Asymmetric Total Syntheses,Stereostructures, and Cytotoxicities of Marine Bromotriterpenoids Aplysiol B (Laurenmariannol) and Saiyacenol A

There are marine cytotoxic bromotriterpenoids, named the thyrsiferol family that are structurally characterized by some tetrahydropyran (THP) and tetrahydrofuran (THF) rings. The thyrsiferol family belongs to natural products that are often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic tetrasubstituted carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, to elucidate ambiguous stereostructures and unassigned absolute configurations of aplysiol B, laurenmariannol, and saiyacenol A, members of the thyrsiferol family, we carried out their asymmetric chemical syntheses featuring 6-exo and 5-exo oxacyclizations of epoxy alcohol precursors and 6-endo bromoetherification of a bishomoallylic alcohol. In this paper, we report total assignments of their stereostructures through their asymmetric chemical syntheses and also their preliminary cytotoxic activities against some tumor cells. These results could not have been achieved without depending on asymmetric total synthesis.     

Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.     

Analysis method of the angiotensin-I converting enzyme inhibitory activity based on micellar electrokinetic chromatography.

A micellar electrokinetic chromatography (MEKC) method was developed for estimating the angiotensin-I converting enzyme (ACE) inhibitory activity by separating the hippuric acid liberated in the ACE reaction mixture in the presence of an inhibitor, captopril. The hippuric acid was successfully separated and detected by MEKC with a 25 mM sodium dodecyl sulfate solution in a 25 mM phosphate-50 mM borate buffer at pH 7.0; the total analysis took about 5 min. A good linear relationship was observed between the inhibitor and the peak area of hippuric acid release. No significant difference in the ACE inhibitory activity (IC50) of captopril (an antihypertensive medicine) or autolyzed-mushrooms (functional foods) was observed between the conventional method and the MEKC method. The MEKC method was found to be a useful technique for a rapid assay of the ACE inhibitory activity.     

The kinetics of the light-induced defect creation in hydrogenated amorphous silicon – Stretched exponential relaxation

Our model for light-induced defect creation in hydrogenated amorphous silicon is applied to its kinetics, i.e., the growing curve of light-induced dangling bond density as a function of illumination time, which is fitted to a stretched exponential function. Two parameters β and τ involved in the function are estimated as functions of saturated dangling bond density in terms of our model. These are compared with two experimental results, i.e., our results obtained from ESR measurements and Shimakawa et al.’s results obtained from photoconductivity measurements. The saturated dangling bond density is also measured as a function of the generation rate of free carriers. The experimental results are compared with calculated results and discussed.     

Classical in-plane negative magnetoresistance and quantum positive magnetoresistance in undoped InSb thin films on GaAs (1 0 0) substrates

Magnetoresistance (MR) effects have been investigated in perpendicular and parallel magnetic fields at 300, 80 K and liquid He temperatures for undoped InSb thin films 0.1–2.3 μm thick grown on GaAs(1 0 0) substrates by MBE. At high temperatures, the intrinsic carriers show the parabolic negative MR observable only in magnetic fields parallel to the film. The skipping-orbit effect due to surface boundary scattering in the classical orbits in the plane vertical to the film has been argued to be responsible for the negative MR. At low temperatures (T=80 K), the transport is dominated by the two-dimensional (2D) electrons in the accumulation layers at the InSb/GaAs(1 0 0) hetero interface; MR is positive and shows a logarithmic increase with anisotropy between parallel and perpendicular field orientation, arising from the 2D weak anti-localization (WAL) that reflects the interplay between the spin-Zeeman effect and strong spin–orbit interaction caused by the asymmetric potential at the interface (Rashba term). The zero-field spin splitting energy of Δ₀13 meV, the electron effective mass of m^*0.10m₀ seven times of the band edge mass in bulk InSb and the effective g-factor of |g^*|15 in the accumulation layer have been inferred from fits of MR for the 0.1 μm thick film to the 2D WL theory.     

Status of heavy element research using a gas-filled recoil separator at RIKEN

A gas-filled type of recoil separator for heavy element research was installed at an experimental hall of RIKEN Linear Accelerator facility to realize getting higher intensity of primary beam and long beam time. Performance of the separator was studied using target recoils and various nuclear reactions. The results show the high performance of the separator for heave element research. As an application of the GARIS, production and identification of an isotope of the 110th element ²⁷¹[110] have been performed using the ²⁰⁸Pb(⁶⁴Ni,1n)²⁷¹[110] reaction. Three decay chains coincide well both in decay times and energies with the ones reported by the group of SHIP experiment at GSI, Germany. Our results provide a confirmation of the synthesis of an isotope ²⁷¹[110] of element 110.     

Compact directed acyclic word graphs for a sliding window

Suffix trees are a well-known and widely-studied data structure highly useful for string matching. The suffix tree of a string w can be constructed in O(n) time and space, where n denotes the length of w. Larsson achieved an efficient algorithm to maintain suffix trees for a sliding window. It contributes to prediction by partial matching (PPM) style statistical data compression scheme. Compact directed acyclic word graphs (CDAWGs) are a more space-economical data structure for indexing strings. In this paper we propose a linear-time algorithm to maintain CDAWGs for a sliding window.     

5-Aza-2′-deoxycytidine reactivates the CDH1 gene without influencing methylation of the entire CpG island or histone modification in a human cancer cell line

It is well-recognized that DNA methylation and histone modifications play critical roles in epigenetic regulation of gene activity through the alteration of chromatin structure. Recent studies have shown that in a subset of cancer cells, the silencing of the human E-cadherin (CDH1) gene is associated with hypermethylation of the CpG island. However, the associated molecular mechanism remains unclear. To understand the mechanism, we have investigated the alteration of CpG island methylation and histone modifications during the reactivation of the CDH1 gene by treatment with 5-aza-2′-deoxycytidine (5-aza-dC). Although the CDH1 gene expression was recovered by treatment with 5-aza-dC in a liver cancer cell line Li21, the methylation status of the entire CpG island and acetylation and methylation status of associated histones were not significantly altered. These results demonstrate that the silenced CDH1 gene can be reactivated without apparent alteration of histone modification or CpG island methylation.