Oncogenic Stress Induced by Acute Hyper-Activation of Bcr-Abl Leads to Cell Death upon Induction of Excessive Aerobic Glycolysis

In response to deregulated oncogene activation, mammalian cells activate disposal programs such as programmed cell death. To investigate the mechanisms behind this oncogenic stress response we used Bcr-Abl over-expressing cells cultivated in presence of imatinib. Imatinib deprivation led to rapid induction of Bcr-Abl activity and over-stimulation of PI3K/Akt-, Ras/MAPK-, and JAK/STAT pathways. This resulted in a delayed necrosis-like cell death starting not before 48 hours after imatinib withdrawal. Cell death was preceded by enhanced glycolysis, glutaminolysis, and amino acid metabolism leading to elevated ATP and protein levels. This enhanced metabolism could be linked to induction of cell death as inhibition of glycolysis or glutaminolysis was sufficient to sustain cell viability. Therefore, these data provide first evidence that metabolic changes induced by Bcr-Abl hyper-activation are important mediators of oncogenic stress-induced cell death

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53–442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 >8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

published_or_final_versio

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Measurement of the cross section for inclusive isolated-photon production in pp collisions at √s=13TeV using the ATLAS detector

Inclusive isolated-photon production in pp collisions at a centre-of-mass energy of 13TeVis studied with the ATLAS detector at the LHC using a data set with an integrated luminosity of 3.2fb−1. The cross section is measured as a function of the photon transverse energy above 125GeVin different regions of photon pseudorapidity. Next-to-leading-order perturbative QCD and Monte Carlo event-generator predictions are compared to the cross-section measurements and provide an adequate description of the data

Measurement of W+W− production in association with one jet in proton–proton collisions at sqrt(s) = 8TeV with the ATLAS detector

The production of W boson pairs in association with one jet in pp collisions at View the MathML sources=8 TeV is studied using data corresponding to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector during 2012 at the CERN Large Hadron Collider. The cross section is measured in a fiducial phase-space region defined by the presence of exactly one electron and one muon, missing transverse momentum and exactly one jet with a transverse momentum above 25 GeV and a pseudorapidity of |η|<4.5|η|<4.5. The leptons are required to have opposite electric charge and to pass transverse momentum and pseudorapidity requirements. The fiducial cross section is found to be View the MathML sourceσWWfid,1-jet=136±6(stat)±14(syst)±3(lumi) fb. In combination with a previous measurement restricted to leptonic final states with no associated jets, the fiducial cross section of WW production with zero or one jet is measured to be View the MathML sourceσWWfid,≤1-jet=511±9(stat)±26(syst)±10(lumi) fb. The ratio of fiducial cross sections in final states with one and zero jets is determined to be 0.36±0.050.36±0.05. Finally, a total cross section extrapolated from the fiducial measurement of WW production with zero or one associated jet is reported. The measurements are compared to theoretical predictions and found in good agreement

Search for pair production of Higgs bosons in the bb¯bb¯ final state using proton-proton collisions at √s=13 TeV with the ATLAS detector

A search for Higgs-boson pair production in the bb ¯ bb ¯ final state is carried out with 3.2  fb −1 of proton-proton collision data collected at s √ =13  TeV with the ATLAS detector. The data are consistent with the estimated background and are used to set upper limits on the production cross section of Higgs-boson pairs times branching ratio to bb ¯ bb ¯ for both nonresonant and resonant production. In the case of resonant production of Kaluza-Klein gravitons within the Randall-Sundrum model, upper limits in the 24 to 91 fb range are obtained for masses between 600 and 3000 GeV, at the 95% confidence level. The production cross section times branching ratio for nonresonant Higgs-boson pairs is also constrained to be less than 1.22 pb, at the 95% confidence level