Abstract: The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject’s spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject’s spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject’s brain.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

Abstract: This disclosure provides methods and compositions for treating lysosomal storage diseases in a subject. In one aspect of the invention, a transgene product is delivered to a subject by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain. The transgene product may be any that is deficient in a lysosomal storage disease.

Abstract: Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.

Abstract: The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.

Abstract: A dampening translator for a sliding building closure comprising a housing having a longitudinal axis and a traveler track with a longitudinally extending portion having a first end. A traveler is carried by the housing and includes a body carrying track followers carried in the traveler track of the housing, and carrying longitudinally spaced walls extending away from the body and establishing a catch space therebetween. A retractor is carried by the housing and has a housing portion coupled to the housing and a traveler portion coupled to the traveler to bias the traveler in a direction toward the first end of the traveler track. A dampener is carried by the housing to decelerate the traveler.

Abstract: The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

Abstract: Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

Abstract: A fenestration assembly includes a frame assembly, a movable sash assembly and a lock assembly. The lock assembly includes a first lock and a second side lock. The first lock operatively locks and unlocks the moveable sash to the frame assembly in a first direction only when the movable sash is in a fully closed position. The first side lock operatively locks and unlocks the movable sash in a second direction perpendicular to the first direction both when the movable sash is in the fully closed position and a partially open position.

Abstract: Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

Abstract: A fenestration assembly includes a frame assembly, a movable sash assembly and a lock assembly. The lock assembly includes a first lock and a second side lock. The first lock operatively locks and unlocks the moveable sash to the frame assembly in a first direction only when the movable sash is in a fully closed position. The first side lock operatively locks and unlocks the movable sash in a second direction perpendicular to the first direction both when the movable sash is in the fully closed position and a partially open position.

Abstract: A building closure operator includes an operator arm pivotable about an arm axis from an arm closed position to an arm open position, an arm lock actuatable to lock the arm in different locked positions and releasable to release the arm, and an articulatable lever pivotable about a lever axis parallel to the arm axis, from a lever home position corresponding to the arm closed position, to a lever actuated position corresponding to the arm open position. The lever includes a lever coupling maintainable in the lever actuated position, and a lever handle pivotable with respect to the lever coupling back to the home position to actuate the arm lock to lock the arm in one of the different locked positions.

Abstract: A dampening translator for a sliding building closure. A housing extends along a longitudinal axis and includes a traveler track with a longitudinally extending portion having a first end. A traveler is carried by the housing and includes a body carrying track followers carried in the traveler track of the housing, and longitudinally spaced walls extending away from the body and establishing a catch space therebetween. A retractor is carried by the housing and has a housing portion coupled to the housing and a traveler portion coupled to the traveler to bias the traveler in a direction toward the first end of the traveler track. A dampener is carried by the housing to decelerate the translator.

Abstract: A building closure operator includes an operator arm pivotable about an arm axis from an arm closed position to an arm open position, an arm lock actuatable to lock the arm in different locked positions and releasable to release the arm, and an articulatable lever pivotable about a lever axis parallel to the arm axis, from a lever home position corresponding to the arm closed position, to a lever actuated position corresponding to the arm open position. The lever includes a lever coupling maintainable in the lever actuated position, and a lever handle pivotable with respect to the lever coupling back to the home position to actuate the arm lock to lock the arm in one of the different locked positions.

Abstract: A machine and system in the art of precision cooking, which can be a stand-alone appliance, or integrated into a thermally insulated chamber; the machine having means to collect geometric, physical, and thermal values; having access to an electronic database of material composition values, a program which through onboard micro-computing or connection to external computing resources, generates a three-dimensional thermo physical model of the irregular shaped food object to be cooked, relating obtained values as to retrieve essential heat conduction variables to render an accurate cook time. The machine and system, once integrated inside a thermally insulated chamber, or in communication with a thermally insulated chamber through an IoT communication platform can, once cook time is calculated, receive feedback from user through a display—this feedback assists in ensuring accurate precision of cooking time by slightly changing the individual users machine to account for irregular variables in the system.

Abstract: The invention relates to dihydroorate dehydrogenase (DHODH) inhibitors useful for the treatment of neurodegenerative diseases, such as amyotrophic lateral sclerosis.