Abstract: An internal combustion engine, primarily for use in motor vehicles, with improved torque and thermal efficiency. The engine comprises pistons configured to move within respective piston cylinders throughout a piston stroke; a rotatable crankshaft; and a piston to crankshaft linkage. A piston connecting rod pivotally connects to the piston at a piston pin; and a crankshaft connecting rod pivotally connects at one end to the piston connecting rod at a connecting rod joint and pivotally connected at another end to the crankshaft. The internal combustion engine also comprises a control arm configured to direct movement of the connecting rod joint to alter an effective length of the piston to crankshaft linkage as the piston to crankshaft linkage is moved via rotation of the crankshaft to form a working crank angle when the piston is a top dead centre position for a predetermined angle of rotation of the crankshaft.

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: An MRI pulse sequence is disclosed. The pulse sequence involves a plurality of slice selective pulses (51,55) which each individually have a desired rotation that is less than or equal to the total desired rotation. The slice selective pulses each cause a rotation about respective axes, which may be different to each other. Optionally phase correction (re-phasing) gradients (53, 56) can also be included in the pulse sequence.

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: 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: 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. We also demonstrated that BTK and the closely related tyrosine kinase Fyn, colocalized at the growth cone process in these cells. HIMF stimulation induced BTK autophosphorylation, which peaked at 2.5 minutes. A transwell migration assay showed that treatment with recombinant murine HIMF induced migration of primary cultured bone marrow cells, which was completely blocked by the BTK inhibitor, LFM-A13.

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: The present invention relates to an improved cannula that enables a plurality of applications to such as tools to be utilized through a single cannula. According to the present invention there is a cannula having a distal end for insertion into a body, the distal end defining an opening to a primary conduit extending along the longitudinal axis of the cannula. The cannula further comprises a tool element for providing a tool function at or adjacent the distal end of the cannula. At least a portion of the tool element is arranged to be moveable outwardly relative to the longitudinal axis of the cannula. Accordingly, it is beneficial that more than one function can be provided at the distal end of the cannula reducing the trauma to the patient and improving access for the surgeon.

Abstract: A composition for the marking of assets comprising: a base material; and two or more encoding compounds wherein each of the two or more encoding compounds are provided at measurable concentrations.

Abstract: According to one aspect, a system is adapted to actively control one or more operating parameters associated with: a wellbore extending in a subterranean formation, and/or wellbore fluid flowing out of the wellbore via a wellhead. The system includes one or more sensors; an electronic controller adapted to receive from the one or more sensors measurement data; and a valve through which the wellbore fluid is adapted to flow. The valve is adapted to be in communication with the electronic controller. The active control of the at least one of the one or more operating parameters is adapted to facilitate: maintenance of the integrity of the wellbore, and/or enhancement of oil and/or gas production out of the wellbore. In one embodiment, the wellbore fluid flow is frac flow-back. In another aspect, a system is adapted to monitor vent gas separated from wellbore fluid flowing out a wellhead.

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 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: 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: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

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 remote sensor device comprises at least one sensor that produces an output signal indicative of the value of a measure, and a reflective display that is positioned such that it is visible along a line of sight from a remote location, the reflective display comprising at least two retro-reflective assemblies, each of which is arranged to reflect a variable fraction of radiation incident upon the reflective assembly back towards a source in response to respective control signals applied to the reflector assemblies. Each of the reflector assemblies preferentially reflects one wavelength of the incident radiation or preferentially removes at least one wavelength of the incident radiation that is not preferentially reflected or removed by the other reflector assembly.

Abstract: Disclosed are novel substituted 2H-isoquinolin-1-one and 3H-quinazolin-4-one derivatives useful as inhibitors of Rho kinase and for treating a variety of diseases and disorders that are mediated or sustained through the activity of Rho kinase, including cardiovascular diseases, pharmaceutical compositions comprising such compounds, methods for using such compounds and processes for making such compounds.

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: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.