ダイオキシン毒性の発症機序におけるcPLA2αおよびAhRの役割

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 松島 綱治, 東京大学教授 岩瀬 博太郎, 東京大学教授 渡辺 知保, 東京大学特任准教授 稲城 玲子, 東京大学講師 張田 豊University of Tokyo(東京大学

Diversified Adversarial Attacks based on Conjugate Gradient Method

Deep learning models are vulnerable to adversarial examples, and adversarial attacks used to generate such examples have attracted considerable research interest. Although existing methods based on the steepest descent have achieved high attack success rates, ill-conditioned problems occasionally reduce their performance. To address this limitation, we utilize the conjugate gradient (CG) method, which is effective for this type of problem, and propose a novel attack algorithm inspired by the CG method, named the Auto Conjugate Gradient (ACG) attack. The results of large-scale evaluation experiments conducted on the latest robust models show that, for most models, ACG was able to find more adversarial examples with fewer iterations than the existing SOTA algorithm Auto-PGD (APGD). We investigated the difference in search performance between ACG and APGD in terms of diversification and intensification, and define a measure called Diversity Index (DI) to quantify the degree of diversity. From the analysis of the diversity using this index, we show that the more diverse search of the proposed method remarkably improves its attack success rate.Comment: Proceedings of the 39th International Conference on Machine Learning (ICML 2022

TCDD-induced chick cardiotoxicity is abolished by a selective cyclooxygenase-2 (COX-2) inhibitor NS398

Halogenated aromatic hydrocarbons, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are known to cause severe heart defects in avian species. However, the mechanism of TCDD-induced chick cardiovascular toxicity is unclear. In this study, we investigated cyclooxygenase-2 (COX-2) as a possible mechanism of TCDD-induced cardiotoxicity. Fertile chicken eggs were injected with TCDD and a COX-2 selective inhibitor, NS398, and we investigated chick heart failure on day 10. We found that the chick heart to body weight ratio and atrial natriuretic factor mRNA expression were increased, but this increase was abolished with treatment of NS398. In addition, the morphological abnormality of an enlarged ventricle resulting from TCDD exposure was also abolished with co-treatment of TCDD and NS398. Our results suggested that TCDD-induced chick heart defects are mediated via the nongenomic pathway and that they do not require the genomic pathway

Molecular evidence predicts aryl hydrocarbon receptor ligand insensitivity in the peregrine falcon (Falco peregrines)

Some wild populations of fish-eating birds and raptors are exposed to high concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds such as other 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans and coplanar polychlorinated biphenyls, resulting in accumulation in their tissues. It has been demonstrated that TCDD-like chemicals cause toxic effects via aryl hydrocarbon receptor (AHR)-mediated signaling pathways. The aim of this study was to characterize the AHR from the peregrine falcon (Falco peregrines) to predict its sensitivity to TCDD-like chemicals. The AHR1, AHR2, and AHR nuclear translocator (ARNT) 1 of the peregrine falcon are more similar in amino acid sequence to avian species less sensitive to TCDD-like chemicals such as the cormorant (95%) than to more sensitive species such as the chicken (90%). From the amino acid sequence, it is likely that the ligand-binding affinity of peregrine falcon AHR1 and AHR2 would be very low compared with the chicken or other sensitive species, and it was actually proved by an in vitro reporter gene assay. We concluded that the peregrine falcon, one of raptor species, may be relatively resistant to TCDD-like chemicals