Le risque de vivre

Myocardial constitutive No production depends on the activity of both endothelial and neuronal NOS (eNOS and nNOS, respectively). Stimulation of myocardial β(3)-adrenergic receptor (β(3)-AR) produces a negative inotropic effect that is dependent on eNOS. We evaluated whether nNOS also plays a role in β(3)-AR signaling and found that the β(3)-AR-mediated reduction in cell shortening and [Ca(2+)](i) transient amplitude was abolished both in eNOS(−/−) and nNOS(−/−) left ventricular (LV) myocytes and in wild type LV myocytes after nNOS inhibition with S-methyl-l-thiocitrulline. LV superoxide (O(2)(˙̄)) production was increased in nNOS(−/−) mice and reduced by l-N(ω)-nitroarginine methyl ester (l-NAME), indicating uncoupling of eNOS activity. eNOS S-glutathionylation and Ser-1177 phosphorylation were significantly increased in nNOS(−/−) myocytes, whereas myocardial tetrahydrobiopterin, eNOS Thr-495 phosphorylation, and arginase activity did not differ between genotypes. Although inhibitors of xanthine oxidoreductase (XOR) or NOX2 NADPH oxidase caused a similar reduction in myocardial O(2)(˙̄), only XOR inhibition reduced eNOS S-glutathionylation and Ser-1177 phosphorylation and restored both eNOS coupled activity and the negative inotropic and [Ca(2+)](i) transient response to β(3)-AR stimulation in nNOS(−/−) mice. In summary, our data show that increased O(2)(˙̄) production by XOR selectively uncouples eNOS activity and abolishes the negative inotropic effect of β(3)-AR stimulation in nNOS(−/−) myocytes. These findings provide unequivocal evidence of a functional interaction between the myocardial constitutive NOS isoforms and indicate that aspects of the myocardial phenotype of nNOS(−/−) mice result from disruption of eNOS signaling

“Plug and play” modular façade construction system for building renovation to achieve nearly Zero Energy Building (nZEB)

Following energy performance improvement policies, there is a need for the massive renovation of the European building stock. The prevalence of multi-rise buildings with concrete structure and poor thermal performance offers a significant opportunity for renovation packages that facilitate the improvement of the building fabric, with its insulation, air-tightness and integration of building services and solar technologies. The RenoZEB project develops a "plug and play" modular facade construction system answering to this need. This prefabricated plug and play modular system has been tested by reproducing the holistic methodology and new technologies in the market by means of real and virtual demonstrators. The applicability and effectiveness of the methodology has been tested by means of a full-scale mock-up system has been constructed and installed in the KUBIK by Tecnalia test facility. The design, construction, manufacture & installation cycle has been tested. Its applicability for a real construction project for a multi-rise residential building in Spain is presented.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 768718

Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers

While pralatrexate (PDX) has been successfully developed for the treatment of T-cell lymphoma, the mechanistic basis for its T-cell selectivity and acquired resistance remains elusive. In an effort to potentially identify synergistic combinations that might circumnavigate or delay acquired PDX resistance, we generated resistant cells lines over a broad concentration range. PDX-resistant cell lines H9-12 and H9-200 were developed, each exhibiting an IC50 of 35 and over 1000 nM, respectively. These lines were established in vitro from parental H9 cells. Expression analysis of the proteins known to be important determinants of antifolate pharmacology revealed increase expression of dihydrofolate reductase (DHFR) due to gene amplification, and reduced folate carrier1 downregulation, as the putative mechanisms of resistance in H9-12 and H9-200 cells. Cross resistance was only seen with methotrexate but not with romidepsin, azacitidine (AZA), decitabine, gemcitabine, doxorubicin, or bortezomib. Resistance to PDX was reversed by pretreatment with hypomethylating agents in a concentration-dependent fashion. Comparison of gene expression profiles of parental and resistant cell lines confirmed markedly different patterns of gene expression, and identified the dual specificity phosphatase four (DUSP4) as one of the molecular target of PDX activity. Reduced STAT5 phosphorylation following exposure to PDX was observed in the H9 but not in the H9-12 and H9-200 cells. These data suggest that combination with hypomethylating agents could be potent, and that DUSP4 and STAT5 could represent putative biomarkers of PDX activity

The Ring Imaging Cherenkov detector (RICH) of the AMS experiment

The Alpha Magnetic Spectrometer (AMS) experiment to be installed on the International Space Station (ISS) will be equipped with a proximity focusing Ring Imaging Cherenkov (RICH) detector for measuring the electric charge and velocity of the charged cosmic particles. A RICH prototype consisting of 96 photomultiplier units, including a piece of the conical reflector, was built and its performance evaluated with ion beam data. Preliminary results of the in-beam tests performed with ion fragments resulting from collisions of a 158 GeV/c/nuc primary beam of Indium ions (CERN SPS) on a Pb target are reported. The collected data included tests to the final front-end electronics and to different aerogel radiators. Cherenkov rings for a large range of charged nuclei and with reflected photons were observed. The data analysis confirms the design goals. Charge separation up to Fe and velocity resolution of the order of 0.1% for singly charged particles are obtained.Comment: 29th International Conference on Cosmic Rays (Pune, India

The AMS-RICH velocity and charge reconstruction

The AMS detector, to be installed on the International Space Station, includes a Ring Imaging Cerenkov detector with two different radiators, silica aerogel (n=1.05) and sodium fluoride (n=1.334). This detector is designed to provide very precise measurements of velocity and electric charge in a wide range of cosmic nuclei energies and atomic numbers. The detector geometry, in particular the presence of a reflector for acceptance purposes, leads to complex Cerenkov patterns detected in a pixelized photomultiplier matrix. The results of different reconstruction methods applied to test beam data as well as to simulated samples are presented. To ensure nominal performances throughout the flight, several detector parameters have to be carefully monitored. The algorithms developed to fulfill these requirements are presented. The velocity and charge measurements provided by the RICH detector endow the AMS spectrometer with precise particle identification capabilities in a wide energy range. The expected performances on light isotope separation are discussed.Comment: Contribution to the ICRC07, Merida, Mexico (2007); Presenter: F. Bara

The RICH detector of the AMS-02 experiment: status and physics prospects

The Alpha Magnetic Spectrometer (AMS), whose final version AMS-02 is to be installed on the International Space Station (ISS) for at least 3 years, is a detector designed to measure charged cosmic ray spectra with energies up to the TeV region and with high energy photon detection capability up to a few hundred GeV. It is equipped with several subsystems, one of which is a proximity focusing RICH detector with a dual radiator (aerogel+NaF) that provides reliable measurements for particle velocity and charge. The assembly and testing of the AMS RICH is currently being finished and the full AMS detector is expected to be ready by the end of 2008. The RICH detector of AMS-02 is presented. Physics prospects are briefly discussed.Comment: 5 pages. Contribution to the 10th ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications (Como 2007). Presenter: Rui Pereir

Unintentional high density p-type modulation doping of a GaAs/AlAs core-multi-shell nanowire

Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of considerable technological importance but remains a challenge due to the amphoteric behavior of the dopant atoms. Here we show that placing a narrow GaAs quantum well in the AlAs shell effectively getters residual carbon acceptors leading to an \emph{unintentional} p-type doping. Magneto-optical studies of such a GaAs/AlAs core multi-shell NW reveal quantum confined emission. Theoretical calculations of NW electronic structure confirm quantum confinement of carriers at the core/shell interface due to the presence of ionized carbon acceptors in the 1~nm GaAs layer in the shell. Micro-photoluminescence in high magnetic field shows a clear signature of avoided crossings of the $n=0$ Landau level emission line with the $n=2$ Landau level TO phonon replica. The coupling is caused by the resonant hole-phonon interaction, which points to a large 2D hole density in the structure.Comment: just published in Nano Letters (http://pubs.acs.org/doi/full/10.1021/nl500818k

Nitric oxide synthase isoforms play distinct roles during acute peritonitis

Background. Acute peritonitis is the most frequent complication of peritoneal dialysis (PD). Increased nitric oxide (NO) release by NO synthase (NOS) isoforms has been implicated in acute peritonitis, but the role played by the NOS isoforms expressed in the peritoneum is unknown

Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58\u2005years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40\u2005mm (2-200)), 9% had resection beyond 1\u2005year of follow-up (3\u2005years (1-20), size at diagnosis: 25\u2005mm (4-140)) and 39% had no surgery (3.6\u2005years (1-23), 25.5\u2005mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1\u2005year (n=1271), size increased in 37% (growth rate: 4\u2005mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN

The Spectrometer/Telescope for Imaging X-rays (STIX)

Aims. The Spectrometer Telescope for Imaging X-rays (STIX) on Solar Orbiter is a hard X-ray imaging spectrometer, which covers the energy range from 4 to 150 keV. STIX observes hard X-ray bremsstrahlung emissions from solar flares and therefore provides diagnostics of the hottest (⪆10 MK) flare plasma while quantifying the location, spectrum, and energy content of flare-accelerated nonthermal electrons. Methods. To accomplish this, STIX applies an indirect bigrid Fourier imaging technique using a set of tungsten grids (at pitches from 0.038 to 1 mm) in front of 32 coarsely pixelated CdTe detectors to provide information on angular scales from 7 to 180 arcsec with 1 keV energy resolution (at 6 keV). The imaging concept of STIX has intrinsically low telemetry and it is therefore well-suited to the limited resources available to the Solar Orbiter payload. To further reduce the downlinked data volume, STIX data are binned on board into 32 selectable energy bins and dynamically-adjusted time bins with a typical duration of 1 s during flares. Results. Through hard X-ray diagnostics, STIX provides critical information for understanding the acceleration of electrons at the Sun and their transport into interplanetary space and for determining the magnetic connection of Solar Orbiter back to the Sun. In this way, STIX serves to link Solar Orbiter’s remote and in-situ measurements