Prediction Models for Agonists and Antagonists of Molecular Initiation Events for Toxicity Pathways Using an Improved Deep-Learning-Based Quantitative Structure–Activity Relationship System

In silico approaches have been studied intensively to assess the toxicological risk of various chemical compounds as alternatives to traditional in vivo animal tests. Among these approaches, quantitative structure–activity relationship (QSAR) analysis has the advantages that it is able to construct models to predict the biological properties of chemicals based on structural information. Previously, we reported a deep learning (DL) algorithm-based QSAR approach called DeepSnap-DL for high-performance prediction modeling of the agonist and antagonist activity of key molecules in molecular initiating events in toxicological pathways using optimized hyperparameters. In the present study, to achieve high throughput in the DeepSnap-DL system–which consists of the preparation of three-dimensional molecular structures of chemical compounds, the generation of snapshot images from the three-dimensional chemical structures, DL, and statistical calculations—we propose an improved DeepSnap-DL approach. Using this improved system, we constructed 59 prediction models for the agonist and antagonist activity of key molecules in the Tox21 10K library. The results indicate that modeling of the agonist and antagonist activity with high prediction performance and high throughput can be achieved by optimizing suitable parameters in the improved DeepSnap-DL system.     

Application of graft-type poly(ether ether ketone)-based polymer electrolyte membranes to electrochemical devices – Fuel cells and electrolytic enrichment of tritium

The polymer electrolyte membrane consisting of poly(styrenesulfonic acid)-grafted poly(ether ether ketone) (PEEK-PEM) was investigated for application to two electrochemical devices; a fuel cell and electrolytic enrichment of tritium. For fuel cells, high temperature operation has been required from the viewpoints of simplification of cooling systems, heat recovery systems and so forth, and durability is one critical issue affecting practical use. We performed a long term durability test for PEEK-PEM (ion exchange capacity = 2.4 mmol/g, conductivity = 0.15 S/cm) under the condition of 110 °C and 50% relative humidity, and achieved a lifetime of 1500 h at a constant current of 0.3 A/cm². The cell voltage maintained 97% of initial voltage after 1300 h of operation. There have been only a few reports that PEMs exhibit longer lifetime than 1000 h at temperatures above 100 °C. For quantitative evaluation of tritium concentration in low-level tritiated water such as environmental water, the tritium enrichment by a solid polymer electrolysis (SPE) method is required prior to the tritium concentration measurements. The SPE device composed of PEEK-PEMs with IECs of 0.9–1.2 mmol/g showed a tritium enrichment ratio of 1.35 at 30 °C, which is 20% higher than that of Nafion. Higher tritium enrichment ratios in PEEK-PEM are explained by the smaller amount of transported water. The water transport coefficient in PEEK-PEM is ～1, which is a half value of Nafion. In addition, the water transport coefficient of PEEK-PEM shows less temperature dependence, at least, up to 60 °C. These features have advantages in electrolytic enrichment of tritium for practical use.     

Instabilities Driven by an Intense Beam in a Plasma-Filled Dielectric-Lined Waveguide Immersed in a Finite Axial Magnetic Field

A linear analysis is described on stabilities driven by an intense relativistic electron beam in an infinitely long, plasma-filled, and dielectric-lined circular waveguide immersed in a finite strength axial magnetic field. A dispersion equation is derived from the cold fluid theory and solved numerically. Beam-plasma instabilities due to interaction between beam modes and the Trivelpiece-Gould modes appear as well as the Cherenkov and the cyclotron Cherenkov instabilities. Parametric researches are carried out varying magnetic field strength, plasma density, and dielectric constant. Effects of a finite magnetic field and plasma filling are discussed in connection with the possibilities of using this system as a microwave radiation source.     

Measurements of neutron induced activation of concrete at 64.5 MeV

The present paper presents the measurement of neutron induced activations on concrete using the 64.5 MeV quasimonoenergetic neutrons produced at the intense ⁷Li(p, n) neutron source at Cyclotron and Radioisotope Center, Tohoku Univeristy (CYRIC). The data were corrected for the effect of continuous neutrons in the source. The neutron energy, neutron yields and the spectrum of continuous neutrons were confirmed with the neutron time-of-flight method and the neutron activation measurement of the ²⁰⁹Bi(n, Xn) reactions having various threshold energy values. The nuclides produced by thermalized source neutrons are negligible. New data were obtained for concrete activation.     

A novel mechanism regulates H(2) S and SO(2) production in Saccharomyces cerevisiae

Sulfite (SO(2) ) plays an important role in flavour stability in alcoholic beverages, whereas hydrogen sulfide (H(2) S) has an undesirable aroma. To discover the cellular processes that control SO(2) and H(2) S production, we screened a library of Saccharomyces cerevisiae deletion mutants. Deletion of 12 genes led to increased H(2) S productivity. Ten of these genes are known to be involved in sulfur-containing amino acid metabolism, whereas UBI4 functions in the ubiquitin-proteasome system and SKP2 encodes an F-box-containing protein whose function is unknown. We found that the skp2 mutant accumulated H(2) S and SO(2) , because the adenosylphophosulfate kinase Met14p is a substrate of SCF(Skp2) and more stable in the skp2 mutant than in the wild-type strain. Furthermore, the skp2 mutant grew more slowly than the wild-type strain under nutrient-limited conditions. Metabolome analysis showed that the concentration of intracellular cysteine is lower in the skp2 mutant than in the wild-type strain. The slow growth of the skp2 mutant was due to a lower concentration of intracellular cysteine, because the addition of cysteine suppressed the slow growth. In the skp2 mutant, the cysteine biosynthesis proteins Str2p, Str3p and Str4p are more stable than in the wild-type strain. Moreover, supplementation with methionine, S-adenosylmethionine, S-adenosylhomocysteine and homocysteine also suppressed the slow growth. Overexpression of STR1 or STR4 caused a more severe defect in the skp2 mutant. These results suggest that the balance of methionine and cysteine biosynthesis is important for yeast cell growth. Thus, Skp2p is one of the key components regulating this balance and H(2) S/SO(2) production.     

原爆存活者染色体畸变的生物学意义

本文报告了关于广岛原爆存活者骨髓细胞(105例)和外周血 T 淋巴细胞(39例)、B 淋巴细胞(4例)的细胞遗传学变化以及发生慢性粒细胞白血病和乳癌的两例病人定期检查的细胞遗传学结果。骨髓细胞染色体畸变分析表明,距离下爆心0.5km 以内和0.5—1 km 的受照者分别有90%和52.4%出现染色体畸变,染色体畸变细胞分别占观察细胞总数的23.2%和12.8%,每一组都有7例出现异常克隆(Clone)。出现的畸变类型大多数是稳定型的,非稳定型的极少见。在 T淋巴细胞染色体畸变分析方面,不同距离的两组出现的稳定型畸变(19.6%,22.1%)或非稳定型畸变(2.0%,2.2%)的发生率几乎一致。592个异常中期细胞断裂点的位置呈现规律性的趋向,存活者也出现 B 淋巴细胞的染色体畸变,33—50%的细胞系为异常核型,结果提示某些异常核型的 B 淋巴细胞在体内正在形成一种克隆。由这些细胞遗传学表现可以认为,从接受照射到白血病发生,似乎包含着染色体质变与量变的许多阶段。     

Immune-Associated Proteins Are Enriched in Lung Tissue-Derived Extracellular Vesicles during Allergen-Induced Eosinophilic Airway Inflammation

Studying the proteomes of tissue-derived extracellular vesicles (EVs) can lead to the identification of biomarkers of disease and can provide a better understanding of cell-to-cell communication in both healthy and diseased tissue. The aim of this study was to apply our previously established tissue-derived EV isolation protocol to mouse lungs in order to determine the changes in the proteomes of lung tissue-derived EVs during allergen-induced eosinophilic airway inflammation. A mouse model for allergic airway inflammation was used by sensitizing the mice intraperitoneal with ovalbumin (OVA), and one week after the final sensitization, the mice were challenged intranasal with OVA or PBS. The animals were sacrificed 24 h after the final challenge, and their lungs were removed and sliced into smaller pieces that were incubated in culture media with DNase I and Collagenase D for 30 min at 37 °C. Vesicles were isolated from the medium by ultracentrifugation and bottom-loaded iodixanol density cushions, and the proteomes were determined using quantitative mass spectrometry. More EVs were present in the lungs of the OVA-challenged mice compared to the PBS-challenged control mice. In total, 4510 proteins were quantified in all samples. Among them, over 1000 proteins were significantly altered (fold change >2), with 614 proteins being increased and 425 proteins being decreased in the EVs from OVA-challenged mice compared to EVs from PBS-challenged animals. The associated cellular components and biological processes were analyzed for the altered EV proteins, and the proteins enriched during allergen-induced airway inflammation were mainly associated with gene ontology (GO) terms related to immune responses. In conclusion, EVs can be isolated from mouse lung tissue, and the EVs’ proteomes undergo changes in response to allergen-induced airway inflammation. This suggests that the composition of lung-derived EVs is altered in diseases associated with inflammation of the lung, which may have implications in type-2 driven eosinophilic asthma pathogenesis.     

Facial expression recognition of a speaker using vowel judgment and thermal image processing

We have previously developed a method for the recognition of the facial expression of a speaker. For facial expression recognition, we previously selected three images: (i) just before speaking, (ii) speaking the first vowel, and (iii) speaking the last vowel in an utterance. By using the speech recognition system named Julius, thermal static images are saved at the timed positions of just before speaking, and when just speaking the phonemes of the first and last vowels. To implement our method, we recorded three subjects who spoke 25 Japanese first names which provided all combinations of the first and last vowels. These recordings were used to prepare first the training data and then the test data. Julius sometimes makes a mistake in recognizing the first and/or last vowel (s). For example, /a/ for the first vowel is sometimes misrecognized as /i/. In the training data, we corrected this misrecognition. However, the correction cannot be carried out in the test data. In the implementation of our method, the facial expressions of the three subjects were distinguished with a mean accuracy of 79.8% when they exhibited one of the intentional facial expressions of “angry,” “happy,” “neutral,” “sad,” and “surprised.” The mean accuracy of the speech recognition of vowels by Julius was 84.1%.