Abstract: The present invention is based on the surprising finding that pairs of HCV NS5A-targeting inhibitors can be identified which display similar resistance profiles yet, when combined, exhibit synergistic inhibition of wild type replicons and/or replicons carrying mutations conferring resistance to the HCV NS5A-targeting inhibitor. In addition, combinations of these molecules result in a higher genetic barrier to resistance, demonstrating their potential utility as novel combination therapies for treatment of HCV.

Abstract: Diagnostics and therapeutics for resistance to weight-loss, which are based upon the identification of a subject's PLIN polymorphisms, haplotype and genotype pattern, are described in this invention.

Abstract: Low sugar solid food product such as a cracker, chip, shelf-stable bread or crouton, that promotes satiety primarily as a result of its high fiber and protein content. The fiber plus protein content, expressed in grams, times n=kcal per portion, where n is from 5 to 10 gives a result from 1 to 3.

Abstract: Diagnostics and therapeutics for resistance to weight-loss, which are based upon the identification of a subject's PLIN polymorphisms, haplotype and genotype pattern, are described in this invention.

Abstract: Low sugar solid food product such as a cracker, chip, shelf-stable bread or crouton, that promotes satiety primarily as a result of its high fiber and protein content. The fiber plus protein content, expressed in grams, times n=kcal per portion, where n is from 5 to 10 gives a result from 1 to 3.

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: 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: 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.