93 research outputs found
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
Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.
Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.Whole-genome sequencing of esophageal adenocarcinoma samples was performed as part of the International Cancer Genome Consortium (ICGC) through the oEsophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium and was funded by Cancer Research UK. We thank the ICGC members for their input on verification standards as part of the benchmarking exercise. We thank the Human Research Tissue Bank, which is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, from Addenbrookeâs Hospital and UCL. Also the University Hospital of Southampton Trust and the Southampton, Birmingham, Edinburgh and UCL Experimental Cancer Medicine Centres and the QEHB charities. This study was partly funded by a project grant from Cancer Research UK. R.C.F. is funded by an NIHR Professorship and receives core funding from the Medical Research Council and infrastructure support from the Biomedical Research Centre and the Experimental Cancer Medicine Centre. We acknowledge the support of The University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited. We would like to thank Dr. Peter Van Loo for providing the NGS version of ASCAT for copy number calling. We are grateful to all the patients who provided written consent for participation in this study and the staff at all participating centres.
Some of the work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Healthâs NIHR Biomedical Research Centres funding scheme. The work at UCLH/UCL was also supported by the CRUK UCL Early Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.365
FACT Prevents the Accumulation of Free Histones Evicted from Transcribed Chromatin and a Subsequent Cell Cycle Delay in G1
The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNAâdamage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication
Astrocytes: biology and pathology
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions
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
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 CKM angle using with decays
A model-dependent amplitude analysis of the decay is performed using proton-proton collision data
corresponding to an integrated luminosity of 3.0fb, recorded at
and by the LHCb experiment. The CP violation observables
and , sensitive to the CKM angle , are measured to
be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm
0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=&
-0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first
uncertainties are statistical, the second systematic and the third arise from
the uncertainty on the amplitude model. These
are the most precise measurements of these observables. They correspond to
and , where is
the magnitude of the ratio of the suppressed and favoured decay amplitudes, in a mass region of around the
mass and for an absolute value of the cosine of the decay
angle larger than .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-2016-007.htm
Search for dark photons produced in 13 TeV collisions
Searches are performed for both promptlike and long-lived dark photons,
A
0
, produced in proton-proton
collisions at a center-of-mass energy of 13 TeV, using
A
0
â
Ό
ĂŸ
Ό
â
decays and a data sample corresponding
to an integrated luminosity of
1
.
6
fb
â
1
collected with the LHCb detector. The promptlike
A
0
search covers
the mass range from near the dimuon threshold up to 70 GeV, while the long-lived
A
0
search is restricted to
the low-mass region
214
<m
Ă°
A
0
Ă
<
350
MeV. No evidence for a signal is found, and 90% confidence
level exclusion limits are placed on the
Îł
â
A
0
kinetic-mixing strength. The constraints placed on promptlike
dark photons are the most stringent to date for the mass range
10
.
6
<m
Ă°
A
0
Ă
<
70
GeV, and are
comparable to the best existing limits for
m
Ă°
A
0
Ă
<
0
.
5
GeV. The search for long-lived dark photons is the
first to achieve sensitivity using a displaced-vertex signature
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