM families (20, 25, 26, 34 and 41), and the structure of the CBM21 has been modelled. Despite differences among the amino acid sequences, the fold of a distorted β-barrel seems to be conserved together with a similar way of substrate binding (mainly stacking interactions between aromatic residues and glucose rings). SBDs have recently been discovered in many non-amylolytic proteins. These may, for example, have regulatory functions in starch metabolism in plants or glycogen metabolism in mammals. SBDs have also found practical uses. Received 25 May 2006; received after revision 26 June 2006; accepted 3 August 2006     

剩余半坡

本文提出半坡(p,+,·),在半坡上引进算子“∝”,“■”,得到的代数系统(p,+,·,∝,■)称为剩余半坡,本文给出剩余半坡p的一些基本性质,且证明了(Mn(p),+,·)是剩余半坡。     

SL(2,R)上的Hardy-Littlewood极大函数的性质

本文给出了SL(2,R)上的Hardy-Littlewood极大函数mf的定义,利用Ergodic定理证明了Hardy-Littlewood极大函数的强(p,p)型性质,p>1.     

扩展乘数法逼近问题

本文建立了扩展乘数法逼近的定量化定理;改进了徐利治与Хлодовский的一些结果。     

基于PiggyBac转座系统的低溢漏诱导型Tet-On过表达体系的建立及应用

为避免诱导基因稳定表达的Tet-On诱导表达系统溢漏表达,实现简便且高效的外源基因稳定诱导表达, 本研究拟在Tet-On调控的转录水平基础上,将基于稳定配体Shield-1的不稳定结构域FK506结合蛋白引入目的基因的N端,从蛋白水平控制其本底表达水平.为验证该系统的效果,本研究以荧光蛋白TdTomato为报告基因,经流式分析结果证明优化后的体系较原体系的溢漏表达在蛋白水平上降低7倍左右.将该系统应用于基于小鼠胚胎干细胞的体外牙向分化模型,在诱导因子Dox和稳定配体Shield-1的协同作用下,诱导表达牙齿发育相关转录因子Hand2提高了牙向分化诱导的完成度.     

|x|在扩展的Chebyshev结点的有理插值

研究|x|在扩展的Chebyshev结点的有理插值,得到逼近阶为O(1/(nln n)).通过数值计算发现相同逼近阶的误差与结点的密集度、结点所在曲线的凹凸性有关.     

用最小均方误差对数短时谱幅值估计法增强语音信号

本文主要研究语音增强系统在短时频域内,以对数最小均方误差作为语音幅值估计的准则.对含噪语音进行消噪处理。首先推导了公式,并从理论上作了分析研究.在此基础上作了大量实验,与类似的最小均方误差短时谱幅值估计法(MMSE STSA)作了性能比较.实验结果表明,由MMSE LOG-STSA增强方法得到的语音输出的质量优于由MMSA STSA方法得到的质量.语音的失真度和清晰度均有显著改善,同时大大降低了语音中的“音乐噪声”.     

地空数据传输系统中单载波频域预均衡技术

在频率选择性瑞利慢衰落信道条件下,提出了一种适用于地空传输系统上行链路的单载波频域预均衡方法。在此基础上设计了预均衡系统模型,地面端将下行链路中的导频信号与本地导频信号对比进行信道状态估计,利用获得的信道状态信息对上行链路信号进行预均衡处理,然后在机载接收端对上行链路信号进行再均衡。基于迫零准则和最小均方误差准则,分析了该方法的信号处理流程,计算得到预均衡系数。通过仿真实验,对比分析了不同均衡方案的误码性能,结果表明:单独在地面发送端进行预均衡,会出现误码率平台效应;而预均衡之后在机载接收端进行再均衡的方法,在误码率为10-5的情况下,与采用线性均衡结构的传统单载波频域均衡方法相比有2~3dB的性能增益。     

基于领域复用的软插件库应用研究

目的研究基于领域复用的软插件的原理和实现模型。方法 结合基于领域复用的基本原则,对构造基于领域复用的软插件库的方法进行讨论,并以商用ＰＯＳ机软插件库有组织构造为例进行了具体说明。结果与结论基于领域复用的软插件比传统方法更有利于软件复用。