Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15,016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15,016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: A percutaneous system in which tubular retractors are utilized as a means of access, visualization, and a controlled orientation for preparation of posterior spinal elements and delivery of graft material for posterior spinal fusion. The tubular retractors are affixed to screw extensions to rotate and articulate relative to multi-axial screws percutaneously inserted into respective pedicles of vertebral bodies. The procedure is done bilaterally, although it could be performed unilaterally in cases where the anatomy or surgeon preference dictates. A number of different deployable graft concepts are disclosed, the primary features being to allow for creation of a graft space volume and a means for delivery of the graft material preferred by the surgeon.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: The invention disclosed herein provides systems and methods for simplifying augmented reality or virtual augmented reality based communication collaboration, and decision making through a streamlined user interface framework that enables both synchronous and asynchronous interactions in immersive environments.

Abstract: The invention disclosed herein provides systems and methods for simplifying augmented reality or virtual augmented reality based communication collaboration, and decision making through a streamlined user interface framework that enables both synchronous and asynchronous interactions in immersive environments.

Abstract: Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta-1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.

Abstract: The present invention provides organic molecules and methods thereof for reactions between organoboron reagents and double bonds, such as imines or carbonyls, to stereoselectively provide chiral products including amines and alcohols, entities useful for the preparation of biologically active molecules.

Abstract: A percutaneous system in which tubular retractors are utilized as a means of access, visualization, and a controlled orientation for preparation of posterior spinal elements and delivery of graft material for posterior spinal fusion. The tubular retractors are affixed to screw extensions to rotate and articulate relative to multi-axial screws percutaneously inserted into respective pedicles of vertebral bodies. The procedure is done bilaterally, although it could be performed unilaterally in cases where the anatomy or surgeon preference dictates. A number of different deployable graft concepts are disclosed, the primary features being to allow for creation of a graft space volume and a means for delivery of the graft material preferred by the surgeon.

Abstract: The present invention provides organic molecules and methods thereof for reactions between organoboron reagents and double bonds, such as imines or carbonyls, to stereoselectively provide chiral products including amines and alcohols, entities useful for the preparation of biologically active molecules.

Abstract: A surgical access system includes retractor for creating an access path between an incision site and a surgical site. The retractor includes a frame having a base member and a pair of generally curved rails extending therefrom. A tubular member is coupled to the frame and includes first and second blade portions that are capable of relative movement with respect to each other by movement on the curved rails. A method of inserting the retractor into a patient includes inserting a guide rod over a guide wire, locating an obturator in the retractor, inserting the obturator and retractor over the guide rod, and removing both the guide rod and obturator to leave the retractor in the body to provide the access path.

Abstract: A surgical access system includes retractor for creating an access path between an incision site and a surgical site. The retractor includes a frame having a base member and a pair of generally curved rails extending therefrom. A tubular member is coupled to the frame and includes first and second blade portions that are capable of relative movement with respect to each other by movement on the curved rails. A method of inserting the retractor into a patient includes inserting a guide rod over a guide wire, locating an obturator in the retractor, inserting the obturator and retractor over the guide rod, and removing both the guide rod and obturator to leave the retractor in the body to provide the access path.

Abstract: A method of, and surgical instrument for accessing first and second pedicle locations of a spinal column area. The surgical instrument including a blade member slidably positionable along first and second wires. The instrument having a nested arrangement of members, including a portal member having an elongated aperture to access the first and second pedicle locations. The nested arrangement further including a plurality of members configured and sized to incrementally expand the access opening to the spinal column area.

Abstract: A surgical access system includes retractor for creating an access path between an incision site and a surgical site. The retractor includes a frame having a base member and a pair of generally curved rails extending therefrom. A tubular member is coupled to the frame and includes first and second blade portions that are capable of relative movement with respect to each other by movement on the curved rails. A method of inserting the retractor into a patient includes inserting a guide rod over a guide wire, locating an obturator in the retractor, inserting the obturator and retractor over the guide rod, and removing both the guide rod and obturator to leave the retractor in the body to provide the access path.

Abstract: A surgical access system includes retractor for creating an access path between an incision site and a surgical site. The retractor includes a frame having a base member and a pair of generally curved rails extending therefrom. A tubular member is coupled to the frame and includes first and second blade portions that are capable of relative movement with respect to each other by movement on the curved rails. A method of inserting the retractor into a patient includes inserting a guide rod over a guide wire, locating an obturator in the retractor, inserting the obturator and retractor over the guide rod, and removing both the guide rod and obturator to leave the retractor in the body to provide the access path.