Tsunami Analysis Method with High-Fidelity Crustal Structure and Geometry Model

Higher fidelity seafloor topography and crustal structure models have become available with accumulation of observation data. Previous studies have shown that the consideration of such high-fidelity models produces significant effects, in some cases, on crustal deformation results that are used as inputs for tsunami analysis. However, it is difficult to apply high-fidelity model of crustal deformation computations to tsunami computations because of large computational costs. In this paper, we propose a new crustal deformation computation method for estimating inputs for tsunami computations, which is based on a finite element analysis method with remarkable reduction of computation costs by efficient use of the arithmetic space and the solution space. This finite element analysis method enables us to conduct 102−3-times crustal deformation computations using high-fidelity models with a degree of freedom on the order of 108 for the 2011 Tohoku earthquake example. Tsunami computations with typical settings are conducted as an application example to present the advantages and characteristics of the proposed method. Comparisons between results of the proposed and the conventional method reveal that large shallow fault slip around the trench axis may lead to significant differences in tsunami waveforms and inundation height distributions in some cases

6U CubeSat for Ultraviolet Time-Domain Astronomy

A wide-field ultraviolet observatory for time-domain astronomy utilizing 6U CubeSat is presented. Ultraviolet waveband is one of the unexplored fields in astronomy. Potential targets are short duration transient sources in UV-band: early-phase emission from gravitational wave sources, supernovae shock-breakouts, tidal disruption events around super massive blackholes, etc. The telescope was designed for covering the large error circle of GW detectors, FoV~100 deg2. Thanks to the high quantum efficiency of “delta-doping” detector, the detection limit achieves 20 mag (AB) for 1800 s exposure in NUV band, which is sufficient to detect UV emission from a binary neutron star merger within 200 Mpc from the earth. The satellite has a high-performance on-board computer for on-orbit analysis to detect transient sources and measure the magnitude and the accurate position of the target. The obtained information is required to be transferred to the ground within 30 min from the detection to start multi-messenger follow-up observations utilizing ground-based observatories and astronomical satellites. In this presentation we show the mission overview and conceptual design of the satellite system

Structure and function of tegmentum vasculosum in avian cochlea

In spite of the importance of endocochlear DC potential (EP) and the K+-rich endolymph for the avian cochlea, the structure and function of the tegmentum vasculosum (TV) has not yet been fully elucidated, compared with those of the stria vascularis in the mammalian cochlea. In this study, we examined structural analysis of the epithelial cells, gene expressions of Na+-K+-ATPase (Atp1A1) and Kir4.1 (Kcnj10), and protein localizations of Na+-K+-ATPase and Kir4.1, in the TV. Tight junctional structures were observed between epithelial dark cells and light cells in the TV. Both Atp1a1 and Kcnj10 genes were detected in the TV. In addition, immunopositive signals for both Na+-K+-ATPase and Kir4.1 were recognized in the TV. These results indicate that Na+-K+-ATPase and Kir4.1 play roles in maintaining the EP and high K+ concentration of the endolymph. Further studies are needed to clarify the physiological functions of the TV. This is the first report which demonstrates that gene and protein expression data contribute to the avian inner ear homeostasis

Aberrant Methylation of p21 Gene in Lung Cancer and Malignant Pleural Mesothelioma

Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs

Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)­(2,4′-bipyridin-3-yl)­methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies