In vivo assessment of the permeability of the blood--brain barrier and blood-retinal barrier to fluorescent indoline derivatives in zebrafish

ABSTRACT: BACKGROUND: Successful delivery of compounds to the brain and retina is a challenge in the development of therapeutic drugs and imaging agents. This challenge arises because internalization of compounds into the brain and retina is restricted by the blood--brain barrier (BBB) and blood-retinal barrier (BRB), respectively. Simple and reliable in vivo assays are necessary to identify compounds that can easily cross the BBB and BRB. METHODS: We developed six fluorescent indoline derivatives (IDs) and examined their ability to cross the BBB and BRB in zebrafish by in vivo fluorescence imaging. These fluorescent IDs were administered to live zebrafish by immersing the zebrafish larvae at 7--8 days post fertilization in medium containing the ID, or by intracardiac injection. We also examined the effect of multidrug resistance proteins (MRPs) on the permeability of the BBB and BRB to the ID using MK571, a selective inhibitor of MRPs. RESULTS: The permeability of these barriers to fluorescent IDs administered by simple immersion was comparable to when administered by intracardiac injection. Thus, this finding supports the validity of drug administration by simple immersion for the assessment of BBB and BRB permeability to fluorescent IDs. Using this zebrafish model, we demonstrated that the length of the methylene chain in these fluorescent IDs significantly affected their ability to cross the BBB and BRB via MRPs. CONCLUSIONS: We demonstrated that in vivo assessment of the permeability of the BBB and BRB to fluorescent IDs could be simply and reliably performed using zebrafish. The structure of fluorescent IDs can be flexibly modified and, thus, the permeability of the BBB and BRB to a large number of IDs can be assessed using this zebrafish-based assay. The large amount of data acquired might be useful for in silico analysis to elucidate the precise mechanisms underlying the interactions between chemical structure and the efflux transporters at the BBB and BRB. In turn, understanding these mechanisms may lead to the efficient design of compounds targeting the brain and retina.     

Evaluation of zinc self-diffusion at the interface between homoepitaxial ZnO thin films and (0001) ZnO substrates

Isotopic ZnO thin films were deposited on the c-plane of ZnO single crystals by pulsed laser deposition. The isotopic abundance of Zn in the films was determined with a secondary ion mass spectrometry before and after the films was diffusion annealed. The diffusion profiles across the film/substrate interface behaved smooth features. The zinc diffusion coefficient (D_Zn) was obtained by analyzing the slope of the profile in the annealed sample. The temperature dependence of D_Zn was determined to be D_Zn(cm²/s)=8.0×10⁴exp(?417[kJ/mol])/RT, where R and T are gas constant and temperature. The zinc ion diffusion coefficients were of the same order as that in a ZnO single crystal. A comparison of the experimental and theoretical values indicated that the zinc ions diffused in the thin film and the single crystal through a vacancy mechanism.     

Electronic properties of iron arsenic high temperature superconductors revealed by angle resolved photoemission spectroscopy (ARPES)

We present an overview of the electronic properties of iron arsenic high temperature superconductors with emphasis on low energy band dispersion, Fermi surface and superconducting gap. ARPES data is compared with full-potential linearized plane wave (FLAPW) calculations. We focus on single layer NdFeAsO_0.9F_0.1 (R1111) and two layer Ba_1?xK_xFe₂As₂ (B122) compounds. We find general similarities between experimental data and calculations in terms of character of Fermi surface pockets, and overall band dispersion. We also find a number of differences in details of the shape and size of the Fermi surfaces as well as the exact energy location of the bands, which indicate that magnetic interaction and ordering significantly affects the electronic properties of these materials. The Fermi surface consists of several hole pockets centered at Γ and electron pockets located in zone corners. The size and shape of the Fermi surface changes significantly with doping. Emergence of a coherent peak below the critical temperature T_c and diminished spectral weight at the chemical potential above T_c closely resembles the spectral characteristics of the cuprates, however the nodeless superconducting gap clearly excludes the possibility of d-wave order parameter. Instead it points to s-wave or extended s-wave symmetry of the order parameter.     

Study of Strangeness Photoproduction on the Neutron in the Threshold Region

Photoproduction of the neutral kaon on the deuteron has been investigated at the Research Center for Electron Photon Science, Tohoku University. We constructed the Neutral Kaon Spectrometer-2 for the detection of charged particles from the decay of the neutral kaon and the hyperon. We obtained a momentum distribution of K ⁰ with the inclusive measurement. It was consistent with the previous measurement. The total cross section of γ + d → K ⁰ + Λ + p was estimated from the measured integral cross section of γ + d → Λ + X. The total cross section with respect to the photon energy was compared with the theoretical calculations. It favored the Saclay-Lyon A model calculation with the ratio of the neutral to charged coupling constants of the axial-vector meson, K ₁, as ~ ?1.5. The energy dependence and the magnitude of the total cross section were similar to the total cross section of γ + p → K ⁺ Λ.     

Glass physics: from fundamentals to applications

The European Physical Journal E -     

Luminescence properties of Tb-activated yttrium gallium garnet phosphors

Comparison of luminescence properties between electron-excited and uv-excited yttrium gallium garnet: Tb phosphors is reported. Although the thermoluminescence and phosphorescence in both cases are quite alike once traps are filled, an apparent difference in the behavior of trap filling has been observed. Small addition of V₂O₃ to these phosphors revealed a unique effect on luminescence properties either with the electron excitation or with the uv excitation.     

Functional organic single crystals for solid‐state laser applications

Because of long‐range order and high chemical purity, organic crystals have exhibit unique properties and attracted a lot of interest for application in solid‐state lasers. As optical gain materials, they exhibit high stimulated emission cross section and broad tunable wavelength emission as similar to their amorphous counterpart; moreover, high purity and high order give them superior properties such as low scattering trap densities, high thermal stability, as well as highly polarized emission. As electronic materials, they are potentially able to support high current densities, thus making it possible to realize current driven lasers. This paper mainly describes recent research progress in organic semiconductor laser crystals. The building molecules, crystal growth methods, as well as their stimulated emission characteristics related with crystal structures are introduced; in addition, the current state‐of‐the‐art in the field of crystal laser devices is reviewed. Furthermore, recent advances of crystal lasers at the nanoscale and single crystal light‐emitting transistors (LETs) are presented. Finally, an outlook and personal view is provided on the further developments of laser crystals and their applications.     

Comparative investigation of Au nano-particle formation process dependent upon various protective agents

Formation process of gold nanoparticles was investigated by near-field heterodyne transient grating method. In the absence of the protective agents, although the diffusion of H[Au^ICl₂] could be observed after the photo-reduction of H[Au^IIICl₄], the diffusion of nanoparticle-seeds was not observed. On the other hand, in the presence of the protective agents, the diffusion of a complex molecule (Au and protective agent) and nanoparticle-seeds could be observed. From these results, it was found that enough amount of the complex is essential for the nanoparticle formation. We also investigated the formation process with four different chemicals as a protective agent. The hydrodynamic radius of nanoparticle-seeds generated in the poly(vinyl pyrrolidone) and TritonX-100 solutions were larger than those generated in the Tween 20 and Brij 58 solutions. The former two have hydrophilic chain in the molecular structure; on the other hand, the latter two have hydrophobic alkyl chain. Based on those facts, we concluded that the interaction between the chains of the complex molecule plays an important role in the nanoparticle formation process.     

Anomalies in the Fermi surface and band dispersion of quasi-one-dimensional CuO chains in the high-temperature superconductor YBa2Cu4O8

We have investigated the electronic states in quasi-one-dimensional CuO chains by microprobe angle resolved photoemission spectroscopy. We find that the quasiparticle Fermi surface consists of six disconnected segments, consistent with recent theoretical calculations that predict the formation of narrow, elongated Fermi surface pockets for coupled CuO chains. In addition, we find a strong renormalization effect with a significant kink structure in the band dispersion. The properties of this latter effect [energy scale (～40 meV), temperature dependence, and behavior with Zn-doping] are identical to those of the bosonic mode observed in CuO2 planes of high-temperature superconductors, indicating they have a common origin.