Molecular Mechanisms and Tumor Biological Aspects of 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells

5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116R^F10. HCT116R^F10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116R^F10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116R^F10 cells. Interestingly, HCT116R^F10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.     

MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.     

基于协同学的Multi Agent合作系统研究*

探讨了协同学在Multi-Agent系统(MAS)合作中的应用;讨论了MAS的协同合作,给出了基于协同学的Multi-Agent的协同模型,量化了Multi-Agent协同机制的协调效应,为其最优协同机制的选择提供了依据.将序参量、自组织理论引入到MAS合作中,为MAS合作问题提供了一个新的解决思路.     

丁腈橡胶硫化反应动力学研究

设计了促进剂A 4种不同用量的丁腈橡胶配方;基于配方,先利用密炼机将丁腈橡胶、硬脂酸和ZnO混炼,再利用开炼机加入硫黄、促进剂和防老剂,再利用无转子硫化仪分别测试了160℃、170℃和180℃下胶料硫化曲线;基于硫化曲线计算出了每组配方胶料硫化反应速率常数K和活化能Ea。结果表明,在焦烧期时,NBR硫化反应为非一级反应,真正的一级反应开始于硫化速率达到最大时,即tdis;焦烧期后的反应可分为2个阶段且遵循一级动力学反应规律。     

考虑风机排序的风电集群分层有功控制策略

随着我国风电的迅速发展,风电场有功调控趋于集群化。为合理调控风电集群有功功率、提高风电消纳量、减少风电机组调控次数,文中提出考虑风机排序控制的风电集群分层有功控制策略。根据风电场所在区域不同并结合超短期风电功率预测,将风电集群分为场群层、风电场层、机组层3个控制层。场群层和风电场层通过不同时间尺度的滚动优化提高风电消纳量;机组层通过选取影响风机调控能力的评价指标,结合熵值法与隶属度函数,计算并排序各机组调控能力评分,通过机组的排序控制减少风机调控次数。基于GAMS及Matlab平台对山西电网实际风电场数据进行分析,结果表明所提控制策略在提高风电消纳量的同时减少了风机调控次数。     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

电液伺服系统的分数阶PID控制研究

针对三阶电液伺服系统,提出了一种新的PID控制器,把传统的PID控制器的阶次推广到分数领域,它不仅适用于分数阶系统,也适用于整数阶系统,并能取得一些优于整数阶PID控制器的效果.用滤波方法进行分数阶的微积分运算,直接求出传递函数,用Matlab/Simulink构造了PID模型,可直接在其它仿真系统中调用.仿真结果证明了该方法的正确性.     

优化混凝-SBR法处理皮革加工废水

对皮革加工废水采用优化混凝-SBR法处理进行了研究,利用均匀设计法优化混凝除Cr3 条件,考察了曝气时间、污泥浓度、沉降时间对SBR反应器降解效果的影响.确定的混凝条件:聚铝投加质量浓度400mg/L、pH=10;SBR后续工艺最佳曝气时间为12 h、沉淀时间为2.0 h、污泥质量浓度为5 g/L.对皮革加工废水采用优化混凝SBR处理的试验结果表明,出水总Cr去除率＞98%,CODcr去除率＞93%,各项主要指标达到国家所规定的一级排放要求.     

SBR法处理校园生活污水为中水的试验研究

根据校园生活污水的水质特点,选择SBR工艺对校园生活污水进行了试验研究,确定了最佳的运行参数。试验结果表明,当采取最佳操作条件运行时,COD、NH4-N、PO43-、BOD5的去除率分别达到了88%、98%、94%、96%以上,其出水色度、嗅味和pH也均达到了中水主要水质标准,处理效果稳定,该试验为校园生活污水的中水回用提供了重要的技术参数。