Abstract: A method of making a golf club head includes the steps of providing a face of a club head, the face having a ball striking surface and a perimeter defining a border of the ball striking surface, providing a golf club head body that includes a crown, a sole, a toe, and a heel, attaching the face to a front portion of the club head body, and milling the ball striking surface and an edge portion of the face to cut a machined surface into the ball striking surface and the edge portion. The milled surface includes a plurality of first grooves located along the ball striking surface and defining a first depth, and a plurality of second grooves located adjacent the perimeter along the edge portion and defining a second depth. The first depth is different than the second depth.

Abstract: In some implementations, an event timeline that includes one or more interactions between a customer and a supplier may be determined. A starting value may be assigned to individual events in the event timeline. A sub-sequence comprising a portion of the event timeline that includes at least one reference event may be selected. A classifier may be used to determine a previous relative value for a previous event that occurred before the reference event and to determine a next relative value for a next event that occurred after the reference event until all events in the event timeline have been processed. The events in the event timeline may be traversed and a monetized value index assigned to individual events in the event timeline.

Abstract: Aspects described herein relate to stable cell line for recombinant viral vector (e.g., recombinant adeno associated viral vector) production comprising at least one inducible promoter operatively linked to a heterologous gene that encodes a toxic protein. Methods for making stable cell lines, and methods for viral vector production are further provided herein.

Abstract: Aspects described herein relate to stable cell line for recombinant viral vector (e.g., recombinant adeno associated viral vector) production comprising at least one inducible promoter operatively linked to a heterologous gene that encodes a toxic protein. Methods for making stable cell lines, and methods for viral vector production are further provided herein.

Abstract: The present invention relates to forskolin-inducible and hypoxia-inducible cis-regulatory elements, promoters and vectors, and methods of their use.

Abstract: Disclosed herein are various optimized nucleic acids encoding the fukutin-related protein (FKRP). Recombinant vectors comprising the optimized nucleic acid (e.g. operatively linked to a muscle specific promoter), such as recombinant adeno-associated virus vectors, for expressing the protein (e.g. in skeletal and cardiac muscle), and therapeutic compositions contains the vectors are also disclosed. Therapeutic methods of administration of the vectors to a subject for the treatment of a subject with a dystroglycanopathy disorder (e.g., limb-girdle muscular dystrophy 2I) are also disclosed.

Abstract: Aspects of the disclosure relate to compositions and methods useful for treating neurological diseases and disorders. In some embodiments, the disclosure provides a method for treating a neurological disease or disorder comprising administration of both a viral vector comprising interfering nucleic acids (e.g., artificial miRNAs) and a viral vector comprising a CYP46A1 protein. In some embodiments, the disclosure provides a method for treating Huntington's disease comprising administration of both a viral vector comprising interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (HTT) and a viral vector comprising a CYP46A1 protein. In some embodiments, the viral vector comprises a modified viral capsid, such as for preferentially targeting cells in the CNS or PNS.

Abstract: The present invention provides a plurality of synthetic nucleic acid comprising (a) a nucleic acid sequence containing at least one unique regulatory element (URE); wherein the URE comprises at least one regulatory element and a plurality of unique barcodes associated with the at least one regulatory element; and (b) a nucleic acid sequence encoding an transcribable reporter sequence, wherein each barcode is between 12-35 nucleotides in length and have a GC content between 25-65%. URE can be one regulatory element or a combination of regulatory elements. Libraries of expression vectors and plasmids expressing the plurality of synthetic nucleic acids are also provided herein. Additional aspects described herein are methods for identifying the strength of a unique regulatory element in vivo or in vitro using the synthetic nucleic acids or libraries expressing the same.

Abstract: The present invention relates to methods of administration of rAAV vectors in a single administration method comprising a series of sub-administrations of sub-doses of rAAV vectors. The present invention also relates to rAAV vectors comprising cardiac-specific promoters, cardiac-cell specific promoters, multi-cell cardiac specific promoters, and elements thereof. The invention also relates to rAAV vectors, pharmaceutical compositions and uses thereof in methods for treating cardiovascular disease, heart diseases and heart failure in subjects in need thereof.

Abstract: The present invention relates to regulatory nucleic acid sequences, in particular NS-specific promoters, cell specific promoters, multi-cell specific promoters, and elements thereof. The invention also relates to expression constructs, vectors, virions, pharmaceutical compositions and cells comprising such promoters and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications.

Abstract: Disclosed herein are methods, systems, and processes for distributed logging for securing non-repudiable transactions. Credentials, request information, response information, and action items generated and received by a requesting computing system and a responding computing system, and transmitted between the requesting computing system and the responding computing system are separately recorded and stored in a requestor log maintained by the requesting computing system and in a responder log maintained by the responding computing system.

Abstract: The present invention relates to regulatory nucleic acid sequences, in particular muscle-specific promoters, elements thereof, and other such nucleic acid sequences, that are capable of enhancing muscle-specific expression of genes. The invention also relates to expression constructs, vectors and cells comprising such muscle-specific regulatory nucleic acid sequences, and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications, but also find utility in other areas such as bioprocessing and biotechnology.

Abstract: The present invention relates to forskolin-inducible and hypoxia-inducible cis-regulatory elements, promoters and vectors, and methods of their use.

Abstract: The present invention relates to regulatory nucleic acid sequences, in particular CNS—specific promoters, and elements thereof. The invention also relates to expression constructs, vectors, virions, pharmaceutical compositions and cells comprising such promoters and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications.

Abstract: In some implementations, an event timeline that includes one or more interactions between a customer and a supplier may be determined. A starting value may be assigned to individual events in the event timeline. A sub-sequence comprising a portion of the event timeline that includes at least one reference event may be selected. A classifier may be used to determine a previous relative value for a previous event that occurred before the reference event and to determine a next relative value for a next event that occurred after the reference event until all events in the event timeline have been processed. The events in the event timeline may be traversed and a monetized value index assigned to individual events in the event timeline.

Abstract: The technology described herein is directed to systems and methods for synthetic regulatory sequence design or production. In several aspects described herein are methods of designing and optionally synthesizing shortened or otherwise modified polynucleotide sequences from polynucleotide sequences with transcriptional regulatory functionality. In other aspects described herein are isolated nucleic acid modules and viral vectors, comprising said shortened or otherwise modified polynucleotide as designed or synthesized herein.

Abstract: The present invention provides a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence.

Abstract: In some implementations, an event timeline that includes one or more interactions between a customer and a supplier may be determined. A starting value may be assigned to individual events in the event timeline. A sub-sequence comprising a portion of the event timeline that includes at least one reference event may be selected. A classifier may be used to determine a previous relative value for a previous event that occurred before the reference event and to determine a next relative value for a next event that occurred after the reference event until all events in the event timeline have been processed. The events in the event timeline may be traversed and a monetized value index assigned to individual events in the event timeline.

Abstract: The present application relates to a system for designing promoters for selective expression of genes. Thereby identified transcription regulatory elements are selected according to a specific methodology and used to create a library of transcription regulatory elements, which are then used to construct specific promoters, especially tissue-specific promoters.

Abstract: Disclosed herein are methods, systems, and processes for distributed logging for securing non-repudiable transactions. Credentials, request information, response information, and action items generated and received by a requesting computing system and a responding computing system, and transmitted between the requesting computing system and the responding computing system are separately recorded and stored in a requestor log maintained by the requesting computing system and in a responder log maintained by the responding computing system.