Abstract: The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: A floating barrier system has a plurality of connected floating barrier units. Capture net segments are positioned on the floating barrier units by support post members, forming a barrier to vessel passage. Lanyards attach the ends of the capture net segments to the floating barrier units. Upon a vessel striking the capture net segments with sufficient force, the capture nets detach from the support post members and/or pull the support post members over, and the forces from the vessel are transferred via the lanyards to the floating barrier unit. The vessel is prevented from fully passing over the floating barrier unit, thus itself forming a barrier to passage by other vessels.

Abstract: A fluid delivery device has a syringe barrel-type reservoir with plunger, and plunger driver assembly comprising double-acting, telescoping lead screws that is located behind and outside of the barrel. Simultaneously and counter-rotating sleeve screw and center screw telescope out of a nested configuration of the plunger driver assembly and into the reservoir at a rate of double their individual and equal pitch and lead parameters when the sleeve screw is rotated. A threaded nut and gear anchor disposed on an end of the barrel receive the sleeve screw and the threaded nut causes the sleeve screw to translate and rotate in response to motor operation. A distal end of the center screw can be keyed to a plunger pusher for anti-rotation constraint when the motor is imparting rotation on the threaded nut and sleeve screw.

Abstract: The invention provides a compound of compound of formula (I): or a salt thereof, wherein R1, n, L, and X have any of the values described herein, as well as compositions and lipid nanoparticles comprising a compound of formula I, and their use for delivering therapeutic agents such as siRNA and mRNA.

Abstract: A hard seal, positive displacement pump is provided which may be included within a fluid delivery system. The pump includes a housing, a sleeve disposed radially within the housing, and a piston disposed radially within the sleeve. An outer shape of a first end of the sleeve contacts a correspondingly-shaped inner shape of a first end of the housing, thereby sealing the first end of the sleeve within the first end of the housing. The piston is radially and axially moveable within the sleeve, and an axially-reciprocating motion of the piston within the sleeve opens and closes a pump chamber defined between a first end of the piston and a first end of the sleeve.

Abstract: A fluid delivery device has a syringe barrel with reservoir chamber for fluid, a plunger that translates along a longitudinal axis to expel fluid, and a pusher dimensioned to translate within the barrel and coupled to a drive mechanism to controllably contact and move the plunger. The pusher contacts the plunger at its mechanical center to reduce tilt in the plunger. Contact faces of the pusher and plunger cooperate as a ball joint to minimize non-axial forces on the plunger face. The pusher can have a protrusion of various lengths extending toward and being at least partially received in a recess of various depths in the plunger. The pusher is rigidly connected to a drive mechanism for anti-rotation. The pusher can have scalloped edges for air venting, and apertures for cooperating with protrusions on the drive mechanism to prevent bottoming out the plunger when filling.

Abstract: The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: A collapsible protective helmet (10) comprises an impact-resistant base body (11) intended to encircle the head of a wearer and an impact-resistant crown (12) coupled to the base body by coupling means to be movable between a protective position in which the crown is supported by the base body in an orientation in which the crown covers the top of the head of the wearer and a stored position inverted relative to the protective position in which the crown is supported by, but nested in, the base body. The helmet further comprises releasable locking means for locking the base body (11) and crown (12) together in each of the two positions of the crown.

Abstract: A waterbody access barrier system has one or more floating barrier segments, and a first floating gate segment for blocking an opening in the barrier system. The first floating gate segment has a latching system to connect it to a capture gear, which is at a fixed barrier termination point or on a second floating gate segment. One or more thrusters are mounted on at least the first floating gate segment. The latching system, and the thrusters, are autonomously or semi-autonomously controlled by a control system, which receives positional signals, for example from a global positioning system (GPS) and/or a light detection and ranging system (LiDAR) operatively connected to the first floating gate segment, and moves the first floating gate segment accordingly.

Abstract: A delivery device for delivering medicament, such as insulin, to a patient includes a housing and a base enclosing an inner cavity. Enclosed within the housing is a reservoir for containing a medicament, a delivery mechanism for delivering the medicament to the patient, and a pump in fluid communication with the reservoir and delivery mechanism. The base has an integrally formed fluid channel covered by a flexible membrane in fluid communication with the reservoir and the delivery mechanism. A peristaltic pump mechanism includes a cam assembly having a plurality of cams and cam follower assembly with a plurality of protrusions to sequentially engaging the flexible membrane to advance the fluid through fluid channel.

Abstract: A rotary pump for a fluid metering system is provided. The rotary pump reciprocates, and is reversed by a signal from a limit switch that is deflected by an actuator arm on a rotating sleeve of the pump system. The sleeve receives a gasket that forms a seal between the sleeve and the housing, the gasket having an opening surrounding a side hole of the sleeve to permit fluid to pass through the side hole between a pump volume and an inlet port or outlet port of the housing.

Abstract: An apparatus and related methods for constructing articles with cured pressure-sensitive adhesives comprising (i) a coater that applies a curable adhesive to a membrane; (ii) a cross-linking apparatus adapted to receive said membrane with said curable adhesive, said cross-linking apparatus comprising a light source positioned a first predetermined height above an aperture plate having an aperture therethrough, wherein said aperture plate is positioned a second predetermined height, said first predetermined height and said second predetermined height selected to define an exposure area of light emitted from said light source on to said curable adhesive to form a composite product; and (iii) a roll adapted to receive said composite product, said roll adapted to control a speed at which said membrane with said curable adhesive is exposed to light from said light source.

Abstract: Aspects of articulating devices and methods are disclosed. An exemplary articulating device may comprise an interior core with a reinforcing extending along a central axis, an exterior layer bonded to the interior core by an interface, and a lumen extending through the exterior layer, exterior of the reinforcing element, and parallel to the central axis. A steering wire may be moveable in the lumen to articulate a distal end of the device relative to the central axis in response to a force applied to the steering wire. Related methods of manufacturing an articulating device are also described.

Abstract: Medication delivery system including a container, reservoir, or chamber for medium or fluid, and a mechanism or driving components configurable outside of medium or fluid chamber for advancing a plunger to dispense medium or fluid. The system can include syringe-style drug container, reservoir, or chamber, containing medium or fluid dispensable by advancing plunger disposed inside the container, where the container includes a sliceable portion and where a cutter or slicer is configurable on plunger holder or pusher behind plunger such that cutter cuts through sliceable portion of container as plunger is advanced dispensing medium out of container. The present disclosure is further directed to a patch pump comprising the system as described above. The present disclosure is further directed to a medicament delivery device comprising the system as described above.

Abstract: The present invention provides compositions comprising mRNA molecules encapsulated within lipid particles. The lipid particles comprise a cationic lipid, a non-cationic lipid, and an mRNA molecule that is encapsulated within the lipid particle. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease. The invention also provides cationic lipids that are useful for preparing the compositions of the invention.

Abstract: The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Abstract: The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel, trialkyl, cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses.

Abstract: Pump subsystem for fluid delivery (e.g., in a wearable patch pump) comprises a fluid chamber with pumping motion and a valve shaft assembly with valving motion, both being driven by the same drive mechanism. Fluid chamber has variable volume chamber provided by a piston driven by the drive mechanism and translated relative to a plug in the pump housing. Piston extends the fluid chamber during an intake stroke and retracts the fluid chamber during a discharge stroke. Valve assembly has at least one valve shaft controllably translated by the drive mechanism to selectively align a first throughway with an opening in the pump chamber and a fluid intake port for an intake stroke to draw fluid into the fluid chamber, and align a second throughway with the opening in the pump hamber and a fluid discharge port for an discharge stroke to discharge fluid from the fluid chamber.

Abstract: A pump subsystem for fluid delivery (e.g., in a wearable patch pump) is provided wherein pumping action is generated by linear piston movement that pulls a plug, which is interconnected to the piston between two mechanical extremes or end stops in a telescopic or variable volume fluid chamber. Such interconnection enables piston and plug to move a certain distance with respect to each other that corresponds to a predefined swept volume of the pump subsystem. Telescoping-like effect of relative piston and plug movement provides for intake and discharge of fluid with respect to the fluid chamber. Movement of plug within piston can be enabled by the friction of seals placed on the plug, which serve to provide resistance to piston motion and therefore force translation motion of the plug to lag relative to the piston translation motion during portions of the pump cycle.