Abstract: The present invention describes a method of concurrent imaging in a mammal comprising: a) administering to said mammal a vitronectin receptor targeted imaging agent and a perfusion imaging agent; and b) concurrently detecting the vitronectin receptor targeted imaging agent bound at the vitronectin receptor and the perfusion imaging agent; and c) forming an image from the detection of said vitronectin targeted imaging agent and said perfusion imaging agent.

Abstract: The present invention relates to (a) the establishment of a direct consequence to the mitochondrial import of phosphorylated p66ShcA and its association with prohibitin, and (b) to a potential function for the prohibitin-p66ShcA complex in the mitochondrial membrane depolarization process that governs metabolic events such as bioenergetics and free radical formation. The present invention can also be employed as a tool for identifying pharmaceutically active compounds that disrupt the prohibitin-p66ShcA interaction, thereby providing treatment options for aging-related diseases such as diabetes, cardiovascular, osteoporosis, cancer and neurodegenerative diseases.

Abstract: The present invention is directed generally to methods and composition for monitoring the processing of epitope-tagged beta-APP. More specifically, the present invention relates to the use of such methods and composition for monitoring responses of cells expressing such epitope-tagged beta-APP or fragments thereof or cell free systems containing the epitope-tagged polypeptides to therapy of diseases associated with an altered metabolism of the beta amyloid precursor protein (APP), and for screening and evaluation of potential drugs for the treatment of these disorders, including Alzheimer's disease (AD).

Abstract: The present invention relates to KCNQ proteins defining potassium channels. In particular, the invention concerns the human KCNQ2, human KCNQ3, murine KCNQ2, and rat KCNQ2 proteins reported herein. KCNQ2 and KCNQ3 proteins are nervous system-selective and may be involved in neurotransmission and neuroprotection. The KCNQ2 and KCNQ3 of the present invention can be used to assay for modulators of the proteins, which would be useful in treatment of such disorders as ataxia, myokymia, seizures, Alzheimer's disease, Parkinson's disease, age-associated memory loss, learning deficiencies, motor neuron diseases, epilepsy, stroke, and the like.

Abstract: An isolated polynucleotide encoding a novel potassium channel polypeptide, KCNQ5, that is expressed primarily in brain and skeletal muscle is described. The new polypeptide has been cloned and isolated from a human brain cDNA library and is a member the KCNQ family of potassium channels. The provided human KCNQ5 nucleic acid sequence and encoded polypeptide can be employed for diagnostic, screening and therapeutic uses.

Abstract: The present invention describes methods of preventing and treating inflammatory and immune-related diseases or disorders using inhibitors of I?B kinase (IKK). Also described are IKK inhibitors effective for the prevention and treatment of inflammatory and immune-related diseases or disorders, as demonstrated in vivo. Further embodiments of the present invention relate to a specific IKK inhibitors, 4(2?-aminoethyl)amino-1,8-dimethylimidazo(1,2-a) quinoxaline and compounds of formula (I), salts thereof, and pharmaceutical compositions.

Abstract: Compounds which function as modulators, particularly, openers, of human KCNQ potassium channel proteins or polypeptides, particularly, central nervous system (CNS)-located KCNQ potassium channels, and heteromultimers thereof, and their use in the treatment of migraine are provided by the present invention. One novel type of potassium channel polypeptide openers provided by the present invention is the fluorooxindole compounds, described for the first time as therapeutics for the treatment of migraine by preventing the asynchronous firing of neurons. Other KCNQ potassium channel opener compounds that are also useful in the treatments of the invention include 2,4-disubstituted pyrimidine-5-carboxamide derivatives. One or more of the compounds according to the present invention may be utilized alone, in combination, or in conjunction with other treatment modalities for reducing, ameliorating and/or alleviating migraine or diseases similar to, or mechanistically related to, migraine, e.g., cluster headache.

Abstract: The present invention describes a method of concurrent imaging in a mammal comprising: a) administering to said mammal a vitronectin receptor targeted imaging agent and a perfusion imaging agent; and b) concurrently detecting the vitronectin receptor targeted imaging agent bound at the vitronectin receptor and the perfusion imaging agent; and c) forming an image from the detection of said vitronectin targeted imaging agent and said perfusion imaging agent.

Abstract: The present invention relates to a novel D-hydantoinase from Ochrobactrum anthropi that enantio-selectively hydrolyzes D-hydantoins to their corresponding D-N-carbamoyl-amino acids; nucleic acids that encode for the enzyme; expression vectors including the nucleic acids; and host cells capable of expressing the enzyme.

Abstract: The present invention provides an isolated, functionally-active protein that catalyzes cleavage of a gamma-secretase substrate. The functional activity of the isolated protein suggests that the isolated protein includes gamma-secretase. In one embodiment, the isolated gamma-secretase protein is associated with PS1. The present invention also relates to homogeneous methods for monitoring cleavage of &bgr;-amyloid precursor protein (&bgr;APP) by gamma-secretase, wherein the steps of of isolating and retrieving cleavage products have been eliminated. Cleavage can be detected by binding a pair of fluorescent adducts to the gamma-cleaved &bgr;APP fragment. Preferably, a first fluorescent adduct binds to the carboxy-terminal end of the gamma-cleaved &bgr;APP fragment, with substantially no cross-reactivity to uncleaved &bgr;APP or to other types of gamma-cleaved &bgr;APP fragments, while a second fluorescent adduct binds to a portion within the amino-terminal region on the gamma-cleaved &bgr;APP fragment.

Abstract: An in vitro method to conduct genomic replication of the viral genomes of viruses that utilize RNA-dependent RNA polymerase for replication (RDRP viruses), such as HCV. The method employs a construct comprising the 3′ and 5′ untranslated regions (UTRs) of the viral genome which are operably linked on the 5′ and 3′ ends of a reporter sequence, in antisense orientation, such that when viral replication is occurring within the cell which produces RDRP, the reporter protein will be made. The method of the invention provides an efficient means for measuring genomic replication in RDRP viruses, and also for the rapid screening of compounds for their ability to inhibit genomic replication of RDRP viruses, including the Hepatitis C virus (HCV).