Au25 cluster-loaded SrTiO3 water-splitting photocatalyst; preparation and elucidation of the effect of cocatalyst refinement on photocatalytic activity

Water-splitting photocatalysts have attracted much attention for decades as materials to produce clean and renewable hydrogen (H2) as a fuel. In this study, we succeeded in precisely loading ultrafine gold cocatalyst particles (Au25 clusters) on the water-splitting photocatalyst SrTiO3 using glutathionate-protected Au25 clusters as a precursor. Photocatalysis experiments using the obtained photocatalyst revealed that the ultraminiaturization of the Au cocatalyst on SrTiO3 improves its water-splitting activity. The main reason for this improvement was attributed to the acceleration of the H2-evolution reaction caused by the ultra-miniaturization of the cocatalyst. This effect of refining the cocatalyst differs from that of Au-loaded BaLa4Ti4O15. These results demonstrate that the effect of ultra-miniaturization of the cocatalyst on photocatalytic activity varies depending on the photocatalyst

Construction of novel metabolic pathways with artificial enzymes

Non-fossil raw materials can be utilized for the production of useful compounds by way of microbial fermentation . Sugars are obtained from carbon fixations of plants or photosynthetic microorganisms, and are used as a carbon source for the biosynthesis of useful target compounds by genetically modified microorganisms. In order for a microorganism to produce enough target compound, techniques for optimal metabolic design must include balance of energy production/consumption, redox pathways, and intracellular carbon flow. With recent innovations in genome analysis technology and information processing technology, computational design tools that can describe more than 1000 genome-scale metabolic reactions to efficiently produce target compounds have been developed worldwide. However, the established tools are not designed to search and create biosynthetic pathways for production of non-natural compounds from fossil resources. We developed BioProV and M-path, new simulation tools that enable metabolic design for the biosynthesis of unnatural compounds. By combining these tools with enzyme engineering technology, we succeeded in expanding the scope of bioproduction targets. The first example is construction of an artificial metabolic pathway to biosynthesize isoprene. Isoprene the raw material for production of synthetic rubber that can be used in automobile tires. Currently, isoprene is industrially produced as a by-product of naphtha pyrolysis. Therefore, by establishing green isoprene production technology, dependence upon petroleum can be reduced. Isoprene is a substance that can exist within cells of many organisms as a monomer of polyisoprene rubber, and also as a structural unit of secondary metabolites. It is difficult to optimize its synthentic pathway due to shortages of intracellular ATP supply, and challenges in the introduction of improved biosynthetic pathways. In nature, isoprene is produced from mevalonic acid through a five-step reaction, but the newly constructed artificial metabolic pathway consists of just two steps from mevalonic acid to isoprene. This results in a three-fold reduction in cellular energy consumption. Furthermore, we succeeded in constructing a highly active enzyme that exhibits 10,000-fold higher isoprene-producing activity relative to natural enzymes. By introducing these artificial metabolic reactions into Escherichia coli, efficient artificial isoprene production was achieved. In addition, we have developed a microbial production system for 1,3-butadiene, another alternative source for synthetic rubber. Moreover, rationally engineered enzymes from insects and plants enzymes have resulted in the construction of an artificial pathway to benzylisoquinoline alkaloids and downstream opioid analgesics

General ion recombination effect in a liquid ionization chamber in high-dose-rate pulsed photon and electron beams

Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and have small perturbations because of their liquid-filled sensitive volume. They require a sensitive volume much smaller than conventional air-filled chambers. However, it has been reported that the collection efficiency has dependencies on the dose per pulse and the pulse repetition frequency of a pulsed beam. The purpose of this study was to evaluate in detail the dependency of the ion collection efficiency on the pulse repetition frequency. A microLion (PTW, Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition frequency was varied, but the dose per pulse was fixed. A theoretical evaluation of the collection efficiency was performed based on Boag’s theory. Linear correlations were observed between the frequency and the relative collection for all energies of the photon and electron beams. The decrease in the collected charge was within 1% for all the flattened photon and electron beams, and they were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams, respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV flattened photon beam with a dose rate of 3 Gy·min−1. It is suggested that the collected charge decreased because of the short time intervals of the beam pulse compared with the ion collection time. Thus, it is important to correctly choose the pulse repetition frequency, particularly when flattening filter-free mode is used for absolute dose measurements

3D‐printable lung phantom for distal falloff verification of proton Bragg peak

In proton therapy, the Bragg peak of a proton beam reportedly deteriorates when passing though heterogeneous structures such as human lungs. Previous studies have used heterogeneous random voxel phantoms, in which soft tissues and air are randomly allotted to render the phantoms the same density as human lungs, for conducting Monte Carlo (MC) simulations. However, measurements of these phantoms are complicated owing to their difficult‐to‐manufacture shape. In the present study, we used Voronoi tessellation to design a phantom that can be manufactured, and prepared a Voronoi lung phantom for which both measurement and MC calculations are possible. Our aim was to evaluate the effectiveness of this phantom as a new lung phantom for investigating proton beam Bragg peak deterioration. For this purpose, we measured and calculated the percentage depth dose and the distal falloff widths (DFW) passing through the phantom. For the 155 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were 0.40 and 0.39 cm, respectively. For the 200 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were both 0.48 cm. Our results indicate that both the measurements and MC calculations exhibited high reproducibility with plastinated lung sample from human body in previous studies. We found that better results were obtained using the Voronoi lung phantom than using other previous phantoms. The designed phantom may contribute significantly to the improvement of measurement precision. This study suggests that the Voronoi lung phantom is useful for simulating the effects of the heterogeneous structure of lungs on proton beam deterioration

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

部位特異的連結反応を介した分子配列による高次機能性タンパク質集合体の創製

主1工学_化学システム工