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: An introducer assembly includes a first actuating mechanism for actuating a constraining sheath between a first state releasably constraining a vascular implant and a second state allowing deployment of the vascular implant; a second actuating mechanism for actuating a blocking mechanism between a blocked state for blocking other functions of the handle and an unblocked state for allowing operation of the other functions of the handle; and an operating knob operatively coupled to both of the first and second actuating mechanisms for concurrent operation of both of the first and second actuating mechanisms in response to actuation of the operating knob.

Abstract: A system for endoluminal delivery of a medical device, wherein the medical device includes a bifurcated stent graft having a trunk, a first leg and a second leg shorter than the first leg. The system includes a sheath having a tubular wall having a cylindrical inner surface defining a lumen for receiving the stent graft therein to constrain the stent graft toward a delivery configuration suitable for endoluminal delivery, and a generally cylindrical core member extending through the lumen. The core member has a first annular surface for engaging an end of the first leg. The core has a second annular surface for engaging an end of the second leg while at least the end of the second leg remains constrained by the sheath.

Abstract: A system for endoluminal delivery of a medical device, wherein the medical device includes a bifurcated stent graft having a trunk, a first leg and a second leg shorter than the first leg. The system includes a sheath having a tubular wall having a cylindrical inner surface defining a lumen for receiving the stent graft therein to constrain the stent graft toward a delivery configuration suitable for endoluminal delivery, and a generally cylindrical core member extending through the lumen. The core member has a first annular surface for engaging an end of the first leg. The core has a second annular surface for engaging an end of the second leg while at least the end of the second leg remains constrained by the sheath.

Abstract: According to an example of the present disclosure, an apparatus to store slack in a system line for a medical device is disclosed. The apparatus comprises a plurality of slack pockets arranged in series. The system line is configured to form a slack loop into each slack pocket, the plurality of slack pockets isolating the slack loops from each other. The plurality of slack pockets are configured such that when tension is applied to the system line, slack is dispensed by each slack loop straightening from each slack pocket without tangling with another one of the slack loops.

Abstract: The present disclosure describes treatment of the vasculature of a patient with an expandable implant. The implant is constrained to a reduced delivery diameter for delivery within the vasculature by at least one sleeve. The implant can be constrained to other diameters, such as an intermediate diameter. The sleeves can be expanded, allowing for expansion of the diameter of the expandable implant, by disengaging a coupling member from the sleeve or sleeves from outside of the body of the patient. The expandable implant can comprise a steering line or lines which facilitate bending and steering of the expandable implant through the vasculature of a patient.

Abstract: An endoprosthesis delivery system includes a branched endoprosthesis having a long leg and a short leg, each leg having an end, the short leg including a tail that extends beyond the end of the short leg, a constraint attached to at least a portion of the long leg prior to deployment. The constraint also retains at least a portion of the tail. The constraint is configured to release both the long leg and the tail when the branched endoprosthesis is fully deployed.

Abstract: The present disclosure describes treatment of the vasculature of a patient with an expandable implant. The implant is constrained to a reduced delivery diameter for delivery within the vasculature by at least one sleeve. The implant can be constrained to other diameters, such as an intermediate diameter. The sleeves can be expanded, allowing for expansion of the diameter of the expandable implant, by disengaging a coupling member from the sleeve or sleeves from outside of the body of the patient. The expandable implant can comprise a steering line or lines which facilitate bending and steering of the expandable implant through the vasculature of a patient.

Abstract: An introducer assembly includes a first actuating mechanism for actuating a constraining sheath between a first state releasably constraining a vascular implant and a second state allowing deployment of the vascular implant; a second actuating mechanism for actuating a blocking mechanism between a blocked state for blocking other functions of the handle and an unblocked state for allowing operation of the other functions of the handle; and an operating knob operatively coupled to both of the first and second actuating mechanisms for concurrent operation of both of the first and second actuating mechanisms in response to actuation of the operating knob.

Abstract: An introducer assembly includes a first actuating mechanism for actuating a constraining sheath between a first state releasably constraining a vascular implant and a second state allowing deployment of the vascular implant; a second actuating mechanism for actuating a blocking mechanism between a blocked state for blocking other functions of the handle and an unblocked state for allowing operation of the other functions of the handle; and an operating knob operatively coupled to both of the first and second actuating mechanisms for concurrent operation of both of the first and second actuating mechanisms in response to actuation of the operating knob.

Abstract: An endoprosthesis delivery system includes a branched endoprosthesis having a long leg and a short leg, each leg having an end, the short leg including a tail that extends beyond the end of the short leg, a constraint attached to at least a portion of the long leg prior to deployment. The constraint also retains at least a portion of the tail. The constraint is configured to release both the long leg and the tail when the branched endoprosthesis is fully deployed.

Abstract: Various aspects of the present disclosure are directed toward apparatuses, systems, and methods for example device delivery. The apparatuses, systems, and methods may include an actuation wire coupled to the expandable device at one or more locations thereon, the actuation wire being configured to steer the expandable device during delivery.

Abstract: A system for endoluminal delivery of a medical device, wherein the medical device includes a bifurcated stent graft having a trunk, a first leg and a second leg shorter than the first leg. The system includes a sheath having a tubular wall having a cylindrical inner surface defining a lumen for receiving the stent graft therein to constrain the stent graft toward a delivery configuration suitable for endoluminal delivery, and a generally cylindrical core member extending through the lumen. The core member has a first annular surface for engaging an end of the first leg. The core has a second annular surface for engaging an end of the second leg while at least the end of the second leg remains constrained by the sheath.

Abstract: An introducer assembly includes a first actuating mechanism for actuating a constraining sheath between a first state releasably constraining a vascular implant and a second state allowing deployment of the vascular implant; a second actuating mechanism for actuating a blocking mechanism between a blocked state for blocking other functions of the handle and an unblocked state for allowing operation of the other functions of the handle; and an operating knob operatively coupled to both of the first and second actuating mechanisms for concurrent operation of both of the first and second actuating mechanisms in response to actuation of the operating knob.

Abstract: A system for endoluminal delivery of a medical device, wherein the medical device includes a bifurcated stent graft having a trunk, a first leg and a second leg shorter than the first leg. The system includes a sheath having a tubular wall having a cylindrical inner surface defining a lumen for receiving the stent graft therein to constrain the stent graft toward a delivery configuration suitable for endoluminal delivery, and a generally cylindrical core member extending through the lumen. The core member has a first annular surface for engaging an end of the first leg. The core has a second annular surface for engaging an end of the second leg while at least the end of the second leg remains constrained by the sheath.

Abstract: The present disclosure describes treatment of the vasculature of a patient with an expandable implant. The implant is constrained to a reduced delivery diameter for delivery within the vasculature by at least one sleeve. The implant can be constrained to other diameters, such as an intermediate diameter. The sleeves can be expanded, allowing for expansion of the diameter of the expandable implant, by disengaging a coupling member from the sleeve or sleeves from outside of the body of the patient. The expandable implant can comprise a steering line or lines which facilitate bending and steering of the expandable implant through the vasculature of a patient.

Abstract: The present disclosure describes treatment of the vasculature of a patient with an expandable implant. The implant is constrained to a reduced delivery diameter for delivery within the vasculature by at least one sleeve. The implant can be constrained to other diameters, such as an intermediate diameter. The sleeves can be expanded, allowing for expansion of the diameter of the expandable implant, by disengaging a coupling member from the sleeve or sleeves from outside of the body of the patient. The expandable implant can comprise a steering line or lines which facilitate bending and steering of the expandable implant through the vasculature of a patient.

Abstract: A catheter assembly includes a tubular first and second catheters in fluid communication with each other, wherein the second catheter includes a port fitting and can be elastically longitudinally strained to cinch the first and second catheters together.

Abstract: An introducer assembly having a handle, at least one fiber operatively coupling at least one handle with one or more functions of the handle; and having a fiber routing system that allows a predetermined amount of slack to be created during assembly in at least one fiber so as to delay by a desired amount of time actuation of the one or more functions of the handle associated with the at least one fiber during operation of the handle.

Abstract: An introducer assembly includes a first actuating mechanism for actuating a constraining sheath between a first state releasably constraining a vascular implant and a second state allowing deployment of the vascular implant; a second actuating mechanism for actuating a blocking mechanism between a blocked state for blocking other functions of the handle and an unblocked state for allowing operation of the other functions of the handle; and an operating knob operatively coupled to both of the first and second actuating mechanisms for concurrent operation of both of the first and second actuating mechanisms in response to actuation of the operating knob.