Abstract: The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

Abstract: Spacecraft servicing systems include a spacecraft servicing device and at least one mission extension pod comprising at least one spacecraft servicing component. The spacecraft servicing device is configured to transfer the at least pod to a target spacecraft in order to service the target spacecraft with the at least one spacecraft servicing component of the at least one pod. Spacecraft servicing pods configured to be supplied to a spacecraft with a spacecraft servicing device include at least one spacecraft servicing component.

Abstract: Provided herein are tetracyclic oxazepinyl compounds useful in the treatment on cancers.

Abstract: The subject matter described herein is directed to myelin-promoting compounds of Formula I and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for the treatment of disorders, such as myelin-related disorders.

Abstract: Provided herein are acyclic oxazepinyl compounds useful in the treatment on cancers.

Abstract: Cinnoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the cinnoline compounds.

Abstract: Provided herein are aza-tetracyclic oxazepinyl compounds useful in the treatment of cancers.

Abstract: One variation of a system includes: a cam block mounted to a deck of a scooter and defining cam lobes arranged about a pivot feature and cam heels between the set of cam lobes; a pivot block pivotably coupled to the pivot feature and defining followers riding over the cam lobes; a pair of wheel uprights locating a pair of wheel assemblies; a first lateral link extending between and coupled to the pair of wheel uprights and pivotably coupled to the pivot block; a second lateral link extending between and coupled to the pair of wheel uprights, vertically offset from the first lateral link, and coupled to the pivot block between pair of wheel uprights; and a spring element driving the followers of the pivot block into cam heels to bias the second lateral link toward a neutral position.

Abstract: A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are defined herein, are useful as inhibitors of one or more Janus kinases. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient are disclosed.

Abstract: Provided herein are aza-tetracyclic oxazepinyl compounds useful in the treatment of cancers.

Abstract: One variation of a system includes: a cam block mounted to a deck of a scooter and defining cam lobes arranged about a pivot feature and cam heels between the set of cam lobes; a pivot block pivotably coupled to the pivot feature and defining followers riding over the cam lobes; a pair of wheel uprights locating a pair of wheel assemblies; a first lateral link extending between and coupled to the pair of wheel uprights and pivotably coupled to the pivot block; a second lateral link extending between and coupled to the pair of wheel uprights, vertically offset from the first lateral link, and coupled to the pivot block between pair of wheel uprights; and a spring element driving the followers of the pivot block into cam heels to bias the second lateral link toward a neutral position.

Abstract: 3-Carbonylamino-8-aminoisoquinoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline compounds.

Abstract: A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are defined herein, are useful as inhibitors of one or more Janus kinases. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a Janus kinase activity in a patient are disclosed.

Abstract: Provided herein are tetracyclic oxazepinyl compounds useful in the treatment on cancers.

Abstract: One variation of a system includes: a cam block mounted to a deck of a scooter and defining cam lobes arranged about a pivot feature and cam heels between the set of cam lobes; a pivot block pivotably coupled to the pivot feature and defining followers riding over the cam lobes; a pair of wheel uprights locating a pair of wheel assemblies; a first lateral link extending between and coupled to the pair of wheel uprights and pivotably coupled to the pivot block; a second lateral link extending between and coupled to the pair of wheel uprights, vertically offset from the first lateral link, and coupled to the pivot block between pair of wheel uprights; and a spring element driving the followers of the pivot block into cam heels to bias the second lateral link toward a neutral position.

Abstract: One variation of a system includes: a cam block mounted to a deck of a scooter and defining cam lobes arranged about a pivot feature and cam heels between the set of cam lobes; a pivot block pivotably coupled to the pivot feature and defining followers riding over the cam lobes; a pair of wheel uprights locating a pair of wheel assemblies; a first lateral link extending between and coupled to the pair of wheel uprights and pivotably coupled to the pivot block; a second lateral link extending between and coupled to the pair of wheel uprights, vertically offset from the first lateral link, and coupled to the pivot block between pair of wheel uprights; and a spring element driving the followers of the pivot block into cam heels to bias the second lateral link toward a neutral position.

Abstract: A unified cache subsystem includes a data memory configured as both a shared memory and a local cache memory. The unified cache subsystem processes different types of memory transactions using different data pathways. To process memory transactions that target shared memory, the unified cache subsystem includes a direct pathway to the data memory. To process memory transactions that do not target shared memory, the unified cache subsystem includes a tag processing pipeline configured to identify cache hits and cache misses. When the tag processing pipeline identifies a cache hit for a given memory transaction, the transaction is rerouted to the direct pathway to data memory. When the tag processing pipeline identifies a cache miss for a given memory transaction, the transaction is pushed into a first-in first-out (FIFO) until miss data is returned from external memory. The tag processing pipeline is also configured to process texture-oriented memory transactions.

Abstract: Cinnoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the cinnoline compounds.

Abstract: 3-Carbonylaminoisoquinoline compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylaminoisoquinoline compounds.

Abstract: The present invention provides for compounds of Formula I-I and embodiments and salts thereof for the treatment of diseases (e.g., neurodegenerative diseases). R1, R2, R3, X1, X2, A and Cy variable in Formula I-I all have the meaning as defined herein.