Abstract: The invention relates to determining the presence of an EZH2 gene mutation in a sample from a subject and inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono-through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Abstract: A disposable gel pad for cushioning the plate of an operating table's patient support apparatus is a block of gel with one face of the block adapted to locate the pad on the plate. Usually the pad will be enclosed in a film envelope. A pocket in the envelope allows the pad to engage the plate. Stick on patches which provide a pocket and sacroiliac pads axe variants. Sacroiliac pads can be cast with a soft gel front for patient contact joined to a hard gel rear for screw or bayonet fixing to the patient support apparatus.

Abstract: A patient positioning support for an operating theatre table (2) has a saddle (18) for clamping to the rail (8) which runs alongside the edge of the table and a pair of articulating arms (26, 32) attached to the saddle for holding a pad in contact with a patients body or limb. The devices are mounted in pairs and are lockable in positions which overlie the tame or lie outboard of the table or below the table when not required. The locking action is by friction but radial arrays of teeth (66, 68), which are locked by hand screws (62), give the preferred locking action. Other items of equipment such as arm boards, neural head supports and stirrups can be substituted for the pad.

Abstract: The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Abstract: A patient positioning support for an operating theatre table (2) has a saddle (18) for clamping to the rail (8) which runs alongside the edge of the table and a pair of articulating arms (26, 32) attached to the saddle for holding a pad in contact with a patients body or limb. The devices are mounted in pairs and are lockable in positions which overlie the tame or lie outboard of the table or below the table when not required. The locking action is by friction but radial arrays of teeth (66, 68), which are locked by hand screws (62), give the preferred locking action. Other items of equipment such as arm boards, neural head supports and stirrups can be substituted for the pad.

Abstract: The present invention provides peptides that specifically bind to BACE at a newly discovered exosite. The invention also provides methods for identifying peptides that bind to a BACE exosite. The invention further provides methods for identifying compounds that bind to a BACE exosite and modulate BACE activity. In another aspect, the invention provides methods for treating or preventing neurodegenerative disorders such as Alzheimer's disease by administering compounds that bind to a BACE exosite and modulate BACE activity.

Abstract: This invention is directed to assays to determine the presence or absence of proteins that exhibit aggrecanase or ADMP activity. This invention also relates to peptides that acts as a substrates for ADMPs, their use in various assays to determine the presence or absence of ADMP activity, and their use as inhibitors of ADMP activity.

Abstract: The present invention provides the crystal structure of BACE-1 complexed with both an active site inhibitor and an exosite peptide containing the core sequence YPYFI. The crystal structure shows the exosite peptide bound to the BACE-1 exosite and identifies a novel peptide binding site on the surface of the BACE-1. The invention also provides the residues that make up the exosite binding site within 6.0 ? of any exosite peptide atom which are: E316, K317, F318, P319, F322, G325, E326, Q327, L328, V329, C330, W331, Q332, A333, T335, D372, V373, A374, S376, D378, D379, C380, Y381.

Abstract: This invention is directed to assays to determine the presence or absence of proteins that exhibit aggrecanase or ADMP activity. This invention also relates to peptides that acts as a substrates for ADMPs, their use in various assays to determine the presence or absence of ADMP activity, and their use as inhibitors of ADMP activity.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: This invention is directed to antineoplastic agents conjugated to enzyme-cleavable peptides comprising the amino acid recognition sequence of a membrane-bound and/or cell-secreted peptidase, and to the use of such conjugated compounds as chemotherapeutic agents in the targeted treatment of cancers.

Abstract: The present invention provides peptides that specifically bind to BACE at a newly discovered exosite. The invention also provides methods for identifying peptides that bind to a BACE exosite. The invention further provides methods for identifying compounds that bind to a BACE exosite and modulate BACE activity. In another aspect, the invention provides methods for treating or preventing neurodegenerative disorders such as Alzheimer's disease by administering compounds that bind to a BACE exosite and modulate BACE activity.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: The subject invention provides liposome formulations that are capable of specifically targeting cell types. The subject invention also provides for the encapsulation of new chemical entities (NCE) or other drug candidate molecules (DCM) within liposomes that specifically target a particular cell type. The subject invention, advantageously, solubilizes compounds, with low solubility in aqueous environments, and permits screening of these compounds against intact cells for biological activity in the absence of detergents that can damage cell membranes. Also provided are methods of preparing liposome formulations that target a specific cell type and methods of delivering therapeutic agents to target cells.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: This invention is directed to assays to determine the presence or absence of proteins that exhibit aggrecanase or ADMP activity. This invention also relates to peptides that acts as a substrates for ADMPs, their use in various assays to determine the presence or absence of ADMP activity, and their use as inhibitors of ADMP activity.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: This invention is directed to antineoplastic agents conjugated to enzyme-cleavable peptides comprising the amino acid recognition sequence of a membrane-bound and/or cell-secreted peptidase, and to the use of such conjugated compounds as chemotherapeutic agents in the targeted treatment of cancers.

Abstract: This invention is directed to assays to determine the presence or absence of proteins that exhibit aggrecanase or ADMP activity. This invention also relates to peptides that acts as a substrates for ADMPs, their use in various assays to determine the presence or absence of ADMP activity, and their use as inhibitors of ADMP activity.