Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope

The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a 3 dimensional matrix of 900 large area photomultiplier tubes housed in pressure resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the PMT chosen for ANTARES

Pharmacogenomics of Gemcitabine Metabolism: Functional Analysis of Genetic Variants in Cytidine Deaminase andDeoxycytidine Kinase.DrugMetab. Dispos

Abstract Gemcitabine (dFdC) is metabolized by cytidine deaminase (CDA) and deoxycytidine kinase (DCK) but the contribution of genetic variation in these enzymes to the variability in systemic exposure and response observed in cancer patients is unclear. Wild-type (WT) enzymes and variants of CDA (Lys27Gln and Ala70Thr) and DCK (Ile24Val, Ala119Gly, and Pro122Ser) were expressed in and purified from E. coli and enzyme kinetic parameters estimated for cytarabine (ara-C), dFdC and its metabolite 2',2'-difluorodeoxyuridine (dFdU) as substrates. All three CDA proteins showed similar K m and V max for ara-C and dFdC deamination, except for CDA70Thr which had a 2.5-fold lower K m and 6-fold lower V max for ara-C deamination. All four DCK proteins yielded comparable metabolic activity for ara-C and dFdC monophosphorylation, except for DCK24Val which demonstrated an approximately 2-fold increase (p<0.05) in the intrinsic clearance of dFdC monophosphorylation due to a 40% decrease in K m (p <0.05). DCK did not significantly contribute to dFdU monophosphorylation. In conclusion, the Lys27Gln substitution does not significantly modulate CDA activity towards dFdC and therefore would not contribute to inter-individual variability in response to gemcitabine. The higher in vitro catalytic efficiency of DCK24Val towards dFdC monophosphorylation may be relevant to dFdC clinical response. The substrate-dependent alterations in activities of CDA70Thr and DCK24Val in vitro were observed for the first time, and demonstrate that the in vivo consequences of these genetic variations should not be extrapolated from one substrate of these enzymes to another. DMD #48769