A pathway profile-based method for drug repositioning

Finding new applications for existing pharmaceuticals,known as drug repositioning,is a validated strategy for resolving the problem of high expenditure but low productivity in drug discovery.Currently,the prevalent computational methods for drug repositioning are focused mainly on the similarity or relevance between known drugs based on their "features",including chemical structure,side effects,gene expression profile,and/or chemical-protein interactome.However,such drug-oriented methods may constrain the newly predicted functions to the pharmacological functional space of the existing drugs.Clinically,many drugs have been found to bind "off-target"(i.e.to receptors other than their primary targets),which can lead to undesirable effects.In this study,which integrates known drug target information,we propose a disease-oriented strategy for evaluating the relationship between drugs and disease based on their pathway profile.The basic hypothesis of this method is that drugs exerting a therapeutic effect may not only directly target the disease-related proteins but also modulate the pathways involved in the pathological process.Upon testing eight of the global best-selling drugs in 2010(each with more than three targets),the FDA(Food and Drug Administration,USA)-approved therapeutic function of each was included in the top 10 predicted indications.On average,60% of predicted results made using our method are proved by literature.This approach could be used to complement existing methods and may provide a new perspective in drug repositioning and side effect evaluation.     

基于激光轮廓检测仪的沥青路面路表离析评价

沥青路面离析必然影响沥青路面性能和使用寿命,是早期病害的重要原因之一。当前目测法、铺砂法和激光断面仪法等路表离析评价技术相对落后,试验数据的主观性强、代表性差。研发了路表轮廓激光检测仪,利用模拟铺砂法铺砂体积的"面区域"测点布局理念,对沥青路面宏观轮廓特征进行研究。提出新的轮廓特征评价指标:轮廓构造深度(QLGS);并利用MATLAB软件平台,实现了试验数据的自动处理。根据基于新指标的离析分级定量界限对离析程度进行了评判。试验表明:该方法操作简单,能真实客观的描述沥青路面的表面轮廓构造,离析评价的结果与路面实际情况比较吻合,可为沥青路施工质量控制提供借鉴。     

常规分析用吸烟机抽吸流量测定仪设计

采用32位微控制器、高灵敏度微压力传感器、16位高速模数转换器以及触摸屏,设计一种应用于常规分析用吸烟机的抽吸流量测定仪。通过抽吸容量测定和不同工作模式对比测试结果,表明该测定仪具有使用简便,数据一致性好,检测速度快等特点。     

设计滚子移动从动件盘形凸轮机构实际轮廓的瞬心法

本文根据相对运动原理,用瞬心法建立滚子从动件盘形凸轮机构实际轮廓相对于动坐标系的直角标方程,然后采用坐标旋转变换得到其相对于定坐标的直角坐标方程,从而为凸轮的设计和制造提供了一种新方法     

泥河湾井儿洼剖面粉砂黏土纹层成分的扫描电镜与能谱分析

利用扫描电镜以及X射线能谱仪,对泥河湾盆地井儿洼剖面的粉砂黏土沉积纹层进行成分分析,结果表明在一个纹层偶中Si和Ca元素的质量含量w存在明显的差异,粉砂纹层中的w(Si)值高,w(Ca)值低;而黏土纹层中的w则正好相反.Si和Ca元素在粉砂纹层和黏土纹层中的交替变化,与碎屑物的组成有关,可能反映了一年中古湖水特征的季节性变化.     

微动剖面探测法在城市轨道交通勘察中的应用及效果：以广州地铁十号线为例

在城市轨道交通工程地球物理勘测中一直面临抗干扰和精准探测难题.以广州市轨道交通十号线寺右新马路段地下人防构筑物探测为例,介绍了二维微动剖面(2D microtremor profile,2DMTP)探测技术的方法理论及其在城市轨道交通工程勘察中的应用效果.通过与钻探成果的对比分析,提出了2DMTP在城市轨道交通勘测、设计不同阶段的使用建议.结果 表明:微动剖面探测方法非常适用于城市复杂强干扰的工作环境,能为轨道交通勘察设计、施工安全提供重要的依据,对提高工程地质勘察精度,降低勘探成本与施工风险,缩短建设工期起到重要作用.     

滨海平原河网浅水动力分区特性研究

以浙江省姚西北地区平原河网为例,简化感潮河段闸门控制运行的数学模型,研究挡潮闸运行期间闸上游河道水面线的扰动规律.据此,对河网进行水动力分区,确定各区洪水水力特性.应用HEC-RAS软件进行数值计算,结果表明,该结论合理、可靠,可为姚西北平原河网水动力分析和防洪调度提供理论和技术支持.     

叶片型线对离心黏油泵性能的影响

针对目前离心油泵的叶片绘型未考虑黏度因素影响的情况,采用FLUENT6.1软件通过数值计算方法研究泵送温度下运动黏度为1、24、60mm2/s 3种黏度的介质在包角分别为90°、110°、130°3种叶片型线对离心泵性能的影响.结果表明:随着叶片包角增大,扬程-流量曲线变得陡峭,相同流量下,泵扬程降低,且此特性与介质黏度无关;设计工况下,130°包角泵输水时的效率最高,而110°包角泵在最优工况下输黏油时效率最高;采用不同黏度的介质时,离心泵内部压力和速度分布与采用清水介质得到的规律基本一致.     

Retrievals of atmospheric boundary layer temperature and moisture profiles by using Atmospheric Emitted Radiance Interferometer （AERI） measurements in Shouxian

The ground-based Atmospheric Emitted Radi- ance Interferometer （AERI） was deployed in Shouxian, China in 2008 to measure down-welling infrared radiances with high resolution. Based on AERI observations, we propose a new method for retrieving vertical temperature and water vapor profiles in the planetary boundary layer （PBL）. The method exclusively uses NCEP-2, a global reanalysis data as a first-guess profile in an iterative recursive algorithm. The PBL profiles of temperature and moisture under clear sky conditions in Shouxian have been retrieved using this new method. Compared with coinci- dent radiosonde measurements, we find that AERI is able to obtain more accurate temperature and water vapor pro- files in the PBL. The retrieval results with high temporal resolution can be used to monitor the PBL stability and evolution.     

定轴横轧螺杆压缩机阴转子的辊型曲线

定轴横轧直接近净成形带有螺旋齿形的螺杆转子是一种新型工艺,轧制耦合曲线是其核心和关键.该轧制工艺中,轧辊和轧件的啮合关系与原有啮合关系有较大差异,因此需要根据轧制工艺需求重新构建具有普遍适用性的轧辊和轧件的耦合曲线.以轧制某型号的螺杆阴转子为例,依据轧辊和轧件的共轭啮合运动关系,构建了适合于定轴横轧工艺的轧辊和轧件耦合曲线的几何模型;结合建立的变换矩阵推导求解了相应耦合曲线的参数化方程,实现了轧制工艺的通用性.三维动态啮合仿真模拟显示啮合过程良好,无冲突干涉现象发生,表明所建立的描述轧辊和轧件耦合曲线的数学模型是正确的.