The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies

VHMPID: a new detector for the ALICE experiment at LHC

This article presents the basic idea of VHMPID, an upgrade detector for the ALICE experiment at LHC, CERN. The main goal of this detector is to extend the particle identification capabilities of ALICE to give more insight into the evolution of the hot and dense matter created in Pb-Pb collisions. Starting from the physics motivations and working principles the challenges and current status of development is detailed.Comment: 4 pages, 6 figures. To be published in EPJ Web of Conference

A study of the centrally produced phiphi system in pp interactions at 450 GeV/c

The reaction pp to pfps(K+K-K+K-) in which the K+K-K+K- system is centrally produced has been studied at 450 GeV/c. Phi phi production has been found to dominate this reaction and is compatible with being produced by double Pomeron exchange. An angular analysis of the phi phi system favours JPC = 2++ and its dPT dependence is similar to that observed for glueball candidates.Comment: 11 pages, Latex, 4 Figure

Measurements of charmed-meson production in interactions between 350 GeV/c π−\pi^- particles and nuclei

Charmed-meson production by $350$~GeV/$c$ {$\pi^-$} particles incident on copper and tungsten targets has been studied in the WA$92$ experiment, performed at the CERN $\Omega^\prime$ spectrometer. Results obtained are reported and discussed. Reconstruction of decays from the set ${\rm D}^0 \rightarrow {\rm K}^- \pi^+$, ${\rm D}^0 \rightarrow {\rm K}^- \pi^- \pi^+ \pi^+$, ${\rm D}^+ \rightarrow {\rm K}^- \pi^+ \pi^+$, ${{\rm D}_{\rm s}}^+ \rightarrow \phi \pi^+$ and charge conjugates has yielded a sample of $7280 \pm 108$ charmed mesons, produced with \xf > 0, \langle \xf \rangle = 0.18 and \langle {\pt}^2 \rangle = 1.86~{\rm (GeV/}c{\rm )}^2. Assuming a relationship $\sigma = \sigma_0 A^\alpha$ between the cross-section, $\sigma$, per nucleus of mass $A$ and the nucleonic cross-section, $\sigma_0$, the $\alpha$ value found for the detected charmed particles is $0.95 \pm 0.06 \pm 0.03$. Taking $\alpha = 1$, the measured cross-sections per nucleon for \xf > 0 production are $7.78 \pm 0.14 \pm 0.52$~$\mu$barn for ${\rm D}^0$/$\bar{\rm D}^0$, $3.28 \pm 0.08 \pm 0.29$~$\mu$barn for ${\rm D}^+$/${\rm D}^-$ and $1.29 \pm 0.16 \pm 0.33$~$\mu$barn for ${{\rm D}_{\rm s}}^+$/${{\rm D}_{\rm s}}^-$. Differential cross-sections with respect to \xf and {\pt}^2 have been determined for the various types of charmed meson, and particle-antiparticle asymmetries have been analysed

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87