647 research outputs found
Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer
Altres ajuts: This work was co-finaced by the European Development Regional Fund, "A way to achieve Europe" ERDF; the Cellex Foundation; and "la Caixa" Banking Foundation (LCF/PR/PR15/ 11100003).Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion
Null-Result Detection and Einstein-Podolsky-Rosen (EPR) Correlations
It follows from Bell's theorem and quantum mechanics that the detection of a
particle of an entangled pair can (somehow) "force" the other distant particle
of the pair into a well-defined state (which is equivalente to a reduction of
the state vector): no property previously shared by the particles can explain
the predicted correlations. This result has been corroborated by experiment.
However, it has not been experimantally proved-and it is far from obvious-that
the absence of detection, as in null-result (NR) experiments could have the
very same effect. In this paper a way to try to bridge this gap is suggested.
As already shown for the case of EPR correlations, if NR detections cannot
induce a reduction of the state vector, then faster-than-light (FTL)
communication becomes possible, at least in pr\'inciple. But it will be
demonstrated that-as entertained by Bohm-this does not necessarily lead to a
causal paradox, or to the rejection of the Lorentz transformations.Comment: 16 pages, 1 figure. Similar to the version published in Foundations
of Physics with an appendix on superluminal signalling without causal paradox
include
Partonic flow and -meson production in Au+Au collisions at = 200 GeV
We present first measurements of the -meson elliptic flow
() and high statistics distributions for different
centralities from = 200 GeV Au+Au collisions at RHIC. In
minimum bias collisions the of the meson is consistent with the
trend observed for mesons. The ratio of the yields of the to those of
the as a function of transverse momentum is consistent with a model
based on the recombination of thermal quarks up to GeV/,
but disagrees at higher momenta. The nuclear modification factor () of
follows the trend observed in the mesons rather than in
baryons, supporting baryon-meson scaling. Since -mesons are
made via coalescence of seemingly thermalized quarks in central Au+Au
collisions, the observations imply hot and dense matter with partonic
collectivity has been formed at RHIC.Comment: 6 pages, 4 figures, submit to PR
High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance
It has been postulated that monitoring measurable residual disease (MRD) could be used as a surrogate marker of progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) patients after treatment with immunochemotherapy regimens. In this study, we analyzed the outcome of 84 patients at 3 years of follow-up after first-line treatment with fludarabine, cyclophosphamide and rituximab (FCR) induction followed by 36 months of rituximab maintenance thearpy. MRD was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4. Eighty out of 84 evaluable patients (95.2%) achieved at least a partial response or better at the end of induction. After clinical evaluation, 74 patients went into rituximab maintenance and the primary endpoint was assessed in the final analysis at 3 years of follow-up. Bone marrow (BM) MRD analysis was performed after the last planned induction course and every 6 months in cases with detectable residual disease during the 36 months of maintenance therapy. Thirty-seven patients (44%) did not have detectable residual disease in the BM prior to maintenance therapy. Interestingly, 29 patients with detectable residual disease in the BM after induction no longer had detectable disease in the BM following maintenance therapy. After a median followup of 6.30 years, the median overall survival (OS) and PFS had not been reached in patients with either undetectable or detectable residual disease in the BM, who had achieved a complete response at the time of starting maintenance therapy. Interestingly, univariate analysis showed that after rituximab maintenance OS was not affected by IGHV status (mutated vs. unmutated OS: 85.7% alive at 7.2 years vs. 79.6% alive at 7.3 years, respectively). As per protocol, 15 patients (17.8%), who achieved a complete response and undetectable peripheral blood and BM residual disease after four courses of induction, were allowed to stop fludarabine and cyclophosphamide and complete two additional courses of rituximab and continue with maintenance therapy for 18 cycles. Surprisingly, the outcome in this population was similar to that observed in patients who received the full six cycles of the induction regimen. These data show that, compared to historic controls, patients treated with FCR followed by rituximab maintenance have high-quality responses with fewer relapses and improved OS. The tolerability of this regime is favorable. Furthermore, attaining an early undetectable residual disease status could shorten the duration of chemoimmunotherapy, reducing toxicities and preventing long-term side effects. The analysis of BM MRD after fludarabine-based induction could be a powerful predictor of post-maintenance outcomes in patients with CLL undergoing rituximab maintenance and could be a valuable tool to identify patients at high risk of relapse, influencing further treatment strategies
Measurement of Transverse Single-Spin Asymmetries for Di-Jet Production in Proton-Proton Collisions at GeV
We report the first measurement of the opening angle distribution between
pairs of jets produced in high-energy collisions of transversely polarized
protons. The measurement probes (Sivers) correlations between the transverse
spin orientation of a proton and the transverse momentum directions of its
partons. With both beams polarized, the wide pseudorapidity () coverage for jets permits separation of Sivers functions for the valence
and sea regions. The resulting asymmetries are all consistent with zero and
considerably smaller than Sivers effects observed in semi-inclusive deep
inelastic scattering (SIDIS). We discuss theoretical attempts to reconcile the
new results with the sizable transverse spin effects seen in SIDIS and forward
hadron production in pp collisions.Comment: 6 pages total, 1 Latex file, 3 PS files with figure
Single Spin Asymmetry in Polarized Proton-Proton Elastic Scattering at GeV
We report a high precision measurement of the transverse single spin
asymmetry at the center of mass energy GeV in elastic
proton-proton scattering by the STAR experiment at RHIC. The was measured
in the four-momentum transfer squared range \GeVcSq, the region of a significant interference between the
electromagnetic and hadronic scattering amplitudes. The measured values of
and its -dependence are consistent with a vanishing hadronic spin-flip
amplitude, thus providing strong constraints on the ratio of the single
spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated
by the Pomeron amplitude at this , we conclude that this measurement
addresses the question about the presence of a hadronic spin flip due to the
Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure
Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV
We report a measurement of the longitudinal double-spin asymmetry A_LL and
the differential cross section for inclusive Pi0 production at midrapidity in
polarized proton collisions at sqrt(s) = 200 GeV. The cross section was
measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be
in good agreement with a next-to-leading order perturbative QCD calculation.
The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T <
11 GeV/c and excludes a maximal positive gluon polarization in the proton. The
mean transverse momentum fraction of Pi0's in their parent jets was found to be
around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC
High non-photonic electron production in + collisions at = 200 GeV
We present the measurement of non-photonic electron production at high
transverse momentum ( 2.5 GeV/) in + collisions at
= 200 GeV using data recorded during 2005 and 2008 by the STAR
experiment at the Relativistic Heavy Ion Collider (RHIC). The measured
cross-sections from the two runs are consistent with each other despite a large
difference in photonic background levels due to different detector
configurations. We compare the measured non-photonic electron cross-sections
with previously published RHIC data and pQCD calculations. Using the relative
contributions of B and D mesons to non-photonic electrons, we determine the
integrated cross sections of electrons () at 3 GeV/10 GeV/ from bottom and charm meson decays to be = 4.0({\rm
stat.})({\rm syst.}) nb and =
6.2({\rm stat.})({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure
Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at GeV
We present first measurements of the evolution of the differential transverse
momentum correlation function, {\it C}, with collision centrality in Au+Au
interactions at GeV. {\it C} exhibits a strong dependence
on collision centrality that is qualitatively similar to that of number
correlations previously reported. We use the observed longitudinal broadening
of the near-side peak of {\it C} with increasing centrality to estimate the
ratio of the shear viscosity to entropy density, , of the matter formed
in central Au+Au interactions. We obtain an upper limit estimate of
that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.
Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV
We present measurements of the charge balance function, from the charged
particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au
collisions at 200 GeV using the STAR detector at RHIC. We observe that the
balance function is boost-invariant within the pseudorapidity coverage [-1.3,
1.3]. The balance function properly scaled by the width of the observed
pseudorapidity window does not depend on the position or size of the
pseudorapidity window. This scaling property also holds for particles in
different transverse momentum ranges. In addition, we find that the width of
the balance function decreases monotonically with increasing transverse
momentum for all centrality classes.Comment: 6 pages, 3 figure
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