Abstract: The present invention relates to therapies and therapeutic agents for use in the treatment of cardiomyopathies. In particular, the invention is concerned with, but not limited to therapies and therapeutic agents for use in the treatment of hypertrophic cardiomyopathy. Such therapeutic agents comprise hypomethylating agents.

Abstract: The invention provides a method of prognosing and/or diagnosing heart disease or heart failure in a subject, comprising determining the methylation status and/or expression level of at least one methylation marker selected from the group consisting of MFSD2B, miR24-1, TTPA, GALNT15, ITGBL1, SMOC2, MSR1, PVT1, MYOM3, COX17, MYBPC3, HEY2, and MRPL44 wherein the methylation status and/or expression level of at least one methylation marker is indicative of the prognosis and/or diagnosis of said subject. A panel of biomarkers, means, a kit and a device for use in assessing risk of HCM, ISCM and DCM are disclosed.

Abstract: The present invention relates to therapies and therapeutic agents for use in the treatment of cardiomyopathies. In particular, the invention is concerned with, but not limited to therapies and therapeutic agents for use in the treatment of hypertrophic cardiomyopathy. Such therapeutic agents comprise hypomethylating agents.

Abstract: Describe herein is a novel CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif gene that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.

Abstract: The present invention relates to therapies and therapeutic agents for use in the treatment of cardiomyopathies. In particular, the invention is concerned with, but not limited to therapies and therapeutic agents for use in the treatment of hypertrophic cardiomyopathy. Such therapeutic agents comprise hypomethylating agents.

Abstract: Describe herein is a novel CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.

Abstract: The invention relates to differentially expressed disease - associated proteins that have potential to identify patients with cardiovascular disease including ventricular dysfunction and heart failure and the potential to predict heart failure in patients. In particular, the invention relates to the use of a panel of biomarkers in the diagnostic and prognostic evaluation of cardiovascular patients. One of the markers is Leucine-rich alpha-2-glycoprotein (LRG).

Abstract: A packer includes one or more anchors for securing the packer in a wellbore and a pair of seal elements that form a fluid seal. The packer assembly is hydraulically set and, thus, it can be located at any desired position within the wellbore. The packer assembly is secured within the wellbore by a staged setting process through use of shear pins that have increasingly stepped shear values. Redundancy in packer sealing is provided by the use of two seal elements to establish fluid sealing. The design of the packer assembly also provides hydraulic isolation of the actuating portions of the packer assembly upon setting.

Abstract: A device and system for improving efficiency of subterranean cutting elements uses a controlled oscillation super imposed on steady drill bit rotation to maintain a selected rock fracture level. In one aspect, a selected oscillation is applied to the cutting element so that at least some of the stress energy stored in an earthen formation is maintained after fracture of the rock is initiated. Thus, this maintained stress energy can thereafter be used for further crack propagation. In one embodiment, an oscillation device positioned adjacent to the drill bit provides the oscillation. A control unit can be used to operate the oscillation device at a selected oscillation. In one arrangement, the control unit performs a frequency sweep to determine an oscillation that optimizes the cutting action of the drill bit and configures the oscillation device accordingly. One or more sensors connected to the control unit measure parameters used in this determination.

Abstract: Describe herein is a CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif gene that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position ?817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.

Abstract: A device and system for improving efficiency of subterranean cutting elements uses a controlled oscillation super imposed on steady drill bit rotation to maintain a selected rock fracture level. In one aspect, a selected oscillation is applied to the cutting element so that at least some of the stress energy stored in an earthen formation is maintained after fracture of the rock is initiated. Thus, this maintained stress energy can thereafter be used for further crack propagation. In one embodiment, an oscillation device positioned adjacent to the drill bit provides the oscillation. A control unit can be used to operate the oscillation device at a selected oscillation. In one arrangement, the control unit performs a frequency sweep to determine an oscillation that optimizes the cutting action of the drill bit and configures the oscillation device accordingly. One or more sensors connected to the control unit measure parameters used in this determination.

Abstract: A packer includes one or more anchors for securing the packer in a wellbore and a pair of seal elements that form a fluid seal. The packer assembly is hydraulically set and, thus, it can be located at any desired position within the wellbore. The packer assembly is secured within the wellbore by a staged setting process through use of shear pins that have increasingly stepped shear values. Redundancy in packer sealing is provided by the use of two seal elements to establish fluid sealing. The design of the packer assembly also provides hydraulic isolation of the actuating portions of the packer assembly upon setting.

Abstract: A tool for dropping one or more balls and then one or more darts features a closable ball drop opening that works automatically after the ball release to minimize damage to the subsequently released dart. A retainer keeps the darts from coming back up above the dart launcher in the event of a pressure surge in the well. The dart launcher features a dedicated movable barrel for each dart that can be locked in a fully misaligned and fully aligned position with the casing or tubular. A handle is retained to the dart housing and can be manipulated to defeat the lock and rotate a given barrel. The darts may be inspected in their respective barrels before launch and the launch order is variable.

Abstract: An expandable tubular pin and box connection is described having a feature of trapping the pin nose after preferably deforming the pin nose plastically in an outward direction away from the longitudinal axis of the connection. The box end is held away from the pin wall before expansion so that its tendency to curl inwardly upon expansion causes it to bend against the pin wall for sealing with it. The thread profile is also optimized to reduce flank separation as a result of expansion.

Abstract: A method of repairing tubulars downhole is described. A swage is secured to a force magnification tool, which is, in turn, supported by an anchor tool. Applied pressure sets the anchor when the swage is properly positioned. The force magnification tool strokes the swage through the collapsed section. The anchor can be released and weight set down on the swage to permit multiple stroking to get through the collapsed area. The swage diameter can be varied.

Abstract: An expandable packer or anchor is disclosed. It features a gripping device integral to or mounted in a sleeve over the mandrel. Upon expansion, a sealing element engages an outer tubular and the gripping device, such as wickers on slips, preferably digs into the outer tubular. The expansion is preferably by pressure and can incorporate pressure intensifiers delivered by slick line or wire line. Release is accomplished by a release tool, which is delivered on slick line or wire line. It stretches the anchor or packer longitudinally, getting it to retract radially, for release. The release tool can be combined with packers or anchors that have a thin walled feature in the mandrel, to release by pulling the mandrel apart.

Abstract: Casing is scored but not penetrated in one embodiment of a method that allows access to the formation without perforating or section milling the casing. In the run in condition the casing is impervious, to allow cement to be pumped through it to seal the annular space between the casing and the wellbore. After the cement is delivered and displaced through a shoe, the casing is expanded in the regions where it was scored to create openings that go against the wellbore wall. In between the expanded sections the cemented casing offers isolation between adjacent formations.

Abstract: An expandable packer or anchor is disclosed. It features a gripping device integral to or mounted in a sleeve over the mandrel. Upon expansion, a sealing element engages an outer tubular and the gripping device, such as wickers on slips, preferably digs into the outer tubular. The expansion is preferably by pressure and can incorporate pressure intensifiers delivered by slick line or wire line. Release is accomplished by a release tool, which is delivered on slick line or wire line. It stretches the anchor or packer longitudinally, getting it to retract radially, for release. The release tool can be combined with packers or anchors that have a thin walled feature in the mandrel, to release by pulling the mandrel apart.

Abstract: Describe herein is a novel CATT-tetranucleotide repeat polymorphism at position −817 of the human Mif gene that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position −817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.