Abstract: The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof; wherein: n is 1 or 2; X is CH or N; Y is selected from CH and C—F; Z is selected from C—Rz and N; R1 is selected from: -(Alk1)t-Cyc1; wherein t is 0 or 1; Optionally substituted C1-6 acyclic hydrocarbon groups R2 is selected from hydrogen; halogen; and C1-3 hydrocarbon groups optionally substituted with one or more fluorine atoms; R3 is hydrogen or a group L1-R7; R4 is selected from hydrogen; methoxy; and optionally substituted C1-3 alkyl; and R4a is selected from hydrogen and a C1-3 alkyl group; wherein Rz, Alk1, Cyc1, L1 and R7 are defined herein; provided that the compound is other than 6-benzyl-3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and 3-{2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}-7,8-dihydro-1,6-naphthyridin-5(6H)-one and salts and tautomers thereof.

Abstract: An incremental forming machine and a process are disclosed that comprise selecting a blank and selecting a stylus tool that has a tip at one end. The stylus tool may be heated to a desired temperature before contacting the blank with the stylus tool to change a characteristic of the blank or part. The stylus tool apparatus may include a tip on an end of a shaft and a resistance heating element disposed inside the tip. Alternatively, the stylus tool apparatus may include an induction heating coil disposed around the tip. The tip of the stylus tool may have a rotatable ball that engages the blank or part.

Abstract: The present disclosure is directed toward a method that includes simulating, by an adhesive analytic model, transformation of at least one vehicular joint joined by a selected adhesive based on one or more system variables, and outputting, by the adhesive analytic model, an adhesive analysis identifying deformation for the selected adhesive along the at least one vehicular joint based on the simulated transformation and a deformation rating scale.

Abstract: An incremental forming machine and a process are disclosed that comprise selecting a blank and selecting a stylus tool that has a tip at one end. The stylus tool may be heated to a desired temperature before contacting the blank with the stylus tool to change a characteristic of the blank or part. The stylus tool apparatus may include a tip on an end of a shaft and a resistance heating element disposed inside the tip. Alternatively, the stylus tool apparatus may include an induction heating coil disposed around the tip. The tip of the stylus tool may have a rotatable ball that engages the blank or part.

Abstract: An incremental forming machine and a process are disclosed that comprise selecting a blank and selecting a stylus that has a tip at one end. The stylus may be heated to a desired temperature before contacting the blank with the stylus to change a characteristic of the blank or part. The stylus apparatus may include a tip on an end of a shaft and a resistance heating element disposed inside the tip. Alternatively, the stylus apparatus may include an induction heating coil disposed around the tip. The tip of the stylus may have a rotatable ball that engages the blank or part.

Abstract: A temporary restraining device is provided that includes a head portion, a central body positioned below the head portion, an upper gap defined between the head portion and the central body, and a base portion positioned below the central body, a lower gap defined between the base portion and the central body. The temporary restraining device maintains a predetermined offset between workpieces disposed within the upper and lower gaps for subsequent manufacturing operations.

Abstract: A method of reducing the cycle time required for flow-drill screw operations by providing a dimple on a part that is engaged by a flow-drill screw. A tip of the flow-drill screw engages a contact band at a location spaced from the tip of the distal end of the flow-drill screw and base portion of the dimple. Friction between the flow-drill screw tip and dimple creates a heat concentration area and results in displaced material fanning a threaded collar. The flow-drill screw is secured by the threads of the threaded collar.

Abstract: The present disclosure is directed toward a method that includes simulating, by an adhesive analytic model, transformation of at least one vehicular joint joined by a selected adhesive based on one or more system variables, and outputting, by the adhesive analytic model, an adhesive analysis identifying deformation for the selected adhesive along the at least one vehicular joint based on the simulated transformation and a deformation rating scale.

Abstract: A method of protecting a repair joint having at least two workpieces joined by a fastener includes selecting a preformed functional body based on at least one joint characteristic and applying the preformed functional body to cover the fastener and at least a portion of one of the workpieces. Generally, the preformed functional body inhibits contamination or moisture ingress at a joint interface, and especially in a repair operation. The preformed functional body in one form defines a material that undergoes a color change to indicate a state of cure, and in another form is cured by UV light, moisture, or heat after application.

Abstract: The present disclosure includes a method for coating a vehicle body-in-white (BIW) in a tank of processing fluid. In one form, the method includes lowering the vehicle BIW in a tank of processing fluid, rotating the vehicle BIW around its lateral axis until the vehicle BIW is completely submerged in the processing fluid, and simultaneously conveying the vehicle BIW along a longitudinal axis of the tank while rotating the vehicle BIW around its longitudinal axis in a “corkscrew” type movement.

Abstract: Systems and methods for reducing or eliminating corrosion in joined materials are disclosed, for example, multi-material joints. The system may include a sealing device including a body and a tip. The tip may be configured to form a seal around a local region of a material having a fastener disposed therein. The sealing device may be configured to apply a sealant material from the tip to the local region and form a cap thereover. The tip of the sealing device may form a cavity between the material and the inner surface of the tip, which may be filled with the sealant material to form the cap. In one embodiment, the sealing device may be configured to couple to the joining device that inserted the fastener. This may allow for accurate and robust placement of the sealant material directly after the fastener is inserted.

Abstract: A fastener for use in joining workpieces, for example automotive body parts such as a roof to a body frame member, is provided that includes a plastically deformable head portion, a platform disposed at a bottom of the head portion, and a distal end portion extending from the platform and defining at least one of elastically deformable locking member. The head portion is heat staked to one workpiece, and the elastically deformable locking member engages another workpiece to secure the workpieces together. The platform provides spacing, or a bond gap in one form, between the workpieces, and a material and geometry of the fastener are configured to compensate for a difference in thermal expansion of the workpieces.

Abstract: Disclosed herein are humanized anti-LGR5 antibodies for the treatment of cancer. Antibodies disclosed herein may bind LGR5 without disrupting LGR5-RSPO1 binding or signaling, and may disrupt LGR5 signaling through Wnt that is independent of RSPO1. Also disclosed are heavy and light chain polypeptide sequences for the biding of LGR5, for example without disrupting LGR5-RSPO binding or signaling.

Abstract: A temporary restraining device is provided that includes a head portion, a central body positioned below the head portion, an upper gap defined between the head portion and the central body, and a base portion positioned below the central body, a lower gap defined between the base portion and the central body. The temporary restraining device maintains a predetermined offset between workpieces disposed within the upper and lower gaps for subsequent manufacturing operations.

Abstract: An assembly is provided that includes a castellated upper substrate defining a plurality of alternating troughs and ridges. A lower substrate is disposed adjacent the upper castellated substrate, and an adhesive material is disposed between the castellated upper substrate and the lower substrate. A fastener extends through a trough of the castellated upper substrate, through the adhesive material, and into the lower substrate. A method of assembling the upper and lower substrates is also provided, which includes plastically deforming the castellated upper substrate to reduce an intake of air between the substrates.

Abstract: A coffee pod is described with an improved sealing surface for a filter disposed within the pod. The improved sealing surface provides better adherence between the filter and a sidewall of the pod so that unadhered portions are minimized and operation is improved. A coffee pod is also described with an improved foot structure having a configuration and thickness designed to minimize buckling while also utilizing a cost-efficient amount of material.

Abstract: Disclosed herein are humanized anti-LGR5 antibodies for the treatment of cancer. Antibodies disclosed herein may bind LGR5 without disrupting LGR5-RSPO1 binding or signaling, and may disrupt LGR5 signaling through Wnt that is independent of RSPO1. Also disclosed are heavy and light chain polypeptide sequences for the biding of LGR5, for example without disrupting LGR5-RSPO binding or signaling.

Abstract: A method of reducing the cycle time required for flow-drill screw operations by providing a dimple on a part that is engaged by a flow-drill screw. A tip of the flow-drill screw engages a contact band at a location spaced from the tip of the distal end of the flow-drill screw and base portion of the dimple. Friction between the flow-drill screw tip and dimple creates a heat concentration area and results in displaced material fanning a threaded collar. The flow-drill screw is secured by the threads of the threaded collar.

Abstract: The present disclosure includes a method for coating a vehicle body-in-white (BIW) in a tank of processing fluid. In one form, the method includes lowering the vehicle BIW in a tank of processing fluid, rotating the vehicle BIW around its lateral axis until the vehicle BIW is completely submerged in the processing fluid, and simultaneously conveying the vehicle BIW along a longitudinal axis of the tank while rotating the vehicle BIW around its longitudinal axis in a “corkscrew” type movement.

Abstract: A method of reducing the cycle time required for flow-drill screw operations by providing a dimple on a part that is engaged by a flow-drill screw. A tip of the flow-drill screw engages a contact band at a location spaced from the tip of the distal end of the flow-drill screw and base portion of the dimple. Friction between the flow-drill screw tip and dimple creates a heat concentration area and results in displaced material forming a threaded sleeve. The flow-drill screw is secured by the threads of the threaded sleeve to secure the top part to the bottom part.