top-down

自上而下
  • 文章类型: Journal Article
    这篇综述描述了绿色协议和常规纳米粒子(NP)合成策略之间的比较,突出每种方法的优点和局限性。详细描述了NP合成中的各种自上而下和自下而上的方法。强调绿色化学原理,以设计纳米材料合成的安全工艺。在绿色生物源植物提取物中,维生素,酶,多糖,真菌(霉菌和蘑菇),细菌,酵母,藻类,和地衣讨论。就原材料的可用性而言,绿色协议的可重复性受到限制,合成协议的变化,并阐述了因地域差异而产生的材料选择。最后,利用绿色化学原理得出结论,&减少废物产生的循环经济战略,为强调可持续性的NP综合提供了一个有前途的框架。
    This review portrays a comparison between green protocols and conventional nanoparticle (NP) synthesis strategies, highlighting each method\'s advantages and limitations. Various top-down and bottom-up methods in NP synthesis are described in detail. The green chemistry principles are emphasized for designing safe processes for nanomaterial synthesis. Among the green biogenic sources plant extracts, vitamins, enzymes, polysaccharides, fungi (Molds and mushrooms), bacteria, yeast, algae, and lichens are discussed. Limitations in the reproducibility of green protocols in terms of availability of raw material, variation in synthetic protocol, and selection of material due to geographical differences are elaborated. Finally, a conclusion is drawn utilizing green chemical principles, & a circular economy strategy to minimize waste generation, offering a promising framework for the synthesis of NPs emphasizing sustainability.
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  • 文章类型: Journal Article
    近年来被确立为揭示完整单克隆抗体异质性的重要途径,天然质谱很少用于通过串联质谱对这些复杂的生物分子进行测序。通常,从变性条件下通过电喷雾电离获得的高电荷前体离子开始进行自上而下的质谱(即,在有机溶剂和酸性pH存在下)。在这里,我们系统地对四种不同的离子解离方法进行了基准测试,即更高能量的碰撞解离,电子转移解离,电子转移解离/高能碰撞解离,和213nm的紫外光解离-在它们表征治疗性单克隆抗体的能力方面,曲妥珠单抗,从变性和天然样前体离子开始。有趣的是,天然自上而下的质谱导致比在变性条件下进行的实验更高的序列覆盖率,除了紫外光离解。全球范围内,电子转移解离,然后是基于碰撞的产物离子活化,在二硫键保护区中产生最大数量的骨架切割,包括互补性决定区域,不管电喷雾电离条件。总的来说,这些发现表明,天然质谱肯定可以用于整个单克隆抗体的气相测序,尽管变性前体离子的解离仍然返回一些在天然实验中未鉴定的主链切割。最后,在变性和天然条件下获得的片段图的比较强烈地指出二硫键是很大程度上重叠的解离模式背后的主要原因。
    Established in recent years as an important approach to unraveling the heterogeneity of intact monoclonal antibodies, native mass spectrometry has been rarely utilized for sequencing these complex biomolecules via tandem mass spectrometry. Typically, top-down mass spectrometry has been performed starting from highly charged precursor ions obtained via electrospray ionization under denaturing conditions (i.e., in the presence of organic solvents and acidic pH). Here we systematically benchmark four distinct ion dissociation methods─namely, higher-energy collisional dissociation, electron transfer dissociation, electron transfer dissociation/higher-energy collisional dissociation, and 213 nm ultraviolet photodissociation─in their capability to characterize a therapeutic monoclonal antibody, trastuzumab, starting from denatured and native-like precursor ions. Interestingly, native top-down mass spectrometry results in higher sequence coverage than the experiments carried out under denaturing conditions, with the exception of ultraviolet photodissociation. Globally, electron transfer dissociation followed by collision-based activation of product ions generates the largest number of backbone cleavages in disulfide protected regions, including the complementarity determining regions, regardless of electrospray ionization conditions. Overall, these findings suggest that native mass spectrometry can certainly be used for the gas-phase sequencing of whole monoclonal antibodies, although the dissociation of denatured precursor ions still returns a few backbone cleavages not identified in native experiments. Finally, a comparison of the fragmentation maps obtained under denaturing and native conditions strongly points toward disulfide bonds as the primary reason behind the largely overlapping dissociation patterns.
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  • 文章类型: Journal Article
    脊柱的动力学需求可以使用自上而下(TD)或自下而上(BU)方法进行评估,从手或脚开始计算,分别。生物力学传统上倾向于BU方法,尽管现有的建模方法鼓励TD方法。无论采用哪种方法,需求都应该相似,假设外力和连接段参数等效测量和建模。证明两种方法之间的一致性水平可以帮助评估模型。Further,当数据不准确或不可用时,这两种方法都是有利的。这项研究的目的是比较多个腰椎和胸椎间关节(IVJ)水平的内部力矩和力从已建立的OpenSim胸腰椎模型应用TD方法和类似的模型修改采用BU方法的提升任务。在不同提升速度和板条箱质量的矢状和横向提升过程中,记录了十二名参与者的运动学和外力。对于这两种方法,使用标准OpenSim建模流水线估计IVJ动力学。BU和TD接近IVJ关节力矩通常在时间上(R2=.94±.17)和主运动平面的大小(RMSE=6.2±3.5Nm)一致。然而,对于低幅度的离轴力矩,存在一些时间拟合例外(即,<10Nm)。Bland-Altman图还显示了IVJ峰值力的可接受一致性(压缩和合成剪切中的BU-TD差12±111和8±31N,恭敬地)。这些结果支持BU方法的应用和模型的分配链接段参数。新的BU模型可在SimTK网站(https://simtk.org/projects/spine_ribcage)上找到。
    The kinetic demands of the spine can be assessed using a top-down (TD) or bottom-up (BU) approach, which start calculations from the either the hands or from the feet, respectively. Biomechanists have traditionally favored a BU approach, though existing modeling approaches encourage a TD approach. Regardless of the approach the demands should be similar, provided the external forces and linked segment parameters are equivalently measured and modeled. Demonstrating a level of agreement between the two approaches can help evaluate a model. Further, having both approaches can be advantageous when data is inaccurate or unavailable for one. The purpose of this study was to compare the internal moments and forces at multiple lumbar and thoracic intervertebral joint (IVJ) levels during lifting tasks from an established OpenSim thoracolumbar spine model that applies a TD approach and a similar model modified to adopt a BU approach. Kinematics and external forces were recorded from twelve participants during sagittal and lateral lifts of different lifting speeds and crate masses. For both approaches IVJ kinetics were estimated using a standard OpenSim modeling pipeline. The BU and TD approach IVJ joint moments generally agreed both temporally (R2 = .94 ± .17) and in magnitude (RMSE=6.2 ± 3.5 Nm) of the primary planes of movement. There were however some temporal fit exceptions for off axes moments with low magnitudes (i.e., < 10 Nm). Bland-Altman plots also indicated acceptable agreement for IVJ peak forces (BU-TD difference of 12 ± 111 and 8 ± 31 N in compression and resultant shear, respectfully). These results support the application of the BU approach and the assigned linked segment parameters of the model. The new BU model is available on the SimTK site (https://simtk.org/projects/spine_ribcage).
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  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fnana.2019.00022。].
    [This corrects the article DOI: 10.3389/fnana.2019.00022.].
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  • 文章类型: Journal Article
    三氟化氮(NF3)是一种有效且长寿命的温室气体,广泛用于半导体制造,光伏电池,和平板显示器。使用来自高级全球大气气体实验(AGAGE)的八个监测站的大气观测,并使用全球3-D大气化学传输模型(GEOS-Chem)进行逆建模,我们量化了2015年至2021年的全球和区域NF3排放量。我们发现,全球排放量从2015年的1.93±0.58Ggyr-1(±一个标准偏差)增长到2021年的3.38±0.61Ggyr-1,年平均增长10%。现有的观测结果使我们能够将大量排放归因于中国(2015年为0.93±0.15Ggyr-1,2021年为1.53±0.20Ggyr-1)和韩国(0.38±0.07Ggyr-1至0.65±0.10Ggyr-1)。从2015年到2021年,东亚地区贡献了全球NF3排放量增长的约73%:约41%的增长来自中国(包括台湾)的排放量。19%来自韩国,13%来自日本。对于日本来说,这是三个国家中唯一一个向《气候公约》提交年度NF3排放量的国家,我们自下而上和自上而下的估计高于报告。随着对电子产品需求的增加,尤其是平板显示器,预计未来排放量将进一步增加。
    Nitrogen trifluoride (NF3) is a potent and long-lived greenhouse gas that is widely used in the manufacture of semiconductors, photovoltaic cells, and flat panel displays. Using atmospheric observations from eight monitoring stations from the Advanced Global Atmospheric Gases Experiment (AGAGE) and inverse modeling with a global 3-D atmospheric chemical transport model (GEOS-Chem), we quantify global and regional NF3 emission from 2015 to 2021. We find that global emissions have grown from 1.93 ± 0.58 Gg yr-1 (± one standard deviation) in 2015 to 3.38 ± 0.61 Gg yr-1 in 2021, with an average annual increase of 10% yr-1. The available observations allow us to attribute significant emissions to China (0.93 ± 0.15 Gg yr-1 in 2015 and 1.53 ± 0.20 Gg yr-1 in 2021) and South Korea (0.38 ± 0.07 Gg yr-1 to 0.65 ± 0.10 Gg yr-1). East Asia contributes around 73% of the global NF3 emission increase from 2015 to 2021: approximately 41% of the increase is from emissions from China (with Taiwan included), 19% from South Korea, and 13% from Japan. For Japan, which is the only one of these three countries to submit annual NF3 emissions to UNFCCC, our bottom-up and top-down estimates are higher than reported. With increasing demand for electronics, especially flat panel displays, emissions are expected to further increase in the future.
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  • 文章类型: Journal Article
    感觉是动态的,快速适应环境或行为背景的突然变化。尽管几十年的工作已经确定,这些动力学是由感觉皮层活动的快速波动介导的,我们对协调这些变化的大脑区域和途径的了解有限。眶额皮质(OFC)中的神经元编码上下文信息,最近的数据表明,其中一些信号被传递到感觉皮层。这些信号是否以及如何塑造感官编码和感知灵敏度仍然不确定。这里,我们询问OFC是否通过在两种行为环境下监测和操纵自由移动的男女蒙古沙鼠的OFC活动来介导听觉皮层灵敏度和声音感知的上下文相关变化:被动声音暴露和参与振幅调制(AM)检测任务.我们发现大多数OFC神经元,包括支配听觉皮层的特定子集,受到任务参与度的强烈调节。OFC的药理学失活阻止了听觉皮层放电的快速环境依赖性变化,并显着损害了行为AM检测。我们的发现表明,来自OFC的上下文信息可介导听觉皮层的快速可塑性,并促进对行为相关声音的感知。
    Sensory perception is dynamic, quickly adapting to sudden shifts in environmental or behavioral context. Although decades of work have established that these dynamics are mediated by rapid fluctuations in sensory cortical activity, we have a limited understanding of the brain regions and pathways that orchestrate these changes. Neurons in the orbitofrontal cortex (OFC) encode contextual information, and recent data suggest that some of these signals are transmitted to sensory cortices. Whether and how these signals shape sensory encoding and perceptual sensitivity remain uncertain. Here, we asked whether the OFC mediates context-dependent changes in auditory cortical sensitivity and sound perception by monitoring and manipulating OFC activity in freely moving Mongolian gerbils of both sexes under two behavioral contexts: passive sound exposure and engagement in an amplitude modulation (AM) detection task. We found that the majority of OFC neurons, including the specific subset that innervates the auditory cortex, were strongly modulated by task engagement. Pharmacological inactivation of the OFC prevented rapid context-dependent changes in auditory cortical firing and significantly impaired behavioral AM detection. Our findings suggest that contextual information from the OFC mediates rapid plasticity in the auditory cortex and facilitates the perception of behaviorally relevant sounds.
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  • 文章类型: Journal Article
    背景:各种神经认知模型探索精神分裂症和普通人群的知觉扭曲和幻觉。预测编码账户的一种变体表明,强先验,比如认知预期,可能会影响感知。这项研究检查了在临床和健康对照组中,更强的认知期望是否会导致更多的听觉错误感知。调查群体差异,并探索了错误感知和幻觉之间的联系。
    方法:被诊断为精神分裂症并有幻听(n=51)和无幻听(n=66)以及健康对照(n=51)的患者在各种预期条件下接受了错误感知任务。检查所有组的幻觉或幻觉样经历的存在和严重程度。
    结果:我们观察到所有组的主要影响,ie,认知预期越强,听觉错误感知的比率越大。然而,听觉错误感知的比率没有群体效应。尽管幻觉组中存在适度的成对相关性,在线性混合模型中,听觉错误感知的比率不能通过幻觉和幻觉样体验的水平来预测.
    结论:当前的研究表明,以认知期望形式出现的强先验影响感知并在感知障碍中发挥作用。在目前的幻觉受试者中,过度依赖强先验可能与幻觉有关。可能,详细讨论了可避免的混杂因素。
    BACKGROUND: Various neurocognitive models explore perceptual distortions and hallucinations in schizophrenia and the general population. A variant of predictive coding account suggests that strong priors, like cognitive expectancy, may influence perception. This study examines if stronger cognitive expectancies result in more auditory false percepts in clinical and healthy control groups, investigates group differences, and explores the association between false percepts and hallucinations.
    METHODS: Patients diagnosed with schizophrenia with current auditory hallucinations (n = 51) and without hallucinations (n = 66) and healthy controls (n = 51) underwent the False Perception Task under various expectancy conditions. All groups were examined for the presence and severity of hallucinations or hallucinatory-like experiences.
    RESULTS: We observed a main effect of condition across all groups, ie, the stronger the cognitive expectancy, the greater the ratio of auditory false percepts. However, there was no group effect for the ratio of auditory false percepts. Despite modest pairwise correlations in the hallucinating group, the ratio of auditory false percepts was not predicted by levels of hallucinations and hallucinatory-like experiences in a linear mixed model.
    CONCLUSIONS: The current study demonstrates that strong priors in the form of cognitive expectancies affect perception and play a role in perceptual disturbances. There is also a tentative possibility that overreliance on strong priors may be associated with hallucinations in currently hallucinating subjects. Possible, avoidable confounding factors are discussed in detail.
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  • 文章类型: Journal Article
    结合了二维(2D)无机纳米片的物理优势以及金属有机框架(MOFs)的模块化设计和编程结构,2DMOFs仍然处于功能材料研究的前沿。尽管付出了巨大的努力,在2D非分层MOFs的合成与所需应用的预先设计的拓扑的精确控制仍然具有挑战性。通过配体交换成功地自下而上地合成2D非层状MOF,促使我们将部分BTC(BTC=1,3,5-苯三羧酸酯)配体解离和CO2封端的配位纳入块状Cu-BTCMOF的自上而下处理中,导致3D非分层网络成功转换为2D基于Cu的拓扑结构。值得注意的是,使用超临界含CO2的溶剂混合物来提供所需的缺陷和协调工程。因此,我们的工作引入了一种基于调制合成的自上而下的新概念,以首次制造高质量的2D非分层MOFs。
    Combining the physical advantages of two-dimensional (2D) inorganic nanosheets and the modular design and programmed structure of metal-organic frameworks (MOFs), 2D MOFs remain at the forefront of functional material research. Despite tremendous efforts, precise control in the synthesis of 2D nonlayered MOFs with predesigned topology for desired applications remains challenging. Success in the bottom-up synthesis of 2D nonlayered MOFs via ligand exchange motivated us to incorporate partial BTC (BTC = 1,3,5-benzenetricarboxylate) ligand dissociation and CO2 capped coordination into the top-down treatment of bulk Cu-BTC MOF, leading to successful conversion of a 3D nonlayered network to a 2D Cu-based topological structure. Notably, a supercritical CO2-containing solvent mixture is employed to provide the desired defect and coordination engineering. Thus, our work introduces a new top-down concept based on modulated synthesis to fabricate high-quality 2D nonlayered MOFs for the first time.
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  • 文章类型: Journal Article
    家禽管理者通过家禽行为分析可以更好地了解家禽的状态。作为行为分析的关键步骤之一,准确估计家禽的姿势是本研究的重点。本研究主要分析了一种自顶向下的多只鸡位姿估计方法。因此,我们提出了“多鸡姿势”(MCP),通过深度学习的多只鸡的姿态估计系统。首先,我们通过鸡探测器从图像中找到每只鸡的位置;然后,使用姿势估计网络对每只鸡的姿势进行估计,这是基于迁移学习。在此基础上,像素误差(PE),均方根误差(RMSE),根据改进的鸡关键点相似度(CKS)分析关键点的图像数量分布。实验结果表明,该算法在不同评价指标下的得分分别为:平均精度(mAP)为0.652,平均召回率(mAR)为0.742,正确关键点百分比(PCKs)为0.789,RMSE为17.30像素。据我们所知,这是首次将迁移学习用于多只鸡作为对象的姿态估计。该方法可为今后的家禽行为分析提供新的路径。
    Poultry managers can better understand the state of poultry through poultry behavior analysis. As one of the key steps in behavior analysis, the accurate estimation of poultry posture is the focus of this research. This study mainly analyzes a top-down pose estimation method of multiple chickens. Therefore, we propose the \"multi-chicken pose\" (MCP), a pose estimation system for multiple chickens through deep learning. Firstly, we find the position of each chicken from the image via the chicken detector; then, an estimate of the pose of each chicken is made using a pose estimation network, which is based on transfer learning. On this basis, the pixel error (PE), root mean square error (RMSE), and image quantity distribution of key points are analyzed according to the improved chicken keypoint similarity (CKS). The experimental results show that the algorithm scores in different evaluation metrics are a mean average precision (mAP) of 0.652, a mean average recall (mAR) of 0.742, a percentage of correct keypoints (PCKs) of 0.789, and an RMSE of 17.30 pixels. To the best of our knowledge, this is the first time that transfer learning has been used for the pose estimation of multiple chickens as objects. The method can provide a new path for future poultry behavior analysis.
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  • 文章类型: Journal Article
    抗体是我们免疫系统最强大的分子武器之一。它们对靶标(抗原)的高特异性和触发不同免疫反应的能力(例如,补体系统激活和抗体依赖性细胞介导的细胞毒性)使它们成为对抗许多不同人类疾病的理想药物。目前,单克隆抗体和基于抗体支架的更复杂的分子都被用作生物制剂。自然,这种高度异质的分子需要专门的分析方法来准确表征。质谱(MS)可以定义抗体的多个特征的存在和相对丰度,包括关键质量属性。单个分子内的小变异和大变异的组合只能通过分析完整的抗体或它们的大(25至100kDa)亚基来确定。因此,在过去的十年中,自上而下(TD)和中下(MD)MS方法已经普及。在这个年轻的科学家特征中,我们讨论了抗体的TD和MDMS分析的演变,包括超越生物制药应用的新领域。我们将展示这个领域现在是如何从“质量控制”分析已知的,从临床样品中分离的复杂抗体库的高通量研究的单一抗体,其中最终目标是通过抗体分子的完整气相测序来表示,而无需任何先验知识。
    Antibodies are one of the most formidable molecular weapons available to our immune system. Their high specificity against a target (antigen) and capability of triggering different immune responses (e.g., complement system activation and antibody-dependent cell-mediated cytotoxicity) make them ideal drugs to fight many different human diseases. Currently, both monoclonal antibodies and more complex molecules based on the antibody scaffold are used as biologics. Naturally, such highly heterogeneous molecules require dedicated analytical methodologies for their accurate characterization. Mass spectrometry (MS) can define the presence and relative abundance of multiple features of antibodies, including critical quality attributes. The combination of small and large variations within a single molecule can only be determined by analyzing intact antibodies or their large (25 to 100 kDa) subunits. Hence, top-down (TD) and middle-down (MD) MS approaches have gained popularity over the last decade. In this Young Scientist Feature we discuss the evolution of TD and MD MS analysis of antibodies, including the new frontiers that go beyond biopharma applications. We will show how this field is now moving from the \"quality control\" analysis of a known, single antibody to the high-throughput investigation of complex antibody repertoires isolated from clinical samples, where the ultimate goal is represented by the complete gas-phase sequencing of antibody molecules without the need of any a priori knowledge.
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