Abstract: The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.

Abstract: The present disclosure provides improved gene therapy vectors comprising a polynucleotide sequence encoding a TCIRG1 polypeptide or functional variant thereof, methods of use thereof, pharmaceutical compositions, and more. In particular, the disclosure provides lentiviral vectors for treatment of infantile malignant osteopetrosis (IMO).

Abstract: A method of sub-ambient pressure processing of blow-molded polymer foams and skin-over-foam sandwich panel configurations for lightweight components having improved structural properties. The method can create either skinned or un-skinned foams that offer smooth interior and exterior surfaces, zero or controlled surface porosity, skins of pre-defined thickness, and foam cells that are expanded and oriented normal to the material plane, effectively spherical or polyhedral in nature, and offering improved bending and compressive strength.

Abstract: The present invention relates generally to methods for genetic modification of hematopoietic cells. In particular, the invention relates to use of Prostaglandin E2 (PGE2), poloxamer, and protamine sulfate to enhance transduction by a recombinant retroviral vector. The compositions and methods of the present disclosure are particularly suitable for gene therapy applications, including the treatment of monogenic genetic diseases and disorders.

Abstract: The present disclosure provides methods for manufacturing a recombinant lentiviral vectors in an adherent bioreactor, for example, by calcium-phosphate transfection of cells grown in adherent mode on low-compaction macrocarriers in an iCELLis® bioreactor system.

Abstract: The disclosure provides amino acid sequence variants of Botulinum neurotoxin (BoNT) proteases that cleave (VAMP1, VAMP2, VAMP7, VAMP8, SNAP25, SNAP23, PTEN, etc.) and methods of evolving the same. In some embodiments, proteases described by the disclosure are useful for cleaving proteins found in a cell, that is in an intracellular environment. In some embodiments, proteases described by the disclosure are useful for treating diseases associated with increased or aberrant VAMP7, VAMP8, SNAP23 or PTEN expression or activity, for example, cancer and neurological disorders. Some aspects of this disclosure provide methods for generating BoNT protease variants by continuous directed evolution.

Abstract: The present invention provides systems and methods for manufacturing and using gene corrected stem cells for gene therapy. In particular, herein provided are methods for treating Fanconi anemia in which a subject's stem cells are selected by a combination of high stringency CD34+ selection and low stringency CD34+ selection, genetically modified using a gene therapy vector encoding a FANC protein or a gene editing system, and administered to the subject.

Abstract: A method of sub-ambient pressure processing of blow-molded polymer foams and skin-over-foam sandwich panel configurations for lightweight components having improved structural properties. The method can create either skinned or un-skinned foams that offer smooth interior and exterior surfaces, zero or controlled surface porosity, skins of pre-defined thickness, and foam cells that are expanded and oriented normal to the material plane, effectively spherical or polyhedral in nature, and offering improved bending and compressive strength.

Abstract: A method of sub-ambient pressure processing of blow-molded polymer foams and skin-over-foam sandwich panel configurations for lightweight components having improved structural properties. The method can create either skinned or un-skinned foams that offer smooth interior and exterior surfaces, zero or controlled surface porosity, skins of pre-defined thickness, and foam cells that are expanded and oriented normal to the material plane, effectively spherical or polyhedral in nature, and offering improved bending and compressive strength.

Abstract: A method of sub-ambient pressure processing of blow-molded polymer foams and skin-over-foam sandwich panel configurations for lightweight components having improved structural properties. The method can create either skinned or un-skinned foams that offer smooth interior and exterior surfaces, zero or controlled surface porosity, skins of pre-defined thickness, and foam cells that are expanded and oriented normal to the material plane, effectively spherical or polyhedral in nature, and offering improved bending and compressive strength.

Abstract: A method of sub-ambient pressure processing of blow-molded polymer foams and skin-over-foam sandwich panel configurations for lightweight components having improved structural properties. The method can create either skinned or un-skinned foams that offer smooth interior and exterior surfaces, zero or controlled surface porosity, skins of pre-defined thickness, and foam cells that are expanded and oriented normal to the material plane, effectively spherical or polyhedral in nature, and offering improved bending and compressive strength.

Abstract: An exercise device (20) includes a frame (22) and a drive mechanism (100) attached to the frame. The drive mechanism includes a first shaft (122) having a first fixed gear (128) and a second shaft (124) having a second fixed gear (130). The first fixed gear and the second fixed gear are mechanically linked to cause the first shaft to rotate in an opposite direction than the second shaft. A first linear input is mechanically linked to the first shaft and a second linear input is mechanically linked to the second shaft.

Abstract: A drive mechanism (20) including a first shaft (324) having a first fixed gear (328) and a second shaft (322) having second fixed gear (330) that engages the first fixed gear to cause the first shaft to rotate in an opposite direction than the second shaft. A first linkage (368) connecting the first shaft and the third shaft and includes a first one-way gear (336). A second linkage (366) connecting the second shaft and the third shaft and includes a second one-way gear (338). The third shaft outputs a unidirectional rotational motion.

Abstract: A drive mechanism (20) including a first shaft (324) having a first fixed gear (328) and a second shaft (322) having second fixed gear (330) that engages the first fixed gear to cause the first shaft to rotate in an opposite direction than the second shaft. A first linkage (368) connecting the first shaft and the third shaft and includes a first one-way gear (336). A second linkage (366) connecting the second shaft and the third shaft and includes a second one-way gear (338). The third shaft outputs a unidirectional rotational motion.

Abstract: An exercise device (20) includes a frame (22) and a drive mechanism (100) attached to the frame. The drive mechanism includes a first shaft (122) having a first fixed gear (128) and a second shaft (124) having a second fixed gear (130). The first fixed gear and the second fixed gear are mechanically linked to cause the first shaft to rotate in an opposite direction than the second shaft. A first linear input is mechanically linked to the first shaft and a second linear input is mechanically linked to the second shaft.