The interactions between polyamidoamine starburst dendrimers (SBDs) and vesicles consisting of dimyristoylphosphatidylcholine (DMPC) and its phosphatidylcholate salt (DMPA-Na) in various relative ratios (from 0% to 40% of DMPA-Na) were studied by electron paramagnetic resonance (EPR) and by transmission electron microscopy (TEM). The EPR spectra were computer-simulated to extract mobility and structural parameters of the probes and labels. The systems were analyzed as a function of the level of protonation of SBDs and generation (G ) 2SBD and G ) 6SBD). Both the hydrophobic 5doxylstearic spin probe (5DSA) and the positively charged nitroxide CAT16, a cationic surfactant with a C16 chain, inserted in the vesicles and monitored the formation of dendrimer-mixed vesicle (DMPC/DMPA-Na) complexes. 5DSA revealed a partial ordering of a double-layer-like structure occurring at the dendrimer surface. The spin labels at the vesicle/dendrimer interface modified the structural and mobility parameters upon complexation with the dendrimer. At high levels of protonation, dendrimers showed a larger interaction with the vesicles, especially for the mixed vesicles, compared to dendrimers at a lower level of protonation. In agreement with EPR results, TEM micrographs showed that the addition of DMPA-Na to DMPC modifies the vesicle shape from spherical to rodlike. The EPR analysis suggested that the vesicles wrap around the large dendrimers whereas the small dendrimer directly interacts with the vesicle surface. The results are very promising for a better understanding of the mechanism of interaction of dendrimers with cell membranes which may be an important feature in the role of SBDs as drug and gene carriers to target cells.
IFMIF, the International Fusion Materials Irradiation Facility, is presently in its engineering validation and engineering design activities (EVEDA) phase under the Broader Approach Agreement. The engineering design activity (EDA) phase was successfully accomplished within the allocated time. The engineering validation activity (EVA) phase has focused on validating the Accelerator Facility (AF), the Target Facility and the Test Facility (TF) by constructing prototypes. The ELTL at JAEA, Oarai successfully demonstrated the long-term stability of a Li flow under the IFMIF’s nominal operational conditions keeping the specified free-surface fluctuations below ±1 mm in a continuous manner for 25 d. A full-scale prototype of the high flux test module (HFTM) was successfully tested in the HELOKA loop (KIT, Karlsruhe), where it was demonstrated that the irradiation temperature can be set individually and kept uniform. LIPAc, designed and constructed in European labs under the coordination of F4E, presently under installation and commissioning in the Rokkasho Fusion Institute, aims at validating the concept of IFMIF accelerators with a D+ beam of 125 mA continuous wave (CW) and 9 MeV. The commissioning phases of the H+/D+ beams at 100 keV are progressing and should be concluded in 2017; in turn, the commissioning of the 5 MeV beam is due to start during 2017. The D+ beam through the superconducting cavities is expected to be achieved within the Broader Approach Agreement time frame with the superconducting cryomodule being assembled in Rokkasho. The realisation of a fusion-relevant neutron source is a necessary step for the successful development of fusion. The ongoing success of the IFMIF/EVEDA involves ruling out concerns about potential technical showstoppers which were raised in the past. Thus, a situation has emerged where soon steps towards constructing a Li(d,xn) fusion-relevant neutron source could be taken, which is also justified in the light of costs which are marginal to those of a fusion plant.
Abstract. The Engineering Validation and Engineering Design Activities (EVEDA) for the International Fusion Materials Irradiation Facility (IFMIF), an international collaboration under the Broader Approach Agreement between Japan Government and EURATOM, aims at allowing a rapid construction phase of IFMIF in due time with an understanding of cost involved. The three main facilities of IFMIF: 1) the Accelerator facility, 2) the Target facility and 3) the Test facility are the subject of validation activities that include the construction of either full scale prototypes or smartly devised scaled down facilities that will allow a straightforward extrapolation to IFMIF needs. By July 2013, the engineering design activities of IFMIF matured with the delivery of an Intermediate IFMIF Engineering Design Report (IIEDR) supported by experimental results. The installation of a Linac of 1.125 MW (125 mA and 9 MeV) of deuterons started in March 2013 in Rokkasho (Japan). The world largest liquid Li test loop is running in Oarai (Japan) with an ambitious experimental programme for the years ahead. A full scale High Flux Test Module that will house ~1000 small specimens developed jointly in Europe and Japan for the Fusion programme has been constructed by KIT (Karlsruhe) together with its He gas cooling loop. A full scale Medium Flux Test Module to carry out on-line creep measurement has been constructed by CRPP (Villigen).
Transmission electron micrographs (TEM) of UO2 2+ -negatively stained starburst dendrimers (SBDs), members of the family of dendritic macromolecules, have been analyzed in the absence and in the presence of dimyristoyl-phosphatidylcoline (DMPC) liposomes and mixed DMPC/DMPA-Na (the sodium salt of DMP-colate) liposomes at different relative percentages of DMPC and DMPA-Na. Under most conditions with dendrimers present, the dendrimers, rather than the liposomes, are visible in the TEM images, demonstrating that the UO2 2+ is complexed to the dendrimers and not to the liposomes. Only at high composition of DMPA-Na in the liposomes (>40%) and under the condition of high protonation of the dendrimer surface are the liposomes imaged by TEM. Mixed liposomes show a rodlike shape. To confirm the TEM results, an EPR study was performed by adding to the SBD solution various amounts of Cu 2+ and UO2 2+ . Uranyl ions compete favorably with copper ions for the complexation with the nitrogen ligand sites at both the external and the internal dendrimer surfaces. The saturation of the dendrimer by Cu(II) occurs at about 33% complexation of the nitrogen groups. The stability constant of the Cu 2+ -SBD complex was evaluated, along with an indirect estimation of the stability of the UO2 2+ -SBD complex. The results demonstrate that starburst dendrimers selectively bind to uranyl ions and that the latter compete effectively for these sites, even with Cu(II) ions, which are well-known for forming stable complexes with nitrogen ligands. These results show that dendrimers have the potential for storing uranium derivatives, a process of great importance in the fields of energy production and environmental cleanup.
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