Targeting tribbles homolog 3 (TRIB3) protein against type 2 diabetes for the identification of potential inhibitors by in silico screening

Tribbles homolog 3 (TRIB3) protein is inhibiting the insulin signaling by directly binding to the Akt/PKB leading to insulin resistance in the pancreas causing type 2 diabetes mellitus. Hence, TRIB3 protein is considered as a possible drug target for the new lead identification against type 2 diabetes. In the present study, the homology model of TRIB3 protein was generated to explore its biochemical function and molecular interactions in the new lead identification. The energy minimization of TRIB3 protein was carried out and evaluated by validation protocols for structure reliability. The druggable binding site of TRIB3 protein was identified for the virtual screening and molecular docking studies. The Asinex-fragments library of 22634 small molecules was docked at TRIB3 active site using the Glide module to identify new chemical entities. A total of 9 molecules were identified as final hits from virtual screening and their potency was ranked using Glide score, Glide energies, and residues interactions. The 6 prioritized lead molecules were further optimized using AutoDock, Prime MM/GBSA, and percentage of human oral absorption for the identification of potential leads. The molecules L2, L5, and L6 are identified as lead inhibitors and are showing consistent interactions with key residues Glu194 and Lys196 of TRIB3 protein. The identified potential leads were analyzed by ADME properties for their drug likeness and HergIC50 values are predicted for the prevention of preclinical failures. The present work sheds light on the identification of the best lead molecules against TRIB3 protein and offers a route to design as novel potential drug candidates for T2DM.     

基于显微共聚焦拉曼技术对三种食源性致病菌的快速鉴别研究

采用显微共聚焦拉曼技术,建立了对三种常见食源性致病菌快速鉴别的检测方法。使用XploRA PLUS共聚焦拉曼光谱仪,在激光功率为5 mW、积分时间为30s、积分次数为1次的条件下,对德尔卑沙门氏菌、副溶血性弧菌和金黄色葡萄球菌进行了拉曼光谱数据的采集。对拉曼光谱采用多项式平滑算法和荧光背底扣除后,采用主成分分析法(PCA)对预处理后的数据进行降维,提取出前三个主成分的累计方差贡献率达到了95.4％,样本明显的聚为了3类。同时结合Fisher判别分析法(FLD)构建分类模型,对三种样本进行交叉验证,分类准确率达到了100％。结果表明,采用显微共聚焦拉曼技术与PCA-FLD方法结合可实现对三种食源性致病菌的快速准确鉴别且模型检测精度高,方法具有一定的实用性及参考价值。     

液相色谱-四极杆/飞行时间质谱法分析29种芬太尼类物质及其碎裂机理北大核心CSCD

芬太尼类物质品种繁多,自我国整类列管后,整类检测是该领域的重点和难点。该文详细研究了29种化合物的二级质谱碎片离子碎裂机理,总结出芬太尼类物质的碎裂规律和特点,为芬太尼物质的整类筛查检测提供参考。建立了分析29种芬太尼类物质的一级和二级质谱库的定性方法,建立了液相色谱-四极杆/飞行时间质谱(LC-QTOF-MS)检测29种芬太尼类物质的定量方法。药品和白色粉末类、蛋白质和乳饮料类样品经乙腈提取,含糖固体或粉末类、饮用水类、果蔬饮料类、保健饮料类、茶饮料类、酒类样品经10%乙腈水溶液提取,提取液经涡旋、离心和过膜后,采用Kinetex C18色谱柱(100 mm×2.1 mm,2.6μm)分离,以乙腈和0.08%甲酸水溶液为流动相进行梯度洗脱,采用四极杆/飞行时间质谱,在正离子模式下,外标法定量检测。结果表明,29种芬太尼类物质在1~20μg/L范围内线性关系良好,相关系数均大于0.995,检出限(LOQ)均为0.01 mg/kg,定量限(LOQ)均为0.05 mg/kg,在降糖药、露露、葡萄糖粉、珍露保健饮料和巧克力样品中3个加标水平平均回收率为85.2%~112.9%,相对标准偏差(RSD)为1.9%~19.8%(n=6)。该方法操作简单,耗时短,灵敏度高,稳定性好,检测品种覆盖范围广,适用于药品类、含糖固体或粉末类、饮料类、饮用水类和酒类等样品中29芬太尼类物质的定性和定量检测。     

高效液相色谱-四极杆-飞行时间质谱快速筛查鉴别食品中非法添加的62种中药材北大核心CSCD

建立了高效液相色谱-四极杆-飞行时间质谱快速筛查鉴别食品中非法添加的62种中药材的方法。依据卫生部关于进一步规范保健食品原料管理的通知(卫法监发[2002]51号)中可用于保健食品的物品名单,确定食品中可能非法添加的62种中药材原料清单,再从62种中药材中筛选其特征组分,获得不同中药材对应的特征组分清单。62种对照药材经甲醇超声提取后,于Thermo Accucore aQ色谱柱(150 mm×2.1 mm,2.6μm)上分离,在电喷雾正负离子扫描模式下,分别以0.1%(v/v)甲酸水溶液-乙腈和水-乙腈为流动相梯度洗脱,进行一级质谱和二级质谱全扫描检测,采用Library View软件建立不同中药材对应的特征组分的一级精确质量数据库和二级碎片质谱库。样品同法处理后上样分析,采用Peak View软件将样品高分辨数据与自建数据库中的质谱图、精确分子离子质量数、碎片离子质量数、保留时间等相关参数进行快速筛查鉴别分析。该工作通过建立“中药材-特征组分”对应清单,构建了食品中易非法添加的62种中药材中共388种特征组分的高分辨质谱库,每种中药材包括5~10种特征组分,通过对实际食品样品配制酒、代用茶及饮料进行筛查分析,1批次配制酒样品与淫羊藿中药材的7种特征组分匹配一致,推断该配制酒样品中加入了淫羊藿中药材。该法可实现无标准品情况下中药材的定性筛查,具有高通量、准确、简便、快捷的特点,解决了食品中非法添加中药材难以识别和确证的难题,可以实现食品中非法添加中药材的快速筛查鉴别分析。     

Experiments on crack identification in cantilever beams

In this paper we present an experimental investigation of the identification of crack location and size. By providing the first three natural frequencies through vibration measurements, curves of crack equivalent stiffness versus crack location are plotted, and the intersection of the three curves predicts the crack location and size. In the experiments, the cracked specimens were made using a wire-cut electrical discharge machine, and the cantilever beams were excited next to the free end by means of an impulse force hammer. In order to obtain the accurate natural frequencies from the transient signal measured, the method of zoom fast Fourier transform is adopted to improve frequency resolution. From experimental results, it is observed that the identification errors of crack location and size are less than 2% and 4%, respectively. The effectiveness of crack identification through vibration measurements is verified.     

基于模糊逻辑的光纤陀螺温度补偿技术

为了消除温度效应并提高陀螺精度,将模糊逻辑应用于光纤陀螺的温度漂移模型的辨识和自补偿中方案中。在模糊逻辑理论的框架下,根据光纤陀螺系统的模糊信息,建立模糊规则,进行模糊推理,实现对陀螺输出的近似辨识。此方法对其他没有温度相似性的陀螺也适用。在实际验证实验中,针对不同的陀螺,通过预先实验建立各自的规则表,然后进行实时补偿,在全温度范围内陀螺的零偏稳定性从0.3647(o)/h减小到0.0868(o)/h,陀螺预热时间缩短到30s以内。目前,在陀螺工艺条件还不够稳定的状态下,此方案是实用和可行的。     

基于虚拟响应信号的结构参数时域辨识研究

在充分考虑线性动力系统的时域响应特性以及小波包分析的频率空间剖分特性的基础上,提出了一种基于虚拟响应信息提取的信号去噪新方法.虚拟响应虽然没有在结构动力检测过程中真实发生,但却是在某种激励下可以实现的一个响应,因此,根据虚拟响应信息同样可以进行结构系统的动力识别.数值研究表明,对于地脉动响应这种有效信号频带与噪声频带相互覆盖的低信噪比信号而言,小波阈值去噪法已无能为力,而基于虚拟响应信息提取的信号去噪方法则有较好的去噪效果.     

一种舰船变形测量方法的研究与应用

以舰船船体结构、惯性导航系统、被试导航设备以及天文经纬仪为物理对象，提出了一套利用光学系统原理和计算机图像处理技术对联合基座进行水平变形测量的方法，解决了各设备因安装位置的不同所造成的安装基座间产生的水平变形量问题。     

圆平板挤压膜实验及其参数识别

完成了简谐激励下水中平行圆板的挤压膜振动实验．用最小二乘法识别出非线性粘性挤压膜力模型中的４个系数．不同挤压膜厚、不同频率和不同振幅情况的数值模拟结果与实验值吻合较好．研究结果表明，所用模型可较好地描述粘性挤压膜运动，识别出的系数在一定范围内给出良好精度的数值模拟．     

A SINGULAR VALUE DECOMPOSITION BASED TRUNCATION ALGORITHM IN SOLVING THE STRUCTURAL DAMAGE EQUATIONS

The structural damage identification through modal data often leads to solving a set of linear equations. Special numerical treatment is sometimes required for an accurate and stable solution owing to the ill conditioning of the equations. Based on the singular value decomposition (SVD) of the coefficient matrix, an error based truncation algorithm is proposed in this paper. By rejection of selected small singular values, the influence of noise can be reduced. A simply-supported beam is used as a simulation example to compare the results to other methods.Illustrative numerical examples demonstrate the good efficiency and stability of the algorithm in the nondestructive identification of structural damage through modal data.