Abstract: The invention relates to compounds of general formula (I-0): wherein R1, R2, R3, R4, R5, R6, R7a, R8a, X, and Y are as defined herein. Compounds of the invention have, based on excellent Wee1 kinase-inhibitory effect, a cell growth-inhibitory effect and an additive/synergistic effect with any other anticancer agent, and are therefore useful in the field of medicine.

Abstract: The invention is to provide a novel anticancer agent or sensitizer for cancer chemotherapy or radiotherapy. A compound of a general formula (I): wherein A means an aryl group or a heteroaryl group, or a group of a formula (a): R1 means a —(C?O)aOb(C1-C6)alkyl group, a —(C?O)aOb(C2-C6)alkenyl group, a —(C?O)aOb(C3-C6)cycloalkyl group, an aryl group or a heteroaryl group; R2 and R3 each mean a hydrogen atom, a halogen atom, a hydroxyl group, a carboxyl group, a —(C?O)aOb(C1-C6)alkyl group or a group of —(C?O)aN(R1e)R2e; R4 means a hydrogen atom or a (C1-C6)alkyl group, and the like have an excellent Wee1-kinase-inhibitory effect, and are therefore useful in the field of medicine, especially in the field of various cancer treatments.

Abstract: Bridged bicyclic sulphamides of formula (I) are disclosed for treatment of cancer.

Abstract: The present invention relates to the crystalline forms of 2-allyl-1-[6-(I-hydroxy-1 methylethyl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one or a salt thereof, which are useful in the field of treatment of various cancers as a kinase inhibitor, especially as a Weel kinase inhibitor.

Abstract: The present invention provides synthetic ?-secretase peptide substrates useful in various assays for measuring ?-secretase activity. Antibodies that recognize the synthetic substrates and uses of the antibodies in various assays are disclosed. The herein disclosed peptide substrates are hydrolyzed at rates substantially faster than the attendant Swedish mutant APP from which the substrate sequences are derived.

Abstract: The present invention provides transgenic animals having an amyloid precursor protein wherein the amino acids flanking the &bgr; secretase cleavage site are NF and EV. The invention also provides tissues and cell lines derived from such animals. The invention further provides methods of screening candidate compounds to determine whether the compounds can alter the rate of cleavage of amyloid precursor protein by &bgr; secretase.

Abstract: A trace amine receptor 1 has been isolated from the genome of Cercopithecus aethiops (African green monkey). Described is the amino acid sequence of the receptor, the nucleic acid encoding the receptor, and methods for using the receptor to identify analytes that are agonists or antagonists of the receptor.

Abstract: Methods of identifying activators and inhibitors of voltage-gated ion channels are provided in which the methods employ electrical field stimulation of the cells in order to manipulate the open/close state transition of the voltage-gated ion channels. This allows for more convenient, more precise experimental manipulation of these transitions, and, coupled with efficient methods of detecting the result of ion flux through the channels, provides methods that are especially suitable for high throughput screening.

Abstract: The gene responsible for Stargardt-like macular dystrophy has been identified, along with its normal allelic form. The mutant gene encodes a mutant protein containing a frameshift mutation, resulting in abnormal fatty acid synthesis and transport in the retina. Also disclosed are assays for Stargardt-like macular dystrophy and therapies.

Abstract: A high molecular weight polysaccharide intracellular adhesin (SAE) antigen having the general structure of poly-1,6,?-2-amidoglucopyranoside, which is variable substituted with N-acetyl and O-succinyl substituents is described. Also, a method is given for isolating this antigen from Staphylococcus aureus. The SAE can be used in a vaccine, either alone, conjugated to an immunogenic protein, and/or with an immunogenic adjuvant.

Abstract: Gamma three protease is provided, a novel aspartyl class protease that is capable of taking part in the processing of amyloid precursor protein (APP) to A? peptide. Gamma three protease may be involved in the development and/or progression of Alzheimers disease. Methods of identifying inhibitors of gamma three protease, useful in the prevention or treatment of Alzheimers disease, are disclosed.

Abstract: The present invention provides synthetic ?-secretase peptide substrates useful in various assays for measuring ?-secretase activity. Antibodies that recognize the synthetic substrates and uses of the antibodies in various assays are disclosed. The herein disclosed peptide substrates are hydrolyzed at rates substantially faster than the attendant Swedish mutant APP from which the substrate sequences are derived.

Abstract: The gene responsible for Stargardt-like macular dystrophy has been identified, along with its normal allelic form. The mutant gene encodes a mutant protein containing a frameshift mutation, resulting in abnormal fatty acid synthesis and transport in the retina. Also disclosed are assays for Stargardt-like macular dystrophy and therapies.

Abstract: Methods of identifying inhibitors of the fusion of two types of cells, particularly when fusion is mediated by the interaction of a viral protein and such cellular proteins as CD4 and chemokine receptors, are disclosed. The methods are suitable for identifying substances that are useful for the treatment and prevention of viral diseases. Particularly preferred methods are useful for the identification of inhibitors of HIV-1 infection.

Abstract: Helper dependent adenoviral vectors encoding erythropoietin (epo) provide high levels of epo to achieve a long-term therapeutically effective dosage, and allow for repeat administration to patients with disorders such as anaemia of Chronic Renal Failure (CFR), anaemias due to beta-thalassaemia, and sickle cell anaemia (SCA).

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.

Abstract: The present invention provides a nucleic acid and amino acid sequence of a human Pif-1 type helicase. The invention also provides methods of screening for compounds that modulate the activity of human Pif-1 type helicase, as well as methods for affecting viability of a cell by contacting the cell with a human Pif-1 helicase modulator. Such contacting specifically increases or decreases the specific activity of the human helicase in the cell, and may affect its viability, by affecting telomere length regulatory processes.

Abstract: The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease.

Abstract: The present invention relates to compositions that inhibit the proliferation and migration of endothelial cells. The compositions contain a pre-activation domain (“PAD”) from plasminogen, or a biologically active fragment thereof, and at least one kringle region from plasminogen, or a biologically active portion thereof. The compositions are useful to treat angiogenic associated disorders.

Abstract: A method for the treatment of T cell mediated disorders is described. The method involves administering to a subject a therapeutically effective amount of an anti-human CD40 antibody. Disease states suitable for treatment with this method include graft versus host disease and transplant rejection and auto immune disease such as type I diabetes, psoriasis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and myesthenia gravis.