Near term perspectives for fusion research and new contributions by the Ignitor program

The main advances made within the Ignitor program, that is aimed at investigating the physics of fusion burning plasmas near ignition, are described. In particular, the operation of the machine in the H and I regimes at the 10 MA plasma current levels has been considered and analyzed. The unique properties of the plasmas that can be generated by operating the machine with reduced parameters (lower magnetic fields and plasma currents) relative to those needed to achieve ignition are identified. A key feature of this operation is the relatively fast duty cycle that can be maintained. The Ideal Ignition Conditions, under which the density barrier due to bremsstrahlung emission in high density plasmas is removed, can be attained in this case. The plasma heating cycles are identified for which the contribution of ICRH is used both to enter the H-regime and to optimize the time needed for ignition. The on going effort to set up a test ICRH facility is described. The initial results (2 km/sec) of the high speed pellet injection system developed for Ignitor and operated at Oak Ridge are reported. The combined structural analysis and integration of the entire machine core (Load Assembly) is discussed. The adopted control system for both the machine and the plasma column has been designed and is described. The design solutions of the vertical field coils made of MgB2 and operating at 10 K have been identified and the relevant R&D program is underway. The analysis of the Caorso site and of its facility for the operation of the Ignitor with approved safety standards is completed. The relevant results are being made available for the operation of Ignitor at the Triniti site within the framework of the Italy-Russia agreement on the joint construction and operation of the Ignitor facility. A development effort concerning the advanced diagnostic systems that is being carried out for fusion burning plasma regimes is described. An initial analysis of the characteristics of a neutron source based on a system of Ignitor-like machines is reported

Effects of semistarvation on transintestinal d-glucose transport and d-glucose uptake in brush border and basolateral membranes of rat enterocytes

The present work shows that semistarvation (8-10 g of food for 10 days) increases net d-glucose, Na+ and water transport in the everted and perfused rat jejunum. A lincar and positive correlation between cell sugar concentration and transport was found in control and semistarved rats, but the phenomenon was more relevant only in semistarved animals. Membrane vesicle experiments showed that semistarvation increases sugar overshoot only in brush border membrane vesicles, while this situation does not occur in basolateral membrane vesicles. The effect of partial food deprivation seems to enhance net sugar transport by mereasing sugar entry across the apical membrane of enterocytes

An endogenous monocarboxylate transport in Xenopus laevis oocytes

We investigated the existence of an endogenous system for lactate transport in Xenopus laevis oocytes. Cl-36-uptake studies excluded the involvement of a DIDS-sensitive anion antiporter as a possible pathway for lactate movement. L-[C-14]lactate uptake was unaffected by superimposed pH gradients, stimulated by the presence of Na+ in the incubating solution, and severely reduced by the monocarboxylate transporter inhibitor p-chloromercuribenzenesulphonate (pCMBS). Transport exhibited a broad cation specificity and was cis inhibited by other monocarboxylates, mostly by pyruvate. These results suggest that lactate uptake is mediated mainly by a transporter and that the preferred anion is pyruvate. [C-14]pyruvate uptake exhibited the same pattern of functional properties evidenced for L-lactate. Kinetic parameters were calculated for both monocarboxylates, and a higher affinity for pyruvate was revealed. Various inhibitors of monocarboxylate transporters reduced significantly pyruvate uptake. These studies demonstrate that Xenopus laevis oocytes possess a monocarboxylate transport system that shares some functional features with the members of the mammalian monocarboxylate cotransporters family, but, in the meanwhile, exhibits some particular properties, mainly concerning cation specificity

Calmodulin-mediated regulation of bicarbonate and lactate transports in rat jejunum

BACKGROUND/AIMS: Ca(2+)/CaM is known to modulate the activity of several transport systems and its regulation can be accomplished either directly or via the involvement of specific protein kinases. Aim of this study was to investigate the possible role of Ca(2+)/CaM on bicarbonate and lactate transports in rat jejunal enterocyte. METHODS: Enzymatic assays in isolated plasma membranes were performed. Moreover membrane vesicles, transiently opened and resealed, were loaded with Ca(2+) and calmodulin, both in the absence and in the presence of ATP, and were used after that to perform uptake studies. RESULTS: Enzymatic assays gave evidence for the presence of Ca(2+)/CaM-dependent protein kinase II (CaMKII) in plasma membranes from rat jejunum. However, uptake experiments suggest that Ca(2+)/CaM, and not CaMKII, inhibits both basolateral Cl(-)/HCO(3)(-) exchange and H(+)-lactate symport, whilst HCO(3)(-) and Cl(-) conductances are unaffected. Neither Ca(2+)/CaM nor CaMKII seem to regulate brush border Na(+)/H(+) exchanger activity. CONCLUSION: These data are consistent with a Ca(2+)/CaM-mediated reduction of bicarbonate and lactate exit from jejunal enterocyte

PKC regulation of rat jejunal transport systems : mechanisms involved in lactate movement

We examined whether PKC modulates the transport systems involved in lactate movements across the plasma membranes of rat jejunum. “In vitro” phosphorylated membrane vesicles were used to perform uptake studies, whose results suggest that PKC activation exerts an inhibitory effect on basolateral H+-lactate symport, as well as on apical Na+-glucose cotransport. The specificity of the response to PKC was confirmed by using staurosporine, chelerythrine or 4--PMA. Experiments performed using the whole tissue incubated "in vitro" confirmed the reduction of lactate transport elicited by PKC and gave evidence for a contemporaneous inhibition of fluid transport. (Na+, K+)-ATPase activity seems to be unaffected by the kinase and inhibited by Ca2+. Taken together, our results suggest that the overall action of PKC results from the contemporaneous modulation of multiple pathways, targeted to a reduction of both lactate and bicarbonate transports without altering cell pH homeostasis

PKC regulation of rat jejunal transport systems : mechanisms involved in lactate movement

We examined whether PKC modulates the transport systems involved in lactate movements across the plasma membranes of rat jejunum. \u201cIn vitro\u201d phosphorylated membrane vesicles were used to perform uptake studies, whose results suggest that PKC activation exerts an inhibitory effect on basolateral H+-lactate symport, as well as on apical Na+-glucose cotransport. The specificity of the response to PKC was confirmed by using staurosporine, chelerythrine or 4-\uf061-PMA. Experiments performed using the whole tissue incubated "in vitro" confirmed the reduction of lactate transport elicited by PKC and gave evidence for a contemporaneous inhibition of fluid transport. (Na+, K+)-ATPase activity seems to be unaffected by the kinase and inhibited by Ca2+. Taken together, our results suggest that the overall action of PKC results from the contemporaneous modulation of multiple pathways, targeted to a reduction of both lactate and bicarbonate transports without altering cell pH homeostasis

Functional expression of basolateral Cl-/HCO3- exchange from rat jejunum in Xenopus laevis oocytes

Poly(A)+ RNA isolated from rat jejunum was injected into Xenopus laevis oocytes and expression of Cl−/HCO3− antiport was investigated by means of 36Cl− uptake. Two days after injection of 50 ng of poly(A)+ RNA, Cl− uptake was significantly increased with respect to water-injected oocytes. The expressed transport was inhibited by 0·2 mM DIDS, whereas endogenous Cl− uptake was unaffected by this disulphonic stilbene. After sucrose density gradient fractionation, the highest expression of DIDS-sensitive Cl− uptake was detected with mRNA size fraction of about 2–4 kb in length. The expressed Cl− uptake can occur against a Cl− concentration gradient and is unaffected by the known Cl− channel blocker anthracene-9-carboxylic acid. Cl− transport mechanism has properties similar to jejunal basolateral Cl−/HCO3− exchange with regard to Na+ dependenc

pH dependence of Cl/HCO3exchanger in the rat jejunal enterocyte

During bicarbonate absorption in rat jejunum, a Cl/HCO3 exchanger mediates bicarbonate extrusion across the basolateral membrane of the enterocyte. Previous studies demonstrated that anion antiport exhibits a particular behaviour: its activity is positively affected by the presence of sodium, but the cation is not translocated by the carrier protein. In view of the particular features of the jejunal Cl/HCO3 antiporter, first we performed a pharmacological characterisation of the transport protein using various Cl channels blockers. Then, since it is well known that anion exchangers play a substantial role in cell pH regulation, we investigated the possible involvement of jejunal basolateral Cl/HCO3 antiporter in intracellular pH maintenance. The sensitivity of the exchanger to pH was investigated by measuring 36Cl uptake into basolateral membrane vesicles either varying simultaneously intra- and extravesicular pH, or presetting at 7.4 external pH and varying only the internal one. Experiments were performed both in the absence and in the presence of Na. In all the tested conditions, uptake peaked at pH of about 7. 3-7.4 and then decreased, suggesting that the main function of Cl/HCO3 exchanger is related to HCO3 absorption rather than to intracellular pH control. Since pH-regulating mechanisms counteracting acidification are well known in the jejunal enterocyte, we investigated how it regulates pH after alkalinisation of the cytosol. We tested both basolateral and brush border membrane vesicles for the presence of a K/H exchanger, but we could not give evidence for its presence by means of 86Rb uptake experiments. In conclusion, the jejunal enterocyte seems to lack a mechanism counteracting cellular alkalinisation: the main purpose of pH homeostasis might be to hinder acidification of the cytosol due to influx of protons and production of acid by the metabolism