Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is pri...Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).展开更多
Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This...Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.展开更多
同时定位与建图(Simultaneous Localization and Mapping,SLAM)技术使移动机器人在缺乏先验环境信息的条件下,能够在估计自身位姿的同时构建环境地图。然而,在海洋、矿洞等复杂环境中,移动机器人容易受到随机突变噪声的干扰,进而导致SLA...同时定位与建图(Simultaneous Localization and Mapping,SLAM)技术使移动机器人在缺乏先验环境信息的条件下,能够在估计自身位姿的同时构建环境地图。然而,在海洋、矿洞等复杂环境中,移动机器人容易受到随机突变噪声的干扰,进而导致SLAM性能下降。现有的概率假设密度(Probability Hypothesis Density,PHD)SLAM算法未考虑随机突变噪声,受到干扰时在线自适应调整能力较弱。为解决移动机器人因随机突变噪声导致状态估计和建图精度降低的问题,本文结合强跟踪滤波器(Strong Tracking Filter,STF)与PHD滤波器,提出了一种基于强跟踪的自适应PHD-SLAM滤波算法(Strong Tracking Probability Hypothesis Density Simultaneous Localization and Mapping,STPHD-SLAM)。该算法以PHD-SLAM为框架,针对过程噪声协方差和量测噪声协方差随机突变问题,本文通过在特征预测协方差中引入STF中的渐消因子,实现了对特征预测的自适应修正和卡尔曼增益的动态调整,从而增强了算法的自适应能力。其中渐消因子根据量测新息递归更新,确保噪声突变时每个时刻的量测新息保持正交,从而充分利用量测信息,准确并且快速地跟踪突变噪声。针对渐消因子激增导致的滤波器发散问题,本文对渐消因子进行边界约束,提高算法的鲁棒性。仿真结果表明,在量测噪声协方差和过程噪声协方差随机突变的情况下,所提算法相较于PHD-SLAM 1.0和PHD-SLAM 2.0的定位和建图精度都得到了提高,同时保证了计算效率。展开更多
“The theory of supposition”是中世纪逻辑最具原创性的理论,但不应被翻译为或者对应为“指代理论”,用他们自己的词项以及语境来理解为“假设理论”。假设理论诞生于12世纪晚期,最早的迹象出现在12世纪70年代,开始使用的语词不是supp...“The theory of supposition”是中世纪逻辑最具原创性的理论,但不应被翻译为或者对应为“指代理论”,用他们自己的词项以及语境来理解为“假设理论”。假设理论诞生于12世纪晚期,最早的迹象出现在12世纪70年代,开始使用的语词不是supponere,suppositum,suppositio中的任何一个,而是appellatio、nominare以及nuncupare,只是到12世纪90年代之后,才被suppositio取代。思想家们主要把它用于解决诡辩问题,对于它的使用最早是从语法意义上开始的,其用法为“作为主项”,“指称”则是第二位的,并且在使用过程中涉及到指称、意义/意指、时态、模态、多元性以及语境关联性等等。假设理论曾经被模式主义理论短暂取代,但是14世纪在奥卡姆和布里丹等人的策划下又重新回归到人们的视野当中,并成为此后中世纪语义分析的主要工具。展开更多
基金supported by the Massachusetts General Hospital Scientific Projects to Accelerate Research and Collaboration (SPARC) awardCure Alzheimer’s Fund (to CZ)the National Institutes of Health (NIH),including R01NS102190,RF1NS120947,and R01HL161253 (to MBW),RF1NS120947 (to RJT)。
文摘Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).
基金supported by National Health Institute(NIH)grant NS099596(to LW and SPY),NS114221(to LW and SPY)Veterans Affair(VA)SPiRE grant RX003865(to SPY)+1 种基金supported by the O.Wayne Rollins Endowment Fund(to SPY)John E.Steinhaus Endowment Fund(to LW)。
文摘Stroke and Alzheimer's disease are common neurological disorders and often occur in the same individuals.The comorbidity of the two neurological disorders represents a grave health threat to older populations.This review presents a brief background of the development of novel concepts and their clinical potentials.The activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal function.An ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic site.This Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute excitotoxicity.Furthermore,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death pathways.Based on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic neuropathogenesis.The N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic excitotoxicity.Ischemic stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time courses.It is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related dementia.This early treatment simultaneously serves as a preconditioning therapy against ischemic stroke that often attacks the same individuals during abnormal aging.
文摘同时定位与建图(Simultaneous Localization and Mapping,SLAM)技术使移动机器人在缺乏先验环境信息的条件下,能够在估计自身位姿的同时构建环境地图。然而,在海洋、矿洞等复杂环境中,移动机器人容易受到随机突变噪声的干扰,进而导致SLAM性能下降。现有的概率假设密度(Probability Hypothesis Density,PHD)SLAM算法未考虑随机突变噪声,受到干扰时在线自适应调整能力较弱。为解决移动机器人因随机突变噪声导致状态估计和建图精度降低的问题,本文结合强跟踪滤波器(Strong Tracking Filter,STF)与PHD滤波器,提出了一种基于强跟踪的自适应PHD-SLAM滤波算法(Strong Tracking Probability Hypothesis Density Simultaneous Localization and Mapping,STPHD-SLAM)。该算法以PHD-SLAM为框架,针对过程噪声协方差和量测噪声协方差随机突变问题,本文通过在特征预测协方差中引入STF中的渐消因子,实现了对特征预测的自适应修正和卡尔曼增益的动态调整,从而增强了算法的自适应能力。其中渐消因子根据量测新息递归更新,确保噪声突变时每个时刻的量测新息保持正交,从而充分利用量测信息,准确并且快速地跟踪突变噪声。针对渐消因子激增导致的滤波器发散问题,本文对渐消因子进行边界约束,提高算法的鲁棒性。仿真结果表明,在量测噪声协方差和过程噪声协方差随机突变的情况下,所提算法相较于PHD-SLAM 1.0和PHD-SLAM 2.0的定位和建图精度都得到了提高,同时保证了计算效率。
文摘“The theory of supposition”是中世纪逻辑最具原创性的理论,但不应被翻译为或者对应为“指代理论”,用他们自己的词项以及语境来理解为“假设理论”。假设理论诞生于12世纪晚期,最早的迹象出现在12世纪70年代,开始使用的语词不是supponere,suppositum,suppositio中的任何一个,而是appellatio、nominare以及nuncupare,只是到12世纪90年代之后,才被suppositio取代。思想家们主要把它用于解决诡辩问题,对于它的使用最早是从语法意义上开始的,其用法为“作为主项”,“指称”则是第二位的,并且在使用过程中涉及到指称、意义/意指、时态、模态、多元性以及语境关联性等等。假设理论曾经被模式主义理论短暂取代,但是14世纪在奥卡姆和布里丹等人的策划下又重新回归到人们的视野当中,并成为此后中世纪语义分析的主要工具。
