Studies of jet quenching using isolated-photon + jet correlations in PbPb and pp collisions at sqrt(s[NN]) = 2.76 TeV

Results from the first study of isolated-photon + jet correlations in relativistic heavy ion collisions are reported. The analysis uses data from PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair corresponding to an integrated luminosity of 150 inverse microbarns recorded by the CMS experiment at the LHC. For events containing an isolated photon with transverse momentum pt(gamma) > 60 GeV and an associated jet with pt(Jet) > 30 GeV, the photon + jet pt imbalance is studied as a function of collision centrality and compared to pp data and PYTHIA calculations at the same collision energy. Using the pt(gamma) of the isolated photon as an estimate of the momentum of the associated parton at production, this measurement allows an unbiased characterisation of the in-medium parton energy loss. For more central PbPb collisions, a significant decrease in the ratio pt(Jet)/pt(gamma) relative to that in the PYTHIA reference is observed. Furthermore, significantly more pt(gamma) > 60 GeV photons in PbPb are observed not to have an associated pt(Jet) > 30 GeV jet, compared to the reference. However, no significant broadening of the photon + jet azimuthal correlation is observed.Comment: Submitted to Physics Letters

Automatic construction of online catalog topologies

10.1109/TSMCC.2002.806055IEEE Transactions on Systems, Man and Cybernetics Part C: Applications and Reviews324382-391ITCR

Defective Cytochrome P450-Catalysed Drug Metabolism in Niemann-Pick Type C Disease

Niemann-Pick type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 gene. NPC is characterised by storage of multiple lipids in the late endosomal/lysosomal compartment, resulting in cellular and organ system dysfunction. The underlying molecular mechanisms that lead to the range of clinical presentations in NPC are not fully understood. While evaluating potential small molecule therapies in Npc1-/- mice, we observed a consistent pattern of toxicity associated with drugs metabolised by the cytochrome P450 system, suggesting a potential drug metabolism defect in NPC1 disease. Investigation of the P450 system in the context of NPC1 dysfunction revealed significant changes in the gene expression of many P450 associated genes across the full lifespan of Npc1-/- mice, decreased activity of cytochrome P450 reductase, and a global decrease of multiple cytochrome P450 catalysed dealkylation reactions. In vivo drug metabolism studies using a prototypic P450 metabolised drug, midazolam, confirmed dysfunction in drug clearance in the Npc1-/- mouse. Expression of the Phase II enzyme uridinediphosphate-glucuronosyltransferase (UGT) was also significantly reduced in Npc1-/- mice. Interestingly, reduced activity within the P450 system was also observed in heterozygous Npc1+/- mice. The reduced activity of P450 enzymes may be the result of bile acid deficiency/imbalance in Npc1-/- mice, as bile acid treatment significantly rescued P450 enzyme activity in Npc1-/- mice and has the potential to be an adjunctive therapy for NPC disease patients. The dysfunction in the cytochrome P450 system were recapitulated in the NPC1 feline model. Additionally, we present the first evidence that there are alterations in the P450 system in NPC1 patients