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: Various embodiments include a device for driving a fastener into tissue, including a handle having a first and second end. A shank extends from the first end of the handle and terminates in a head. An inertial measurement unit (“IMU”) is disposed at the second end of the handle. At least one torque sensor is incorporated in the device. At least one of an indicator or a transmitter is operably coupled to the IMU and the torque sensor. A method of driving a fastener into a tissue with a driver includes recording a previous state and a current state, and using the previous state and current state to predict mechanical properties of the tissue and the optimal torque to be applied. In various embodiment the device predicts a future state of the fastener. The driver notifies the user if the optimal torque has been reached or whether another state has been detected.

Abstract: Various embodiments include a device for driving a fastener into tissue, including a handle having a first and second end. A shank extends from the first end of the handle and terminates in a head. An inertial measurement unit (“IMU”) is disposed at the second end of the handle. At least one torque sensor is incorporated in the device. At least one of an indicator or a transmitter is operably coupled to the IMU and the torque sensor. A method of driving a fastener into a tissue with a driver includes recording a previous state and a current state, and using the previous state and current state to predict mechanical properties of the tissue and the optimal torque to be applied. In various embodiment the device predicts a future state of the fastener. The driver notifies the user if the optimal torque has been reached or whether another state has been detected.