BACKGROUND AND PURPOSE Buprenorphine is a potent analgesic with high affinity at μ, δ and κ and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro...

By repeatedly combining the source node's nearest neighbor, we propose a node combination (NC) method to implement the Dijkstra's algorithm. The NC algorithm finds the shortest paths with three simple iterative steps: find the nearest neighbor of the source node, combine that node with the source node, and modify the weights on edges that connect to the nearest neighbor. The NC algorithm is mor...

Metabolites of two structurally related chemical carcinogens, benzo[a]pyrene and 1-nitropyrene, were compared for their ability to cause cytotoxicity and induce mutations in normally repairing or nucleotide excision repair-deficient diploid human fibroblasts; for their ability to induce mutations in a defined gene sequence, supF, when a plasmid containing adducts formed by these carcinogens rep...

Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol analog that displays a similar binding pr...

The USDA established the National Organic Program (NOP) to develop national standards for organically produced agricultural products and establish an organic certification program as required by the Organic Foods Production Act (OFPA) passed by Congress in 1990. Organic crop production excludes conventional pesticides, petroleum – based fertilizers, and sewage sludge based fertilizers with some...

We study the skip-thought model proposed by Kiros et al. (2015) with neighborhood information as weak supervision. More specifically, we propose a skip-thought neighbor model to consider the adjacent sentences as a neighborhood. We train our skip-thought neighbor model on a large corpus with continuous sentences, and then evaluate the trained model on 7 tasks, which include semantic relatedness...

Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NO...

The evolution of DNA sequences can be described by discrete state continuous time Markov processes on a phylogenetic tree. We consider neighbor-dependent evolutionary models where the instantaneous rate of substitution at a site depends on the states of the neighboring sites. Neighbor-dependent substitution models are analytically intractable and must be analyzed using either approximate or sim...