1564 Background: The selective tyrosine kinase inhibitor imatinib mesylate (Gleevec) effectively inhibits the activity of the abl, PDGF receptor (PDGFR) and c-kit tyrosine kinases. Because of the specific target profile of this orally available and generally well tolerated drug, imatinib is under intensive investigation for the potential treatment of other diseases. Malignant gliomas frequently show a high expression of PDGF receptor which is involved in tumorigenesis by formation of an autocrine loop. A role in DNA repair carried out through c-abl and c-kit was previously described both for c-abl and c-kit. In this study we address the potential use of imatinib mesylate and concomitant ionizing radiation (IR) to improve the radiosensitivity of the glioblastoma cell line RuSi RS1.Cells of the primary glioblastoma cell line RuSi RS1, as well as of the colon cancer cell line WiDr and of BT20, a human breast cancer cell line, were incubated with different concentrations of imatinib mesylate 30 minutes prior to irradiation (doses between 0 and 16 Gy). Western blots were done comparing the different expression of c-abl, PDGFR alpha and beta, and c-kit in the different cell lines. Immunoprecipitation was performed to assess inhibition of the different kinases by imatinib mesylate.Under combined treatment with imatinib and IR a significant shift of the IC50 (dose needed to reduce the survival fraction by 50%) was detected in RuSi RS1 compared to IR alone. This effect was not seen in WiDr or BT20. RuSi RS1 showed an overexpression of PDGFR beta. Inhibition of tyrosine kinase phosphorylation by imatinib could be shown for PDGFR beta and c-abl (the IP failed for c-kit).Concomitant administration of imatinib mesylate and ionizing radiation increases the radiosensitivity of the glioblastoma cell line RuSi RS1. This effect might partly be due to disruption of an autocrine loop of the PDGF/PDGFR system. Inhibition of DNA repair mechanisms in which the tyrosine kinase activity of c-abl and c-kit is involved might be important causes of this observed phenomenon as well. No significant financial relationships to disclose.

The need for large-scale production of highly accurate simulated event samples for the extensive physics programme of the ATLAS experiment at the Large Hadron Collider motivates the development of new simulation techniques. Building on the recent success of deep learning algorithms, variational autoencoders and generative adversarial networks are investigated for modelling the response of the central region of the ATLAS electromagnetic calorimeter to photons of various energies. The properties of synthesised showers are compared with showers from a full detector simulation using geant4. Both variational autoencoders and generative adversarial networks are capable of quickly simulating electromagnetic showers with correct total energies and stochasticity, though the modelling of some shower shape distributions requires more refinement. This feasibility study demonstrates the potential of using such algorithms for ATLAS fast calorimeter simulation in the future and shows a possible way to complement current simulation techniques.

Abstract: The ratio of branching ratios of the W boson to muons and electrons, $$R^{\,\mu /e}_W={{\mathcal {B}}(W\rightarrow \mu u )}$$ R W μ / e = B ( W → μ ν ) /$${{\mathcal {B}}(W\rightarrow e u )}$$ B ( W → e ν ) , has been measured using $$140\,\text{ fb}^{-1}\,$$ 140 fb - 1 of pp collision data at $$\sqrt{s}=13$$ s = 13  $$\text {T}\text {e}\hspace{-1.00006pt}\text {V}$$ Te V collected with the ATLAS detector at the LHC, probing the universality of lepton couplings. The ratio is obtained from measurements of the $$t\bar{t}$$ t t ¯ production cross-section in the ee, $$e\mu $$ e μ and $$\mu \mu $$ μ μ dilepton final states. To reduce systematic uncertainties, it is normalised by the square root of the corresponding ratio $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e for the Z boson measured in inclusive $$Z\rightarrow ee$$ Z → e e and $$Z\rightarrow \mu \mu $$ Z → μ μ events. By using the precise value of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e determined from $$e^+e^-$$ e + e - colliders, the ratio $$R^{\,\mu /e}_W$$ R W μ / e is determined to be $$\begin{aligned} R^{\,\mu /e}_W&= 0.9995\pm 0.0022\,\mathrm {(stat)}\,\pm 0.0036\,\mathrm {(syst)}\ &\quad \pm 0.0014\,\mathrm {(ext)} . \end{aligned}$$ R W μ / e = 0.9995 ± 0.0022 ( stat ) ± 0.0036 ( syst ) ± 0.0014 ( ext ) . The three uncertainties correspond to data statistics, experimental systematics and the external measurement of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e , giving a total uncertainty of 0.0045, and confirming the Standard Model assumption of lepton flavour universality in W-boson decays at the 0.5% level.

A search for a long-lived, heavy neutral lepton (N) in 139  fb^{-1} of sqrt[s]=13  TeV pp collision data collected by the ATLAS detector at the Large Hadron Collider is reported. The N is produced via W→Nμ or W→Ne and decays into two charged leptons and a neutrino, forming a displaced vertex. The N mass is used to discriminate between signal and background. No signal is observed, and limits are set on the squared mixing parameters of the N with the left-handed neutrino states for the N mass range 3  GeV