Multidimensional De Novo Design Reveals 5‐HT2B Receptor‐Selective Ligands

We report a multi‐objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer‐generated 5‐HT_2B receptor ligands with accurately predicted target‐binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand‐efficient 5‐HT_2B modulators with sustained cell‐based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics‐assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.     

Fragment‐Based De Novo Design Reveals a Small‐Molecule Inhibitor of Helicobacter Pylori HtrA

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment‐based, computer‐assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best‐in‐class HtrA inhibitor. The results obtained reinforce the validity of ligand‐based de novo design and binding‐kinetics‐guided optimization for the efficient discovery of pioneering lead structures and prototyping drug‐like chemical probes with tailored bioactivity.     

工程结构静力分析和屈曲分析程序系统DDJTJQ及其应用

DDJTJQ是一个国内开发的组合结构静力分析和屈曲分析有限元程序系统,自1986年通过技术鉴定以来又有了许多发展。本文介绍该程序系统的功能和特点、求解能力以及在不同工程领域结构分析中的应用。     

混合型有限元双向分配法解有侧移刚架及其微机程序

本文应用混合型有限元双向分配法得到有侧移刚架的数值解。文中给出了计算机程序,具有占用内存少、收敛快等特点。文末给出了算例。     

Symbolic generation of large multibody system dynamic equations using a new semi-explicit Newton/Euler recursive scheme

Summary The aim of this paper is to show that multibody systems with a large number of degrees of freedom can be efficiently modelled, taking conjointly advantage of a recursive formulation of the equations of motion and of the symbolic generation capabilities.Recursive schemes are widely used in the field of multibody dynamics since they avoid the explosion of the number of arithmetical operations in case of large multibody models. Within the context of our field of applications (railway dynamics simulation), explicit integration schemes are still prefered and thus oblige us to compute the generalized accelerations at each time step. To achieve this, we propose a new formulation of the well-known Newton/Euler recursive method, whose efficiency will be compared with a so-called O(N) formulation.A regards the symbolic generation, often decried due to the size of the equations in case of large systems, we have recently implemented recursive multibody formalisms in the symbolic programme ROBOTRAN [1]. As we shall explain, the recursive nature of these formalisms is particularly well-suited to symbolic manipulation.All these developments have been successfully applied in the field of railway dynamics, and in particular allowed us to analyse the dynamic behaviour of several railway vehicles. Some typical results related to a completely non-conventional bogie will be presented before concluding.     

大变位时物体变形测量的相关性恢复方法

本文提出根据白光散斑图像数据模拟刚体位移复位的相关性恢复方法，以解决物体大变位情况下的变形测量问题     

三种典型磨粒磨损磨屑形成过程的研究

作者利用扫描电子显微镜、光学显微镜和计算机图象分析系统,对3种典型磨粒磨损磨屑的形成特点和典型试验条件下材料的磨粒磨损过程进行了研究。结果表明,在磨粒磨损条件下,典型的磨屑形态主要是切屑和块状屑,同时还有极少量的球状屑和花状屑。作者指出,切屑和块状屑分别是磨粒与被磨材料表面一次和多次相互作用的产物。在三体磨粒磨损条件下,切削是造成编号为2M和3M等硬质材料磨损的主要原因,也是4M和几种奥氏体锰钢在高载荷下磨损的重要形式;块状屑的形成是塑性较好的材料在各种磨损条件下磨损的主要形式。球状屑的形成是磨粒与被磨材料表面的接触点产生高温致使材料熔化的结果。球状屑一般是中空且表面有很多孔洞的球壳,其形成与气体有关。     

多模式自适应重要抽样法及其应用

针对多模式的可靠性分析，研究了其失效概率计算的自适应重要抽样法，该方法用模拟退火 算法来自动调整每个失效模式的重要抽样函数，使其逐渐趋近于估计方差最小的重要抽样 函数. 对于多个模式系统失效概率的计算，采用混合加权自适应重要抽样的方法, 反映了每个 失效模式对系统失效概率的贡献；对于系统失效模式所含基本变量不全相同的情况，提出了 扩展自适应重要抽样法, 来统一所有失效模式中的基本变量，从而使得混合自适应 重要抽样, 可以方便地求解变量不全相同时的系统失效概率. 对估计值方差和变异系数的计算公 式进行了推导. 验证算例结果, 充分说明方法的合理性与可行性.     

汽车稳定杆拟动态实验分析

本文主要通过汽车稳定杆在疲劳试验中应力、刚度拟动态试验，采用电测法^[1]，在分析杆件中实际应变和位移的基础上进行逆解分析，从而确定稳定杆的实际刚度，支座摩阻反力矩和应力集中系数，为建立稳定杆的简化力学分析及其疲劳寿命预测提供试验依据．