Malcolm John

Abstract:

The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that has an extracellular bilobed venus flytrap domain (VFTD) predicted to contain five calcium (Ca(2+))-binding sites. To elucidate the structure-function relationships of the VFTD, we investigated 294 unrelated probands with familial hypocalciuric hypercalcaemia (FHH), neonatal severe primary hyperparathyroidism (NSHPT) or autosomal dominant hypocalcaemic hypercalciuria (ADHH) for CaSR mutations and performed in vitro functional expression studies and three-dimensional modelling of mutations involving the VFTD. A total of 70 different CaSR mutations were identified: 35 in FHH, 10 in NSHPT and 25 in ADHH patients. Furthermore, a CaSR variant (Glu250Lys) was identified in FHH and ADHH probands and demonstrated to represent a functionally neutral polymorphism. NSHPT was associated with a large proportion of truncating CaSR mutations that occurred in the homozygous or compound heterozygous state. Thirty-four VFTD missense mutations were identified, and 18 mutations were located within 10 Å of one or more of the predicted Ca(2+)-binding sites, particularly at the VFTD cleft, which is the principal site of Ca(2+) binding. Mutations of residues 173 and 221, which are located at the entrance to the VFTD cleft binding site, were associated with both receptor activation (Leu173Phe and Pro221Leu) and inactivation (Leu173Pro and Pro221Gln), thereby highlighting the importance of these residues for entry and binding of Ca(2+) by the CaSR. Thus, these studies of disease-associated CaSR mutations have further elucidated the role of the VFTD cleft region in Ca(2+) binding and the function of the CaSR.

Abstract:

The interference between the K +K - S-wave and P-wave amplitudes in Bs0→J/ψK +K - decays with the K +K - pairs in the region around the (1020) resonance is used to determine the variation of the difference of the strong phase between these amplitudes as a function of K +K - invariant mass. Combined with the results from our CP asymmetry measurement in Bs0→J/ψ decays, we conclude that the Bs0 mass eigenstate that is almost CP=+1 is lighter and decays faster than the mass eigenstate that is almost CP=-1. This determines the sign of the decay width difference ΔΓ sΓ L-Γ H to be positive. Our result also resolves the ambiguity in the past measurements of the CP violating phase s to be close to zero rather than π. These conclusions are in agreement with the standard model expectations. © 2012 CERN.

Abstract:

Searches for heavy Majorana neutrinos in B - decays in final states containing hadrons plus a μ -μ - pair have been performed using 0.41fb -1 of data collected with the LHCb detector in proton-proton collisions at a center-of-mass energy of 7 TeV. The D +μ -μ - and D *+μ -μ - final states can arise from the presence of virtual Majorana neutrinos of any mass. Other final states containing π +, Ds+, or D0π + can be mediated by an on-shell Majorana neutrino. No signals are found and upper limits are set on Majorana neutrino production as a function of mass, and also on the B - decay branching fractions. © 2012 CERN. Published by the American Physical Society.

Abstract:

The production of ϒ (1S), ϒ (2S) and ϒ (3S) mesons in proton-proton collisions at the centre-of-mass energy of √s = 7 TeV is studied with the LHCb detector. The analysis is based on a data sample of 25 pb−1 collected at the Large Hadron Collider. The ϒ mesons are reconstructed in the decay mode ϒ →μ + μ − and the signal yields are extracted from a fit to the μ + μ − invariant mass distributions. The differential production cross-sections times dimuon branching fractions are measured as a function of the ϒ transverse momentum pT and rapidity y, over the range pT < 15 GeV/c and 2.0

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