Abstract: Disclosed herein are compositions and methods for increasing the lifespan of a non-rodent mammal or a mature mammal in need thereof. The compositions and methods comprise therapeutically effective amounts of a nucleic acid encoding a target protein or a functional fragment or variant thereof or therapeutically effective amounts of a modified protein comprising target protein or a functional fragment or variant thereof.

Abstract: An animal model for motor neuron dysfunction in disease, e.g., amyotrophic lateral sclerosis (ALS), comprising a genetically modified non-human animal that comprises a genetically modified DR6 allele and exhibits normal phenotypes at birth and for a few weeks or months after birth. However, as the non-human animal ages, it develops motor neuron dysfunction that presents as one or more ALS-like symptoms, which may progress rapidly after onset. Methods of identifying candidate agents that may be used to prevent, delay or treat ALS are also provided.

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

Abstract: An animal model for motor neuron dysfunction in disease, e.g., amyotrophic lateral sclerosis (ALS), comprising a genetically modified non-human animal that comprises a genetically modified DR6 allele and exhibits normal phenotypes at birth and for a few weeks or months after birth. However, as the non-human animal ages, it develops motor neuron dysfunction that presents as one or more ALS-like symptoms, which may progress rapidly after onset. Methods of identifying candidate agents that may be used to prevent, delay or treat ALS are also provided.

Abstract: An animal model for motor neuron dysfunction in disease, e.g., amyotrophic lateral sclerosis (ALS), comprising a genetically modified non-human animal that comprises a genetically modified DR6 allele and exhibits normal phenotypes at birth and for a few weeks or months after birth. However, as the non-human animal ages, it develops motor neuron dysfunction that presents as one or more ALS-like symptoms, which may progress rapidly after onset. Methods of identifying candidate agents that may be used to prevent, delay or treat ALS are also provided.

Abstract: Methods and systems are provided for deactivating a valve actuation mechanism. In one example, a system may include a hydraulic gallery that may deliver a restricted flow of hydraulic fluid from a hydraulic flow restrictor to a pressure relief valve within a valve deactivation oil control valve, and during a second condition may deliver an unrestricted flow of hydraulic fluid from the valve deactivation oil control valve to the hydraulic flow restrictor. The hydraulic flow restrictor may comprise two vertical bores within the camshaft carrier that are fluidically coupled via a restrictive groove on the bottom surface of the camshaft carrier.

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

Abstract: Methods and systems are provided for deactivating a valve actuation mechanism. In one example, a system may include a hydraulic gallery that may deliver a restricted flow of hydraulic fluid from a hydraulic flow restrictor to a pressure relief valve within a valve deactivation oil control valve, and during a second condition may deliver an unrestricted flow of hydraulic fluid from the valve deactivation oil control valve to the hydraulic flow restrictor. The hydraulic flow restrictor may comprise two vertical bores within the camshaft carrier that are fluidically coupled via a restrictive groove on the bottom surface of the camshaft carrier.

Abstract: Methods and systems are provided for regulating oil flow to advance and retard chambers of a variable cam timing (VCT) system and to a thrust bearing of a camshaft via an oil control valve. In one example, an oil control valve may be housed within a cam journal cap the cam journal cap comprising a thrust bearing for receiving and retaining a camshaft. The cam journal cap may include a vertical bore configured to house the control valve, where the vertical bore may include a first port for receiving oil from an oil pump, a second port for flowing oil to an advance chamber of a VCT system, a third port for flowing oil to a retard chamber of the VCT system, a fourth port, coupled to the thrust bearing for flowing oil thereto, and a drain port for flowing oil to an oil sump.

Abstract: Methods and systems are provided for deactivating a valve actuation mechanism. In one example, a system may include a hydraulic gallery that may deliver a restricted flow of hydraulic fluid from a hydraulic flow restrictor to a pressure relief valve within a valve deactivation oil control valve, and during a second condition may deliver an unrestricted flow of hydraulic fluid from the valve deactivation oil control valve to the hydraulic flow restrictor. The hydraulic flow restrictor may comprise two vertical bores within the camshaft carrier that are fluidically coupled via a restrictive groove on the bottom surface of the camshaft carrier.

Abstract: Methods and systems are provided for regulating oil flow to advance and retard chambers of a variable cam timing (VCT) system and to a thrust bearing of a camshaft via an oil control valve. In one example, an oil control valve may be housed within a cam journal cap the cam journal cap comprising a thrust bearing for receiving and retaining a camshaft. The cam journal cap may include a vertical bore configured to house the control valve, where the vertical bore may include a first port for receiving oil from an oil pump, a second port for flowing oil to an advance chamber of a VCT system, a third port for flowing oil to a retard chamber of the VCT system, a fourth port, coupled to the thrust bearing for flowing oil thereto, and a drain port for flowing oil to an oil sump.

Abstract: Methods and systems are provided for deactivating a valve actuation mechanism. In one example, a system may include a hydraulic gallery that may deliver a restricted flow of hydraulic fluid from a hydraulic flow restrictor to a pressure relief valve within a valve deactivation oil control valve, and during a second condition may deliver an unrestricted flow of hydraulic fluid from the valve deactivation oil control valve to the hydraulic flow restrictor. The hydraulic flow restrictor may comprise two vertical bores within the camshaft carrier that are fluidically coupled via a restrictive groove on the bottom surface of the camshaft carrier.

Abstract: An animal model for motor neuron dysfunction in disease, e.g., amyotrophic lateral sclerosis (ALS), comprising a genetically modified non-human animal that comprises a genetically modified DR6 allele and exhibits normal phenotypes at birth and for a few weeks or months after birth. However, as the non-human animal ages, it develops motor neuron dysfunction that presents as one or more ALS-like symptoms, which may progress rapidly after onset. Methods of identifying candidate agents that may be used to prevent, delay or treat ALS are also provided.

Abstract: The invention relates to a method of, and system for, linear speed control for an electric motor, in which a digital to analog converter means is used for converting an 8-bit digital signal to an analog voltage for setting voltage across a motor, a digital state machine means is used for converting the duty cycle of an input signal for output to the digital to analog converter means, and a closed loop feedback loop means is used for monitoring and setting the voltage across the motor. An over-current sense circuit can be used for monitoring the current across the electric motor. An over/under voltage sense circuit can be used for monitoring voltage of the electric motor. The resulting 8-bit digital control signal is converted to an analog voltage for the electric motor. Such methods and systems find particular use in automotive applications.

Abstract: An electric fluid pump includes an upper housing having a fluid inlet and outlet. An impeller is seated within the upper housing for pumping fluid between the inlet and the outlet. The impeller includes at least one magnet secured thereto. A lower housing mates with the upper housing. The lower housing has an upper wall for closing the upper housing and a shaft extending from the upper wall for rotatably supporting the impeller. A stator is seated within the lower housing and spaced from the impeller by the upper wall. The stator includes a plurality of pillars supporting a winding of coils for producing a magnetic field to energize the magnet and rotate the impeller, and a plurality of top plates covering each of the coils and spaced apart by a predetermined gap for maintaining the magnetic field between the stator and the impeller. An end cap closes the stator within the lower housing.