Plasma Dynamics

Contains research objectives and reports on three research projects.National Science Foundation under Grant G-9930Air Force Cambridge Research Center under Contract AF-19(604)-5992WADC Contract AF33(616)-3984, with the Electronic Systems LaboratoryContract AF19(604)-4551 with Air Force Cambridge Research CenterAtomic Energy Commission under Contract AT(30-1)184

Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1

Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3. Antagonism of CRF-R1 with CP-154526 caused an accumulation of intracellular calcium (Ca2+) over time and cell death. These effects could be prevented with the non-selective cation channel blocker Gadolinium (Gd3+). Therefore, opening of a non-selective cation channel causes cell death and Ucn1 maintains this channel in a closed conformation. This channel was identified to be the mechanosensitive channel Piezo1. We go on to determine that this channel inhibition by Ucn1 is mediated initially by an increase in cyclic adenosine monophosphate (cAMP) and a subsequent inactivation of phospholipase A2 (PLA2), whose metabolites are known to modulate ion channels. Knowledge of these novel pathways may present opportunities for interventions that could abrogate the progression of OA

Head-end reprocessing studies with irradiated HTGR-type fuels. III. Studies with RTE-7: TRISO UCsub2sub 2-TRISO ThCsub2sub 2

Head-end reprocessing studies on irradiated Fort St. Vrain type HTGR fuel (TRISO coated UC$sub 2$-TRISO coated ThC$sub 2$) were performed. Fuel sticks were burned quiescently in oxygen at 750$sup 0$C, the ash was screened to separate the fissile SiC-coated particles from the fertile SiC-coated particles, each particle fraction was crushed and burned separately in oxygen, and the secondary burner ash products were leached. These studies concentrated on the release of radionuclides to the burner off-gases after passing through a 20-$mu$ m sintered metal frit held at 500$sup 0$C. Fission product and heavy metal inventories were made on the process gaseous, liquid, and solid streams. Experimental results are compared with pre-irradiation average fuel stick compositions and with calculated fission product inventories. (auth