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BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition.
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones
Variation in Surface Ionization Potentials of Pristine and Hydrated BiVO4
This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.The work was funded by the
EPSRC (Grant No. EP/K004956/1) and the ERC (Grant No.
277757). The calculations used the ARCHER supercomputer
through membership of the UK’s HPC Materials Chemistry
Consortium (EPSRC Grant No. EP/L000202)
Measurements of elliptic and triangular flow in high-multiplicity HeAu collisions at GeV
We present the first measurement of elliptic () and triangular ()
flow in high-multiplicity HeAu collisions at
GeV. Two-particle correlations, where the particles have a large separation in
pseudorapidity, are compared in HeAu and in collisions and
indicate that collective effects dominate the second and third Fourier
components for the correlations observed in the HeAu system. The
collective behavior is quantified in terms of elliptic and triangular
anisotropy coefficients measured with respect to their corresponding
event planes. The values are comparable to those previously measured in
Au collisions at the same nucleon-nucleon center-of-mass energy.
Comparison with various theoretical predictions are made, including to models
where the hot spots created by the impact of the three He nucleons on the
Au nucleus expand hydrodynamically to generate the triangular flow. The
agreement of these models with data may indicate the formation of low-viscosity
quark-gluon plasma even in these small collision systems.Comment: 630 authors, 9 pages, 4 figures, 2 tables. v2 is the version accepted
for publication by Physical Review Letters. Plain text data tables for the
points plotted in figures for this and previous PHENIX publications are (or
will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Upsilon (1S+2S+3S) production in d+Au and p+p collisions at sqrt(s_NN)=200 GeV and cold-nuclear matter effects
The three Upsilon states, Upsilon(1S+2S+3S), are measured in d+Au and p+p
collisions at sqrt(s_NN)=200 GeV and rapidities 1.2<|y|<2.2 by the PHENIX
experiment at the Relativistic Heavy-Ion Collider. Cross sections for the
inclusive Upsilon(1S+2S+3S) production are obtained. The inclusive yields per
binary collision for d+Au collisions relative to those in p+p collisions
(R_dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going
direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going
direction. The measured results are compared to a nuclear-shadowing model,
EPS09 [JHEP 04, 065 (2009)], combined with a final-state breakup cross section,
sigma_br, and compared to lower energy p+A results. We also compare the results
to the PHENIX J/psi results [Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity
dependence of the observed Upsilon suppression is consistent with lower energy
p+A measurements.Comment: 495 authors, 11 pages, 9 figures, 5 tables. Submitted to Phys. Rev.
C. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Transverse energy production and charged-particle multiplicity at midrapidity in various systems from to 200 GeV
Measurements of midrapidity charged particle multiplicity distributions,
, and midrapidity transverse-energy distributions,
, are presented for a variety of collision systems and energies.
Included are distributions for AuAu collisions at ,
130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, CuCu collisions at
and 62.4 GeV, CuAu collisions at
GeV, UU collisions at GeV,
Au collisions at GeV, HeAu collisions at
GeV, and collisions at
GeV. Centrality-dependent distributions at midrapidity are presented in terms
of the number of nucleon participants, , and the number of
constituent quark participants, . For all collisions
down to GeV, it is observed that the midrapidity data
are better described by scaling with than scaling with . Also presented are estimates of the Bjorken energy density,
, and the ratio of to ,
the latter of which is seen to be constant as a function of centrality for all
systems.Comment: 706 authors, 32 pages, 20 figures, 34 tables, 2004, 2005, 2008, 2010,
2011, and 2012 data. v2 is version accepted for publication in Phys. Rev.
Medium modification of jet fragmentation in Au+Au collisions at sqrt(s_NN)=200 GeV measured in direct photon-hadron correlations
The jet fragmentation function is measured with direct photon-hadron
correlations in p+p and Au+Au collisions at sqrt(s_NN)=200 GeV. The p_T of the
photon is an excellent approximation to the initial p_T of the jet and the
ratio z_T=p_T^h/p_T^\gamma is used as a proxy for the jet fragmentation
function. A statistical subtraction is used to extract the direct photon-hadron
yields in Au+Au collisions while a photon isolation cut is applied in p+p. I_
AA, the ratio of jet fragment yield in Au+Au to that in p+p, indicates
modification of the jet fragmentation function. Suppression, most likely due to
energy loss in the medium, is seen at high z_T. The fragment yield at low z_T
is enhanced at large angles. Such a trend is expected from redistribution of
the lost energy into increased production of low-momentum particles.Comment: 562 authors, 70 insitutions, 8 pages, and 3 figures. Submitted to
Phys. Rev. Lett. v2 has minor changes to improve clarity. Plain text data
tables for the points plotted in figures for this and previous PHENIX
publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Cold Nuclear Matter Effects on J/psi Yields as a Function of Rapidity and Nuclear Geometry in Deuteron-Gold Collisions at sqrt(s_NN) = 200 GeV
We present measurements of J/psi yields in d+Au collisions at sqrt(s_NN) =
200 GeV recorded by the PHENIX experiment and compare with yields in p+p
collisions at the same energy per nucleon-nucleon collision. The measurements
cover a large kinematic range in J/psi rapidity (-2.2 < y < 2.4) with high
statistical precision and are compared with two theoretical models: one with
nuclear shadowing combined with final state breakup and one with coherent gluon
saturation effects. To remove model dependent systematic uncertainties we also
compare the data to a simple geometric model. We find that calculations where
the nuclear modification is linear or exponential in the density weighted
longitudinal thickness are difficult to reconcile with the forward rapidity
data.Comment: 449 authors from 66 institutions, 6 pages, 3 figures. Submitted to
Physical Review Letters. Plain text data tables for the points plotted in
figures for this and previous PHENIX publications are (or will be) publicly
available at http://www.phenix.bnl.gov/papers.htm
Centrality dependence of charged hadron production in deuteron+gold and nucleon+gold collisions at sqrt(s_NN)=200 GeV
We present transverse momentum (p_T) spectra of charged hadrons measured in
deuteron-gold and nucleon-gold collisions at \sqrts = 200 GeV for four
centrality classes. Nucleon-gold collisions were selected by tagging events in
which a spectator nucleon was observed in one of two forward rapidity
detectors. The spectra and yields were investigated as a function of the number
of binary nucleon-nucleon collisions, \nu, suffered by deuteron nucleons. A
comparison of charged particle yields to those in p+p collisions show that the
yield per nucleon-nucleon collision saturates with \nu for high momentum
particles. We also present the charged hadron to neutral pion ratios as a
function of p_T.Comment: 330 authors, 15 pages text, 16 figures, 3 tables. Submitted to Phys.
Rev. Lett. v2 has minor changes to reflect revisions during review process.
Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Azimuthal Angle Correlations for Rapidity Separated Hadron Pairs in d+Au Collisions at sqrt(s_NN) = 200 GeV
We report on two-particle azimuthal angle correlations between charged
hadrons at forward/backward (deuteron/gold going direction) rapidity and
charged hadrons at mid-rapidity in deuteron-gold (d+Au) and proton-proton (p+p)
collisions at sqrt(s_NN) = 200 GeV. Jet structures are observed in the
correlations which we quantify in terms of the conditional yield and angular
width of away side partners. The kinematic region studied here samples partons
in the gold nucleus carrying nucleon momentum fraction x~0.1 to x~0.01. Within
this range, we find no x dependence of the jet structure in d+Au collisions.Comment: 330 authors, 6 pages text, 4 figures, no tables. Submitted to Phys.
Rev. Lett. Plain text data tables for the points plotted in figures for this
and previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
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