197 research outputs found
Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction
Analogs of the known inhibitor (peptide pDI) of the p53/MDM2 proteinâprotein interaction are reported, which are stapled by linkers bearing a photoisomerizable diarylethene moiety. The corresponding photoisomers possess significantly different affinities to the p53-interacting domain of the human MDM2. Apparent dissociation constants are in the picomolar-to-low nanomolar range for those isomers with diarylethene in the âopenâ configuration, but up to eight times larger for the corresponding âclosedâ isomers. Spectroscopic, structural, and computational studies showed that the stapling linkers of the peptides contribute to their binding. Calorimetry revealed that the binding of the âclosedâ isomers is mostly enthalpy-driven, whereas the âopenâ photoforms bind to the protein stronger due to their increased binding entropy. The results suggest that conformational dynamics of the protein-peptide complexes may explain the differences in the thermodynamic profiles of the binding
Search for CP violation in D+âÏÏ+ and D+sâK0SÏ+ decays
A search for CP violation in D + â ÏÏ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fbâ1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (â0.04 ± 0.14 ± 0.14)% for candidates with K â K + mass within 20 MeV/c 2 of the Ï meson mass. A search for a CP -violating asymmetry that varies across the Ï mass region of the D + â K â K + Ï + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+sâK0SÏ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System
The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins
Updated measurements of exclusive J/Ï and Ï(2S) production cross-sections in pp collisions at âs = 7 TeV
The differential cross-section as a function of rapidity has been measured for the exclusive production of J/Ï and Ï(2S) mesons in protonâproton collisions at âs = 7 TeV, using data collected by the LHCb experiment, corresponding to an integrated luminosity of 930 pbâ1. The cross-sections times branching fractions to two muons having pseudorapidities between 2.0 and 4.5 are measured to be where the first uncertainty is statistical and the second is systematic. The measurements agree with next-to-leading order QCD predictions as well as with models that include saturation effects
Measurement of the Îb0, Îb-, and Ωb- Baryon Masses
Bottom baryons decaying to a J/Ï meson and a hyperon are reconstructed using 1.0ââfb-1 of data collected in 2011 with the LHCb detector. Significant Îb0âJ/ÏÎ, Îb-âJ/ÏÎ- and Ωb-âJ/ÏΩ- signals are observed and the corresponding masses are measured to be M(Îb0)=5619.53±0.13(stat.)±0.45(syst.)ââMeV/c2, M(Îb-)=5795.8±0.9(stat.)±0.4(syst.)ââMeV/c2, M(Ωb-)=6046.0±2.2(stat.)±0.5(syst.)ââMeV/c2, while the differences with respect to the Îb0 mass are M(Îb-)-M(Îb0)=176.2±0.9(stat.)±0.1(syst.)ââMeV/c2, M(Ωb-)-M(Îb0)=426.4±2.2(stat.)±0.4(syst.)ââMeV/c2. These are the most precise mass measurements of the Îb0, Îb- and Ωb- baryons to date. Averaging the above Îb0 mass measurement with that published by LHCb using 35ââpb-1 of data collected in 2010 yields M(Îb0)=5619.44±0.13(stat.)±0.38(syst.)ââMeV/c2
First Measurement of the Charge Asymmetry in Beauty-Quark Pair Production
The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in b (b) over bar pair production at a hadron collider. The data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the b (b) over bar system. The results obtained are A(C)(b (b) over bar) (40 10(5) GeV/c(2)) = 1.6 +/- 1.7 +/- 0.6%,where A(C)(b (b) over bar) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 20 GeV, and have an opening angle in the transverse plane Delta phi > 2.6 rad. These measurements are consistent with the predictions of the standard model
Measurement of the B0s âJ/Ïη lifetime
Using a data set corresponding to an integrated luminosity of 3 fbâ1, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV, the effective lifetime in the Bs0âJ/Ïη decay mode, Ïeff, is measured to be
Ïeff=1.479±0.034 (stat)±0.011 (syst) ps. Assuming CP conservation, Ïeff corresponds to the lifetime of the light Bs0 mass eigenstate. This is the first measurement of the effective lifetime in this decay mode
Observation of B+c â D0K+ decays
Using proton-proton collision data corresponding to an integrated luminosity of 3.0 fbâ1, recorded by
the LHCb detector at center-of-mass energies of 7 and 8 TeV, the B+
c â D0K+ decay is observed with a
statistical significance of 5.1 standard deviations. By normalizing to B+ â DÂŻ 0Ï+ decays, a measurement of
the branching fraction multiplied by the production rates for B+
c relative to B+ mesons in the LHCb
acceptance is obtained, R
D
0
K
=
(
f
c
/
f
u
)
Ă
B
(
B
+
c
â
D
0
K
+
)
=
(
9.
3
+
2.8
â
2.5
±
0.6
)
Ă
10
â
7, where the first
uncertainty is statistical and the second is systematic. This decay is expected to proceed predominantly
through weak annihilation and penguin amplitudes, and is the first B+
c decay of this nature to be observed
Measurement of the B_{s}^{0}âÎŒ^{+}ÎŒ^{-} Branching Fraction and Effective Lifetime and Search for B^{0}âÎŒ^{+}ÎŒ^{-} Decays.
A search for the rare decays B_{s}^{0}âÎŒ^{+}ÎŒ^{-} and B^{0}âÎŒ^{+}ÎŒ^{-} is performed at the LHCb experiment using data collected in pp collisions corresponding to a total integrated luminosity of 4.4ââfb^{-1}. An excess of B_{s}^{0}âÎŒ^{+}ÎŒ^{-} decays is observed with a significance of 7.8 standard deviations, representing the first observation of this decay in a single experiment. The branching fraction is measured to be B(B_{s}^{0}âÎŒ^{+}ÎŒ^{-})=(3.0±0.6_{-0.2}^{+0.3})Ă10^{-9}, where the first uncertainty is statistical and the second systematic. The first measurement of the B_{s}^{0}âÎŒ^{+}ÎŒ^{-} effective lifetime, Ï(B_{s}^{0}âÎŒ^{+}ÎŒ^{-})=2.04±0.44±0.05ââps, is reported. No significant excess of B^{0}âÎŒ^{+}ÎŒ^{-} decays is found, and a 95% confidence level upper limit, B(B^{0}âÎŒ^{+}ÎŒ^{-})<3.4Ă10^{-10}, is determined. All results are in agreement with the standard model expectations
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