JETSET: Physics at LEAR with an Internal Gas Jet Target and an Advanced General Purpose Detector

ABSTRACT We argue the importance of installing at LEAR an internal gas jet target together with a powerful detection system. We discuss an advanced detector which will offer large acceptance and complete information on charged and neutral tracks, in its final implementation. We propose here a phase 1 realisation of this detector which will allow us to carry out a set of fundamental experiments at LEAR during the early operation of ACOL. They comprise studies of .p.p and K\K O s production, on both Wlpolarized and polarized hydrogen targets, over the range 1960 < .Js < 2400 :vleV

Sodium accumulation promotes diastolic dysfunction in end-stage heart failure following Serca2 knockout

Alterations in trans-sarcolemmal and sarcoplasmic reticulum (SR) Ca2+ fluxes may contribute to impaired cardiomyocyte contraction and relaxation in heart failure. We investigated the mechanisms underlying heart failure progression in mice with conditional, cardiomyocyte-specific excision of the SR Ca2+-ATPase (SERCA) gene. At 4 weeks following gene deletion (4-week KO) cardiac function remained near normal values. However, end-stage heart failure developed by 7 weeks (7-week KO) as systolic and diastolic performance declined. Contractions in isolated myocytes were reduced between 4- and 7-week KO, and relaxation was slowed. Ca2+ transients were similarly altered. Reduction in Ca2+ transient magnitude resulted from complete loss of SR Ca2+ release between 4- and 7-week KO, due to loss of a small remaining pool of SERCA2. Declining SR Ca2+ release was partly offset by increased L-type Ca2+ current, which was facilitated by AP prolongation in 7-week KO. Ca2+ entry via reverse-mode Na+–Ca2+ exchange (NCX) was also enhanced. Up-regulation of NCX and plasma membrane Ca2+-ATPase increased Ca2+ extrusion rates in 4-week KO. Diastolic dysfunction in 7-week KO resulted from further SERCA2 loss, but also impaired NCX-mediated Ca2+ extrusion following Na+ accumulation. Reduced Na+-K+-ATPase activity contributed to the Na+ gain. Normalizing [Na+] by dialysis increased the Ca2+ decline rate in 7-week KO beyond 4-week values. Thus, while SERCA2 loss promotes both systolic and diastolic dysfunction, Na+ accumulation additionally impairs relaxation in this model. Our observations indicate that if cytosolic Na+ gain is prevented, up-regulated Ca2+ extrusion mechanisms can maintain near-normal diastolic function in the absence of SERCA2