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31. 发明授权

US06552053B2 Controlling attention and memory by altering neuronal carbonic anhydrase activity 失效
公开(公告)号：US06552053B2
公开(公告)日：2003-04-22
申请号：US09875283
申请日：2001-06-07
申请人： Miao-Kun Sun , Daniel L. Alkon , Wei-Qin Zhao
发明人： Miao-Kun Sun , Daniel L. Alkon , Wei-Qin Zhao
IPC分类号： A61K3141
CPC分类号： A61K31/00 , A61K31/433
摘要： The invention provides a method for modulating attentive cognition comprising administering a compound that alters intraneuronal carbonic anhydrase activity thereby affecting establishment of a theta rhythm. The metabolic pathway of the compound preferably involves bicarbonate-mediated GABAergic depolarization. The term “attentive cognition” is meant to encompass memory formation, learning, spatial memory, and attention. The modulating may be stimulating, or the compound may have the multiple effects of inhibiting intraneuronal carbonic anhydrase activity, establishment of a theta rhythm, and memory acquisition. The invention further provides a method of modulating memory and attention comprising switching theta rhythm on and off, the switching comprising potentiating or inhibiting intraneuronal carbonic anhydrase activity.

32. 发明授权

US5119469A Neural network with weight adjustment based on prior history of input signals 失效
标题翻译：基于输入信号先前历史的神经网络与重量调整
公开(公告)号：US5119469A
公开(公告)日：1992-06-02
申请号：US448090
申请日：1989-12-12
申请人： Daniel L. Alkon , Thomas P. Vogl , Kim L. Blackwell
发明人： Daniel L. Alkon , Thomas P. Vogl , Kim L. Blackwell
IPC分类号： G06N3/04
CPC分类号： G06N3/04
摘要： A dynamically stable associative learning neural network system include a plurality of synapses and a non-linear function circuit and includes an adaptive weight circuit for adjusting the weight of each synapse based upon the present signal and the prior history of signals applied to the input of the particular synapse and the present signal and the prior history of signals applied to the input of a predetermined set of other collateral synapses. A flow-through neuron circuit embodiment includes a flow-through synapse having a predetermined fixed weight. A neural network is formed employing neuron circuits of both the above types. A set of flow-through neuron circuits are connected by flow-through synapses to form separate paths between each input terminal and a corresponding output terminal. Other neuron circuits having only adjustable weight synapses are included within the network. This neuron network is initialized by setting the adjustable synapses at some value near the minimum weight. The neural network is taught by successively application of sets of inputs signals to the input terminals until a dynamic equilibrium is reached.
摘要翻译：动态稳定的关联学习神经网络系统包括多个突触和非线性函数电路，并且包括一个自适应加权电路，用于根据当前信号调整每个突触的重量，以及应用于输入的信号的先前历史特定突触和当前信号以及施加到预定的一组其他附属突触的输入的信号的先前历史。流过神经元电路实施例包括具有预定固定重量的流通突触。使用上述类型的神经元电路形成神经网络。一组流通神经元电路通过流通突触连接，以在每个输入端子和相应的输出端子之间形成单独的路径。具有可调重量突触的其他神经元电路包括在网络内。通过将可调节突触设置在接近最小重量的某个值来初始化该神经元网络。通过将输入信号组连续地应用到输入端来教导神经网络，直到达到动态平衡。

33. 发明授权

US08703812B2 Protein synthesis required for long-term memory is induced by PKC activation on days preceding associative learning 有权
标题翻译：长期记忆所需的蛋白质合成是通过PKC激活在关联学习之前的几天引起的
公开(公告)号：US08703812B2
公开(公告)日：2014-04-22
申请号：US13561770
申请日：2012-07-30
申请人： Daniel L. Alkon
发明人： Daniel L. Alkon
IPC分类号： A01N43/02 , A61K31/335 , A01N43/38 , A61K31/40 , A01N43/00 , A61K31/33
CPC分类号： A61K31/366 , A61K31/365 , A61K31/40 , A61K31/4015 , A61K31/407 , A61K31/437
摘要： The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.
摘要翻译：本发明提供使蛋白激酶C（PKC）激活剂与PKC激活剂以足以刺激足以巩固长期记忆的蛋白质合成的方式接触的方法。本发明还提供了以足以下调PKC的方式使蛋白激酶C（PKC）活化剂与PKC激活剂接触的方法。

34. 发明授权

US08658134B2 Fibroblast growth patterns for diagnosis of Alzheimer's disease 有权
标题翻译：成纤维细胞生长模式用于诊断阿尔茨海默病
公开(公告)号：US08658134B2
公开(公告)日：2014-02-25
申请号：US12896862
申请日：2010-10-02
申请人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
发明人： Florin Valentin Chirila , Tapan Kumar Khan , Daniel L. Alkon
IPC分类号： G01N33/483 , C12N5/07
CPC分类号： G01N33/5091 , G01N33/6896 , G01N2800/2821
摘要： Methods of diagnosing Alzheimer's disease are provided. At least five methods of diagnostic measurements are presented: Method 1: Integrated score; Method 2: Average aggregate area per number of aggregates; Method 3: Cell migration analysis; Method 4; Fractal analysis; Method 5: Lacunarity Analysis. In certain embodiments, a sample of a subject's skin provides a network of fibroblasts that is imaged and a fractal dimension of the image is calculated. The fractal dimension can be compared to an aged-matched control (non-Alzheimer's) database to determine if the subject has Alzheimer's disease. The network of fibroblasts may be cultured in a matrix, for example in a protein mixture.
摘要翻译：提供了诊断阿尔茨海默病的方法。提出了至少五种诊断测量方法：方法1：综合评分; 方法2：每个聚集体的平均聚集面积; 方法3：细胞迁移分析; 方法4; 分形分析; 方法5：Lacunarity分析。在某些实施方案中，受试者皮肤的样品提供成像的成纤维细胞的网络，并且计算图像的分形维数。可以将分形维数与老年匹配对照（非阿尔茨海默病）数据库进行比较，以确定受试者是否患有阿尔茨海默氏病。成纤维细胞的网络可以在基质中培养，例如在蛋白质混合物中。

35. 发明申请

US20130331444A1 TREATMENT OF COGNITIVE DISORDERS ASSOCIATED WITH ABNORMAL DENDRITIC SPINES USING PKC ACTIVATORS 有权
标题翻译：使用PKC激活剂治疗与异常脱发性脊髓相关的认知障碍
公开(公告)号：US20130331444A1
公开(公告)日：2013-12-12
申请号：US13817040
申请日：2011-08-19
申请人： Miao-kun Sun , Daniel L. Alkon
发明人： Miao-kun Sun , Daniel L. Alkon
IPC分类号： A61K31/365
CPC分类号： A61K31/365
摘要： The present disclosure provides methods of treating a cognitive disorder associated with abnormal dendritic spines, such as Fragile X Syndrome, Fragile X Associated Tremor/Ataxia Syndrome, autism, or mental retardation, using PKC activators.
摘要翻译：本公开提供使用PKC激活剂治疗与异常树突棘相关的认知障碍（例如脆性X综合征，脆性X相关震颤/共济失调综合征，自闭症或智力迟钝）的方法。

36. 发明申请

US20130165453A1 THERAPEUTIC EFFECTS OF BRYOSTATINS, BRYOLOGS, AND OTHER RELATED SUBSTANCES ON ISCHEMIA/STROKE-INDUCED MEMORY IMPAIRMENT AND BRAIN INJURY 审中-公开
标题翻译： BRYOSTATINS，BRYOSS，和其他相关物质对异位/诱导性记忆损伤和脑损伤的治疗效果
公开(公告)号：US20130165453A1
公开(公告)日：2013-06-27
申请号：US13553565
申请日：2012-07-19
申请人： Miao-Kun Sun , Daniel L. Alkon
发明人： Miao-Kun Sun , Daniel L. Alkon
IPC分类号： A61K31/365 , A61K31/194
CPC分类号： A61K31/05 , A61K31/00 , A61K31/335 , A61K31/35 , A61K31/365 , A61K31/395 , A61K31/4015 , A61K38/00 , A61K38/1825
摘要： The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) or other neurotrophic factors to treat stroke. Specifically, the present invention provides methods of treating stroke comprising the steps of identifying a subject having suffered a stroke and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of stroke.
摘要翻译：本发明提供了使用蛋白激酶激活剂或神经生长因子（NGF）的促进剂，脑源性神经营养因子（BDNF）或其他神经营养因子来治疗中风。具体地说，本发明提供治疗中风的方法，其包括以下步骤：鉴定遭受中风的个体，并向所述受试者施用一定量的包含蛋白激酶C（PKC）激活剂或4-甲基儿茶酚乙酸（MCBA）的药物组合物，和有效治疗中风的至少一种症状的药学上可接受的载体。

37. 发明申请

US20120289557A1 Protein Synthesis Required for Long-Term Memory is Induced by PKC Activation on Days Preceding Associative Learning 有权
标题翻译：长期记忆所需的蛋白质合成是通过PKC激活在前一关联学习引起的
公开(公告)号：US20120289557A1
公开(公告)日：2012-11-15
申请号：US13561770
申请日：2012-07-30
申请人： Daniel L. Alkon
发明人： Daniel L. Alkon
IPC分类号： A61K31/366 , A61K31/4015 , C12N5/079 , A61K31/407 , A61P25/00 , A61K31/395 , A61K31/426
CPC分类号： A61K31/366 , A61K31/365 , A61K31/40 , A61K31/4015 , A61K31/407 , A61K31/437
摘要： The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.
摘要翻译：本发明提供使蛋白激酶C（PKC）激活剂与PKC激活剂以足以刺激足以巩固长期记忆的蛋白质合成的方式接触的方法。本发明还提供了以足以下调PKC的方式使蛋白激酶C（PKC）活化剂与PKC激活剂接触的方法。

38. 发明授权

US08163800B2 PKC-activating compounds for the treatment of neurodegenerative diseases 有权
标题翻译：用于治疗神经变性疾病的PKC活化化合物
公开(公告)号：US08163800B2
公开(公告)日：2012-04-24
申请号：US12510681
申请日：2009-07-28
申请人： Thomas J. Nelson , Daniel L. Alkon
发明人： Thomas J. Nelson , Daniel L. Alkon
IPC分类号： A61K31/19 , A61K31/20
CPC分类号： C07D303/42 , A61K31/045 , A61K31/201 , A61K31/23 , A61K31/231 , A61K31/335 , C07C31/13 , C07C31/1333 , C07C53/134 , C07C69/608 , C07D303/40 , C12N9/12 , C12Y207/11013
摘要： The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.
摘要翻译：本发明涉及使用单和多不饱和脂肪酸的环丙烷化或环氧化衍生物来激活蛋白激酶C（PKC）的同种型以治疗包括阿尔茨海默氏病和中风的神经疾病的方法。本发明还涉及使用单和多不饱和脂肪酸的环丙烷化或环氧化衍生物减少神经变性的方法。

39. 发明授权

US07682807B2 Alzheimer's disease diagnosis based on mitogen-activated protein kinase phosphorylation 有权
标题翻译：基于丝裂原活化蛋白激酶磷酸化的阿尔茨海默病诊断
公开(公告)号：US07682807B2
公开(公告)日：2010-03-23
申请号：US10469164
申请日：2002-02-27
申请人： Wei-Qin Zhao , Daniel L. Alkon
发明人： Wei-Qin Zhao , Daniel L. Alkon
IPC分类号： G01N33/567 , C12Q1/00 , G01N33/00
CPC分类号： G01N33/6896 , A61K31/404 , A61K31/519 , A61K31/5377 , A61K31/69 , G01N2333/4709 , G01N2333/91205 , G01N2500/00 , G01N2500/10 , G01N2800/2821
摘要： A method of diagnosing Alzheimer's disease in a patient comprises determining whether the phosphorylation level of an indicator protein in cells of the patient after stimulus with an activator compound is abnormally elevated as compared to a basal phosphorylation level, the indicator protein being e.g. Erk1/2 and the activator compound being e.g. bradykinin.
摘要翻译：在患者中诊断阿尔茨海默病的方法包括确定与基础磷酸化水平相比，用活化剂化合物刺激之后的患者细胞中的指示蛋白的磷酸化水平是否异常升高。 Erk1 / 2和活化剂化合物是例如。缓激肽

40. 发明申请

US20090041667A1 Treatment of Depressive Disorders 审中-公开
标题翻译：治疗抑郁症
公开(公告)号：US20090041667A1
公开(公告)日：2009-02-12
申请号：US10594420
申请日：2005-05-18
申请人： Miao-Kun Sun , Daniel L. Alkon
发明人： Miao-Kun Sun , Daniel L. Alkon
IPC分类号： A61K31/135 , A61K31/195 , A61K31/4164 , A61K31/4184 , A61K31/4172 , A61K31/197 , A61K31/137 , A61P25/24 , A61K31/335 , A61K49/00
CPC分类号： A61K38/1825 , A61K31/045 , A61K31/05 , A61K31/192 , A61K31/196 , A61K31/365 , A61K31/366 , A61K31/4164 , A61K31/4172
摘要： The invention provides for the use of carbonic anhydrase activators; protein kinase C activators and FGF-18 to treat depressive disorders. The invention also relates to improved animal models and methods for screening and identifying compounds the treatment of depressive disorders.
摘要翻译：本发明提供了使用碳酸酐酶活化剂; 蛋白激酶C激活剂和FGF-18治疗抑郁障碍。本发明还涉及用于筛选和鉴定化合物治疗抑郁症的改进的动物模型和方法。

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