Abstract: A pharmaceutical combination comprising an ALK inhibitor, in free form or a pharmaceutically acceptable salt thereof, and a SHP2 inhibitor, in free form or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier, for simultaneous or sequential administration; the uses of such combination in the treatment of proliferative diseases; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Abstract: The present invention relates to a loaded-to-frame detection equipment for backfill grouting of a shield tunnel, including an automatic loaded-to-frame transmission apparatus, a ground penetrating radar, and an intelligent backfill grouting processing and analysis software. The equipment is integrated by using software and hardware, and can implement real-time visual detection of a backfill grouting layer in a shield construction process. The loaded-to-frame automatic transmission apparatus mainly includes a track, a synchronous belt, a transmission mechanism, a servo machine, and a drive and reducer; and a new air-coupled radar detection apparatus is carried on the loaded-to-frame automatic transmission apparatus and is installed on a shield frame. With the shield performs tunneling, circular detection on a grouting body of the shield and visual layered display of the grouting body are implemented.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A pharmaceutical combination comprising (a) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, and (b) at least one HDMA-2/p53 receptor inhibitor or a pharmaceutically acceptable salt, or at least one BRaf inhibitor or a pharmaceutically acceptable salt, and optionally a pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of cancer; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Abstract: The present invention relates to a pharmaceutical combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor or pharmaceutically acceptable salt thereof, and (b) at least one c-Met receptor tyrosine kinase inhibitor or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential administration for the treatment of a proliferative disease, particularly a c-Met dependent proliferative disease; a pharmaceutical composition comprising such combination; a method of treating a subject having a proliferative disease comprising administration of said combination to a subject in need thereof; use of such combination for the treatment of proliferative disease; and a commercial package comprising such combination.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: Methods for accurately modeling blends in a solid model and corresponding systems and computer-readable mediums. A method includes receiving a solid model including a plurality of faces and bosses, and identifying a pocket from the plurality of faces, including one or more pocket edges to be blended. The method includes performing an analyze pockets process on the pocket and identifying at least one of a tool type, a tool method, or a tool dimension for machining the pocket. The method includes performing a blend pocket process to model blends on the pocket edges and adding blends to the solid model at the pocket edges in a predefined order, according to the blend pocket analysis, to produce a modified solid model. The method includes displaying the modified solid model by the data processing system.

Abstract: Methods for modifying geometric models and corresponding systems and computer-readable mediums. A method includes receiving a geometric model, the geometric model including a plurality of curves. The method includes receiving a selection of one or more curves of the plurality of curves, finding at least one other curve of the plurality of curves that is related to the selected curve, and finding relationships between the selected curve and the other curve(s), including adding the selected curve, the other curve(s), and the relationships to a selected curve set. The method includes pre-processing the selected curve set, including de-activating a set of constraints for the geometric model. The method includes receiving a modification of the selected curve and modifying the selected curve set to produce a modified geometric model and modified selected curve set. The method includes post-processing the modified selected curve set, including re-activating and applying constraints for the geometric model.

Abstract: Product Data Management (PDM) systems and methods. A method includes receiving a target body and a tool body, and evaluating a body type of the target body and a body type of the tool body. The method includes evaluating interactions between the target body and the tool body, and applying comparison criteria to determine spatial relation and relative convexity of an intersection between the target body and the tool body. The method includes identifying tool face regions of the tool body based on the evaluations and the determined spatial relation and relative convexity of the intersection. The method includes adding the tool face regions to the target body to produce a modified target body.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A pharmaceutical combination comprising (a) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, and (b) at least one HDMA-2/p53 receptor inhibitor or a pharmaceutically acceptable salt, or at least one BRaf inhibitor or a pharmaceutically acceptable salt, and optionally a pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of cancer; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A pharmaceutical combination comprising (a) a compound of formula (I), or pharmaceutically acceptable salts thereof; and (b) one or more at least one compound targeting, decreasing or inhibiting the intrinsic ATPase activity of Hsp90 and/or degrading, targeting, decreasing or inhibiting the Hsp90 client proteins via the ubiquitin proteosome pathway; the uses of such combination in the treatment or prevention of proliferative diseases; and methods of treating a subject suffering.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A pharmaceutical combination comprising (a) an ALK inhibitor, or a pharmaceutically acceptable salt thereof, and (b) at least one HDMA-2/p53 receptor inhibitor or a pharmaceutically acceptable salt, or at least one BRaf inhibitor or a pharmaceutically acceptable salt, and optionally a pharmaceutically acceptable carrier, for simultaneous, separate or sequential administration; the uses of such combination in the treatment of cancer; and methods of treating a subject suffering from a proliferative disease comprising administering a therapeutically effective amount of such combination.

Abstract: The disclosure relates to a pharmaceutical combination of a mdm2/4 inhibitor, namely (S)-1-(4-Chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one or (S)-5-(5-Chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one, and a cyclin dependent kinase 4/6 (CDK4/6) inhibitor 7-Cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide. In addition, the disclosure relates to a pharmaceutical combination product. The disclosure also relates to corresponding pharmaceutical formulations, uses and treatment methods comprising said mdm2/4 inhibitor or a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

Abstract: A pharmaceutical combination comprising (a) a compound of formula (I), or pharmaceutically acceptable salts thereof; and (b) one or more at least one compound targeting, decreasing or inhibiting the intrinsic ATPase activity of Hsp90 and/or degrading, targeting, decreasing or inhibiting the Hsp90 client proteins via the ubiquitin proteosome pathway; the uses of such combination in the treatment or prevention of proliferative diseases; and methods of treating a subject suffering.

Abstract: The present invention relates to a pharmaceutical combination comprising a 2-carboxamide cycloamino urea derivative compound of formula (I) and inhibitors of Heat Shock Protein 90, and the uses of such combinations in the treatment of proliferative diseases, more specifically PI3K dependent diseases, more specifically PI3K-alpha dependent diseases.

Abstract: Methods for modifying geometric models and corresponding systems and computer-readable mediums. A method includes receiving a geometric model, the geometric model including a plurality of curves. The method includes receiving a selection of one or more curves of the plurality of curves, finding at least one other curve of the plurality of curves that is related to the selected curve, and finding relationships between the selected curve and the other curve(s), including adding the selected curve, the other curve(s), and the relationships to a selected curve set. The method includes pre-processing the selected curve set, including de-activating a set of constraints for the geometric model. The method includes receiving a modification of the selected curve and modifying the selected curve set to produce a modified geometric model and modified selected curve set. The method includes post-processing the modified selected curve set, including re-activating and applying constraints for the geometric model.

Abstract: Methods for accurately modeling blends in a solid model and corresponding systems and computer-readable mediums. A method includes receiving a solid model including a plurality of faces and identifying a pocket from the plurality of faces, including one or more pocket edges to be blended. The method includes performing an analyze pockets process on the pocket and identifying at least one of a tool type, a tool method, or a tool dimension for machining the pocket. The method includes performing a blend pocket process to model blends on the pocket edge and adding a blend to the solid model at the pocket edges, according to the blend pocket process, to produce a modified solid model. The method includes displaying the modified solid model by the data processing system.