181 research outputs found
Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis
Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of transthyretin (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, a rare, but fatal, disorder in which TTR aggregates in the brain. The disease remains intractable, since liver transplantation, the reference therapy for systemic ATTR, does not stop mutant TTR production in the brain. In addition, despite current pharmacological strategies have shown to be effective against in vivo TTR aggregation by stabilizing the tetramer native structure and precluding its dissociation, they display low brain permeability. Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently, inhibiting their aggregation. Because tolcapone is an FDA-approved drug that crosses the blood-brain barrier, our results suggest that it can translate into a first disease-modifying therapy for leptomeningeal amyloidosis. Databases PDB codes for A25T-TTR, V30G-TTR, and Y114C-TTR bound to tolcapone are 6TXV, 6TXW, and 6XTK, respectively
Compactlight design study
H2020 CompactLight Project aims at designing the next generation of compact hard X-Rays Free-Electron Lasers, relying on very high accelerating gradients and on novel undulator concepts. CompactLight intends to design a compact Hard X-ray FEL facility based on very high-gradient acceleration in the X band of frequencies, on a very bright photo injector, and on short-period/superconductive undulators to enable smaller electron beam energy. If compared to existing facilities, the proposed facility will benefit from a lower electron beam energy, due to the enhanced undulators performance, be significantly more compact, as a consequence both of the lower energy and of the high-gradient X-band structures, have lower electrical power demand and a smaller footprint. CompactLight is a consortium of 24 institutes (21 European + 3 extra Europeans), gathering the world-leading experts both in the domains of X-band acceleration and undulator design
Search for CP violation in decays
A model-independent search for direct CP violation in the Cabibbo suppressed
decay in a sample of approximately 370,000 decays is
carried out. The data were collected by the LHCb experiment in 2010 and
correspond to an integrated luminosity of 35 pb. The normalized Dalitz
plot distributions for and are compared using four different
binning schemes that are sensitive to different manifestations of CP violation.
No evidence for CP asymmetry is found.Comment: 13 pages, 8 figures, submitted to Phys. Rev.
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Opposite-side flavour tagging of B mesons at the LHCb experiment
The calibration and performance of the oppositeside
flavour tagging algorithms used for the measurements
of time-dependent asymmetries at the LHCb experiment
are described. The algorithms have been developed using
simulated events and optimized and calibrated with
B
+ âJ/ÏK
+, B0 âJ/ÏK
â0 and B0 âD
ââ
Ό
+
ΜΌ decay
modes with 0.37 fbâ1 of data collected in pp collisions
at
â
s = 7 TeV during the 2011 physics run. The oppositeside
tagging power is determined in the B
+ â J/ÏK
+
channel to be (2.10 ± 0.08 ± 0.24) %, where the first uncertainty
is statistical and the second is systematic
Strong constraints on the rare decays Bs -> mu+ mu- and B0 -> mu+ mu-
A search for Bs -> mu+ mu- and B0 -> mu+ mu- decays is performed using 1.0
fb^-1 of pp collision data collected at \sqrt{s}=7 TeV with the LHCb experiment
at the Large Hadron Collider. For both decays the number of observed events is
consistent with expectation from background and Standard Model signal
predictions. Upper limits on the branching fractions are determined to be BR(Bs
-> mu+ mu-) mu+ mu-) < 1.0 (0.81) x 10^-9 at
95% (90%) confidence level.Comment: 2+6 pages; 4 figures; Accepted for publication in Physical Review
Letter
Measurements of the branching fractions of the decays B°s â Dâs K± and B°s â DÂŻsÏ+
The decay mode B°s â Dâs K± allows for one of the theoretically cleanest measurements of the CKM angle Îł through the study of time-dependent CP violation. This paper reports a measurement of its branching fraction relative to the Cabibbo-favoured mode B°s â DÂŻsÏ+ based on a data sample corresponding to 0.37 fbÂŻÂč of proton-proton collisions at âs = 7TeV collected in 2011 with the LHCb detector. In addition, the ratio of B meson production fractions fs/fd, determined from semileptonic decays, together with the known branching fraction of the control channel B°s â DÂŻsÏ+ is used to perform an absolute measurement of the branching fractions: B(B°s â DÂŻsÏ+) = (2.95 ± 0.05 ± 0.17 -0.22 +0.18) Ă 10ÂŻÂł ; B(B°s â Dâs K±) = (1.90 ± 0.12 ± 0.13 -0.14 +0.12) Ă 10ÂŻ4 ; where the first uncertainty is statistical, the second the experimental systematic uncertainty, and the third the uncertainty due to f s/f
Observation of excited Lambda_b0 baryons
Using pp collision data corresponding to 1.0 fb-1 integrated luminosity
collected by the LHCb detector, two narrow states are observed in the
Lambda_b0pi+pi- spectrum with masses 5911.97 +- 0.12(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2 and 5919.77 +- 0.08(stat) +- 0.02(syst) +-
0.66(Lambda_b0 mass) MeV/c^2. The significances of the observations are 5.2 and
10.2 standard deviations, respectively. These states are interpreted as the
orbitally-excited Lambda_b0 baryons, Lambda_b*0(5912) and Lambda_b*0(5920).Comment: Replaced by version published in Phys. Rev. Lett, modified fit with
better mass resolution treatmen
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Measurement of the CP-violating phase phi_s in the decay Bs->J/psi phi
We present a measurement of the time-dependent CP-violating asymmetry in B_s
-> J/psi phi decays, using data collected with the LHCb detector at the LHC.
The decay time distribution of B_s -> J/psi phi is characterized by the decay
widths Gamma_H and Gamma_L of the heavy and light mass eigenstates of the
B_s-B_s-bar system and by a CP-violating phase phi_s. In a sample of about 8500
B_s -> J/psi phi events isolated from 0.37 fb^-1 of pp collisions at sqrt(s)=7
TeV we measure phi_s = 0.15 +/- 0.18 (stat) +/- 0.06 (syst) rad. We also find
an average B_s decay width Gamma_s == (Gamma_L + Gamma_H)/2 = 0.657 +/- 0.009
(stat) +/- 0.008 (syst) ps^-1 and a decay width difference Delta Gamma_s ==
Gamma_L - Gamma_H} = 0.123 +/- 0.029 (stat) +/- 0.011 (syst) ps^-1. Our
measurement is insensitive to the transformation (phi_s,DeltaGamma_s --> pi -
phi_s, - Delta Gamma_s.Comment: 9 pages, 3 figure
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