In vivo and in vitro studies of [M(η6-pseudoerlotinib)2]+ sandwich complexes (M = Re, 99mTc)

The pursuit of molecular imaging for tumors has led to endeavors focused on targeting epidermal growth factor receptors (EGFR) through monoclonal antibodies or radionuclide-labelled EGF analogs with 99mTc, 111In, or 131I. In this context, various 99mTc-labeled EGFR inhibitors using quinazoline structures have been reported based on the so-called pendant approach and on two types of complexes and labelling strategies: “4 + 1” mixed ligand complexes and fac-tricarbonyl complexes. Apart from this approach, which alters lead structures by linking pharmacophores to chelator frameworks through different connectors, the integrated incorporation of topoisomerase and tyrosine kinase inhibitors into Re and 99mTc complexes has not been explored. Here we present [M(η6-inhibitor)2]+ (M = Re, 99mTc) and [Re(η6-bz)(η6-inhibitor)]+ complexes, where the core structure of an EGFR tyrosine kinase inhibitor binds directly to the metal center. These complexes exhibit potential for tumor imaging: initial biological investigations highlight the influence of one versus two bound inhibitors on the metal center

The RESEARCH project. Soil-related hazards and archaeological heritage in the challenge of climate change

Archaeological Heritage, naturally endangered by environmental processes and anthropogenic pressures, is today increasingly at risk, because of intense human activities and climate change, and their impact on atmosphere and soil. European research is increasingly dedicated to the development of good practices for monitoring archaeological sites and their preservation. One of the running projects about these topics is RESEARCH (Remote Sensing techniques for Archaeology; H2020-MSCA-RISE, grant agreement: 823987), started in 2018 and ending in 2022. RESEARCH aims at testing risk assessment methodology using an integrated system of documentation and research in the fields of archaeology and environmental studies. It will introduce a strategy and select the most efficient tools for the harmonization of different data, criteria, and indicators in order to produce an effective risk assessment. These will be used to assess and monitor the impact of soil erosion, land movement, and land-use change on tangible archaeological heritage assets. As a final product, the Project addresses the development of a multi-task thematic platform, combining advanced remote sensing technologies with GIS application. The demonstration and validation of the Platform will be conducted on six case studies located in Italy, Greece, Cyprus, and Poland, and variously affected by the threats considered by the Project. In the frame of RISE (Research and Innovation Staff Exchange), RESEARCH will coordinate the existing expertise and research efforts of seven beneficiaries into a synergetic plan of collaborations and exchanges of personnel (Ph.D. students and research staff), to offer a comprehensive transfer of knowledge and training environment for the researchers in the specific area. This paper aims at illustrating the results of the activities conducted during the first year of the Project, which consisted in developing an effective risk assessment methodology for soil-related threats affecting archaeological heritage, and defining the scientific requirements and the user requirements of the Platform. The activities have been conducted in synergy with all the Partners and were supported by the possibility of staff exchange allowed by the funding frame MSCA-RISE

In a Small Moment: Class Size and Moral Hazard in the Italian Mezzogiorno

Instrumental variables (IV) estimates show strong class-size effects in Southern Italy. But Italy's Mezzogiorno is distinguished by manipulation of standardized test scores as well as by economic disadvantage. IV estimates suggest small classes increase manipulation. We argue that score manipulation is a consequence of teacher shirking. IV estimates of a causal model for achievement as a function of class size and score manipulation show that class-size effects on measured achievement are driven entirely by the relationship between class size and manipulation. These results illustrate how consequential score manipulation can arise even in assessment systems with few accountability concerns

Design of a high power production target for the Beam Dump Facility at CERN

The Beam Dump Facility (BDF) project is a proposed general-purpose facility at CERN, dedicated to beam dump and fixed target experiments. In its initial phase, the facility is foreseen to be exploited by the Search for Hidden Particles (SHiP) experiment. Physics requirements call for a pulsed 400 GeV/c proton beam as well as the highest possible number of protons on target (POT) each year of operation, in order to search for feebly interacting particles. The target/dump assembly lies at the heart of the facility, with the aim of safely absorbing the full high intensity Super Proton Synchrotron (SPS) beam, while maximizing the production of charmed and beauty mesons. High-Z materials are required for the target/dump, in order to have the shortest possible absorber and reduce muon background for the downstream experiment. The high average power deposited on target (305 kW) creates a challenge for heat removal. During the BDF facility Comprehensive Design Study (CDS), launched by CERN in 2016, extensive studies have been carried out in order to define and assess the target assembly design. These studies are described in the present contribution, which details the proposed design of the BDF production target, as well as the material selection process and the optimization of the target configuration and beam dilution. One of the specific challenges and novelty of this work is the need to consider new target materials, such as a molybdenum alloy (TZM) as core absorbing material and Ta2.5W as cladding. Thermo-structural and fluid dynamics calculations have been performed to evaluate the reliability of the target and its cooling system under beam operation. In the framework of the target comprehensive design, a preliminary mechanical design of the full target assembly has also been carried out, assessing the feasibility of the whole target system.Comment: 17 pages, 18 figure

Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model

Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO2), the aim of this study was to investigate the effectiveness and safety of different DO2, using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO2 (p = 0.008) and oxygen consumption ( V O \u2d9 2) (p < 0.001); lactate clearance (p < 0.001), potassium (p < 0.001), and glucose (p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM (p = 0.031). V O \u2d9 2 and DO2 were highly correlated (p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO2 and V O \u2d9 2. No human RBC related damage was detected. In conclusion, an optimized DO2 significantly reduces hypoxic damage-related effects occurring during NMP. Human RBCs can be safely used as oxygen carriers

Development of a custom on-line ultrasonic vapour analyzer/flowmeter for the ATLAS inner detector, with application to gaseous tracking and Cherenkov detectors

Precision sound velocity measurements can simultaneously determine binary gas composition and flow. We have developed an analyzer with custom electronics, currently in use in the ATLAS inner detector, with numerous potential applications. The instrument has demonstrated ~0.3% mixture precision for C3F8/C2F6 mixtures and < 10-4 resolution for N2/C3F8 mixtures. Moderate and high flow versions of the instrument have demonstrated flow resolutions of +/- 2% F.S. for flows up to 250 l.min-1, and +/- 1.9% F.S. for linear flow velocities up to 15 ms-1; the latter flow approaching that expected in the vapour return of the thermosiphon fluorocarbon coolant recirculator being built for the ATLAS silicon tracker.Comment: Paper submitted to TWEPP2012; Topical Workshop on Electronics for Particle Physics, Oxford, UK, September 17-21, 2012. KEYWORDS: Sonar; Saturated fluorocarbons; Flowmetry; Sound velocity, Gas mixture analysis. 8 pages, 7 figure

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation.Comment: Technical Proposa

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson