Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: The disclosed modulators of Rb:Raf-1 interactions are potent, selective disruptors of Rb:Raf-1 binding, with IC50 values ranging from 80 nM to 500 nM. Further, these compounds are surprisingly effective in inhibiting a wide variety of cancer cells, including osteosarcoma, epithelial lung carcinoma, non-small cell lung carcinoma, three different pancreatic cancer cell lines, two different glioblastoma cell lines, metastatic breast cancer, melanoma, and prostate cancer. Moreover, the disclosed compounds effectively disrupt angiogenesis and significantly inhibited tumors in nude mice derived from human epithelial lung carcinoma tumors. Accordingly, the disclosed compounds, pharmaceutical compositions comprising the compounds, methods of inhibiting cell proliferation, methods of treating subjects with cancer, and methods of preparing the disclosed compounds are provided.

Abstract: The subject matter disclosed herein relates to compositions and methods of making and using the compositions. In a further aspect, the subject matter disclosed herein relates to inhibitors of STAT3 dimerization. Methods of making these compositions as well as compositions comprising these compositions are also disclosed. Also disclosed are methods of treating or preventing certain cancers by administering to an individual in need thereof and effective amount of the compounds disclosed herein. Still further, disclosed herein are methods of inhibiting STAT3 by contacting a cell with a compound or composition as disclosed herein.

Abstract: A concentric camshaft arrangement comprises an inner shaft, an outer tube concentrically arranged around the inner shaft and rotatably supported in a cylinder head. A first set of lobes is fixed for rotation with the outer tube and a second set of lobes is rotatably supported by bearing journals on the outer tube and connected for rotation with the inner shaft. The outer tube is supported in the cylinder head by means of a roller bearing and an oil feed is provided for supplying oil for lubricating the bearing journals of the second set of cam lobes. At least part of the oil feed is defined by a radial clearance between the outer surface and an inner surface of the cylinder head that is sealed at its axial ends, the radial clearance being larger than any radial clearance at the roller bearing so that loads on the camshaft are supported at least predominantly by the roller bearing.

Abstract: The present invention relates to stilbene and quinine compounds related to combretastatin A-4 and their use as anticancer compounds and prodrugs. The compounds include those with an alkyl group on the double bond of cis- or trans-stilbenes, compounds with one or more (and preferably 2 or 3) alkyl group substituents on the stilbene A ring, compounds with an alkoxy group other than methoxy at position 3, 4, and/or 5 of the stilbene A ring, compounds (or prodrugs) in which BBOC amino acid esters are formed with the phenolic hydroxyl at the 3-position of the B ring and compounds (or prodrugs) based on a benzoquinone B ring. The present invention further relates to the photochemical reactions of stilbene compounds, either the above compounds disclosed for the first time herein or compounds based on prior stilbenes.

Abstract: The disclosed modulators of Rb:Raf-1 interactions are potent, selective disruptors of Rb:Raf-1 binding, with IC50 values ranging from 80 nM to 500 nM. Further, these compounds are surprisingly effective in inhibiting a wide variety of cancer cells, including osteosarcoma, epithelial lung carcinoma, non-small cell lung carcinoma, three different pancreatic cancer cell lines, two different glioblastoma cell lines, metastatic breast cancer, melanoma, and prostate cancer. Moreover, the disclosed compounds effectively disrupt angiogenesis and significantly inhibited tumors in nude mice derived from human epithelial lung carcinoma tumors. Accordingly, the disclosed compounds, pharmaceutical compositions comprising the compounds, methods of inhibiting cell proliferation, methods of treating subjects with cancer, and methods of preparing the disclosed compounds are provided.

Abstract: A valve mechanism is disclosed for a cylinder of an internal combustion engine which comprises two gas exchange poppet valves mounted in a cylinder head, a bridge 122 acting on the two valves, a cam for actuating the two valves, a slider 124 movable by the cam and slidable relative to the bridge 122, and a hydraulically controlled locking system having a latched position in which the slider transmits the force of the cam to the bridge 122 to actuate the two valves and a released position in which the valves are deactivated and the slider slides freely relative to the bridge. In the invention, the slider 124 is urged towards the cam by a spring 134 acting between the slider 124 and the cylinder head.

Abstract: The disclosed modulators of Rb:Raf-1 interactions are potent, selective disruptors of Rb:Raf-1 binding, with IC50 values ranging from 80 nM to 500 nM. Further, these compounds are surprisingly effective in inhibiting a wide variety of cancer cells, including osteosarcoma, epithelial lung carcinoma, non-small cell lung carcinoma, three different pancreatic cancer cell lines, two different glioblastoma cell lines, metastatic breast cancer, melanoma, and prostate cancer. Moreover, the disclosed compounds effectively disrupt angiogenesis and significantly inhibited tumors in nude mice derived from human epithelial lung carcinoma tumors. Accordingly, the disclosed compounds, pharmaceutical compositions comprising the compounds, methods of inhibiting cell proliferation, methods of treating subjects with cancer, and methods of preparing the disclosed compounds are provided.

Abstract: Protein tyrosine phosphatase (PTP) Shp2 is a non-receptor PTP that involved in cell signaling and regulation of cell proliferation, differentiation, and migration. Shp2 mediates activation of kinases that are involved in the pathogenesis of human carcinoma. A high throughput screen identified compounds that inhibit the PTP Shp2. Several compounds were identified that selectively inhibit Shp2 over Shp1 with low to sub-micromolar activity. Also disclosed are methods of inhibiting a protein tyrosine phosphatase in a cell and treating cancer through selective inhibition of Shp2.

Abstract: A valve mechanism is disclosed for a cylinder of an internal combustion engine which comprises two gas exchange poppet valves mounted in a cylinder head, a bridge 122 acting on the two valves, a cam for actuating the two valves, a slider 124 movable by the cam and slidable relative to the bridge 122, and a hydraulically controlled locking system having a latched position in which the slider transmits the force of the cam to the bridge 122 to actuate the two valves and a released position in which the valves are deactivated and the slider slides freely relative to the bridge. In the invention, the slider 124 is urged towards the cam by a spring 134 acting between the slider 124 and the cylinder head.

Abstract: A camshaft assembly is disclosed which comprises an inner shaft (12), an outer tube (14) surrounding and rotatable relative to the inner shaft (12), and two groups of cam lobes mounted on the outer tube, the first group of cam lobes being fast in rotation with the outer tube, and each cam (10) lobe (18) of the second group being rotatably mounted on the outer surface of the tube (14) and connected for rotation with the inner shaft (12) by means of one or more drive members (50) passing through circumferentially elongated slots in the outer tube. In the invention, each drive member comprises a (15) drive component (50d) engaged with fixed alignment in the cam lobe (18) and a separate fastener (50b) that is rotatable to clamp the drive component against a flat surface on the inner shaft (12), each drive member (50) being constructed such that during the tightening of the fastener (50b) no relative (20) sliding movement is required at the interface between the drive component (50d) and the inner shaft (12).

Abstract: The present invention relates to stilbene and quinine compounds related to combretastatin A-4 and their use as anticancer compounds and prodrugs. The compounds include those with an alkyl group on the double bond of cis- or trans-stilbenes, compounds with one or more (and preferably 2 or 3) alkyl group substituents on the stilbene A ring, compounds with an alkoxy group other than methoxy at position 3, 4, and/or 5 of the stilbene A ring, compounds (or prodrugs) in which BBOC amino acid esters are formed with the phenolic hydroxyl at the 3 -position of the B ring and compounds (or prodrugs) based on a benzoquinone B ring. The present invention further relates to the photochemical reactions of stilbene compounds, either the above compounds disclosed for the first time herein or compounds based on prior stilbenes.

Abstract: An improvement is disclosed for an engine valve system with variable lift and duration of the type that includes two cams mounted coaxially, a summation rocker coupled to cam followers in contact with both cams and movable in proportion to the instantaneous sum of the lifts of the respective cams, and a valve actuating rocker pivotably coupled to the summation rocker and serving to open an engine valve in dependence upon the movement of the summation rocker. In the invention, at least one of the couplings of the summation rocker with the cam followers and with the valve actuating rocker incorporates an adjustable eccentric which is rotatable to enable the clearance within the valve system to be set.

Abstract: The invention relates to a camshaft assembly comprising an inner shaft, an outer tube rotatable relative to the inner shaft, and two groups of cams mounted on the outer tube, the first group of cams being fast in rotation with the outer tube, and the second group being rotatably mounted on the outer surface of the tube and being connected for rotation with the inner shaft by means of connecting members that pass through circumferentially elongated slots in the outer tube. In the invention, the outer tube surrounds the inner shaft with clearance and the members connecting different ones of the cams of the second group to the inner shaft are inclined relative to one another and act to locate the axis of the inner shaft relative to the outer tube.

Abstract: Protein tyrosine phosphatase (PTP) Shp2 is a non-receptor PTP that involved in cell signaling and regulation of cell proliferation, differentiation, and migration. Shp2 mediates activation of kinases that are involved in the pathogenesis of human carcinoma. A high throughput screen identified compounds that inhibit the PTP Shp2. Several compounds were identified that selectively inhibit Shp2 over Shp1 with low to sub-micromolar activity. Also disclosed are methods of inhibiting a protein tyrosine phosphatase in a cell and treating cancer through selective inhibition of Shp2.

Abstract: A camshaft assembly is disclosed which comprises an inner shaft, an outer tube surrounding and rotatable relative to the inner shaft, and two groups of cam lobes mounted on the outer tube, the first group of cam lobes being fast in rotation with the outer tube, the second group being rotatably mounted on the outer surface of the tube and connected for rotation with the inner shaft. The connection between the second group of cam lobes and the inner shaft is effected by means of driving members whose positions are adjustable in order to compensate for significant manufacturing inaccuracies between the inner shaft and its associated group of cam lobes.