Abstract: A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.

Abstract: A compound of formula (I): in free or salt form, wherein R1, R3, Qa, Qb and Q are as defined herein, for the treatment of a disease mediated by the S1P2 or S1P3 receptor, such as inflammatory or obstructive airways disease.

Abstract: A system and method for directionally casting an elongated device are provided. The method includes orienting a mold within a furnace such that a first portion of the mold points downward. The first portion of the mold defines a space within the mold used to form a first end of the device. The first end of the device, when formed, has a greater mass than a second end of the device. The method also includes filling the mold with molten metal and lowering the mold out of the furnace into a liquid metal bath to immerse the first portion of the mold in the liquid metal bath. The method includes concurrently lowering the mold and the liquid metal bath to cool the molten metal.

Abstract: Hypoxia induced mitogenic factor (HIMF) is a member of the “found in inflammatory zone” (FIZZ)/resistin family of proteins and has potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. The receptor/binding partners for this family of proteins have been largely unknown. We identified Bruton's tyrosine kinase (BTK) as a functional HIMF binding partner through GST-HIMF pull-downs and mass spectrometry. Using primary cultured HIMF-stimulated murine bone marrow cells, we demonstrated that BTK was recruited to the leading edge of the cells. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells, which was completely blocked by a BTK inhibitor. In vivo studies revealed that HIMF can stimulate angiogenesis in the hypoxic tissue.

Abstract: Embodiments of the present invention provide a footwear construction and method of constructing footwear that may include an outsole having a sidewall that defines a perimeter of the outsole. The footwear construction may also include an upper coupled to the sidewall around the perimeter of the outsole, wherein the sidewall overlaps the upper by less than the critical distance for at least 60% of the perimeter of the outsole.

Abstract: The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein A1, A2, L1 and B are as defined herein. The compounds of formula (I) are useful as inhibitors of leukotriene A4 hydrolase (LTA4H) and treating LTA4H related disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of formula (I), methods of using these compounds in the treatment of various diseases and disorders, and processes for preparing these compounds.

Abstract: A compound of formula (I): in free or salt form, wherein A, R1, R3, Qa, Qb and Q are as defined herein, for the treatment of a disease mediated by the S1P2 or S1P3 receptor, such as inflammatory or obstructive airways disease.

Abstract: A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.

Abstract: This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R1, R2, R4. Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR10.

Abstract: Embodiments of the present invention provide a footwear construction and method of constructing footwear that may include an outsole having a sidewall that defines a perimeter of the outsole. The footwear construction may also include an upper coupled to the sidewall around the perimeter of the outsole, wherein the sidewall overlaps the upper by less than the critical distance for at least 60% of the perimeter of the outsole.

Abstract: Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.

Abstract: We found that FIZZ1/RELM? is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM? was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM? protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-I or angiotensin II.

Abstract: Methods for casting a metallic material to form a component are described. The component can be a superalloy-containing turbine part, for example. The general method includes the step of pouring the metallic material, in molten form, into an investment mold; and then rapidly immersing the entire investment mold into a bath that contains a low-melting liquid coolant metal, so as to achieve substantially uniform, multi-directional heat transfer out of the molten material. The molten material that solidifies to form the component is characterized by a fine-grained, equiaxed grain structure. Related embodiments include the use of two ingots that constitute the superalloy material. One ingot includes the oxygen-reactive elements, and is prepared by a vacuum-melting technique. The other ingot includes the remainder of the elements, and can be prepared by a number of techniques, such as air-melting processes.

Abstract: The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5 and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract: Compounds of formula (I) that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.

Abstract: A core for an electric machine includes a core component having a plurality of core teeth defining a plurality of core slots between adjacent core teeth of the plurality of core teeth. The plurality of core slots are receptive of one or more windings. A coolant flowpath through the core component is formed through at least one core tooth. The at least one core tooth has one or more coolant tube banks and one or more mixing chambers arranged in an alternating pattern along the at least one core tooth.

Abstract: Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention.

Abstract: We found that FIZZ1/RELM? is inducible by hypoxia in lung. The hypoxia-upregulated expression of FIZZ1/RELM? was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. Recombinant FIZZ1/RELM? protein stimulates rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibits HIMF-activated Akt phosphorylation. It also inhibits HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. HIMF also has angiogenic and vasoconstrictive activity. Notably, HIMF increases pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Abstract: A capacitance sensing apparatus for use in a position sensing apparatus, comprising a first set of electrodes and a second set of electrodes and a capacitance sensing circuit arranged to determine, in use in a normal operating mode, the capacitance between each pairing of electrodes comprising one from the first set and one from the second set, in which the apparatus is further provided with at least one group switch arranged to selectively electrically connect together groups of the electrodes within the sets of electrodes, in which, in use in a low resolution mode of the apparatus the or each group switch connects together the groups of electrodes and the capacitance sensing circuit is arranged to determine the capacitance between the each pairing of groups of electrodes in one set and the electrodes or groups of electrodes of the other set. Typically, the apparatus is used in conjunction with a display to form a touch-sensitive display.

Abstract: The present invention is a device for aiming a dental x-ray beam to be centered parallel to the area of contact between two adjacent teeth so that the resultant bite wing radiographic image is one that shows at least those two teeth as distinct and not superimposed images. The device, comprising a marginal ridge angulation locator that indexes into the substantially v-shaped groove on the biting surfaces between two adjacent teeth, locates and indicates an aiming vector centered over and parallel to the area of contact between those two teeth for the purpose of aiming an x-ray beam then exposing the radiographic image desired.