Processing LHC data in the UK.

The Large Hadron Collider (LHC) is one of the greatest scientific endeavours to date. The construction of the collider itself and the experiments that collect data from it represent a huge investment, both financially and in terms of human effort, in our hope to understand the way the Universe works at a deeper level. Yet the volumes of data produced are so large that they cannot be analysed at any single computing centre. Instead, the experiments have all adopted distributed computing models based on the LHC Computing Grid. Without the correct functioning of this grid infrastructure the experiments would not be able to understand the data that they have collected. Within the UK, the Grid infrastructure needed by the experiments is provided by the GridPP project. We report on the operations, performance and contributions made to the experiments by the GridPP project during the years of 2010 and 2011--the first two significant years of the running of the LHC.

Evidence that P2X purinoceptors mediate the excitatory effects of alphabetamethylene-ADP in rat locus coeruleus neurones.

Extracellular and whole-cell patch clamp recordings were used to study the excitatory responses elicited by purine nucleotides in pontine slices of the rat brain containing the locus coeruleus (LC). The P2 purinoceptor agonists, alphabeta-methyleneadenosine 5'-triphosphate (alphabetameATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPalphabetaS), and a novel purinoceptor agonist, alphabeta-methyleneadenosine 5'-diphosphate (alphabetameADP), elicited concentration-dependent increases in the spontaneous firing rate over the concentration range (1-300 microM). On vagus nerve or dorsal root preparations alphabetameADP (100 microM) had no agonist activity. In the presence of both alphabetameATP (300 microM), ADPbetaS (300 microM) elicited a further and significant increase in the firing rate of the LC neurones, whilst neither alphabetameATP nor alphabetameADP (300 microM) elicited a further response. The P2 purinoceptor antagonists, suramin (100 microM) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 30 microM), markedly attenuated responses to all three agonists. Whole-cell recording of membrane current showed that, at - 60 mV, alphabetameATP and alphabetameADP (both 100 microM) elicited inward currents of a similar magnitude, whilst the inward currents elicited by a lower concentration of ADPbetaS (30 microM) were larger and faded in the presence of this agonist. In the presence of tetrodotoxin and a combination of other neurotransmission blockers, both alphabetameATP and alphabetameADP still produced inward currents. Based on the known selectivity of the agonists used in this study, there appear to be two distinct P2 purinoceptor types present on neurones in the LC, which correspond to the P2X and P2Y types. The responses elicited by alphabetameADP appear to be mediated through a putative P2X purinoceptor, although further work is required to determine which P2X receptor subtype(s) are involved.

Evidence for P2X3 receptors in the developing rat brain.

P2X receptor-mediated responses to the ATP analogue, alpha,beta-methylene ATP, in rat brain cannot be accounted for by the receptor proteins known to be present. Such experiments are often performed on cells from neonates and, since differential developmental regulation of P2X1 and P2X2 receptor messenger RNAs has already been demonstrated, this is likely to be the case for other P2X receptors. This study was designed to address the possible existence of alpha,beta-methylene ATP-sensitive P2X3 receptors in rat brains of various ages using a P2X3 receptor-selective antibody. P2X3 receptor protein was found in discrete regions of the embryonic (E16) and neonatal rat brain (P7 and P14) but was not detectable in adult animals. This is the first demonstration of the presence of these receptors in brains from various ages of rat and the differential expression of these receptors in neonates may account for some reported electrophysiological responses to alpha,beta-methylene ATP.