A dynamic role of mastermind-like 1. A journey through the main (path)ways between development and cancer

Major signaling pathways, such as Notch, Hedgehog (Hh), Wnt/β-catenin and Hippo, are targeted by a plethora of physiological and pathological stimuli, ultimately resulting in the modulation of genes that act coordinately to establish specific biological processes. Many biological programs are strictly controlled by the assembly of multiprotein complexes into the nucleus, where a regulated recruitment of specific transcription factors and coactivators on gene promoter region leads to different transcriptional outcomes. MAML1 results to be a versatile coactivator, able to set up synergistic interlinking with pivotal signaling cascades and able to coordinate the network of cross-talking pathways. Accordingly, despite its original identification as a component of the Notch signaling pathway, several recent reports suggest a more articulated role for MAML1 protein, showing that it is able to sustain/empower Wnt/β-catenin, Hh and Hippo pathways, in a Notch-independent manner. For this reason, MAML1 may be associated to a molecular “switch”, with the function to control the activation of major signaling pathways, triggering in this way critical biological processes during embryonic and post-natal life. In this review, we summarize the current knowledge about the pleiotropic role played by MAML proteins, in particular MAML1, and we recapitulate how it takes part actively in physiological and pathological signaling networks. On this point, we also discuss the contribution of MAML proteins to malignant transformation. Accordingly, genetic alterations or impaired expression of MAML proteins may lead to a deregulated crosstalk among the pathways, culminating in a series of pathological disorders, including cancer development. Given their central role, a better knowledge of the molecular mechanisms that regulate the interplay of MAML proteins with several signaling pathways involved in tumorigenesis may open up novel opportunities for an attractive molecular targeted anticancer therapy

GNAM and OHP: Monitoring Tools for ATLAS experiment at LHC.

ATLAS is one of the four experiments under construction along the Large Hadron Collider (LHC) ring at CERN. The LHC will produce interactions at a center-of-mass energy equal to âs = 14 TeV at 40 MHz rate. The detector consists of more than 140 million electronic channels. The challenging experimental environment and the extreme detector complexity impose the necessity of a common scalable distributed monitoring framework, which can be tuned for the optimal use by different ATLAS sub-detectors at the various levels of the ATLAS data flow. This note presents two monitoring tools that have been developed for this aim within the architecture ATLAS Monitoring Framework and the Data Acquisition System: GNAM and OHP. The first one is a framework for online histogram production; the second one is graphical application for histogram presentation. This tools are now widely used during the ATLAS commissioning and their performances are reported in this not

Limits on Dark Matter Effective Field Theory Parameters with CRESST-II

CRESST is a direct dark matter search experiment, aiming for an observation of nuclear recoils induced by the interaction of dark matter particles with cryogenic scintillating calcium tungstate crystals. Instead of confining ourselves to standard spin-independent and spin-dependent searches, we re-analyze data from CRESST-II using a more general effective field theory (EFT) framework. On many of the EFT coupling constants, improved exclusion limits in the low-mass region (< 3-4 GeV) are presented.Comment: 7 pages, 9 figure

COSINUS: Cryogenic Calorimeters for the Direct Dark Matter Search with NaI Crystals

COSINUS (Cryogenic Observatory for SIgnatures seen in Next-generation Underground Searches) is an experiment employing cryogenic calorimeters, dedicated to direct dark matter search in underground laboratories. Its goal is to cross-check the annual modulation signal the DAMA collaboration has been detecting for about 20 years (Bernabei et al. in Nucl Part Phys Proc 303-305:74-79, 2018. 10.1016/j.nuclphysbps.2019.03.015) and which has been ruled out by other experiments in certain dark matter scenarios. COSINUS can provide a model-independent test by the use of the same target material (NaI), with the additional chance of discriminating beta/gamma events from nuclear recoils on an event-by-event basis, by the application of a well-established temperature sensor technology developed within the CRESST collaboration. Each module is constituted by two detectors: the light detector, that is a silicon beaker equipped with a transition edge sensor (TES), and the phonon detector, a small cubic NaI crystal interfaced with a carrier of a harder material (e.g. CdWO4), also instrumented with a TES. This technology had so far never been applied to NaI crystals because of several well-known obstacles, and COSINUS is the first experiment which succeeded in operating NaI crystals as cryogenic calorimeters. Here, we present the COSINUS project, describe the achievements and the challenges of the COSINUS prototype development and discuss the status and the perspectives of this NaI-based cryogenic frontier

Electronic and Magnetic Structures of Sr2FeMoO6

We have investigated the electronic and magnetic structures of Sr2FeMoO6 employing site-specific direct probes, namely x-ray absorption spectroscopy with linearly and circularly polarized photons. In contrast to some previous suggestions, the results clearly establish that Fe is in the formal trivalent state in this compound. With the help of circularly polarized light, it is unambiguously shown that the moment at the Mo sites is below the limit of detection (< 0.25mu_B), resolving a previous controversy. We also show that the decrease of the observed moment in magnetization measurements from the theoretically expected value is driven by the presence of mis-site disorder between Fe and Mo sites.Comment: To appear in Physical Review Letter

First results from the CRESST-III low-mass dark matter program

The CRESST experiment is a direct dark matter search which aims to measure interactions of potential dark matter particles in an earth-bound detector. With the current stage, CRESST-III, we focus on a low energy threshold for increased sensitivity towards light dark matter particles. In this manuscript we describe the analysis of one detector operated in the first run of CRESST-III (05/2016-02/2018) achieving a nuclear recoil threshold of 30.1eV. This result was obtained with a 23.6g CaWO$_4$ crystal operated as a cryogenic scintillating calorimeter in the CRESST setup at the Laboratori Nazionali del Gran Sasso (LNGS). Both the primary phonon/heat signal and the simultaneously emitted scintillation light, which is absorbed in a separate silicon-on-sapphire light absorber, are measured with highly sensitive transition edge sensors operated at ~15mK. The unique combination of these sensors with the light element oxygen present in our target yields sensitivity to dark matter particle masses as low as 160MeV/c$^2$.Comment: 9 pages, 9 figure

Measurement of the branching fraction for the decay KS --> pi e nu

We present a measurement of the branching ratio BR(KS --> pi e nu) performed using the KLOE detector. KS mesons are produced in the reaction e+ e- --> phi --> KS KL at the DAFNE collider. In a sample of about 5 million KS-tagged events we find 624 +- 30 semileptonic KS decays. Normalizing to the KS --> pi+ pi- count in the same data sample, we obtain BR(KS --> pi e nu) = (6.91 +- 0.37) 10^-4, in agreement with the Standard Model expectation.Comment: 9 pages, 5 Encapsulated Postscript figures. Submitted to Phys. Lett.

System Test of the ATLAS Muon Spectrometer in the H8 Beam at the CERN SPS

An extensive system test of the ATLAS muon spectrometer has been performed in the H8 beam line at the CERN SPS during the last four years. This spectrometer will use pressurized Monitored Drift Tube (MDT) chambers and Cathode Strip Chambers (CSC) for precision tracking, Resistive Plate Chambers (RPCs) for triggering in the barrel and Thin Gap Chambers (TGCs) for triggering in the end-cap region. The test set-up emulates one projective tower of the barrel (six MDT chambers and six RPCs) and one end-cap octant (six MDT chambers, A CSC and three TGCs). The barrel and end-cap stands have also been equipped with optical alignment systems, aiming at a relative positioning of the precision chambers in each tower to 30-40 micrometers. In addition to the performance of the detectors and the alignment scheme, many other systems aspects of the ATLAS muon spectrometer have been tested and validated with this setup, such as the mechanical detector integration and installation, the detector control system, the data acquisition, high level trigger software and off-line event reconstruction. Measurements with muon energies ranging from 20 to 300 GeV have allowed measuring the trigger and tracking performance of this set-up, in a configuration very similar to the final spectrometer. A special bunched muon beam with 25 ns bunch spacing, emulating the LHC bunch structure, has been used to study the timing resolution and bunch identification performance of the trigger chambers. The ATLAS first-level trigger chain has been operated with muon trigger signals for the first time

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of s√=7TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV