Abstract: The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, Z, J, M, and R1 to R8 are defined herein, these compounds are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: A cable for transmitting electricity may include a core including a first conductive material, a core shield surrounding the core, an insulation layer surrounding the core shield, the insulation layer comprising a material providing electrical insulating properties, an insulation shield surrounding the insulation layer; and at least one of the following at least partially surrounding the insulation shield: (a) a bedding layer including a first semi-conductive material, (b) a tape layer including a metallic tape intercalated with an insulating tape, and (c) a protection layer.

Abstract: The present application provides novel pyrimido-pyridazinone compounds and methods for preparing and using these compounds. These compounds are useful in treating inflammation in patients by administering one or more of the compounds to a patient. In one embodiment, the novel pyrimido-pyridazinone compound is of Formula (I) and R1 and R2 are defined herein.

Abstract: The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, Z, J, M, and R1 to R8 are defined herein, these compounds are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: We disclose herein a rotatable sole assembly for a shoe which comprises a first plate (305), a second plate (320); and a coating layer (330) between the first and second plates. The coating layer (330) is configured to rotate one of the first and second plates with respect to the other of the first and second plates. The sole assembly is designed to reduce ACL injuries as well as the incidence of other lower leg injuries related to high torque forces.

Abstract: The present application provides novel pyrimido-pyridazinone compounds and methods for preparing and using these compounds. These compounds are useful in treating inflammation in patients by administering one or more of the compounds to a patient. In one embodiment, the novel pyrimido-pyridazinone compound is of Formula (I) and R1 and R2 are defined herein.

Abstract: The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, Z, J, M, and R1 to R8 are defined herein, these compounds are effective in treating conditions associated with dysregulation of the RAS/RAF/MEK/ERK pathway. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: A business software application system and method are provided that include a feed system for distributing changes about the application/module to a group of users and a cloud connector system that links external data sources to the business software application system and method.

Abstract: This disclosure is directed to fiber optic pulsed polarimeters based on either streak camera or photodiode detection using a backscatter tailored optical fiber and the polarization optical time domain reflectometry technique for conducting remote diagnostic measurements of inducing fields along the fiber. The backscatter tailored optical fiber comprises a single mode fiber with an array of fiber Bragg gratings written to produce a predetermined distribution of backscatter signal in intensity and spectral content in response to a pulse propagating along the array. The fiber optic pulsed polarimeter includes a directional coupler that diverts the backscatter from the backscatter-tailored optical fiber to a polarization detection system for determining the polarization state of the backscatter as the polarized light pulse transits the backscatter-tailored optical fiber.

Abstract: Provided herein are methods and compositions for the targeted delivery to myometrial tissue of one or more agents capable of regulating contractility of myometrial tissue, wherein the one or more agents are contained or encapsulated within a polymeric delivery vehicle conjugated with one or more molecules that recognizes and/or is capable of binding, directly or indirectly, to the oxytocin receptor.

Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

Abstract: Provided herein are methods and compositions for the targeted delivery to myometrial tissue of one or more agents capable of regulating contractility of myometrial tissue, wherein the one or more agents are contained or encapsulated within a polymeric delivery vehicle conjugated with one or more molecules that recognizes and/or is capable of binding, directly or indirectly, to the oxytocin receptor.

Abstract: A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

Abstract: The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8? are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: The present application provides novel inhibitors of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase, metabolites thereof, and pharmaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. A therapeutically effective amount of one or more of the compounds of formula (I) is useful in treating diseases resulting from dysregulation of the kynurenine pathway. Compounds of formula (I) act by inhibiting the enzymatic activity or expression of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxy-genase.

Abstract: The present application provides novel pyrimido-pyridazinone compounds and methods for preparing and using these compounds. These compounds are useful in treating inflammation in patients by administering one or more of the compounds to a patient. In one embodiment, the novel pyrimido-pyridazinone compound is of Formula (I) and R1 and R2 are defined herein.

Abstract: The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8? are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer.

Abstract: Techniques for determining conditions of power lines in a power distribution system based on data collected by a plurality of sensor units deployed in the power distribution system. The techniques include obtaining data associated with measurements collected by at least two sensor units in the plurality of sensor units, and determining, by using at least one processor, at least one condition of at least one power line in the power distribution system by using the data obtained by the at least two sensor units.

Abstract: The invention features a diagnostic platform utilizing T2 magnetic resonance to directly measure integrated reactions in whole blood samples such as clotting, fibrinogen, clot contraction, and fibrinolysis to provide a comprehensive assessment of hemostatic parameters on a single instrument in minutes. The methods of the invention can be performed with less than 1 ml of blood and minimal sample handling.