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A human mast cell line LAD2 that more closely resembles normal in vivo and in vitro human mast cells by expressing functional FcepsilonRI receptors and responding to stem cell factor (SCF) with proliferation, as described in Leuk Res. 2003 Aug;27(8):677-82 and developed by the laboratory of Dr. Dean Metcalfe at the National Institute of Allergy and Infectious Diseases.  This cell line also releases mediators by cross-linking FcgammaRI (CD64) receptors and express FcgammaRII (CD32).

The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (delta30) in the 3'-untranslated region (UTR) of the genome of dengue virus serotypes 1, 2, 3, and 4. The previously identified delta30 attenuating mutation, created in dengue virus type 4 (DEN4) by the removal of 30 nucleotides from the 3'-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1).

NF-kB has been found to be important in immune responses, cell proliferation, apoptosis, and in organ development. Several years ago it was discovered that an IKKgamma/NEMO protein was essential as an adaptor molecule to mediate TNF-alpha, IL-1, and oncoprotein induced activation of NF-kB. Mutation in IKKgamma/NEMO also results in two human genetic diseases, Familial incontinentia pigmenti and hypohidrotic/anhidrotic ectodermal dysplasia. The NIH announces mouse monoclonal antibodies to IKKgamma/NEMO that are far superior to other immunological reagents.

Bitter taste has evolved in mammals as a central warning signal against ingestion of poisonous or toxic compounds. However, many beneficial compounds are also bitter and taste masking of bitter tasting pharmaceutical compounds is a billion dollar industry. The diversity of compounds that elicit bitter-taste sensations is vast and more than two dozen members of the TAS2R bitter taste receptor gene family have been identified.

The noroviruses (known as "Norwalk-like viruses") are associated with an estimated 23,000,000 cases of acute gastroenteritis in the United States each year. Norovirus illness often occurs in outbreaks, affecting large numbers of individuals, illustrated recently by well-publicized reports of gastroenteritis outbreaks on several recreational cruise ships and in settings such as hospitals and schools. Norovirus disease is clearly important in terms of medical costs and missed workdays, and accumulating data support its emerging recognition as important agents of diarrhea-related morbidity.

Bitter taste has evolved in mammals as a crucial, important warning signal against ingestion of poisonous or toxic compounds. However, many beneficial compounds are also bitter, and taste masking of bitter tasting pharmaceutical compounds is a billion dollar industry. The diversity of compounds that elicit bitter-taste sensations is very large and more than two dozen members of the T2R bitter taste receptor family have been identified. Individuals are now known to be genetically predisposed to respond or not to respond to the bitter taste of a number of substances.

Aversive or anticraving medications are currently used to supplement behavioral treatment of alcohol dependence. However, there is a need for developing more effective medications than those available. Neuropeptide Y (NPY) is a neurotransmitter known for increasing appetite and possibly having a role in alcohol preference and dependence. This is likely to be mediated by activation of the post-synaptic NPY-Y1 receptor, but developing molecules suitable for human therapeutics that activate that receptor represents a major challenge.

This technology includes a chemical series, including the NCGC00538279 compound, that selectively activates the GHSR1a G-protein pathway for calcium mobilization while only partially activating the beta-arrestin-2 translocation pathway. The resulting chemical series may be therapeutically valuable for addictive disorders. Activation of the GHSR1a G-protein pathway promotes production and secretion of multiple hormones, including insulin, growth hormone, and IGF1. Activation of the beta-arrestin-2 pathway stimulates dopamine production and may mediate addictive behaviors.

Summary: 

The National Cancer Institute (NCI) is actively seeking potential licensees and/or co-development research collaboration partners interested in further developing this family of oxynitidine derivatives as tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors and radiosensitizers for the treatment of cancer. 

Summary:

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for viral peptide (CE1)-based therapeutics for HCC prevention and treatment.