摘要：In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo *** assays indicated that most of the compounds significantly inhibited multiple cancer cells *** addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory *** mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 *** study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

摘要：DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor *** this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual *** assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 ***,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle *** docking models explained the functional mechanism of 204 inhibiting DNMT1 and *** studies on metabolic profiles revealed that 204 showed desirable stability in liver *** study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.

摘要：Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.

摘要：为研究涉路施工作业区对高速公路交通安全之间相互影响,本文以需要封闭内侧车道的涉路施工合流风险为研究对象,基于改进的涉路施工交通特性下的元胞自动机,选取上游过渡区长度、货车比例、限速值以及交通量等作为仿真参数,对封内车道路段进行交通仿真试验,对路段的追尾冲突和换道冲突进行研究。根据车辆距离碰撞时间(TTC-Time To Collision)和后侵入时间(PET-Post Encroachment Time)在施工区特性下的阈值,并分析4个因素对涉路合流冲突影响程度大小,结果表明不同参数对作业区交通安全的影响依次为:交通量>过渡区长度>限速大小>货车比例;并建立交通冲突风险指数值(M_(tc))与交通量、过渡区长度、限速大小和货车比例的关系模型。研究结果对提高涉路施工封闭内车道交通安全提供相关理论依据,对改进施工区交通组织具有一定的应用价值。

摘要：从公路安全运行迫切需求出发,着眼于震后公路沿线地质灾害发育程度,选取山区公路地质灾害风险评价指标及其权重,并结合地质灾害危险性与防护工程新技术,建立山区公路地质灾害风险评估体系。该评估体系将灾损公路分两阶段进行评分,两阶段根据相应的评价指标和权重系数,计算出灾害风险总得分,从而确定威胁公路的地质灾害风险等级。以典型的泥石流灾害为例开展工程案例分析,验证山区公路地质灾害风险评估体系的适用程度。结果表明,该评价体系在川九公路艰险路段震后恢复重建工作中有较好的实用性和可靠性。

摘要：针对翅片管与汇集箱的焊接,基于混合粒子群遗传算法(hybrid particle swarm optimization and genetic algorithm,HPSOGA)讨论了一类带有螺距约束的焊接路径规划问题.在翅片管与汇集箱的焊点路径规划问题中,引入螺距约束进行描述多个翅片管焊点间的关系,将遗传算法和粒子群算法进行恰当的混合,利用遗传算法提高了粒子的多样性,经过变异操作优化全局搜索能力,并运用交换算子和交换序列对粒子状态的更新过程进行离散化,搜索机械臂的焊接最短路径.设计了仿真实验,分别采用粒子群算法、遗传算法和文中所设计算法进行焊点的路径规划.经过多次的实验表明,在文中所设计的算法下,机械臂能够获得较为平滑的焊接轨迹,且焊点路径最短,验证了该算法在解决一类带有螺距约束的焊接路径规划问题的有效性和正确性.

摘要：传统的公交信号优先策略往往依据公交车到达交叉口时刻或公交车固定载客量,无法有效地反映公交车实际载客量影响。针对该问题,考虑公交车实时载客量,以通过交叉口所有乘客的人均延误最小为优化目标,建立了交叉口公交信号优先控制模型;将公交IC卡和GPS数据进行匹配,比对公交站点乘客上车数,推算公交站点乘客下车数,分析了公交车通过交叉口时的实时载客量;提出了公交信号优先改进策略,分析该策略下各相位延误,引入公交优先强度系数;构建了交叉口人均延误模型和公交信号优先控制模型,采用启发式搜索算法求解该模型。研究结果表明:与传统的公交信号优先策略相比,考虑实时载客量的改进绿灯延长、改进绿灯早启公交信号优先策略的周期人均延误分别降低了20.98%、18.11%。

摘要：随着我国高速公路建设不断向西部山区发展,面临的崩塌、滑坡、泥石流等不良地质问题日益突出,迫切需要在选线阶段利用新的技术手段对拟建高速公路沿线不良地质体进行早期识别。以西昌—香格里拉拟建高速公路廊道为研究区,利用“天-空-地”一体化综合遥感手段,识别出不良地质体174处,其中滑坡74处、崩塌40处、泥石流16处、堆积体44处,利用小基线集合成孔径雷达干涉测量技术探测到26处不良地质体具有形变信号。针对磨盘山隧道—雅砻江桥段、牦牛山隧道出口段和下麦地隧道出口段不良地质体发育密集、规模大、稳定性差、对拟建线路威胁极大的区段,项目组开展了详细调查和分析评价。研究结果为西香高速线路比选和后期详细勘查提供了支撑,也为线路工程的不良地质体调查评价提供参考。

摘要：为研究泄爆夹层内障碍物位置对燃气泄爆效果的影响,以某大型商业综合体暗厨房为研究对象,考虑泄爆夹层中结构梁不同位置的泄爆效果,对暗厨房燃气爆炸的泄爆过程开展数值模拟研究。研究结果表明:在火焰没有到达泄爆窗前的爆炸初始阶段,障碍物对火焰结构和传播速度基本没有影响,当火焰进入泄爆夹层后,障碍物的存在可引发火焰加速现象;当障碍物距离泄爆窗1.7 m时,火焰加速现象较为明显,火焰最大传播速度可达591.5 m/s,此时厨房内压力峰值约2.9 MPa,约为没有结构梁情况下1.42倍;障碍物距离泄爆窗较近时,二者将协同影响火焰传播;厨房内压力峰值随着障碍物与泄爆窗距离的增大遵循增大-突降-增大的规律。研究结果可为商业综合体暗厨房泄爆设计提供一定理论依据。

摘要：在新常态下,我国城市交通发展面临全面转型升级,从增量规划逐渐迈入存量规划。传统观念认为,城市道路拥堵制约着城市的发展,而拥堵源于“过度需求”,大多数人集中在一天中同一时段出行,导致既有道路系统无法满足快速出行。针对大城市拥堵通病,从根源上分析拥堵成因,提出交通拥堵与人口、经济等因素成正相关关系,大都市高峰时段拥堵不可避免的结论,并以深圳市南山区南油片区交通综合改善规划为例,针对性地提出相应的优化措施。