オンドノユレノキソケンキュウトソノオウヨウ

京都大学0048新制・課程博士工学博士甲第1046号工博第233号新制||工||171(附属図書館)2633UT51-46-A580京都大学大学院工学研究科原子核工学専攻(主査)教授 岐美 格, 教授 佐藤 俊, 教授 西原 宏学位規則第5条第1項該当Kyoto UniversityDA

Compiler Provenance Recovery for Multi-CPU Architectures Using a Centrifuge Mechanism

Bit-stream recognition (BSR) has many applications, such as forensic investigations, detection of copyright infringement, and malware analysis. We propose the first BSR that takes a bare input bit-stream and outputs a class label without any preprocessing. To achieve our goal, we propose a centrifuge mechanism, where the upstream layers (sub-net) capture global features and tell the downstream layers (main-net) to switch the focus, even if a part of the input bit-stream has the same value. We applied the centrifuge mechanism to compiler provenance recovery, a type of BSR, and achieved excellent classification. Additionally, downstream transfer learning (DTL), one of the learning methods we propose for the centrifuge mechanism, pre-trains the main-net using the sub-net's ground truth instead of the sub-net's output. We found that sub-predictions made by DTL tend to be highly accurate when the sub-label classification contributes to the essence of the main prediction.Comment: 8 pages, 4 figures, 5 table

Meiotic gene silencing complex MTREC/NURS recruits the nuclear exosome to YTH-RNA-binding protein Mmi1.

Accurate target recognition in transcript degradation is crucial for regulation of gene expression. In the fission yeast Schizosaccharomyces pombe, a number of meiotic transcripts are recognized by a YTH-family RNA-binding protein, Mmi1, and selectively degraded by the nuclear exosome during mitotic growth. Mmi1 forms nuclear foci in mitotically growing cells, and the nuclear exosome colocalizes to such foci. However, it remains elusive how Mmi1 and the nuclear exosome are connected. Here, we show that a complex called MTREC (Mtl1-Red1 core) or NURS (nuclear RNA silencing) that consists of a zinc-finger protein, Red1, and an RNA helicase, Mtl1, is required for the recruitment of the nuclear exosome to Mmi1 foci. Physical interaction between Mmi1 and the nuclear exosome depends on Red1. Furthermore, a chimeric protein involving Mmi1 and Rrp6, which is a nuclear-specific component of the exosome, suppresses the ectopic expression phenotype of meiotic transcripts in red1Δ cells and mtl1 mutant cells. These data indicate that the primary function of MTREC/NURS in meiotic transcript elimination is to link Mmi1 to the nuclear exosome physically

Shock Excitation in Narrow Line Regions Powered by AGN Outflows

Outflows in the Active Galactic Nucleus (AGN) are considered to play a key role in the host galaxy evolution through transfer of a large amount of energy. A Narrow Line Region (NLR) in the AGN is composed of ionized gas extending from pc-scales to kpc-scales. It has been suggested that shocks are required for ionization of the NLR gas. If AGN outflows generate such shocks, they will sweep through the NLR and the outflow energy will be transferred into a galaxy-scale region. In order to study contribution of the AGN outflow to the NLR-scale shock, we measure the [\ion{Fe}{2}]$\lambda12570$/[\ion{P}{2}]$\lambda11886$ line ratio, which is a good tracer of shocks, using near-infrared spectroscopic observations with WINERED (Warm INfrared Echelle spectrograph to Realize Extreme Dispersion and sensitivity) mounted on the New Technology Telescope. Among 13 Seyfert galaxies we observed, the [\ion{Fe}{2}] and [\ion{P}{2}] lines were detected in 12 and 6 targets, respectively. The [\ion{Fe}{2}]/[\ion{P}{2}] ratios in 4 targets were found to be higher than 10, which implies the existence of shocks. We also found that the shock is likely to exist where an ionized outflow, i.e., a blue wing in [\ion{S}{3}]$\lambda9533$, is present. Our result implies that the ionized outflow present over a NLR-scale region sweeps through the interstellar medium and generates a shock.Comment: Accepted for ApJ, 20 pages, 11 figure

A Novel Diagnostic Method for Thyroid Follicular Tumors Based on Immunofluorescence Analysis of p53-Binding Protein 1 Expression: Detection of Genomic Instability

The preoperative diagnosis of thyroid follicular carcinomas (FCs) by fine-needle aspiration cytology is almost impossible. It was previously demonstrated that p53-binding protein 1 (53BP1) expression, based on immunofluorescence (IF),can serve as a valuable biomarker to estimate the malignant potential of various cancers. 53BP1 belongs to a class of DNA damage response molecules that rapidly localize to the site of DNA double-strand breaks,forming nuclear foci (NF). This study aimed to elucidate the utility of 53BP1 NF expression as a biomarker to differentiate follicular tumors (FTs). Methods: Associations between 53BP1 expression based on IF and histological types of FTs were analyzed using 27 follicular adenomas (FAs), 28 minimally invasive FCs, and 14 widely invasive FCs. Furthermore, the study clarified the relationship between 53BP1 NF and copy number aberrations (CNAs) based on array comparative genomic hybridization, a hallmark of genomic instability (GIN). Results: This study demonstrates differences in 53BP1 NF expression between FA and FC. The incidence of 53BP1 at NF significantly increased with FT progression in the following order: normal follicle < FA < minimally invasive FCs< widely invasive FCs. In contrast, no significant differences were observed in CNAs among the FT samples. Furthermore, there was no significant correlation between CNAs and 53BP1 at NF in FTs. Thus, based on a comparison of these two indicators of GIN, 53BP1 NF (by IF) was better able to estimate the malignancy of FTs compared to CNA (by array comparative genomic hybridization). Interestingly, IF revealed a heterogenous distribution of 53BP1 NF,which occurred more frequently in the invasive or subcapsular area than in the center of the tumor, suggesting intratumoral heterogeneity of GIN in FTs. Conclusions: It is proposed that IF analysis of 53BP1 expression could be a novel diagnostic method to estimate the malignant potential of FTs. Because 53BP1 NF reflect DNA double-strand breaks, it is hypothesized that the incidence of 53BP1 at NF can represent the level of GIN in tumor cells. IF analysis of 53BP1 expression will not only be　an auxiliary histologic technique to diagnose FTs accurately, but also a novel technique for preoperative diagnosis　using fine-needle aspiration cytology

Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism

神経芽腫の新たな診断法と治療戦略を創出 --がん細胞の生存戦略「がん代謝」を逆用する--. 京都大学プレスリリース. 2022-11-02.Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed the DNA methylation and expression datasets of neuroblastomas, extracted a candidate gene characterizing the aggressive features, and conducted functional studies. Based on the DNA methylation data, we identified a subgroup of neuroblastoma cases with 11q loss of heterozygosity with extremely poor prognosis. PHGDH, a serine metabolism-related gene, was extracted as a candidate with strong expression and characteristic methylation in this subgroup as well as in cases with MYCN amplification. PHGDH inhibition suppressed neuroblastoma cell proliferation in vitro and in vivo, indicating that the inhibition of serine metabolism by PHGDH inhibitors is a therapeutic alternative for neuroblastoma. Inhibiting the arginine metabolism, which is closely related to serine metabolism using arginine deiminase, had a combination effect both in vitro and in vivo, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. Expression and metabolome analyses of post-dose cells confirmed the synergistic effects of treatments targeting serine and arginine indicated that xCT inhibitors that inhibit cystine uptake could be candidates for further combinatorial treatment. Our results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma