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A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as(More)
SIRT1 is a protein deacetylase that has emerged as a therapeutic target for the development of activators to treat diseases of aging. SIRT1-activating compounds (STACs) have been developed that produce biological effects consistent with direct SIRT1 activation. At the molecular level, the mechanism by which STACs activate SIRT1 remains elusive. In the(More)
SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases. We report the first sets(More)
The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of(More)
SIRT1, the founding member of the mammalian family of seven NAD(+)-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation(More)
Many overlay multicast schemes have been proposed recently at the application level to support video-on-demand service over the Internet. With the proliferation of mobile devices and the increasing coverage of high speed wireless networks, such services are likely to be extended to support clients connected to the Internet through a wireless last hop.(More)
Carba-NAD is a synthetic compound identical to NAD except for one substitution, where an oxygen atom adjacent to the anomeric linkage bearing nicotinamide is replaced with a methylene group. Because it is inert in nicotinamide displacement reactions, carba-NAD is an unreactive substrate analogue for NAD-consuming enzymes. SIRT3 and SIRT5 are NAD-consuming(More)
Marginanism and egalitarianism are two main standpoints in economics. The Shapley value has been characterized in many ways from the view of marginalism. In this paper, we characterize the Solidarity value with respect to the egalitarianism by three approaches applied to the Shapley value. We introduce a revised potential function and deduce the recursive(More)
In economic allocation problems, egalitarianism and marginalism are two major thoughts to distribute the benefits of cooperation. The α-CIS value reconciles the two thoughts in some variable extent by a parameter α ∈ [0, 1]. The α-CIS value is the center of gravity of the corresponding α-imputation set given the α-imputation set is nonempty. From the(More)