A road map for the realization of global-scale thorium breeding fuel cycle by single molten-fluoride flow. Energy Conversion and Management 49

Abstract For global survival, we need to launch a rapid regeneration of the nuclear power industry. The replacement of the present fossil fuel industry requires a doubling time for alternative energy sources of 5-7 years and only nuclear energy has the capability to achieve this. The liquid metal cooled fast breeder reactors (LMFBR) have the best breeding criteria but the doubling time exceeds 20 years. Further, the use of plutonium in these systems has the potential of nuclear proliferation. The Thorium Molten-Salt Nuclear Energy Synergetic System [THORIMS-NES], described here is a symbiotic system, based on the thorium-uranium-233 cycle. The production of trans-uranium elements is essentially absent in Th-U system, which simplifies the issue of nuclear waste management. The use of 233 U contaminated with 232 U as fissile material, instead of plutonium/ 235 U makes this system nuclear proliferation resistant. The energy is produced in molten-salt reactors (FUJI) and fissile 233 U is produced by spallation in Accelerator Molten-Salt Breeders (AMSB). This system uses the multi-functional ''single-phase molten-fluoride" circulation system for all operations. There are no difficulties relating to ''radiation-damage", ''heat-removal" and ''chemical processing" owing to the simple ''idealistic ionic liquid" character of the fuel. FUJI is size-flexible, and can use all kinds of fissile material achieving a nearly fuel self-sustaining condition without continuous chemical processing of fuel salt and without core-graphite replacement for the life of the reactor. The AMSB is based on a single-fluid molten-salt target/blanket concept. Several AMSBs can be accommodated in regional centers for the production of fissile 233 U, with batch chemical processing including radio-waste management. FUJI reactor and the AMSB can also be used for the transmutation of long-lived radioactive elements in the wastes and has a high potential for producing hydrogen-fuel in molten-salt reactors. The development and launching of THORIMS-NES requires the following three programs during the next three decades: 0196-8904/$ -see front matter

Inhibition of STAT3 Signaling Reduces IgA1 Autoantigen Production in IgA Nephropathy

IgA nephropathy is a chronic renal disease characterized by mesangial immunodeposits that contain autoantigen, which is aberrantly glycosylated IgA1 with some hinge-region O-glycans deficient in galactose. Macroscopic hematuria during an upper respiratory tract infection is common among patients with IgA nephropathy, which suggests a connection between inflammation and disease activity. Interleukin-6 (IL-6) is an inflammatory cytokine involved in IgA immune response. We previously showed that IL-6 selectively increases production of galactose-deficient IgA1 in IgA1-secreting cells from patients with IgA nephropathy. Methods: We characterized IL-6 signaling pathways involved in the overproduction of galactose-deficient IgA1. To understand molecular mechanisms, IL-6 signaling was analyzed by kinomic activity profiling and Western blotting, followed by confirmation assays using siRNA knock-down and small-molecule inhibitors. Results: STAT3 was differentially activated by IL-6 in IgA1-secreting cells from patients with IgA nephropathy compared with those from healthy control subjects. Specifically, IL-6 induced enhanced and prolonged phosphorylation of STAT3 in the cells from patients with IgA nephropathy, which resulted in overproduction of galactose-deficient IgA1. This IL-6−mediated overproduction of galactose-deficient IgA1 could be blocked by small molecule inhibitors of JAK/STAT signaling. Discussion: Our results revealed that IL-6−induced aberrant activation of STAT3-mediated overproduction of galactose-deficient IgA1. STAT3 signaling pathway may thus represent a new target for disease-specific therapy of IgA nephropathy