立式钻铣床动力头设计与三维造型

多工位钻铣床实现了一台机床对一个零件做不同加工的功能,节省了机床,也缩小了占地面积,同时提高了加工精度和生产率,对工人劳动强度也降低很多。本设计中,钻头的固定采用拉杆式楔形固定,钻头采用套筒及主轴轴面为拉杆的结构,套筒外侧用绝缘胶固定了一个支撑架,钻头的动力由同步齿形带传递到钻头,比起万向轴传递动力要准确且刚性好。动力采用行星轮的传递方式,保证了各工位的同步工作,节省空间,本机构紧凑,各啮合齿轮之间中心距不超过100 mm,因而,用齿轮传动可以满足要求,这样可以用标准件对机床快速装配完工,对缩短加工周期有很大好处。     

Rational Design of CYP3A4 Inhibitors: A One-Atom Linker Elongation in Ritonavir-Like Compounds Leads to a Marked Improvement in the Binding Strength

Inhibition of the major human drug-metabolizing cytochrome P450 3A4 (CYP3A4) by pharmaceuticals and other xenobiotics could lead to toxicity, drug–drug interactions and other adverse effects, as well as pharmacoenhancement. Despite serious clinical implications, the structural basis and attributes required for the potent inhibition of CYP3A4 remain to be established. We utilized a rational inhibitor design to investigate the structure–activity relationships in the analogues of ritonavir, the most potent CYP3A4 inhibitor in clinical use. This study elucidated the optimal length of the head-group spacer using eleven (series V) analogues with the R₁/R₂ side-groups as phenyls or R₁–phenyl/R₂–indole/naphthalene in various stereo configurations. Spectral, functional and structural characterization of the inhibitory complexes showed that a one-atom head-group linker elongation, from pyridyl–ethyl to pyridyl–propyl, was beneficial and markedly improved K_s, IC₅₀ and thermostability of CYP3A4. In contrast, a two-atom linker extension led to a multi-fold decrease in the binding and inhibitory strength, possibly due to spatial and/or conformational constraints. The lead compound, 3h, was among the best inhibitors designed so far and overall, the strongest binder (K_s and IC₅₀ of 0.007 and 0.090 µM, respectively). 3h was the fourth structurally simpler inhibitor superior to ritonavir, which further demonstrates the power of our approach.     

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

A Web Server for Designing Molecular Switches Composed of Two Interacting RNAs

The programmability of RNA–RNA interactions through intermolecular base-pairing has been successfully exploited to design a variety of RNA devices that artificially regulate gene expression. An in silico design for interacting structured RNA sequences that satisfies multiple design criteria becomes a complex multi-objective problem. Although multi-objective optimization is a powerful technique that explores a vast solution space without empirical weights between design objectives, to date, no web service for multi-objective design of RNA switches that utilizes RNA–RNA interaction has been proposed. We developed a web server, which is based on a multi-objective design algorithm called MODENA, to design two interacting RNAs that form a complex in silico. By predicting the secondary structures with RactIP during the design process, we can design RNAs that form a joint secondary structure with an external pseudoknot. The energy barrier upon the complex formation is modeled by an interaction seed that is optimized in the design algorithm. We benchmarked the RNA switch design approaches (MODENA+RactIP and MODENA+RNAcofold) for the target structures based on natural RNA-RNA interactions. As a result, MODENA+RactIP showed high design performance for the benchmark datasets.     

地方高校转型背景下生物工程专业课程设计教学改革与探索

以地方本科高校转型发展为背景,以提高生物工程专业应用技术人才培养质量为目标,针对地方高校生物工程专业课程设计教学的特点和存在的问题,以生物工程专业的本科教学为例,探讨课程设计教学改革的有效措施,为探索课程设计教学环节的改革措施提供了参考。     

基于热电联产的汽轮机组油膜振荡故障诊断系统设计

常规振荡故障诊断系统,采集振荡信号噪声较大,导致诊断的故障类别信任度较低。针对这一问题,提出基于热电联产的汽轮机组油膜振荡故障诊断系统。耦合热电联产生产方式,循环汽轮机组多余排汽,通过排汽热量增加系统发电量完成硬件设计;采用小波包降噪算法,消除采集振荡信号噪声,分解信号各个时刻和频带,排序频带内时域子信号能量值,构成故障信号特征向量,输入神经网络,训练后输出振荡故障诊断模式完成软件设计。采集满负荷、最小负荷、噪声条件下的油膜振荡信号,设置对比实验,结果表明,所设计系统提高了故障诊断信任度,故障诊断结果更为准确可靠。     

《单片机原理及应用》课程思政的实践探索——以“单片机的存储器结构”知识点讲解为例

针对《单片机原理及应用》及其相关课程在课程思政建设中存在的问题,提出一种课程思政设计思路,即选取合适的授课内容与思政素材,从教学目标和教学设计出发,将思政素材自然融入到授课内容中。并以“单片机的存储器结构”知识点讲解为例,详细介绍了以上课程思政设计思路的具体设计与实施过程,具有较强的创新性与可操作性,对单片机类课程线上及线下教学的课程思政建设有一定的借鉴意义。     

工业设计决策网络构建及其动态演化仿真

针对工业设计过程多阶段方案决策的意见演化问题,融合复杂网络理论建立工业设计决策网络模型,通过意见动力学进行决策意见动态演化仿真.基于图论建立设计决策有权无向网络,以网络效率变化确定决策者权重,借助意见距离识别设计决策网络节点信任集合,利用加权平均意见驱动设计决策网络更新与演化. 提出工业设计决策网络的演化仿真流程,结合产品设计方案决策数据进行动态仿真分析,结果表明：信任阈值决定设计决策网络拓扑构成,随着网络演化的进行,决策个体间意见差异逐步缩小并最终达成共识;设计决策网络分析能够析出噪声节点及其意见变化,在实际产品设计决策中应重点关注;意见演化能够辅助确定工业设计方案决策轮次,明确方案在各指标上的表现并识别设计改进方向;仿真分析有助于发现设计决策中的关键因素和意见演化规律.     

带特征指标约束描述的设计模式分类挖掘

为解决设计模式挖掘正确率较低的问题, 提出一种带特征指标约束描述的设计模式分类挖掘方法。归纳了47种特征指标, 给出了设计模式约束定义, 对设计模式特征进行了描述, 以Adapter模式、Command模式、Factory Method模式为例, 分结构型、行为型与创建型3类挖掘设计模式, 设计了3个基准系统与4个经典系统的设计模式挖掘试验。试验结果表明, 本研究方法对基准系统的Adapter模式、Command模式、Factory Method模式挖掘正确率为96.13%、91.67%、72.23%, 对经典系统挖掘正确率分别为84.3%、81.26%、73.17%, 与传统方法比较, 本研究方法取得了较好的效果。     

双色挤塑成型

以彩色毛笔杆为例 ,分析了双色挤塑成型的基本原理 ,介绍了设计制造双色挤塑成型简易设备的方法。