Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

美国网络空间领域战略思想及发展重点研究

美军将网络空间视为继陆、海、空、天外的第五大作战域,并将其列为国防部11项现代化优先事项之一,在美国等军事大国推动下,网络空间成为国家安全竞争和军事斗争的新疆域.文中对近年美国联邦政府、各部门及各军种发布的网络空间领域主要战略政策、规划计划进行梳理,研究其主要战略思想;分析美军2022财年国防预算、研究经费投向投量及重点项目的 研发情况.形成的研究成果将对我国网络空间安全领域研究提供技术支撑.     

基于SRAM的通用存算一体架构平台在物联网中的应用

最近,存算一体(IMC)架构引起了广泛关注,并被认为有望成为突破冯诺依曼瓶颈的新型计算机架构,特别是在数据密集型(data-intensive)计算中能够带来显著的性能和功耗优势.其中,基于SRAM的IMC架构方案也被大量研究与应用.该文在一款基于SRAM的通用存算一体架构平台——DM-IMCA的基础上,探索IMC架构在物联网领域中的应用价值.具体来说,该文选取了物联网中包括信息安全、二值神经网络和图像处理在内的多个轻量级数据密集型应用,对算法进行分析或拆分,并将关键算法映射到DM-IMCA中的SRAM中,以达到加速应用计算的目的.实验结果显示,与基于传统冯诺依曼架构的基准系统相比,利用DM-IMCA来实现物联网中的轻量级计算密集型应用,可获得高达24倍的计算加速比.     

基于有限元的区域分解方法在永磁聚焦系统仿真中的应用

随着计算机技术以及并行求解技术的发展,区域分解方法越来越多地应用于计算电磁学的各个领域.针对微波管中的永磁聚焦系统仿真,该文提出一种基于有限元的非重叠区域分解方法,其引入一种新型传输条件,并采用内罚的方式推导出有限元弱形式.该区域分解法的最大优势是不需要引入多余的未知量,并且最终集成的有限元矩阵满足对称正定性,适合采用预处理共轭梯度法进行矩阵方程的求解.该文仿真了多个微波管永磁聚焦系统,并与商业软件Maxwell进行了详细的对比,结果表明所提出的区域分解方法和Maxwell精度相当,却拥有着更加优越的计算性能.     

Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

Performance analysis of bit error rate of data link system under pulse LFM interference in time-varying rayleigh channel

Wireless Networks - In such mobile platforms as ships and aircraft, the detection and reconnaissance devices are near to the communication facilities. When working at the same time, they will...     

供水管网DMA优化分区设计方案

实施独立计量分区(district metered area,DMA)是辅助供水管网管理和漏损识别的重要手段.图划分算法是进行DMA分区的方法之一,常规图划分算法应用中,存在解空间受限、分区后原水流状态易发生较大改变、形成较多串联分区(对流量计算不利)的缺点.在常规图划分算法基础上进行了改进:粗化阶段按照特定规则匹配、合并非输水干管两端的节点,形成简化的管网拓扑结构;分区阶段得到管网初步分区方案;细化阶段提出基于贪心算法、枚举算法、蒙特卡洛算法的分区调整方法,结合改进的仪表安置方法、水力模拟、优劣解距离法(technique for order preference by similarity to an ideal solution,TOPSIS),对分区方案进行调整.将该方法应用于YX市供水管网,成功进行了分区.     

浅谈压力式温度计示值误差测量结果的不确定度评定

为了帮助试验人员深入了解压力式温度计的原理及作用,详细介绍了温度计示值误差测量结果的不确定度评定方法。影响压力式温度计示值误差结果的主要因素是,被检温度计的示值重复性、恒温槽温度不均匀性和恒温槽温场的波动。为了保证压力式温度计测量结果不确定度评定具有较高的可靠性,试验人员需要对影响评定可靠性的各种因素进行全面的分析,找出温度计示值的误差,从而确保温度计能够更好的被投入使用。     

喷油方式对斜齿轮齿面温度的影响

为探讨喷油方式对齿面温度的影响，以斜齿轮为研究对象，通过CFD仿真和试验研究不同喷油方式对斜齿轮齿面温度的影响。针对斜齿轮喷油润滑过程的特点，分析其齿面摩擦生热量，简化轮齿喷油润滑计算模型，并基于CFX进行齿面对流换热仿真研究，得到了不同喷油方式下的齿面温度；基于功率开放式斜齿轮试验平台，对不同喷油方式下的齿面温度进行了试验测量，与仿真计算结果进行对比分析。结果表明：在高速重载斜齿轮传动系统中，啮出侧喷油润滑的方式比啮入侧喷油润滑方式的冷却降温效果要好。