Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells. Inhibitory effects of MAGEA1 on cell proliferation and migration were observed using both gain-of- (MAGEA1 overexpression) and loss-of- (siRNA interference) function approaches in breast (MCF-7 and MDA-MB-231) and ovarian (SKOV3 and SKOV3ip) cancer cell lines. We revealed a novel interaction between MAGEA1 and the intracellular segment of NOTCH1 receptor (NICD1). MAGEA1 reduced NICD1's stability by promoting the ubiquitin modification of NICD1. MAGEA1 also interacted with FBXW7, subunit of E3 ubiquitin protein ligase complex SCF, and the latter was functionally involved in NICD1 ubiquitination and degradation. In addition, siRNA interference of FBXW7 reversed the inhibitory effect of MAGEA1 on migration and proliferation of MCF-7 and MDA-MB-231 cells. These newly discovered MAGEA1-NICD1 and MAGEA1-FBXW7 interactions have potential clinical implications in breast and ovarian cancer treatment.

Thermoluminescence signals and morphological studies are reported for a new phosphor of Gd2O3. The phosphor particle material was synthesized by an aerosol technique and it is heavily doped with Eu. Annealing at 1200 °C increases the luminescence efficiency by ∼1000-fold relative to the as-prepared material. The emission spectra are primarily from the red transitions of the Eu, but weaker short wavelength emissions can also be detected during low temperature thermoluminescence. There are numerous wavelength dependent differences between the low temperature thermoluminescence curves. These variations are interpreted to show that there are a range of defect and luminescence sites in the Gd2O3:Eu phosphors. These are associated with the symmetry of the crystal field around the europium ion, which is a function of the phase content, i.e. resulting from sample preparation and annealing. The sites are almost independent in terms of their emission spectra, but the stability of some sites is enhanced by the presence of Eu so that the TL peaks appear at higher temperatures than the intrinsic defect TL of the host material. The synthesis of uniform and submicron sized spherical particles with nano-clustered inner structure is demonstrated with various analysis techniques (XRPD, FE-SEM and HR-TEM). The effect of processing parameters and post-annealing treatment is discussed from the viewpoint of different phase formation.

Measurements of the temperature dependence of the dark current for standard commercial photomultipliers with multialkali photocathodes (type S20) have been contrasted with data from new prototype tubes with greatly enhanced long wavelength performance. The analyses suggest that for the larger structures part of the cathode is closer to a bialkali composition. This reduces the activation energy of the dark current from ∼1.1 eV for normal S20 cathodes down to ∼0.8 eV. Many tubes show a lower activation energy component near 0.6 eV which may represent a sensitization process from monolayers of molecular oxygen. Similarly, monolayers of water can play a significant role, but do so by reducing cathode sensitivity. Several tubes display a sharp transition in gain at the limiting temperature for water desorption (i.e. a sublimation transition). The commercial structured cathodes can show evidence for up to 70% improvements in quantum efficiency by operation at low temperature which can be immediately exploited. Prototype tubes with greatly improved performance were studied but for very small area illumination spots there can be problems of local variations in gain and wavelength response across the structural features of pyramidal modified cathode windows. Overall the data suggest that not only is improved performance already available with existing photomultiplier tubes but also with structured photocathode windows, and/or the introduction of surface ‘defects’ in the window, even further improvements are feasible.