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31. 发明授权

US10039930B2 Method and apparatus for multimodal electrical modulation of pain 有权
公开(公告)号：US10039930B2
公开(公告)日：2018-08-07
申请号：US15075550
申请日：2016-03-21
申请人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
发明人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
IPC分类号： A61N1/36 , A61N2/00 , A61N1/05
摘要： Apparatus and methods for managing pain uses separate varying electromagnetic fields, with a variety of temporal and amplitude characteristics, which are applied to a particular neural structure to modulate glial and neuronal interactions as a mechanism for relieving chronic pain. In another embodiment, a single composite modulation/stimulation signal which has rhythmically varying characteristics is used to achieve the same results as separate varying electromagnetic fields. Also, disclosed is an apparatus and method for modulating the expression of genes involved in diverse pathways including inflammatory/immune system mediators, ion channels and neurotransmitters, in both the Spinal Cord (SC) and Dorsal Root Ganglion (DRG) where such expression modulation is caused by spinal cord stimulation or peripheral nerve stimulation using the disclosed apparatus and techniques. In one embodiment of multimodal modulation therapy, the prime signal may be monophasic, or biphasic, in which the polarity of the first phase of the biphasic prime signal may be either cathodic or anodic while the tonic signal may be either monophasic, or biphasic, with the polarity of the first phase of the biphasic tonic signal being either cathodic or anodic.

32. 发明申请

US20180185645A1 SYSTEM AND METHOD OF PAIN RELIEF BASED ON FREQUENCY BASED ANALYSIS OF TEMPORAL NOCICEPTIVE SIGNALS 审中-公开
公开(公告)号：US20180185645A1
公开(公告)日：2018-07-05
申请号：US15860117
申请日：2018-01-02
申请人： Ricardo Vallejo , David Leonardo Cedeno , William J. Smith
发明人： Ricardo Vallejo , David Leonardo Cedeno , William J. Smith
IPC分类号： A61N1/36 , A61B5/04 , A61B5/048
CPC分类号： A61N1/36071 , A61B5/04001 , A61B5/04017 , A61B5/048 , A61B5/4047 , A61B5/4824 , A61B5/4836 , A61N1/0556 , A61N1/36139 , A61N1/36171 , A61N1/37264
摘要： An apparatus, system and technique selectively eliminates the noxious signal components in a neuronal signal by creating an interfering electrical signal that is tuned to a given frequency corresponding to the oscillatory pattern of the noxious signal, resulting in a modified neuronal signal that substantially reproduces a normal, no-pain neuronal signal. The disclosed system and technique of pain relief is based on the hypothesis that the temporal profile of pain signals encodes particular components that oscillate at unique and quantifiable frequencies, which are responsible for pain processing in the brain.

33. 发明申请

US20160256689A1 METHOD AND APPARATUS FOR MULTIMODAL ELECTRICAL MODULATION OF PAIN 有权
公开(公告)号：US20160256689A1
公开(公告)日：2016-09-08
申请号：US15075565
申请日：2016-03-21
申请人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
发明人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
IPC分类号： A61N1/36 , A61N1/05
CPC分类号： A61N1/36071 , A61N1/0551 , A61N1/36192 , A61N1/36196 , A61N2/002 , A61N2/008
摘要： Apparatus and methods for managing pain uses separate varying electromagnetic fields, with a variety of temporal and amplitude characteristics, which are applied to a particular neural structure to modulate glial and neuronal interactions as a mechanism for relieving chronic pain. In another embodiment, a single composite modulation/stimulation signal which has rhythmically varying characteristics is used to achieve the same results as separate varying electromagnetic fields. Also, disclosed is an apparatus and method for modulating the expression of genes involved in diverse pathways including inflammatory/immune system mediators, ion channels and neurotransmitters, in both the Spinal Cord (SC) and Dorsal Root Ganglion (DRG) where such expression modulation is caused by spinal cord stimulation or peripheral nerve stimulation using the disclosed apparatus and techniques. In one embodiment of multimodal modulation therapy, the prime signal may be monophasic, or biphasic, in which the polarity of the first phase of the biphasic prime signal may be either cathodic or anodic while the tonic signal may be either monophasic, or biphasic, with the polarity of the first phase of the biphasic tonic signal being either cathodic or anodic.

34. 发明申请

US20110296540A1 ASSAY FOR SCREENING ANTIDEPRESSANTS 审中-公开
标题翻译：用于筛选抗生素的测定
公开(公告)号：US20110296540A1
公开(公告)日：2011-12-01
申请号：US13131558
申请日：2009-12-01
申请人： Rene Hen , Jingwen Wang , Eduardo David Leonardo , Jesse Richardson-Jones
发明人： Rene Hen , Jingwen Wang , Eduardo David Leonardo , Jesse Richardson-Jones
IPC分类号： G01N33/48 , A01K67/00 , G01N33/82 , A61K49/00 , C12Q1/68
CPC分类号： G01N33/5058 , A01K67/0275 , A01K2217/054 , A01K2217/203 , A01K2217/206 , A01K2227/105 , A01K2267/0356 , C12N15/8509 , G01N33/5088
摘要： This invention provides a method for identifying a small molecule as an antidepressant, a method for identifying a small molecule as an anxiolytic, and a method for identifying a small molecule as able to increase dendritic arborization, decrease expression of an immaturity marker, increase expression of a maturity marker, or enhance artificial cerebrospinal fluid-type long-term potentiation in central nervous system. This invention also provides a transgenic mouse model for SSRI-non-responders.
摘要翻译：本发明提供了用于鉴定作为抗抑郁药的小分子的方法，用于鉴定作为抗焦虑药的小分子的方法，以及用于鉴定能够增加树突状结构的小分子，降低未成熟标记物的表达，增加表达的方法成熟标志物，或增强人脑中枢神经系统长期增强的脑脊液。本发明还提供了用于SSRI-无应答者的转基因小鼠模型。

35. 发明授权

US07919588B2 Netrin receptors 有权
标题翻译： Netrin受体
公开(公告)号：US07919588B2
公开(公告)日：2011-04-05
申请号：US12151062
申请日：2008-05-01
申请人： Marc Tessier-Lavigne , E. David Leonardo , Lindsay Hinck , Masayuki Masu , Kazuko Keino-Masu
发明人： Marc Tessier-Lavigne , E. David Leonardo , Lindsay Hinck , Masayuki Masu , Kazuko Keino-Masu
IPC分类号： G01N33/53 , C07K14/435
CPC分类号： C07K14/71 , A61K39/00 , C07K16/2803 , C07K16/2863 , G01N33/6872
摘要： The invention provides methods and compositions relating to vertebrate UNC-5 proteins which function as receptor proteins for netrins, a family of cell guidance proteins. The proteins may be produced recombinantly from transformed host cells from the disclosed vertebrate UNC-5 encoding nucleic acid or purified from human cells. The invention provides specific hybridization probes and primers capable of specifically hybridizing with the disclosed vertebrate unc-5 gene, vertebrate UNC-5-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.
摘要翻译：本发明提供了与作为网蛋白的受体蛋白（一种细胞指导蛋白）起作用的脊椎动物UNC-5蛋白质相关的方法和组合物。可以从所公开的编码脊椎动物UNC-5的核酸的转化宿主细胞重组产生蛋白质，或者从人细胞纯化。本发明提供能够与所公开的脊椎动物unc-5基因，脊椎动物UNC-5特异性结合剂如特异性抗体特异性杂交的特异性杂交探针和引物，以及制备和使用本发明组合物在诊断，治疗和生物制药行业。

36. 发明授权

US6087326A Neurological drug screens 失效
标题翻译：神经药物筛选
公开(公告)号：US6087326A
公开(公告)日：2000-07-11
申请号：US007604
申请日：1998-01-15
申请人： Lindsay Hinck , Kasuko Masu , Masayuki Masu , David Leonardo , Marc Tessier-Lavigne
发明人： Lindsay Hinck , Kasuko Masu , Masayuki Masu , David Leonardo , Marc Tessier-Lavigne
IPC分类号： G01N33/53 , A61K38/00 , C07K14/475 , C07K14/48 , C07K14/52 , C07K14/71 , C07K14/715 , C12N15/00 , C12N15/09 , C12Q1/02 , G01N33/566 , A61K38/02 , A61K38/17 , C07K2/00 , C07K14/435
CPC分类号： C07K14/71 , C07K14/475 , A61K38/00
摘要： Compositions for identifying lead compounds for pharmacological agents useful in the diagnosis or treatment of neurological disease or injury include mixtures comprising an isolated netrin and an isolated natural netrin receptor such as "Deleted in Colorectal Carcinoma" (DCC) and neogenin. The general methods involve incubating a mixture of an isolated mammalian netrin, an isolated natural mammalian netrin receptor, and a candidate pharmacological agent, and determining if the presence of the agent modulates the binding of the netrin to the receptor.
摘要翻译：用于鉴定可用于诊断或治疗神经疾病或损伤的药理学试剂的铅化合物的组合物包括包含分离的网状蛋白和分离的天然netrin受体的混合物，例如“在结肠直肠癌中被删除”（DCC）和新生素。一般方法包括孵育分离的哺乳动物netrin，分离的天然哺乳动物netrin受体和候选药理学试剂的混合物，并确定试剂的存在是否调节netrin与受体的结合。

37. 发明授权

US5747262A Neurological drug screens 失效
公开(公告)号：US5747262A
公开(公告)日：1998-05-05
申请号：US551874
申请日：1995-10-16
申请人： Lindsay Hinck , Kasuko Masu , Masayuki Masu , David Leonardo , Marc Tessier Lavigne
发明人： Lindsay Hinck , Kasuko Masu , Masayuki Masu , David Leonardo , Marc Tessier Lavigne
IPC分类号： G01N33/53 , A61K38/00 , C07K14/475 , C07K14/48 , C07K14/52 , C07K14/71 , C07K14/715 , C12N15/00 , C12N15/09 , C12Q1/02 , G01N33/566
CPC分类号： C07K14/71 , C07K14/475 , A61K38/00
摘要： Compositions for identifying lead compounds for pharmacological agents useful in the diagnosis or treatment of neurological disease or injury include mixtures comprising an isolated netrin and an isolated natural netrin receptor such as "Deleted in Colorectal Carcinoma" (DCC) and neogenin. The general methods involve incubating a mixture of an isolated mammalian netrin, an isolated natural mammalian netrin receptor, and a candidate pharmacological agent, and determining if the presence of the agent modulates the binding of the netrin to the receptor.

38. 发明授权

US10193498B2 Method and system for boosting the supply of power amplifier 有权
公开(公告)号：US10193498B2
公开(公告)日：2019-01-29
申请号：US14124727
申请日：2012-06-14
申请人： David Leonardo Fleischer
发明人： David Leonardo Fleischer
IPC分类号： H03G3/20 , H03F1/02 , H03F3/24 , H04L27/26 , H03F3/189
摘要： The present invention relates to a system for boosting the power supply of an RF power amplifier in high peak to average power ratio applications, wherein said power amplifier is coupled to receive and amplify a digital data stream of a baseband signal, (e.g., which after modulation with a carrier wave are supplied as the RF input signal to said power amplifier to generate an RF output signal). Said system comprises: a) a first circuit for controlling said boost by said digital data stream of said baseband signal in open-loop, wherein the timing of said boost event can be adjusted according to delays in the data stream of said system, wherein said boost event is imparted as a copy of the most significant bits of said baseband signal; and b) a second circuit for adjusting the precise timing of said boost event in such a way that the signal which controls said second circuit is the result of a comparison between a digital form of said RF input signal and/or a digital representation of the waveform of said power supply and said digital baseband signal, wherein said comparison represents the substantial matching of the delays in the paths of RF input signal and said power supply.

39. 发明申请

US20160271413A1 METHOD AND APPARATUS FOR MULTIMODAL ELECTRICAL MODULATION OF PAIN 审中-公开
标题翻译：多用途电气调制方法与装置
公开(公告)号：US20160271413A1
公开(公告)日：2016-09-22
申请号：US15075582
申请日：2016-03-21
申请人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
发明人： Ricardo Vallejo , David Leonardo Cedeno , Ramsin M. Benyamin
IPC分类号： A61N2/00
CPC分类号： A61N1/36071 , A61N1/0551 , A61N1/36062 , A61N1/36189 , A61N1/36192 , A61N1/36196 , A61N2/002 , A61N2/008
摘要： Apparatus and methods for managing pain uses separate varying electromagnetic fields, with a variety of temporal and amplitude characteristics, which are applied to a particular neural structure to modulate glial and neuronal interactions as a mechanism for relieving chronic pain. In another embodiment, a single composite modulation/stimulation signal which has rhythmically varying characteristics is used to achieve the same results as separate varying electromagnetic fields. Also, disclosed is an apparatus and method for modulating the expression of genes involved in diverse pathways including inflammatory/immune system mediators, ion channels and neurotransmitters, in both the Spinal Cord (SC) and Dorsal Root Ganglion (DRG) where such expression modulation is caused by spinal cord stimulation or peripheral nerve stimulation using the disclosed apparatus and techniques. In one embodiment of multimodal modulation therapy, the prime signal may be monophasic, or biphasic, in which the polarity of the first phase of the biphasic prime signal may be either cathodic or anodic while the tonic signal may be either monophasic, or biphasic, with the polarity of the first phase of the biphasic tonic signal being either cathodic or anodic.
摘要翻译：用于治疗疼痛的装置和方法使用单独的变化的电磁场，具有各种时间和幅度特征，其被应用于特定神经结构以调节胶质和神经元相互作用，作为缓解慢性疼痛的机制。在另一个实施例中，使用具有节奏变化特性的单个复合调制/刺激信号来获得与单独变化的电磁场相同的结果。此外，公开了一种用于调节在脊髓（SC）和背根神经节（DRG）中的各种途径（包括炎症/免疫系统介质，离子通道和神经递质）的基因表达的装置和方法，其中这种表达调节是使用所公开的装置和技术由脊髓刺激或周围神经刺激引起。在多模调制治疗的一个实施例中，主信号可以是单相或双相，其中双相主信号的第一相的极性可以是阴极或阳极，而补音信号可以是单相的或双相的，双相滋补信号的第一相极性为阴极或阳极。

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