Abstract: Provided for herein are polynucleotides, including codon-optimized polynucleotides, encoding genes for use in, for example, virally-mediated gene therapy for Friedreich's ataxia. Some embodiments related to viral vector constructs for use in such gene therapy. Also provided are dosing regimens and therapeutic combinations or systems for use in modulating immune responses to such viral vectors.

Abstract: The present disclosure relates to compositions and methods for the treatment of TECPR2-associated diseases or disorders. Several embodiments provided for herein relate to virally-mediated transfer of a gene to target cells to induce expression of an encoded polypeptide, protein or other product in order to ameliorate one or more symptoms of a TECPR2-associated disease or disorder in a subject. In several embodiments, the disclosed methods and compositions relate to recombinant adeno-associated virus particles encoding human TECPR2 in order to treat TECPR2-associated diseases or disorders, including spastic paraplegic type 49 (SPG49) and/or hereditary sensory and autonomic neuropathy 9 (HSAN9).

Abstract: Provided herein are methods related to co-packaging of multiple rAAV particles, e.g., by introducing multiple nucleic acid vectors encoding proteins or polypeptides or RNAs of interest into a single cell preparation.

Abstract: A neural-symbolic computing engine can have two or more modules that are configured to cooperate with each other in order to create one or more gradient-based machine learning models that use machine learning on i) knowledge representations and ii) reasoning to solve an issue. A model representation module in the neural-symbolic computing engine is configured to apply one or more mathematical functions, at least including a logit transform, to truth values from first order logic elements supplied from a language module of the neural-symbolic computing engine.

Abstract: Among other things, the present disclosure provides RHO oligonucleotides, compositions, and methods. In some embodiments, provided oligonucleotides comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, the present disclosure provides RHO oligonucleotides, compositions and methods for preventing and/or treating RHO-related conditions, disorders or diseases, such as retinopathy (e.g, retinal degeneration, retinal degenerative disease, retinal degenerative disorder, inherited retinal degenerative disorder, retinitis pigmentosa, autosomal dominant retinitis pigmentosa, etc.).

Abstract: A valve actuator may include a valve control shaft extending at least partially through a housing of the valve actuator, wherein the valve control shaft is configured for controlling a valve position of a diverter valve. A first cam wheel may be included, where the first am wheel at least partially surrounds the valve control shaft. A first cam may be fixed to the first cam wheel, and a first microswitch may have an actuator located in a rotational path of the first cam. The valve actuator may also include a second cam wheel at least partially surrounding the valve control shaft, where a second cam is fixed to the second cam wheel, and where a second microswitch has an actuator located in a rotational path of the second cam.

Abstract: A neural-symbolic computing engine can have two or more modules that are configured to cooperate with each other in order to create one or more gradient-based machine learning models that use machine learning on i) knowledge representations and ii) reasoning to solve an issue. A model representation module in the neural-symbolic computing engine is configured to apply one or more mathematical functions, at least including a log it transform, to truth values from first order logic elements supplied from a language module of the neural-symbolic computing engine.

Abstract: Provided herein are methods related to co-packaging of multiple rAAV particles, e.g., by introducing multiple nucleic acid vectors encoding proteins or polypeptides or RNAs of interest into a single cell preparation.

Abstract: Provided herein are modified AAV capsid proteins, particles, nucleic acid vectors, and compositions thereof, as well as methods of their use.

Abstract: Provided herein are compositions, kits and methods related to permitting a human or non-human primate subject to receive multiple doses of recombinant adeno-associate virus (rAAV) vectors. In some aspects, provided herein are methods comprising administering an anti-CD20 antibody, optionally in combination with an mTOR inhibitor, to the subject to permit multiple doses of an rAAV vector to be administered.

Abstract: An artificial intelligence engine that has two or more modules cooperating with each other in order to create one or more machine learning models that use an adaptive semantic learning for knowledge representations and reasoning. The modules cause encoding the representations and reasoning from one or more sources in a particular field with terminology used by one or more human sources in that field into a set of rules that act as constraints and that are graphed into a neural network understandable by a first machine learning model, and then ii) adapting an interpretation of that set of encoded rules. The understanding of that set of encoded rules is adapted by i) allowing for semantically similar terms and ii) by conclusions derived from training data, to create an understanding of that set of encoded rules utilized by the machine learning model and the AI engine.

Abstract: Provided herein are nucleic acids, recombinant adeno-associated viral particles, compositions and methods related to treating Friedreich's ataxia. In some examples, the nucleic acids, recombinant adeno-associated viral particles, compositions and methods involve us of a FXN coding sequence, a truncated FXN 3? UTR, and a prompter.

Abstract: A vehicle system including a vehicle component and a controller is provided. The controller may selectively activate the vehicle component and communicate with a mobile unit including an interface. The controller may be programmed to interact with the mobile unit upon detection by accessing vehicle sleep mode instructions preprogrammed by a user via the interface in which the controller activates the vehicle component according to an escalation sequence schedule to disengage a vehicle sleep mode. The system may further include a sensor in communication with the vehicle component and the controller. The controller may be further programed to activate the vehicle component according to the escalation sequence schedule based on receipt of a signal from a sensor indicating a passenger is asleep.

Abstract: Provided herein are methods of improving rAAV production in cells, the method comprising increasing the salt concentration in the media in which the cells are infected or transfected, cultured, or in which they produce AAV. Aspects of the disclosure relate to improved methods of rAAV production by co-infecting suspension adapted cells (e.g., suspension adapted HEK293 cells) with viruses that encode one or more AAV components for producing rAAV particles within the suspension adapted cells.

Abstract: Methods of producing and isolating 68Ga, 89Zr, 64Cu, 63Zn, 86Y, 61Cu, 99mTc, 45Ti, 13N, 52Mn, or 44Sc and solution targets for use in the methods are disclosed. The methods of producing 68Ga, 89Zr, 64Cu, 63Zn, 86Y, 61Cu, 99mTc, 45Ti, 13N, 52Mn, or 44Sc include irradiating a closed target system with a proton beam. The system can include a solution target. The methods of producing isolated 68Ga, 89Zr, 64Cu, 63Zn, 86Y, 61Cu, 99mTc, 45Ti, 52Mn, or 44Sc further include isolating 68Ga, 89Zr, 64Cu, 63Zn, 86Y, 61Cu, 99mTc, 45Ti, 52Mn, or 44Sc by ion exchange chromatography. An example target includes a target body including a target cavity for receiving the target material; a housing defining a passageway for directing a particle beam at the target cavity; a target window for covering an opening of the target cavity; and a coolant gas flow path disposed in the passageway upstream of the target window.

Abstract: Methods and systems for managing inventory movements are disclosed. Transfer orders are issued to move inventory from location to location in response to real-time demand events. One method includes receiving an inventory request in response to demand signals. The inventory request is analyzed to determine if inventory needs to be moved within the supply chain to satisfy the request. Origin locations are identified that have available stock of the requested items. Transfer orders are issued for each movement on an individual item basis regardless of the type of event that prompted the transfer. The transfer management system responds in real-time to inventory demands from both online and in-store sales.

Abstract: The present invention provides compositions and methods of use pertaining to rAAV-mediated delivery of therapeutically effective molecules for treatment of diseases such as Pompe disease. These compositions in combination with various routes and methods of administration result in targeted expression of therapeutic molecules in specific organs, tissues and cells.

Abstract: Provided herein are methods of improving rAAV production in cells, the method comprising increasing the salt concentration in the media in which the cells are infected or transfected, cultured, or in which they produce AAV. Aspects of the disclosure relate to improved methods of rAAV production by co-infecting suspension adapted cells (e.g., suspension adapted HEK293 cells) with viruses that encode one or more AAV components for producing rAAV particles within the suspension adapted cells.

Abstract: Provided herein are nucleic acids, recombinant adeno-associated viral particles, compositions and methods related to treating Friedreich's ataxia. In some examples, the nucleic acids, recombinant adeno-associated viral particles, compositions and methods involve us of a FXN coding sequence, a truncated FXN 3? UTR, and a prompter.

Abstract: Provided herein are nucleic acids, recombinant adeno-associated viral particles, compositions and methods related to treating Friedreich's ataxia. In some examples, the nucleic acids, recombinant adeno-associated viral particles, compositions and methods involve use of a FXN coding sequence, a truncated FXN 3? UTR, and a promoter.