Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming.

Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules

Mild Pd-Catalyzed Aminocarbonylation of (Hetero)Aryl Bromides with a Palladacycle Precatalyst

A palladacyclic precatalyst is employed to cleanly generate a highly active XantPhos-ligated Pd-catalyst. Its use in low temperature aminocarbonylations of (hetero)aryl bromides provides access to a range of challenging products in good to excellent yields with low catalyst loading and only a slight excess of CO. Some products are unattainable by traditional carbonylative coupling.National Institutes of Health (U.S.) (Award GM46059)Danish National Research Foundation (Grant DNRF59)Villum FoundationDanish Council for Independent Researc

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Utilisation des methodes nucleaires d'analyse en ultra-vide. Application au dosage de l'hydrogene dans les solides

SIGLEAvailable from CEN Saclay, Service de Documentation, 91191 Gif-sur-Yvette Cedex (France) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

UHV equipment for in situ studies of hydrogen interaction with materials based on NRA

For the application of the $^1H(^{15}N, \alpha\gamma)^{12}C$ resonant nuclear reaction to hydrogen measurement in surface studies, an ultrahigh vacuum equipment (2 × 10${-8}$Pa) has been developed which includes two interconnected UHV chambers for analysis and target preparation, respectively. The analysis chamber equipped with a quadrupole mass spectrometer and a precision leak valve for gas admission, is connected to a 4 MV Van de Graaff accelerator through a two-stage differentially pumped beam line. The beam intensity is monitored with a transmission Faraday cup. Samples can be analysed at controlled temperature over the range 300–700 K. The preparation chamber is equipped with a sputter ion gun, an electron bombardment gun for high-temperature heating and an electron beam evaporation station for thin film deposition. The performance of the system will be discussed through the following applications. Hydrogen concentration in sputtered thin films (20–30 nm) of amorphous Cu-Zr alloys has been measured from room temperature to crystallization temperature. Preliminary results have been obtained in a study of hydrogen adsorption on polycrystalline nickel

Establishing PIXE Analysis Conditions for Sweat Analysis

This paper describes a technical analysis of biological samples of sweat by proton induced X-ray emission (hereafter referred to as PIXE). The choice of the irradiation conditions, the preparation of the targets, and the processing treatment of spectra are described. Two excitation systems were used, one under vacuum and the other in atmospheric pressure under helium. Advantages and disadvantages of the two systems are described and detection limits obtained in both cases are presented. A comparison with results obtained by X-ray analysis induced by radioactive sources is made

[Pd(IPr*)(acac)Cl]: An Easily Synthesized, Bulky Precatalyst for C–N Bond Formation

A very straightforward synthesis of [Pd­(IPr*)­(acac)­Cl] has been developed from commercially available Pd­(acac)₂ and the easily prepared IPr*·HCl (acac = acetylacetonate; IPr* = <i>N</i>,<i>N</i>′-bis­(2,6-bis­(diphenylmethyl)-4-methylphenyl)­imidazol-2-ylidene). The reactivity of the resulting complex [Pd­(IPr*)­(acac)­Cl] (<b>1</b>) as a highly active Pd^II precatalyst for the Buchwald–Hartwig arylamination coupling has been explored. A wide range of substrates with varying electronic and steric demands of both coupling partners has been screened successfully. The chemoselectivity of the reaction was also explored by using aryl heterodihalides