Abstract: The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof, wherein X1, X2, Y, R1, R2, RA, RB and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.

Abstract: An electrical device comprising a substrate of diamond material and elongate metal protrusions extending into respective recesses in the substrate. Doped semiconductor layers, arranged between respective protrusions and the substrate, behave as n type semiconducting material on application of an electric field, between the protrusions and the substrate, suitable to cause a regions of positive space charge within the semiconductor layers.

Abstract: A fuel system is provided that includes a fuel system frame and in some cases access steps. The frame can be mounted to a vehicle frame rail. Bracket assemblies can be coupled to the fuel system frame at a plurality of positions. The fuel tank can be mounted at neck portions thereof and can be supported on the frame rail between the neck portions, e.g., spaced a distance from the neck portions in a longitudinal direction of the fuel system. The access steps can be non-rectangular to provide a wide stepping portion even if the fuel system includes large tanks. The steps can be directly supported by an outside surface of the tank.

Abstract: A guitar comprises a body having a bottom and sides and a top. An outer perimeter of a top is attached to an upper rim of the sides, wherein an upper surface of the top is in tension due to bending of the top into a substantially domed shape and wherein the thickness of the top is thinner in the area of the outer perimeter than a central portion, thereby reducing the tension in the upper surface of the top in the area of the outer perimeter.

Abstract: Various aspects include a speaker including: an acoustic transducer for providing an audio output; a set of microphones for detecting a user voice command; and a controller coupled with the acoustic transducer and the set of microphones, wherein the controller is configured to: in response to detecting a power down command, switch the set of microphones from an active listening mode to a standby mode for a parking period, in response to detecting a power up command during the parking period, switch the set of microphones from the standby mode to the active listening mode after a first time period, and in response to detecting the power up command after expiration of the parking period switch the set of microphones from the standby mode to the active listening mode after a second time period that is greater than the first time period.

Abstract: Chemical reactors (10) and methods crack hydrocarbons in process fluids by accelerating the process fluid to a velocity greater than Mach 1 with an axial impulse impeller (40) and generating a shock wave (90) in the process fluid by decelerating it in a static diffuser (70) having diverging diffuser passages (72). Temperature increase of the process fluid downstream of the shockwave cracks the entrained hydrocarbons in a single pass, through a unidirectional flow path (F), within a single stage, without recirculating the process fluid for another pass through the same stage. In some embodiments, the turbomachine chemical reactor (110) has multiple successive stages of one or more axial impulse impellers (40A, 40B), paired with a diverging passage, static diffuser (70). Successive stages crack additional hydrocarbons by successively raising temperature of the flowing process fluid.

Abstract: Embodiments of the present disclosure relates to a string instrument, such as a guitar, having a neck support-fingerboard brace unit. The neck support-fingerboard brace unit is formed as a unitary unit or formed by fixedly attaching a neck support to a fingerboard brace before attaching the fingerboard brace to a guitar top. The solid connection between the neck support and the fingerboard brace allows the fingerboard brace, which rests on a guitar side, to provide support to the guitar neck, thus, reducing deformation in the guitar neck and the fret board.

Abstract: A saddle for a string instrument includes a string contact surface comprising a first material, a saddle end surface, generally opposite the string contact surface, comprising the first material, and two opposing side surfaces comprising a vibration-absorbent material different than the first material.

Abstract: An integrated circuit chip (die) may include a force mitigation system for reducing or mitigating under-pad stresses typically caused by wire bonding. The IC die may include wire bond pads and a force mitigation system formed below each wire bond pad. The force mitigation system may include a “shock plate” (e.g., metal region), a sealing layer located above the shock plate, and a force mitigation layer including an array of sealed voids between the metal region and the sealing layer. The sealed voids in the force mitigation layer may be defined by forming openings in an oxide dielectric layer and forming a non-conformal sealing layer over the openings to define an array of sealed voids. The force mitigation system may mitigate stresses caused by a wire bond on each wire bond pad, which may reduce or eliminate wire-bond-related damage to semiconductor devices located in the under-pad regions of the die.

Abstract: An integrated circuit chip (die) may include a force mitigation system for reducing or mitigating under-pad stresses typically caused by wire bonding. The IC die may include wire bond pads and a force mitigation system formed below each wire bond pad. The force mitigation system may include a “shock plate” (e.g., metal region), a sealing layer located above the shock plate, and a force mitigation layer including an array of sealed voids between the metal region and the sealing layer. The sealed voids in the force mitigation layer may be defined by forming openings in an oxide dielectric layer and forming a non-conformal sealing layer over the openings to define an array of sealed voids. The force mitigation system may mitigate stresses caused by a wire bond on each wire bond pad, which may reduce or eliminate wire-bond-related damage to semiconductor devices located in the under-pad regions of the die.

Abstract: A device for controlling electron flow is provided. The device comprises a cathode, an elongate electrical conductor embedded in a diamond substrate, an anode, and a control electrode provided on the substrate surface for modifying the electric field in the region of the end of the conductor. A method of manufacturing the device is also provided.

Abstract: A method for preparing exosomes or exosome-like vesicles packaged with a nucleic acid of interest is provided. In certain embodiments, the method may comprise: introducing into an exosome-producing cell a nucleic acid construct comprising the nucleic acid sequence of interest incorporated in a pre-miR-451 structural mimic, and allowing the cell to produce exosomes. Nucleic acid constructs, compositions, and uses thereof are also provided.

Abstract: The present invention relates to PCSK9 allosteric binding compounds of Formula I: (Formula (I)) and pharmaceutically acceptable salts thereof wherein X1, X2, Y, R1, R2, RA, RB and n are as defined herein. The present invention also relates to compositions which comprise an allosteric binding compound of the invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The invention further relates, inter alia, to methods for inducing PCSK9 protein degradation in a subject, and methods for treating atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions, comprising administering to a subject an effective amount of a compound or a pharmaceutically acceptable salt of the invention. The invention also provides a means for the in vitro labeling, detection and/or quantification of PCSK9 in biological samples.

Abstract: A method that receives, at a first compute server of a plurality of compute servers, a request from a client device, wherein the request is a request for a network resource. The method locates at least one content item in response to the request for the network resource, detects possible dynamic content in the at least one content item, compares a first dynamic value in a first copy of the at least one content item to a second dynamic value in a second copy of the at least one content item from an origin server, and stores the at least one content item in a local cache as a safe content item to be returned for subsequent requests of the at least one content item in response to the first dynamic value matching the second dynamic value.

Abstract: A method for manufacturing a thin film resistor (TFR) module includes forming a TFR element over a substrate; annealing the TFR element to reduce the temperature coefficient of resistance (TCR) of the TFR element; and after forming and annealing the TFR element, forming a pair of conductive TFR heads in contact with the TFR element. By forming the TFR element before the TFR heads, the TFR element may be annealed without affecting the TFR heads, and thus may be formed from various materials with different annealing properties, e.g., SiCCr and SiCr. Thus, the TFR element may be annealed to achieve a near 0 ppm TCR, without affecting the later-formed TFR heads. The TFR module may be formed using a damascene CMP approach and using only a single added mask layer. Further, vertically-extending “ridges” at edges of the TFR element may be removed or eliminated to further improve the TCR performance.

Abstract: A software input string is received and tokenized into a sequence of tokens. The sequence of tokens is applied to a trained sequence-dependent lock/unlock classifier so that each of the tokens is classified as a token that should be locked, or remain unlocked, for subsequent translation. The software input string is converted to a converted string, in which the locked tokens are identified and the converted string is submitted for machine translation. A machine translation result is received and converted so that the locked tokens are replaced in the machine translation result, to obtain a translated software string.

Abstract: A request is received from a client device over a Virtual Private Network (VPN) tunnel. The request is received at a first one of a plurality of edge servers of a distributed cloud computing network. A destination of the request is determined and an optimized route for transmitting the request toward an origin server is determined. The optimized route is based at least in part on probe data between edge servers of the distributed cloud computing network. The request is transmitted to a next hop as defined by the optimized route.

Abstract: A computing system for obtaining authentication credentials from users can be configured to perform operations. The operations can include receiving, at a user computing device from a server computing device, data describing a security query requesting an authentication credential; determining, by the user computing device, an input format for receiving a user input that describes the requested authentication credential; receiving, by the user computing device, the user input according to the input format determined by the user computing device, the user input describing the requested authentication credential; and transmitting, from the user computing device to the server computing device, data describing the requested authentication credential.

Abstract: A computer-implemented method to provide information characterizing real-estate market conditions within a geographic sub-region included within a larger geographic region is described herein. An indication of the geographic sub-region is received from a user. A memory device on which is stored information characterizing a set of parcels of real property that have been listed for sale is accessed. A parcel of real property located in the sub-region and for which a purchase offer has been made is identified from the stored information. If a purchase transaction for the parcel of real property has not closed, a range of a plurality of values characterizing the purchase offer is provided in at least one graphical user interface. If a purchase transaction for the parcel of real property has closed, a specific value of the plurality of values characterizing the purchase offer is provided in at least one graphical user interface.

Abstract: A de-icing assembly for a surface of an aircraft includes a carcass, seams, inflation passages, a manifold, and a reinforcement stitchline. The carcass includes a first layer, a second layer, and a carcass centerline. The seams are sewn into the carcass and join the first and second layers of the carcass together. The inflation passages are formed by the seams and are disposed between the first and second layers of the carcass. The manifold includes a width and a manifold centerline oriented approximately perpendicular to the carcass centerline and is fluidly connected to and is disposed beneath the carcass. The first reinforcement stitchline is sewn into the carcass adjacent to one of the plurality of seams and is disposed at a location on the carcass overlapping with the manifold. The first reinforcement stitchline is disposed approximately perpendicular to the manifold centerline and extends across the width of the manifold.