检索结果-内蒙古大学图书馆

discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease

Acta Pharmaceutica Sinica B 2025年第4期15卷 2134-2155页

作者： Sang, Zhipei Huang, Shuheng Tan, Wanying Ban, Yujuan Wang, Keren Fan, Yufan Chen, Hongsong Zhang, Qiyao Liang, Chanchan Mi, Jing Gao, Yunqi Zhang, Ya Liu, Wenmin Wang, Jianta dong, Wu Tan, Zhenghuai Tang, Lei Luo, Haibin State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D Guizhou Medical University Guiyang 550004 China Key Laboratory of Tropical Biological Resources of Ministry of Education and One Health Institute School of Pharmaceutical Sciences Hainan University Haikou 570228 China Center of Infectious Diseases West China Hospital of Sichuan University Chengdu 610041 China College of Chemistry and Pharmaceutical Engineering Nanyang Normal University Nanyang 473061 China Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine Shanghai 201203 China College of Animal Science and Technology Inner Mongolia Minzu University Inner Mongolia Tongliao 028000 China Institute of Traditional Chinese Medicine Pharmacology and Toxicology Sichuan Academy of Chinese Medicine Sciences Chengdu 610041 China

Alzheimer's disease (Ad) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood–brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish Ad models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLdLr), offering valuable insights into its potential modulation of the reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of Ad, with significant implications for further exploration into its mechanisms of action and therapeutic applications. © 2025 The Author(s)

关键词： Alzheimer's disease Mechanism of action Pharmacodynamic studies Pharmacokinetic studies Selective BuChE inhibitor

来源：评论

学校读者我要写书评

暂无评论

Crystal direction dependences of Anisotropic Magnetoresistance Effects in Co2MnGa and Co2MnAl Heusler Alloy Epitaxial Thin Films

Crystal Direction Dependences of Anisotropic Magnetoresistan...

引用

2023 IEEE International Magnetic Conference - Short Papers, INTErMAG Short Papers 2023

作者： Sato, Takashi Kokado, Satoshi Tsujikawa, Masahito Shinya, Hikari Ogawa, Tomoyuki Kosaka, Satoru Miura, Atsushi Shirai, Masafumi Tsunoda, Masakiyo Toyota Central R&D Labs. Inc. Nagakute480-1192 Japan Shizuoka University Graduate School of Integrated Science and Technology Hamamatsu432-8561 Japan Tohoku University Research Institute of Electrical Communication Sendai980-8577 Japan Osaka560-8531 Japan Tohoku University Graduate School of Engineering Department of Electronic Engineering Sendai980-8579 Japan Tohoku University Center for Science and Innovation in Spintronics Organization of Advanced Studies Sendai980-8577 Japan

ISBN: (纸本)9798350338362

The crystal direction dependences of anisotropic magnetoresistances in Co2MnGa and Co2MnAl epitaxial thin films grown on MgO(100) substrate were investigated experimentally and theoretically by changing the Co content. Both Co2MnGa and Co2MnAl films showed the maximum values in the AMr ratios at the Co content of approximately 50 at%. The AMr ratios of Co2MnGa showed the negative values for the current direction I // Co2MnGa[110] and positive values for I // Co2MnGa[100], whereas Co2MnAl showed only the positive AMr ratios independent of the current direction. The calculated AMr ratios from s-d scattering theory of the electrons, including the density of state (dOS) information from first principles calculations, well reproduced the experimental features. We found that the AMr ratios of Co2MnGa and Co2MnAl can be explained by s-d scattering depending on the current direction against the crystal axis. © 2023 IEEE.

关键词： Ternary alloys

来源：评论

学校读者我要写书评

暂无评论

Application of HATEOAS Principle in rESTful API design

Application of HATEOAS Principle in RESTful API Design

引用

International Symposium on Computational Intelligence and Informatics

作者： Fikri Aydemir Fatih Basciftci Information Technologies R&D Center Istanbul Kuveyt Turkt Bank Turkey Dept. of Computer Engineering Faculty of Technology Selcuk University Konya Turkey

ISBN: (纸本)9798350398830

Hypermedia as the Engine of Application State (HATEOAS) is a principle that has been built upon the term hypermedia to refer to a constraint on the representational State Transfer (rEST) application architecture. This principle distinguishes rEST from other application architectures, such as Simple Object Access Protocol in a way that client applications (e.g., a web app or a mobile app) need no prior knowledge for interacting with a rEST-based Application Programming Interface (API) beyond a generic understanding of its hypermedia. Ion is an intuitive JavaScript Object Notation-based hypermedia type for rEST, which can help software developers realize the principle of HATEOAS in their API design with ease. The goal of the work that is described in this paper has been to practically demonstrate the use of Ion in practice to have a self-documented rEST API. For this purpose, a C# library has been implemented to demonstrate the use of Ion in having a rEST API with self-documentation.

关键词： restful API Computer architecture Hypermedia Ions Libraries Software C# languages

来源：评论

学校读者我要写书评

暂无评论

Self-Supervised Monocular depth Estimation: Solving the Edge-Fattening Problem

arXiv

引用

arXiv 2022年

作者： Chen, Xingyu Zhang, ruonan Jiang, Ji Wang, Yan Li, Ge Li, Thomas H. School of Electronic and Computer Engineering Peking University China Advanced Institute of Information Technology Peking University China Information Technology R&D Innovation Center Peking University China

Self-supervised monocular depth estimation (MdE) models universally suffer from the notorious edge-fattening issue. Triplet loss, as a widespread metric learning strategy, has largely succeeded in many computer vision applications. In this paper, we redesign the patch-based triplet loss in MdE to alleviate the ubiquitous edge-fattening issue. We show two drawbacks of the raw triplet loss in MdE and demonstrate our problem-driven redesigns. First, we present a min. operator based strategy applied to all negative samples, to prevent well-performing negatives sheltering the error of edge-fattening negatives. Second, we split the anchor-positive distance and anchor-negative distance from within the original triplet, which directly optimizes the positives without any mutual effect with the negatives. Extensive experiments show the combination of these two small redesigns can achieve unprecedented results: Our powerful and versatile triplet loss not only makes our model outperform all previous SoTA by a large margin, but also provides substantial performance boosts to a large number of existing models, while introducing no extra inference computation at all. Copyright © 2022, The Authors. All rights reserved.

关键词： Machine learning

来源：评论

学校读者我要写书评

暂无评论

detecting the open-world objects with the help of the Brain

arXiv

引用

arXiv 2023年

作者： Ma, Shuailei Wang, Yuefeng Wei, Ying Chen, Peihao Ye, Zhixiang Fan, Jiaqi Zhang, Enming Li, Thomas H. Northeast University Shenyang China Information Technology R&D Innovation Center Peking University China South China University of Technology China Nanjing University of Information Science and Technology China School of Electronic and Computer Engineering Peking University Shenzhen Graduate School Shenzhen China

Open World Object detection (OWOd) is a novel computer vision task with a considerable challenge, bridging the gap between classic object detection (Od) benchmarks and real-world object detection. In addition to detecting and classifying seen/known objects, OWOd algorithms are expected to detect unseen/unknown objects and incrementally learn them. The natural instinct of humans to identify unknown objects in their environments mainly depends on their brains’ knowledge base. It is difficult for a model to do this only by learning from the annotation of several tiny datasets. The large pre-trained grounded language-image models - VL (i.e. GLIP) have rich knowledge about the open world but are limited to the text prompt. We propose leveraging the VL as the "Brain" of the open-world detector by simply generating unknown labels. Leveraging it is non-trivial because the unknown labels impair the model’s learning of known objects. In this paper, we alleviate these problems by proposing the down-weight loss function and decoupled detection structure. Moreover, our detector leverages the "Brain" to learn novel objects beyond VL through our pseudo-labeling scheme. Comprehensive experiments performed on MS-COCO and PASCAL VOC (Ours results in the bolded font) show that our model significantly outperforms the existing open-world detectors in terms of U-recall on two existing splits (12.1, 9.4, 11.6 vs. 39.0, 36.7, 36.1 in OrE split, 5.7, 6.2, 6.9 vs. 60.9, 60.0, 58.6 in OW-dETr split), without loss of performance on known classes. Compared with the GLIP, our model still achieves better performance (37.0, 35.5, 34.9 vs. 39.0, 36.7, 36.1 in OrE split, 52.6, 54.5, 53.3 vs. 60.9, 60.0, 58.6 in OW-dETr split) for open-world object detection, with a faster inference speed (9.22 seconds / per image vs. 0.08 seconds / per image) and less computational cost (FLOPs 965GMac vs. 212GMac, Param# 321.9M vs. 42.9M). The code is available at https:// ***/xiaomabufei/dOWB. Copyright © 20

关键词： Object detection

来源：评论

学校读者我要写书评

暂无评论

Synchronous PWM Method Considering Motor Current Control for 2Level-3Phase Inverter

Synchronous PWM Method Considering Motor Current Control for...

引用

International Conference on Electrical Machines and Systems (ICEMS)

作者： Shinichi Furutani Shinji doki Advanced Technology R&D Center Mitsubishi Electric Corporation Amagasaki Hyogo Japan Department of Information and Communication Engineering Graduate School of Engineering Nagoya University Nagoya Aichi Japan

ISBN: (数字)9781665493024

ISBN: (纸本)9781665493031

This paper proposes a Synchronous PWM method considering motor current control for 3 phase - 2 level inverter. For this purpose, the proposed method generates switching reference allowing for voltage changes within fundamental section. the proposed method is applied to motor current control simulation to confirm the effectiveness of the proposed method.

关键词： Current control Impedance matching Switches Pulse width modulation Synchronous motors Inverters Voltage control

来源：评论

学校读者我要写书评

暂无评论

development of a High Sensitive Label-Free Electrochemical Immunosensor Using Aunps@Zif-8@F-Mwcnts Nanocomposites for Ovarian Cancer diagnosis Via Ca-125 detection

SSRN

引用

SSrN 2024年

作者： runprapan, Nattharika Wang, Fu-Ming Yuan, Chiou-Chung Graduate Institute of Applied Science and Technology National Taiwan University of Science and Technology Taipei Taiwan Sustainable Energy Center National Taiwan University of Science and Technology Taipei Taiwan Department of Chemical Engineering Chung Yuan Christian University Taoyuan Taiwan R&D Center for Membrane Technology Chung Yuan Christian University Taoyuan Taiwan Department of Obstetrics and Gynecology Cheng Hsin General Hospital Taipei Taiwan

Early diagnosis of ovarian cancer (OC) is critical for effective treatment and improved patient outcomes. This study presents a novel label-free electrochemical immunosensor, a biomarker associated with OC, for high-sensitivity detection of CA-125. Our approach involves a unique immobilization strategy utilizing nanocomposites of gold nanoparticles/zeolitic imidazolate framework-8/carboxylic acid-functionalized multi-walled carbon nanotubes (AuNPs@ZIF-8@f-MWCNTs). This results in ingenuity, which facilitates the direct measurement of antibody (Ab) capture with antigen (Ag), simplifying the biosensor fabrication process and eliminating the need for extra Ab, thus reducing the need for a laboratory. The synergistic effect of AuNPs, ZIF-8, and f-MWCNTs within the nanocomposites enhances stability, electrical conductivity, and electrochemical signal while providing a large surface area with numerous binding sites for increased Ab loading. Experimental results demonstrate the label-free immunosensor’s wide linear detection range (10 to 10−6 µg/mL) and impressive sensitivity, with a lower detection limit (LOd) of 1 pg/mL. Notably, our proposed immunosensor shows promise for detecting CA-125 in human serum samples, underscoring its potential for early OC diagnosis—a crucial advancement in healthcare. © 2024, The Authors. All rights reserved.

关键词： Gold nanoparticles

来源：评论

学校读者我要写书评

暂无评论

Frequency-Aware Self-Supervised Monocular depth Estimation

arXiv

引用

arXiv 2022年

作者： Chen, Xingyu Li, Thomas H. Zhang, ruonan Li, Ge School of Electronic and Computer Engineering Peking University China Advanced Institute of Information Technology Peking University China Information Technology R&D Innovation Center of Peking University China

We present two versatile methods to generally enhance self-supervised monocular depth estimation (MdE) models. The high generalizability of our methods is achieved by solving the fundamental and ubiquitous problems in photometric loss function. In particular, from the perspective of spatial frequency, we first propose Ambiguity-Masking to suppress the incorrect supervision under photometric loss at specific object boundaries, the cause of which could be traced to pixel-level ambiguity. Second, we present a novel frequency-adaptive Gaussian low-pass filter, designed to robustify the photometric loss in high-frequency regions. We are the first to propose blurring images to improve depth estimators with an interpretable analysis. Both modules are lightweight, adding no parameters and no need to manually change the network structures. Experiments show that our methods provide performance boosts to a large number of existing models, including those who claimed state-of-the-art, while introducing no extra inference computation at all. Copyright © 2022, The Authors. All rights reserved.

关键词： Low pass filters

来源：评论

学校读者我要写书评

暂无评论

Performance Analysis of the Modified Flux-Coupling-Type SFCL in VSC-HVdC System

Performance Analysis of the Modified Flux-Coupling-Type SFCL...

引用

Iranian Conference on Electrical engineering (ICEE)

作者： Mohammad Khakroei Ashkan Mirzaei rajeooni Mahdi rahimi Pirbasti Hossein Heydari MAPNA Electric & Control Engineering & Manufacturing Company (MECO) Alborz Iran Department of Engineering and R&D MAPNA Generator Engineering and Manufacturing Company (PARS) Alborz Iran Department of Electrical Engineering (Center of Excellence for Power System Automation and Operation) Iran University of Science and Technology (IUST) Tehran Iran

Although Voltage Source Converters based on HVdC (VSC-HVdC) systems have several advantages, they are vulnerable to dC fault currents. Concerning the inherent characteristics of high-temperature superconducting (HTS) material, using HTS in the fault current limiter could be a solution to limit the current in VSC-HVdC. The present paper seeks to provide an elaborately better solution to the problem mentioned above of the fault currents than what has previously been proposed. The object of this research is a modified flux coupling type superconductor fault current limiter (MFC-SFCL) to attenuate the fault current in VSC-HVdC network. The principle mechanism and operation of the SFCL and VSC-HVdC systems are modeled in detail, involving interplay or synergy between electrical and thermal properties. The simulation results demonstrate that the purposed MFC-SFCL has the proper function to mitigate the fault current.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Initial stage of degradation process of alumina-silica refractory by molten Al-5Mg alloy

引用

Keikinzoku/Journal of Japan Institute of Light Metals 2022年第11期72卷 631-637页

作者： Tamura, Yosuke Soda, Hiroshi McLean, Alexander Ishikawa, Takaaki Ishizuka, Michio Kawasaki, Masato Mizuno, Kentaro Motegi, Tetsuichi Department of Advanced Materials Science and Engineering Chiba Institute of Technology 2-17-1 Tsudanuma Chiba Narashino-shi275-0016 Japan University of Toronto TorontoONM5S 3E4 Canada Chiba Industrial Technology Research Institute Chiba Chiba-shi Japan R&D Center Ceramics Div. Rozai Kogyo Kaisha Ltd. Hyogo Ako-shi Japan Development Center AGC Ceramics Co. Ltd. Hyogo Takasago-shi Japan Zmag Ltd. Chiba Shiroi-shi Japan Chiba Institute of Technology Chiba Funabashi-shi Japan

Initial stages of the refractory degradation process by molten Al-5Mg alloy were investigated by analyzing the degradation structures caused by an interaction with molten metal during heat cycles. The refractory aggregate, found to be poly-crystalline, consisting of cristobalite (SiO2) and mullite (Al6Si2O13), was deteriorated ahead of the surrounding matrix. Metal permeated into the refractory, forming a thin metal layer along the crucible surface below the molten metal line at an early stage of degradation process, which would later serve as the bases for the metal infiltration path through the refractory above the molten metal line. A discontinuous film (thickness2O4, was formed at the "melt / refractory" interface. At the experimental temperature of 1150°C, Mg in the molten metal would build up as Mg gas at MgAl2O4 film/refractory interface and easily diffuse into the aggregate body and react with the aggregate components of SiO2 and Al6Si2O13 to form MgAl2O4 and Al-Mg-Si-O compounds. This was followed by the molten metal infiltration into the refractory while reducing the Al-Mg-Si-O compound to form MgAl2O4. Through the initial degradation process MgAl2O4 would finally form in a successive chain of reactions, resulting in deterioration of the crucible. © 2022 The Japan Institute of Light Metals.

关键词： Corundum

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：