最大熵原理的洪水预报误差分布规律推求——以三峡水库为例

洪水预报已成为提高水库洪水资源利用效率的必要手段,然而由于水文系统不确定性因素的存在,洪水预报误差不可避免.洪水预报误差极大影响水库预报调度成败,并且针对具体水库洪水预报误差通常会偏离正态分布,对洪水预报误差分布规律进行推求意义重大.当前,作为推求洪水预报误差分布规律的有力方法——最大熵原理正在广泛使用,但是对洪水预报误差分布规律推求问题本身和最大熵原理方法的认识仍存在局限.对洪水预报误差分布规律推求问题本质及最大熵原理适用理由做了进一步说明,三峡水库汛期洪水预报相对误差分布规律推求的实例研究表明,最大熵原理在其应用中是可行且有效的,值得进一步推广应用.     

Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton

TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC₅₀ value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.     

三峡水库蓄水后重庆河段冲淤特性研究

三峡水库蓄水对重庆河段冲淤影响的研究具有重要的科学价值和应用前景。根据水沙连续原理和重庆河段输沙特点,考虑嘉陵江汇流和水沙变化特征,导出了重庆河段泥沙淤积比的公式,分析了不同时期河段冲淤变化特点,论证了重庆河段淤积比与嘉陵江汇流比和寸滩站流量有重要关系。三峡水库蓄水初期重庆河段冲淤特点与蓄水前基本一致,具有汛期淤积、非汛期冲刷的特点。试验性蓄水以来河段冲淤特性发生变化,汛后蓄水期和汛前消落期河段有冲有淤,总体发生淤积。汛期河道有冲有淤,淤积有所减轻,甚至发生冲刷。河道采砂对重庆主城区河段冲淤产生重要影响。     

基于原型沙的三峡库区细颗粒泥沙冲淤模型试验研究

三峡水库常年回水区淤积物多为中值粒径在0.01 mm左右的细颗粒泥沙,按传统理论对此类细沙模型试验进行设计存在困难。提出了一种基于原型沙的库区细颗粒泥沙模型试验方法,流速比尺的确定考虑水深影响,泥沙冲淤时间比尺与水流运动时间比尺一致,含沙量比尺取决于垂直比尺和干容重比尺。黄花城河段2003-2011年以及典型流量水位组合下的泥沙模型试验结果表明,淤积厚度和平面分布与原型符合较好,初步说明该方法适用于三峡库区细颗粒泥沙运动的模拟。     

仙女山断裂与三峡库首诱发地震和滑坡的相关性

仙女山活动断裂诱发地震及其对滑坡的控制是三峡库首区重大地质问题。野外地层剖面记录表明,仙女山活动断裂经历了两次强烈抬升,为滑坡形成提供了物质基础;依据地震与滑坡在时间和空间上的相关性分析,仙女山断裂可能对新滩滑坡的产生具有控制作用;引入摩尔-库仑准则对仙女山断裂活动性进行分析后认为,库水位涨落引起断裂三维应力状态变化,且诱发地震在高低两极水位和蓄水回落阶段高发。该研究可为揭示仙女山活动断裂与地震和滑坡的相关性提供依据。     

库水波动下堆积层滑坡稳定性研究

堆积层滑坡是三峡库区中最常见的地质灾害类型。库水位的不同变化速率对滑坡稳定性影响显著。以三峡库区凉水井滑坡为例,分析了±0.2、±0.4、±0.6、±0.8、±1.0、±1.2、±1.4、±1.6、±1.8和±2.0 m/d 10种速率下,0.01、0.1、1和10 m/d 4种不同饱和渗透系数的堆积层滑坡在库水上升和下降过程中的稳定性变化规律。在此基础上提出了针对堆积层滑坡的三峡库区水位调度风险等级划分方案,认为库水位升降速率小于0.6 m/d为低风险,在0.6 m/d与0.8 m/d之间为中风险,大于0.8 m/d为高风险。利用实际库水位变动获得的安全系数曲线结合地质灾害等级划分方法,直观地显示了凉水井滑坡长期风险过程。研究结果对于滑坡的监测预警和水库调度具有一定的应用价值。     

Design,Synthesis, and Structure–Activity Relationships of 3,4,5‐Trisubstituted 4,5‐Dihydro‐1,2,4‐oxadiazoles as TGR5 Agonists

Given its role in the mediation of energy and glucose homeostasis, the G‐protein‐coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand‐based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5‐trisubstituted 4,5‐dihydro‐1,2,4‐oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5‐dihydro‐1,2,4‐oxadiazoles and extensive structure–activity relationship studies are reported herein. Compound (R)‐ 54 n , the structure of which was determined by single‐crystal X‐ray diffraction and quantum chemical solid‐state TDDFT‐ECD calculations, showed the best potency, with an EC₅₀ value of 1.4 nM toward hTGR5. Its favorable properties in vitro warrant further investigation.