Synthesis and antitumor evaluation of fluoroquinolone C3 fused heterocycles(Ⅱ):From triazolothiadiazines to pyrazolotriazoles

To further expand an effective modified route for the shift from an antibacterial fluoroquinolone（FQ） to an antitumor FQ,two series of title compounds based on an isostere of the FQ C3 carboxylic group with two fused heterocyclic rings,[1,2,4]triazolo[3,4- b][1,3,4]thiadiazine and pyrazolo[5,1-c][1,2,4]triazole,respectively,were designed and synthesized starting from the current antibacterial FQs,and their in vitro antitumor activity against L1210,CHO cell lines were evaluated via their respective IC₅₀ values.     

克拉玛依市维吾尔族居民膳食调查

为了解新疆克拉玛依市维吾尔族居民膳食营养状况,采用食物频率法对该地区401名维吾尔族居民进行膳食调查和营养评价.结果表明,克拉玛依市维吾尔族居民膳食种类比较单一,导致能量、碳水化合物、硫胺素、核黄素、钙等营养素未达到RNI的要求,而脂肪、胆固醇、盐摄入量偏高.提示硫胺素、核黄素、钙、镁为当地维吾尔族缺乏的营养素,建议对...     

Can we trust docking results? Evaluation of seven commonly used programs on PDBbind database

Docking is one of the most commonly used techniques in drug design. It is used for both identifying correct poses of a ligand in the binding site of a protein as well as for the estimation of the strength of protein–ligand interaction. Because millions of compounds must be screened, before a suitable target for biological testing can be identified, all calculations should be done in a reasonable time frame. Thus, all programs currently in use exploit empirically based algorithms, avoiding systematic search of the conformational space. Similarly, the scoring is done using simple equations, which makes it possible to speed up the entire process. Therefore, docking results have to be verified by subsequent in vitro studies. The purpose of our work was to evaluate seven popular docking programs (Surflex, LigandFit, Glide, GOLD, FlexX, eHiTS, and AutoDock) on the extensive dataset composed of 1300 protein–ligands complexes from PDBbind 2007 database, where experimentally measured binding affinity values were also available. We compared independently the ability of proper posing [according to Root mean square deviation (or Root mean square distance) of predicted conformations versus the corresponding native one] and scoring (by calculating the correlation between docking score and ligand binding strength). To our knowledge, it is the first large‐scale docking evaluation that covers both aspects of docking programs, that is, predicting ligand conformation and calculating the strength of its binding. More than 1000 protein–ligand pairs cover a wide range of different protein families and inhibitor classes. Our results clearly showed that the ligand binding conformation could be identified in most cases by using the existing software, yet we still observed the lack of universal scoring function for all types of molecules and protein families. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011     

新型三维可调共聚焦激光诱导荧光检测器的研制与评价

共聚焦结构是激光诱导荧光检测器(LIFD)中使用最广泛的光路结构之一,增强光路系统同轴精度和降低系统杂散光是降低仪器基线噪声水平、提高其信噪比(S/N)的两种有效手段。采用精密三维反光镜调节架和模块化设计光路系统,研制了一种高效液相色谱用高精度共聚焦激光诱导荧光检测器,对异硫氰酸荧光素(fluorescein isothiocyanate, FITC)的检出限为1×10~12 mol/L。基线噪声与漂移较改进前降低了一个数量级,分别达到8.0×10~3 mV和1.4×10~3 mV/h,且稳定性好,5×10~9 mol/L FITC样品连续5次进样分析的峰面积和峰高相对标准偏差(RSD)均小于0.5%。进一步用FITC衍生化生物胺对研制的检测器进行评价,检出限(S/N=3)达到0.01～0.02 nmol/L。新研制的LIFD噪声低、稳定性好、灵敏度高,适用于生物、食品和环境样品中痕量物质的分析。     

cgRNASP-CN: a minimal coarse-grained representation-based statistical potential for RNA 3D structure evaluation

Knowledge of RNA 3-dimensional (3D) structures is critical to understand the important biological functions of RNAs, and various models have been developed to predict RNA 3D structures in silico. However, there is still lack of a reliable and efficient statistical potential for RNA 3D structure evaluation. For this purpose, we developed a statistical potential based on a minimal coarse-grained representation and residue separation, where every nucleotide is represented by C4' atom for backbone and N1 (or N9) atom for base. In analogy to the newly developed all-atom rsRNASP, cgRNASP-CN is composed of short-ranged and long-ranged potentials, and the short-ranged one was involved more subtly. The examination indicates that the performance of cgRNASP-CN is close to that of the all-atom rsRNASP and is superior to other top all-atom traditional statistical potentials and scoring functions trained from neural networks, for two realistic test datasets including the RNA-Puzzles dataset. Very importantly, cgRNASP-CN is about 100 times more efficient than existing all-atom statistical potentials/scoring functions including rsRNASP. cgRNASP-CN is available at website: https://github.com/Tan-group/cgRNASP-CN.     

一种海面水包油溢油量等效评估算法的研究

水包油乳化液的溢油量是海面溢油污染评估分析的一个重要指标。激光诱导荧光(LIF)是目前海面溢油遥感探测领域一项最好的技术之一。基于LIF探测技术的海面水包油溢油量的评估目前尚无一套有效且完整的算法。鉴于此,首先设计了一种水包油乳化液溢油量的等效评估模型：将水包油乳化液中分散相油滴假设聚集为漂浮在海面上的成片油膜,如此就将水包油乳化液溢油量的评估问题转化为具有相同荧光效果的等效模型中油膜厚度的估测问题;其次基于LIF探测机理和荧光辐射传输过程,建立了LIF系统接收的荧光信号方程,进而反演求得油膜厚度的计算公式;最后选择具有代表性的重质、轻质两种油品,通过仿真实验验证了等效模型的正确性和将探测的水包油乳化液的荧光信号强度通过等效算法求取了油膜厚度,并对等效误差进行了分析,得出了等效评估算法的适用条件：即当水包油乳化液的实际溢油厚度≤其荧光平稳时的最小溢油厚度时,本文的等效评估算法具有较高精度,其平均误差在8%以内;而当实际溢油厚度＞荧光平稳时的最小溢油厚度时,等效评估误差增大,其平均值超出25%。另外,采用本文算法对重质、轻质水包油乳化液的溢油量进行等效评估时,实际溢油厚度分别不大于2和16 μm时可得到较好估测结果。所以,本文研究内容对基于LIF技术探测的海面水包油乳化液的溢油量评估是一种可行和有借鉴意义的方法。     

连续激光干扰效果评估方法北大核心CSCD

采用改进后的图像相关度计算方法,在精确配准干扰前后图像的基础上,以像素为单位计算图像相关度,根据人眼识别效果在评估前确定干扰阈值,计算图像有效干扰像元统计值,定量描述激光干扰效果;开展多波段激光干扰成像系统试验,采集不同干扰功率下的激光干扰图像,评估干扰效果。结果表明,该方法能精确识别图像局部变化,客观反映图像质量变化,对各波段不同功率下的激光干扰成像图像给出科学评估结果,对单对图像的处理速度优于s级,具有一定的工程应用价值。     

限购政策对杭州新建商品住宅价格的影响

断点回归（regression discontinuity,RD）是检验因果关系的有效方法,近年来,其在宏观政策评价中的应用越来越广泛。2016年G20峰会召开、货币政策调整等利好导致杭州房地产市场过快增长,杭州市政府于同年9月重启限购政策,并于2017年3月加大限购力度,限购范围扩大至杭州市户籍居民家庭。从实证角度研究了限购政策对新建住宅价格的影响。结果表明,限购政策均对新建商品住宅价格产生了具统计学意义的显著负向影响,2次降幅分别为400.26元和4 082.2元。回归模型通过了有效性检验,且在不同的阶数、核函数、带宽下具有稳健性,说明杭州市住房限购政策的实施在短期内对投资性购房需求起到了一定的抑制作用。     

智能感官分析技术结合传统感官评价对细点圆趾蟹蟹肉制品品质特性研究

采用智能感官分析技术结合传统感官评价,研究了细点圆趾蟹蟹肉、细点圆趾蟹重组蟹肉、仿蟹肉块和仿蟹肉棒的感官品质。4类均为低脂类、可放心食用的食品。用电子舌技术与主成分分析法对4类蟹肉样品进行了区分和识别,用质构仪检测了4类样品的适口性（包括硬度、弹性、黏结性、胶性、咀嚼性和回复性）。结果表明,仿蟹肉制品与纯蟹肉在味道上存在明显差异,纯蟹肉较仿蟹肉制品具有更强的鲜味回味,但苦味、涩味和苦味回味相对较高;蛋白质类添加剂（TG酶）有利于提高纯蟹肉的感官品质,尤其可大幅度改良口感和质地,全质构分析测定结果与人的感官评价结果一致性较高。     

基于概率犹豫模糊相似度的交互式群体决策方法

概率犹豫模糊集（probabilistic hesitant fuzzy set,PHFS）是犹豫模糊集的推广,在犹豫模糊集基础上通过为每个隶属度添加与之相对应的概率,以全面表达专家赋予的初始决策信息,是处理多属性指标决策问题的一种有效工具。首先,介绍了概率犹豫模糊数（PHFN）的基本定义和相关运算,指出了传统PHFN的得分函数和汉明距离的不足,并给出了改进方法。其次,通过适当补充隶属度集合中的元素数量提出了PHFN的汉明距离和相似度概念,依据专家赋予的评价矩阵引入了概率犹豫模糊矩阵（PHFM）相似度。最后,在概率犹豫模糊环境下基于PHFM相似度提出了一种交互式群体评价算法,并用实例验证了算法的有效性。