Numerical Simulation of Urban Inundation Processes and Their Hydraulic Quantities : Tsunami Analysis Hackathon Theme 1

The detailed understanding of tsunami hazard risk using numerical simulations requires a numerical model that can accurately predict tsunami inundation phenomena on land. In such models, the structural effects are indirectly considered using the variation of bottom roughness as a proxy for the differences in building densities. Only a few studies have conducted intermodel tests to investigate tsunami inundation in complex coastal urban cities. During the tsunami analysis hackathon held in September 2020, eight research groups met to have a detailed discussion on the current urban inundation problems. In this study, we conducted an intermodel comparison of the numerical tsunami models, using the data from physical experiments that were performed on a detailed urban model. Our objective was to investigate the necessary conditions of an accurate numerical model based that can ensure high reproducibility and practicality. It was confirmed that the accuracy of topographic data is an important parameter for tsunami inundation simulations in complex urban areas. Based on the computational cost and accuracy, we suggest that a resolution of 1 cm of topographic data is a sufficient condition for tsunami inundation simulations on 1/250 scale model

Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study

Objectives: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. Methods: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m2/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. Results: The S-1 recommended dose was 80 mg/m2/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. Conclusions: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present

Abnormal Heart Development and Lung Remodeling in Mice Lacking the Hypoxia-Inducible Factor-Related Basic Helix-Loop-Helix PAS Protein NEPAS▿

Hypoxia-inducible factors (HIFs) are crucial for oxygen homeostasis during both embryonic development and postnatal life. Here we show that a novel HIF family basic helix-loop-helix (bHLH) PAS (Per-Arnt-Sim) protein, which is expressed predominantly during embryonic and neonatal stages and thereby designated NEPAS (neonatal and embryonic PAS), acts as a negative regulator of HIF-mediated gene expression. NEPAS mRNA is derived from the HIF-3α gene by alternative splicing, replacing the first exon of HIF-3α with that of inhibitory PAS. NEPAS can dimerize with Arnt and exhibits only low levels of transcriptional activity, similar to that of HIF-3α. NEPAS suppressed reporter gene expression driven by HIF-1α and HIF-2α. By generating mice with a targeted disruption of the NEPAS/HIF-3α locus, we found that homozygous mutant mice (NEPAS/HIF-3α−/−) were viable but displayed enlargement of the right ventricle and impaired lung remodeling. The expression of endothelin 1 and platelet-derived growth factor β was increased in the lung endothelial cells of NEPAS/HIF-3α-null mice. These results demonstrate a novel regulatory mechanism in which the activities of HIF-1α and HIF-2α are negatively regulated by NEPAS in endothelial cells, which is pertinent to lung and heart development during the embryonic and neonatal stages