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Glycosphingolipids are organizational building blocks of plasma membranes that participate in key cellular functions, such as signaling and cell-to-cell interactions. Glucosylceramide synthase - encoded by the Ugcg gene - controls the first committed step in the major pathway of glycosphingolipid synthesis. Global disruption of the Ugcg gene in mice is lethal during gastrulation. The inventors have established a Ugcg allele flanked by loxP sites (floxed).

This technology relates to compositions and methods for improving the growth characteristics of cells engineered to produce live viruses such as the Influenza virus. Featured is a method that uses the gene candidate, siat7e, or its expressed or inhibited products in Madin Darby Canine Kidney (MDCK) cells. The gene expression modulates anchorage-dependence of the cell line thereby allowing scale-up on bioreactor platforms without the use of microcarrier beads and reducing production costs.

Novel A₃ adenosine antagonists available for licensing. A₃ receptors are particularly highly expressed in inflammatory cells, making it a potentially desirable target for inflammatory diseases. This technology relates to highly specific antagonists and partial agonists of A₃ adenosine receptors, which are negatively coupled to adenylate cyclase and have been broadly implicated in inflammation, cardiovascular disease, endocrine conditions and cancer. Further, A₃ adenosine receptors have been implicated in asthma and glaucoma.

X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present, no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. This technology provides a unique and viable animal model of XNDI. NIH investigators have generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen.

The compounds described in this technology may be useful in the development of nucleic acid detection kits for various pathogens.

Available for licensing is a software system useful in applications involving nuclear magnetic resonance (NMR). The software system, called NMRPipe, is written in the C programming language, and makes use of the TCL/TK scripting environment. The system includes over 500 modules for processing and analyzing experimental data of one to four dimensions collected on NMR spectrometers. The system exploits the UNIX computer operating system facilities of pipelines and scripts to link modules in a highly flexible, user-definable manner.

This technology relates to specific (N)-methanocarba adenine nucleosides that have been developed and dendrimers that connect these compounds to create molecules with multiple targets. Dendrimers are essentially repeated molecular branches presenting the core receptor-binding molecules. The compounds synthesized function as agonists and antagonists of a receptor of the G-protein coupled receptor (GPCR) superfamily.

Multivalent interactions are important in cell attachment, wound healing and immune responses. Such interactions are associated with cancer metastasis, blood clotting and the generation of antibodies from a vaccination. Mimicking multivalent interactions on a synthetic scaffold is challenging especially when large numbers of ligands (such as 5 or more) need to be displayed. There are numerous synthetic scaffolds that have been developed, but there are significant limitations that remain.

The inventors have isolated and characterized an alkaloid, phantasmidine, from the skin of the Ecuadoran poison frog E. anthonyi. Phantasmidine is selective for beta4-containing receptor subtypes, unlike many nicotinic receptor agonists currently in development, which target beta2-containing receptor subtypes.

The global market for cancer therapeutics is over $40 billion and is anticipated to continue to rise in the future. There remains a significant unmet need for therapeutics for cancers that affect blood, bone marrow, and lymph nodes and the immune system, such as leukemia, multiple myeloma, and lymphoma. The proteasome inhibitor bortezomib, which may prevent degradation of pro-apoptotic factors permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways, has been a successful mode of treatment for such cancers.