Supplementary Methods, Figures 1-10 from Impaired Turnover of Prolactin Receptor Contributes to Transformation of Human Breast Cells

Ability of adapting to different users is considered key to maximize the impact and effectiveness of Serious Games (SGs). Advances in neurosciences are making it possible to continuously monitor the player status. This paper reports the research work on the monitoring of the player flow status with a simple (4 electrode) commercial electroencephalogram (EEG). In particular, we focus on three consequential research questions: is it possible to statistically distinguish a flow from a boredom condition? For which wavelengths? Can different levels of boredom and flow be identified? Results - even if limited because of the small size of the test, are promising and enable further research. Statistically significant differences could be observed for brainwaves under various conditions. A machine learning classifier (SVM) was successful in the 2-level distinction case, in particular with personalized training.

The breakdown voltage of radiation damaged polyimide is investigated. Motivated by the application of polyimide as insulator used in ion accelerator magnets of the future Facility for Antiproton and Ion Research (FAIR), two different kinds of polyimides were irradiated with different high energetic ion beams (p, C, Ni, Ru and Au) and with gamma radiation from a Co-60 source. Breakdown voltage measurements showed that the dielectric strength of irradiated polyimide was found to decrease as a function of the irradiation dose. The rate of decrease was found to be dependent on i) the type of radiation and ii) the angle of incident beam. Gamma and proton radiation leads only to minor changes in the observed dose regime while heavy ion irradiation drastically decreases the dielectric strength at even low doses. For heavy ion irradiation the rate of decrease is found to be dependent on the energy loss of the used particle beams. Furthermore an increase in incident beam angle, i.e. closer to the surface normal gives a lower decrease in the dielectric strength suggesting that the breakdown follows the path length of the produced ion tracks. Weibull analysis was used on a selected data set to discuss failure expectations for the later FAIR magnets.

Contribution of step-in geometric discontinuity to the longitudinal coupling impedance has been obtained analytically using exact field matching. We assumed a perfectly conducting beam-pipe wall of two different radii connected coaxially at z=0 so that the contribution to the longitudinal coupling impedance is purely due to the beam-pipe geometric discontinuity. We also obtained the longitudinal loss factor for a Gaussian beam as a function of beam energy and bunch length. Results have been analyzed numerically for some representative parameters close to real machine parameters. Analytical results have also been compared with numerical simulation from CST at relativistic beam energies. We found a very good agreement between theory and simulation.

Abstract Signaling by polypeptide hormone prolactin (PRL) is mediated by its cognate receptor (PRLr). PRLr is commonly stabilized in human breast cancer due to decreased phosphorylation of residue Ser349, which when phosphorylated recruits the βTrcp E3 ubiquitin ligase and facilitates PRLr degradation. Here, we show that an impaired PRLr turnover results in an augmented PRL signaling and PRL-induced transcription. Human mammary epithelial cells harboring degradation-resistant PRLr display accelerated proliferation and increased invasive growth. Conversely, a decrease in PRLr levels achieved by either pharmacologic or genetic means in human breast cancer cells dramatically reduced transformation and tumorigenic properties of these cells. Consequences of alteration of PRLr turnover for homeostasis of mammary cells and development of breast cancers, as well as the utility of therapies that target PRLr function in these malignancies, are discussed. [Cancer Res 2009;69(7):3165–72]

The paper reviews the activities and reports the current results of GSI-INTAS projects that are dealing with investigations of construction materials for high-power accelerators and their components. Three types of materials have been investigated, namely metals (stainless steel and copper), metallic glasses (Nanoperm, Finemet and Vitrovac) and organic materials (polyimide insulators and glass fiber reinforced plastics/GFRP). The materials were irradiated by different ion beams with various fluencies and energies. The influence of radiation on selected physical properties of these materials has been investigated with the aid of gamma-ray spectroscopy, transmission Mossbauer spectroscopy (TMS), conversion electrons Mossbauer spectroscopy (CEMS), optical spectroscopy (IR and UV/VIS) and other analytical methods. Some experiments were accompanied with computer simulations by FLUKA, SHIELD and SRIM codes. Validity of the codes was verified by comparison of the simulation results with experiments. After the validation, the codes were used to complete the data that could not be obtained experimentally.

During long-term operation of the new FAIR facility, parts of the superconducting magnets will be exposed to high radiation levels, cryogenic temperatures, and dynamic mechanical loads (Lorentzian forces during pulsed operation). Depending on the position of the different components, the radiation due to beam losses consists of a cocktail of gammas, neutrons, protons, and heavier particles [1]. Although the number of heavy fragments of the initial projectiles is small compared to neutrons, protons, or light fragments (e.g. α particles), their large energy deposition can induce extensive damage at rather low fluences (dose calculations show that the contribution of heavy ions to the total accumulated dose can reach 80% [2]). In the MeV to GeV energy regime, beam-induced radiation damage strongly depends on the specific sensitivity of the material and scales with fluence and electronic energy loss of the ions. In particular, organic polymers to be used e.g., as cable insulation for the superconducting FAIR magnets, may undergo severe degradation accompanied by outgassing of small volatile radiolysis products [3,4]. This study tackles the dielectric strength of polyimide (Kapton) as electrical insulation and G11-type epoxy/glassfiber composites as structural support material. Kapton foils of thickness 12, 25, and 50 μm were irradiated with 21 and 800 MeV protons (ITEP) and with various heavy ions of MeV-GeV energy (UNILAC, GSI). In addition, three types of 1-mm thick epoxy/glassfiber sheets were exposed to 180-MeV/u Xe ions (SIS, GSI). The irradiation experiments with protons and Xe ions took place in air, while the UNILAC irradiations were performed in vacuum. To test degradation of the insulating properties, breakdown voltage measurements were carried out using a current-limited 20-kV high voltage tester available at CERN. The ramping speed of the DC voltage was 1.3 kV/s. The location of breakdown events was inspected by means of optical microscopy and typically occurred inside the Rogowski-type stainless steal electrodes having a diameter of 10 mm. Any significant geometric influence on the electric field is therefore excluded. The tests took place in air, at room temperature, and at a humidity of 24-30%. No systematic errors due to temperature and/or humidity fluctuations were found. For Kapton, the measurements show an overall decrease of the breakdown voltage with increasing dose (Fig. 1). For light projectiles, such as protons and C ions of rather small electronic energy loss (dE/dx between 0.03 and 0.5 keV/nm), the decrease of the breakdown voltage becomes significant at doses above 1 MGy. In the case of heavy ions (dE/dx .> 16 keV/nm), the breakdown voltage changes at a much lower dose (note the semi-log presentation of Fig. 1). The expected maximum voltage in the superconducting coils of the FAIR magnets is about 3 kV. In the tested dose regime up to ~80 MGy, the degradation due to light ions is insignificant for the operation voltage. The situation is much more crucial for heavy ions, where already a dose of a few kGy results in a severe decrease of the breakdown voltage. At around 0.1 MGy, the values are close to the voltage requirement for the FAIR magnets. These results give a first indication that individual tracks completely passing through the Kapton insulation may represent a serious security risk for the insulation of the FAIR magnet coils.

The design of an air-backed fiber-optic hydrophone is presented. With respect to the previous models this prototype is optimized to provide a bandwidth sufficiently large to detect acoustic signals produced by high energy hadronic showers in water. In addiction to the geometrical configuration and to the choice of the materials, the preliminary results of the measured performances in air are presented.

Passive, fiber-optics-based hydrophones are already used for marine acoustic positioning systems, oceanographic and geophysics research, as well as for military application. An existing concept has been optimized in order to increase device frequency bandwidth and operating depth, thus making the device attractive for new fields of application. A full-detailed design has been done and a prototype assembled to have an overview of all manufacturing issues. That hydrophone will be submitted to a full qualification test campaign, to validate the design approach in view of further optimization.

We describe how we have realized the prototype of an optic fiber air backed mandrel hydrophone designed to measure frequencies up to 20 kHz. The characteristics of the materials we have selected, the procedure of winding the optic fibers and the coating process are described in detail.

We have studied the design of an air-backed optic fiber hydrophone. With respect to the previous models, this prototype is optimized to provide a band width sufficiently large to detect acoustic signals produced by high energy hadronic showers in water. After a discussion on the geometrical configuration and on the choice of the materials we evaluate the expected performances on the basis of simple analytical calculations.

Transport properties of Mn-doped ruthenium silicide Ru2Si3 were studied both experimentally and theoretically. The precipitation-free Ru2Si3 single crystals were grown by the zone melting technique with radiation heating. The temperature dependence of the electrical resistivity and Hall coefficients of the crystals were measured. The electrical resistivity of 1% Mn-doped Ru2Si3 was lower than that of undoped crystals. The carrier concentration in the doped samples is about 1018 cm−3 at room temperature. Mn-doped Ru2Si3 has a twice higher carrier mobility compared to the undoped one. Theoretical calculation of the charge carrier mobility is based on the effective masses which are estimated from the ab initio electronic band structure and classical scattering mechanisms.

Isotropic and anisotropic nanocrystalline Nd14Fe80B6 and Nd12Dy2Fe73.2Co6.6Ga0.6B5.6 magnets have been produced from melt-spun materials by hot pressing and subsequent die-upsetting. The microstructure has been characterized using XRD, scanning electron microscope and energy dispersive X-ray analysis. The corrosion behaviour of die-upset NdFeB-based magnets has been studied in 0.1 M H2SO4 by inductively coupled plasma solution analysis and electrochemical polarization techniques and compared with their hot-pressed counterparts. Texturing of hot-pressed (isotropic) NdFeB-based magnets via die-upsetting significantly modifies their corrosion performance. Textured Nd12Dy2Fe73.2Co6.6Ga0.6B5.6 magnets exhibit the highest corrosion resistance in this study. The low effective diffusivity of corrosion hydrogen inside the bulk magnet and the reduction in the strength of galvanic coupling between magnet phases are the main reasons for the observed improvement in the corrosion resistance. The corrosion behaviour of the magnets in relation to their phase composition and phase distribution is discussed in terms of dissolution, hydrogenation and pulverization. Pulverization trends are correlated with hydrides formation and hydrogen-trapping sites using thermal desorption analysis.

In the present work we investigate the coherent electron transport in a symmetrically designed ballistic ring uniformly covered by a top metal gate. We find that as the Fermi energy is varied, the phase of Aharonov–Bohm (AB) oscillations near zero magnetic field switches between 0 and π. It seems unlikely that this behaviour can be explained by some accidental asymmetry in the structures. We give a qualitative explanation of our results using a model where the ring is considered to be weakly coupled to the leads and the conductance is calculated on the basis of an exact energy spectrum of an ideal ring. This model predicts that a variation of the phase of AB oscillations with gate voltage may be observed in a symmetrical ring.

The temperature dependence of the amplitude of the Aharonov-Bohm (AB) oscillations in a single mode ballistic ring has been measured. The experimental data is analyzed using the exact energy spectrum of an ideal ring with a finite width and the Landauer-Buttiker formula to calculate the conductance of the ring. We show that the temperature dependence of the AB oscillations can be explained in terms of the thermally averaged transmission probability through the energy levels of the ring provided the additional charging energy is taken into account. This demonstrates the effect of Coulomb repulsion on the AB oscillations in a ring interferometer.

Simulation of the SIS100 slow extraction area with part of the tunnel and niches have been done by using FLUKA code. In simulation have been used the beam of the U28 with energy 2.7 GeV per nucleon. Results gave the values of doses and neutrons fluxes in the targets situated in different place of the area and showed necessity in additional shielding of the electronics.

In the frame of the FAIR project irradiation test of superconducting magnet components was performed at GSI Darmstadt in May 2008. As a part of the experiment stainless steel samples were irradiated by 1 GeV/u 238 U ions. In contrast to the previous experimental studies performed with thick cylindrical samples, the target was a thin plate irradiated at small angle. The target was constituted as a set of individual foils. This stacked-foil target configuration was foreseen for depth-profiling of residual activity. Gamma-ray spectroscopy was used as the main analytical technique. The isotopes with dominating contribution to the residual activity induced in the samples were identified and their contributions were quantified. Depth-profiling of the residual activity of all identified isotopes was performed by measurements of the individual target foils. The characteristic shape of the depth-profiles for the products of target activation and projectile fragments was found and described. Monte Carlo code FLUKA was used for simulations of the residual activity and for estimation of the number of ions delivered to the target and their distribution. The measured data are relevant for assessment of radiation situation at high-energy accelerators during the "hands- on" maintenance as well for assessment of the tolerable beam-losses.

In spring 2008 an irradiation test of superconducting magnet components was done at GSI Darmstadt in the frame of the FAIR project. Cave HHD with the beam dump of SIS synchrotron was used for irradiation. The irradiation set-up modeled a scenario of beam loss in a FAIR accelerator: U beam with energy of 1 GeV/u was used to irradiate a thin stainless steel bar at very small angle, so that the test samples situated behind the stainless steel bar were exposed to the beam of secondary particles created in the bar. The total number of U ions dumped on the target assembly was about 2·10 14 . Presently, in spring 2009 some samples are still radioactive. In the paper we present the estimates of the energy deposition and secondary particle fluences in the test samples and also discuss some results of the irradiation campaign. EXPERIMENTAL SET-UP