Improvement and benchmarking of the deterministic transport calculation code CBZ to design beam shaping assembly for BNCT.

The quick and accurate neutron and photon transport calculations are desired in the optimization calculations for the neutron source design, and in the present work, we establish the deterministic neutron and photon transport calculation procedure with the nuclear reactor physics calculation code system CBZ. Numerical calculation conditions are carefully chosen, and the efficient and practical condition is determined. Test calculations are carried out for the simple cylindrical systems with various kinds of neutron moderators, and the results are compared with the reference solutions obtained by the continuous-energy Monte Carlo code PHITS. Generally good agreements are obtained for all the benchmark problems. In addition, another problem with the detailed geometry for the neutron source is prepared. In this realistic problem also, good agreement is obtained between CBZ and PHITS. These results demonstrate the high accuracy of CBZ in the application to the design optimization calculations for the neutron source.

Artificial Notch Signaling Activation Method Using Immobilized Ligand Beads.

Activation of Notch signaling requires physical interaction between ligand- and receptor-expressing cells and pulling force to release the Notch intracellular domain. Therefore, the soluble recombinant ligand protein is not suitable for the activation of Notch signaling in a cell culture system. Here, we describe an efficient method for transient activation of Notch signaling using immobilized ligand beads. Using this method, the timing of Notch signaling can be efficiently controlled.

Immobilized DLL4-induced Notch signaling is mediated by dynamics of the actin cytoskeleton.

Notch signaling, which is essential for tissue development and homeostasis, has received attention as an attractive target for cancer therapy, tissue engineering and regenerative medicine. For signal activation, the Notch receptor undergoes proteolysis after binding to its ligand. This process is mediated by a mechanical pulling force, and receptor trans-endocytosis is known to play a central role in supplying the force. On the other hand, Notch ligands immobilized on carrier materials also induce artificial Notch activation. However, the mechanism of signal activation by immobilized ligand proteins is not fully understood. Here, we found that the actin cytoskeleton in Notch1-expressing cells contributes to signal activation induced by immobilized DLL4 (Delta-like ligand 4), and the results showed that pharmacological inhibition of actin dynamics impaired Notch signaling induced by DLL4-coated beads. Moreover, inhibition of actin dynamics remarkably impaired cell migration and was correlated with Notch signaling activity. We also investigated the contribution of Notch cis-endocytosis (the endocytosis of Notch receptor into signal-receiving cells) as an actin-mediated cell biological process to further explore the mechanism of Notch activation by DLL4-coated beads. Compromising the receptor cis-endocytosis pathway with the dynamin inhibitor did not alter DLL4-coated bead-induced Notch signaling, indicating that signal activation is not mediated by dynamin-dependent receptor cis-endocytosis. These findings suggest that Notch activation by immobilized ligands is primarily driven by actin-based cell movement, which might supply a sufficient mechanical force for receptor cleavage, but not by receptor cis-endocytosis.