共查询到19条相似文献，搜索用时 328 毫秒
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本文介绍了高通量药物筛选的原理,体外筛选模型及常用的检测方法和技术,并结合药物研究过程论述了高通量药物筛选在新药研发中的过程,分析了其对药物开发策略的转变和影响。 相似文献
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在高通量药物筛选中 ,数学模型被认为是实现对样品库大规模筛选及筛选过程自动化的基础 .从热力学及动力学的角度对药物筛选的原理与方法进行了分析研究 ;同时也对药物与靶点的 3种可能的作用体系进行了研究 ,获得了药物筛选过程的热力学与动力学综合模型和基础数学模型 相似文献
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<正>1928年，英国科学家亚历山大·弗莱明（AlexandraFleming）发现青霉素并开创了微生物药物的新领域。在随后的几十年里，天然产物的药物开发一直是新药研发领域的热点和前沿。后来，随着分子靶位筛选理论和高通量筛选技术的应用，传统的天然产物药物研究策略逐渐失去了优势。如今，基因组测序探明微生物中蕴含着大量未开发的次级代谢产物基因簇，天然产物的药物开发迎来了新的时机，再次成为热点和前沿。 相似文献
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把毒性病理学研究提高到一个新水平 总被引：1，自引：0，他引：1
加速具有我国知识产权的新药的开发，是我国加入世界贸易组织（WT
O）后的必由之
路。预测上市新药对人类健康危害的可能，提供新药对人类健康可能产生影响的科学依据，
是决定新药能否进入市场的关键因素之一。而其中最重要的基础工作，就是毒性病理学的检
测和研究。当前，我们要在传统的毒性病理学研究的基础上务实求新，在建立系统的、规范
的毒性病理学评价标准体系的同时，将眼光要放在快和新两个字上，注重免疫毒性评价的新
动向，建立新的快速替代模型，引进新的现代分子生物学技术，以深入开展毒性机制的研究
。我们还应该建立创新药物高通量筛选体系中的毒性评价体系，以便把药物安全性评价工作
从临床前阶段提早到药物发现阶段来进行。 相似文献
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韩利文 《科技成果管理与研究》2016,(8):85-86
斑马鱼被美国FDA列为继人和啮齿类动物之后的第三大模式生物。斑马鱼与人类基因同源性高达85%;其信号传导通路、生物结构和生理功能等与哺乳动物高度相似;具有饲养成本低、体积小、发育周期短、体外受精、透明易观察、单次产卵数较高等特点。利用斑马鱼模型可在2～3天内完成体内活性实验,所用药物量极小;在显微镜下可全程、完整观察药物对斑马鱼体内器官、组织、靶点的作用。以斑马鱼作为模式生物进行实验,既具有体外细胞实验的高通量性,又具有整体动物实验的高内涵性等特征,且实验周期短、成本低。因此斑马鱼已成为药物筛选评价体系中,衔接细胞和哺乳动物模型的重要环节。2009年,欧洲斑马鱼药物筛选技术服务公司Biobide获得FDA和EMEA的GLP认证。2015年,我国制定了中国实验用鱼（斑马鱼）质量控制标准。自2006年起,山东省科学院药物筛选技术平台针对中药现代化的实际需求,在国家高端外国专家项目、山东省重大科技专项、山东省自然基金等项目资助下,开始基于斑马鱼模型的中药心血管活性筛选评价新技术与应用的研究,取得以下阶段性创新成果。 相似文献
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生物医药技术与产业的发展具有重大的社会效益和经济效益 ,在我国新世纪的经济和社会发展中占有重要的地位。我国医药工业过去一直以仿制国外产品为主 ,新药设计和筛选的基础薄弱 ,技术条件落后 ,缺乏具有国际竞争力的新药研究开发机制 ,致使产业经济效益低下 ,难以应对加入ＷＴＯ后所面临的冲击与挑战。为改变我国医药工业的现状 ,必须大力提高我国创新药物研究开发的实力和水平 ,建立符合国际规范的新药研究和生产体系 ,实现医药产业从仿制为主到创新为主的历史性转变。化合物活性筛选是创新药物研究的起点和具有决定意义的步骤。离开筛选… 相似文献
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Excel提供了数据的两种筛选操作——自动筛选和高级筛选。自动筛选一般用于条件简单的筛选操作．而高级筛选所能实现的功能远比自动筛选强大。通过Excel高级筛选条件区域设置的实例,对条件区域的设置作了详细介绍。 相似文献
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本文将描述超导体各向异性的有效质量理论，即各向异性Ginzburg—Landau 理论（G—L理论），与临界态模型(CS模型)相结合，建立了高温超导带材的交流损耗与临界电流的各向异性理论模型; 利用不可逆应变的定义，给出了临界电流与应变的关系，并利用临界电流与应变的关系及Norris方程，导出了高温超导带材的交流损耗与应变的关系; 利用所建立的交流损耗与临界电流的各向异性理论公式，建立了依据超导短样带材的特性(临界电流，交流损耗），计算高温超导线圈交流损耗的数值计算模型. 相似文献
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通过对高能量药物筛选基本过程的分析 ,探索了靶分子固定化可能对筛选质量构成的影响 .从分子相互作用看 ,实际的过程远较理想的情况复杂 .分子间存在的静电力、疏水作用力及氢键力能对固定化的机理构成较大影响 ,甚至可能诱发多层吸附的固定化模式 .基于固定化过程中可能存在的靶分子与靶分子、靶分子与微球、体相与表面相之间的相互作用 ,构筑了相应的数学物理模型 ,为实际的筛选工作提供了可参考的理论依据 . 相似文献
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为了解决现有主成分法存在的无法赋权及合理筛选指标的问题,提出了基于信息敏感性的指标筛选与赋权模型。本文的主要创新与特色:一是通过主成分占原始指标集信息的比例与每个被保留的主成分对指标的偏导数乘积的和,反映该指标对原始指标集信息的影响程度。依据信息敏感性指标筛选标准确定累积信息含量,通过累积信息含量的大小遴选指标。二是通过指标的信息敏感性占全部指标信息敏感性的比例进行指标的赋权,以使指标的权重反映不同指标相对信息含量的大小。最后,通过一个实例将提出的指标筛选方法与现有主成分指标筛选方法进行了对比分析,以此说明所提出的指标筛选方法的可行性及有效性。 相似文献
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《Journal of The Franklin Institute》2021,358(13):6490-6507
The performance of the existing frequency control strategies for MT-HVDC systems relies on the accuracy of the mathematical models. However, it is hard to obtain the exact mathematical models of MT-HVDC systems. To deal with this challenge, this paper presents a distributed cooperative frequency control strategy for MT-HVDC systems by using a reinforcement learning method, i.e., value iteration algorithm. Specifically, the proposed control strategy is data driven and hence model free. Besides, the proposed control strategy is distributed in the sense that each AC area only requires the local and neighboring information, rather than the information of all the AC areas. Moreover, the proposed control strategy makes the connected AC areas compensate load disturbances together by sharing their power reserves via HVDC grids, which greatly decreases the operation costs of MT-HVDC systems. The performance of the proposed control strategy is validated by cases study. 相似文献
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The AC electrothermal technique is very promising for biofluid micropumping, due to its ability to pump high conductivity fluids. However, compared to electroosmotic micropumps, a lack of high fluid flow is a disadvantage. In this paper, a novel AC multiple array electrothermal (MAET) micropump, utilizing multiple microelectrode arrays placed on the side-walls of the fluidic channel of the micropump, is introduced. Asymmetric coplanar microelectrodes are placed on all sides of the microfluidic channel, and are actuated in different phases: one, two opposing, two adjacent, three, or all sides at the same time. Micropumps with different combinations of side electrodes and cross sections are numerically investigated in this paper. The effect of the governing parameters with respect to thermal, fluidic, and electrical properties are studied and discussed. To verify the simulations, the AC MAET concept was then fabricated and experimentally tested. The resulted fluid flow achieved by the experiments showed good agreement with the corresponding simulations. The number of side electrode arrays and the actuation patterns were also found to greatly influence the micropump performance. This study shows that the new multiple array electrothermal micropump design can be used in a wide range of applications such as drug delivery and lab-on-a-chip, where high flow rate and high precision micropumping devices for high conductivity fluids are needed. 相似文献
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《Information processing & management》2023,60(5):103445
Argument mining (AM) aims to automatically generate a graph that represents the argument structure of a document. Most previous AM models only pay attention to a single argument component (AC) to classify the type of the AC or a pair of ACs to identify and classify the argumentative relation (AR) between the two ACs. These models ignore the impact of global argument structure of the documents, which is important, especially in some highly structured genres such as scientific papers, where the process of argumentation is relatively fixed. Inspired by this, we propose a novel two-stage model which leverages global structure information to support AM. The first stage uses a multi-turn question-answering model to incrementally generate an initial argumentative graph that identifies relations among ACs. At each turn, all ACs related to the query AC are generated simultaneously, such that the sibling global information between the answer ACs is considered. In addition, the partially constructed graph is used as global structure information to support the extension of the graph with additional ACs. After the whole initial graph structure has been determined, the second stage assigns semantic types to both the ACs and ARs among them, leveraging information from this initial graph as global structure information. We test the proposed methods on two scientific datasets (one is the AbstRCT dataset including 659 abstracts about cancer research and the other is the SciARG dataset that consists of 225 computer linguistic abstracts and 285 biomedical abstracts) and a student essay dataset PE with 402 essays. Our experiments show that our model improves the state-of-the-art performance on two scientific datasets for different AM subtasks, with average improvements of 1%, 2.41%, 1.1% for the ACC, ARI and ARC task respectively on the AbstRCT dataset, and 2.36%, 1.84%, 8.87% for the ACC, ARI and ARC task on the SciARG dataset. Our model also achieves comparative results on the PE datasets: 87.7% of F1 scores for the ACC task, 81.4% for the ARI task and 78.8% for the ARC task. 相似文献
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《Information processing & management》2020,57(3):102214
Information systems for un-regimented domains such as museums, art and book collections, face representational and usability challenges that surpass the demands of traditional information systems for regimented domains. While the former require complex conceptual models supporting a set of dynamic and evolving qualitative properties of a small number of objects, the latter focus on the quantitative aspects of a possibly very large number of objects but with a relatively small and stable set of properties. In this paper we study the use of a non-monotonic knowledge-base system for the development of information systems for un-regimented domains. We discuss the ontological assumptions of the formalism, its structure and its inferential mechanisms through a simple example. Then we present an information system for a highly un-regimented domain in the digital humanities with promising results. The present study shows that the so-called extensible, flexible, dynamic or evolving information systems need the expressive power of non-monotonic knowledge-base systems, and that such phenomena should be addressed explicitly. 相似文献
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流域水土资源优化配置的几种方法比较 总被引：9，自引：0，他引：9
目前关于流域水土资源优化配置研究的特点表现为：对单项的水、土资源优化配置研究较多,把两者结合起来的研究较少;分别从宏观和微观两个尺度研究的较多,将两种尺度结合起来研究的较少;越来越重视资源配置模式下的生态系统服务功能状况及其能否满足特定区域可持续发展的需要;研究方法逐渐由定性向定量化转变,在定量研究中,较多使用一般线性规划、灰色线性规划、动态规划、多目标决策和系统动力学等方法;越来越重视以3S技术为基础,结合专业模型进行模拟,为水土资源配置和管理提供高质量的科学决策支持,但目前还没有建立完善的区域性的支持系统。通过重点对水土资源优化配置的定量化方法进行比较分析,今后的研究应当重视：①进一步完善流域水土资源优化配置的理论与方法,特别是与区域特点相结合,利用系统科学等多种学科的理论和方法实现宏观尺度上的优化配置;②加强GIS技术与定量模型的契合;③着力解决若干重要的科学和实践问题,如： 特定地区生态效益的量化、生态效益与经济效益比例的确定、生态需水量的理论与方法、森林植被的水文效应、农业节水与水资源管理关键技术等;④开发建立流域水土资源优化的决策支持系统。 相似文献