Repair Inspection Technique Based on Elastic-Wave Tomography Applied for Deteriorated Concrete Structures

Applying elastic wave tomography as an innovative NDT method, the evaluation of velocity distribution in three-dimensional (3D) before and after the repair is introduced in this study. The increase in the velocity with penetration of the repair material according to the repair effect is identified visually and quantitatively. The 3D tomography technique is newly proposed for one-side access inspection, using drill hammering to generate an elastic wave. Accordingly, the elastic wave velocity distribution result enables to visualize the internal quality of concrete after patch repair is successfully done. In addition, an attempt for reinforced concrete (RC) slab panels is made to confirm the effectiveness of the repair by comparing the velocity distribution of elastic waves obtained from acoustic emission (AE) tomography analysis, before and after the repair. Thus, the velocity recoveries due to injection are found in all the slab panels, and it is confirmed that the elastic wave velocities obtained using this technique can serve as an indicator for examining the state of crack and void filling with injected material. Further, a good correlation is found between the low-velocity region before repair and the amount of injection. These results show the potential of the AE tomography technique to be used as a method for estimating the effect of injection repair

Absence of Radial Spokes in Mouse Node Cilia Is Required for Rotational Movement but Confers Ultrastructural Instability as a Trade-Off

SummaryDetermination of left-right asymmetry in mouse embryos is established by a leftward fluid flow that is generated by clockwise rotation of node cilia. How node cilia achieve stable unidirectional rotation has remained unknown, however. Here we show that brief exposure to the microtubule-stabilizing drug paclitaxel (Taxol) induces randomly directed rotation and changes the ultrastructure of node cilia. In vivo observations and a computer simulation revealed that a regular 9+0 arrangement of doublet microtubules is essential for stable unidirectional rotation of node cilia. The 9+2 motile cilia of the airway, which manifest planar beating, are resistant to Taxol treatment. However, the airway cilia of mice lacking the radial spoke head protein Rsph4a undergo rotational movement instead of planar beating, are prone to microtubule rearrangement, and are sensitive to Taxol. Our results suggest that the absence of radial spokes allows node cilia to rotate unidirectionally but, as a trade-off, renders them ultrastructurally fragile

knn-seq: Efficient, Extensible kNN-MT Framework

k-nearest-neighbor machine translation (kNN-MT) boosts the translation quality of a pre-trained neural machine translation (NMT) model by utilizing translation examples during decoding. Translation examples are stored in a vector database, called a datastore, which contains one entry for each target token from the parallel data it is made from. Due to its size, it is computationally expensive both to construct and to retrieve examples from the datastore. In this paper, we present an efficient and extensible kNN-MT framework, knn-seq, for researchers and developers that is carefully designed to run efficiently, even with a billion-scale large datastore. knn-seq is developed as a plug-in on fairseq and easy to switch models and kNN indexes. Experimental results show that our implemented kNN-MT achieves a comparable gain to the original kNN-MT, and the billion-scale datastore construction took 2.21 hours in the WMT'19 German-to-English translation task. We publish our knn-seq as an MIT-licensed open-source project and the code is available on https://github.com/naist-nlp/knn-seq . The demo video is available on https://youtu.be/zTDzEOq80m0

Ultra-high voltage electron microscopy of primitive algae illuminates 3D ultrastructures of the first photosynthetic eukaryote

A heterotrophic organism 1–2 billion years ago enslaved a cyanobacterium to become the first photosynthetic eukaryote, and has diverged globally. The primary phototrophs, glaucophytes, are thought to retain ancestral features of the first photosynthetic eukaryote, but examining the protoplast ultrastructure has previously been problematic in the coccoid glaucophyte Glaucocystis due to its thick cell wall. Here, we examined the three-dimensional (3D) ultrastructure in two divergent species of Glaucocystis using ultra-high voltage electron microscopy. Three-dimensional modelling of Glaucocystis cells using electron tomography clearly showed that numerous, leaflet-like flattened vesicles are distributed throughout the protoplast periphery just underneath a single-layered plasma membrane. This 3D feature is essentially identical to that of another glaucophyte genus Cyanophora, as well as the secondary phototrophs in Alveolata. Thus, the common ancestor of glaucophytes and/or the first photosynthetic eukaryote may have shown similar 3D structures.UTokyo Research掲載「原始植物細胞内の三次元構造が明らかに」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/3d-internal-structure-of-primitive-plant-cell.htmlUTokyo Research "3D internal structure of primitive plant cell" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/3d-internal-structure-of-primitive-plant-cell.htm

Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens

We report the identification of two novel minor histocompatibility antigens (mHAgs), encoded by two separate single nucleotide polymorphisms on a single gene, BCL2A1, and restricted by human histocompatibility leukocyte antigen (HLA)-A*2402 (the most common HLA-A allele in Japanese) and B*4403, respectively. Two cytotoxic T lymphocyte (CTL) clones specific for these mHAgs were first isolated from two distinct recipients after hematopoietic cell transplantation. Both clones lyse only normal and malignant cells within the hematopoietic lineage. To localize the gene encoding the mHAgs, two-point linkage analysis was performed on the CTL lytic patterns of restricting HLA-transfected B lymphoblastoid cell lines obtained from Centre d'Etude du Polymorphisme Humain. Both CTL clones showed a completely identical lytic pattern for 4 pedigrees and the gene was localized within a 3.6-cM interval of 15q24.3–25.1 region that encodes at least 46 genes. Of those, only BCL2A1 has been reported to be expressed in hematopoietic cells and possess three nonsynonymous nucleotide changes. Minigene transfection and epitope reconstitution assays with synthetic peptides identified both HLA-A*2402– and B*4403-restricted mHAg epitopes to be encoded by distinct polymorphisms within BCL2A1

The Motion of An Inv Nodal Cilium: a Realistic Model Revealing Dynein-Driven Ciliary Motion with Microtubule Mislocalization

Background/Aims: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. Methods: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. Results: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. Conclusion: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation

Being Praised for Prosocial Behaviors Longitudinally Reduces Depressive Symptoms in Early Adolescents: A Population-Based Cohort Study

BackgroundDepression is highly prevalent and causes a heavy burden in adolescent life. Being praised for prosocial behavior might be a preventive factor because both being praised and prosocial behavior are protective against depression. Here, we investigated the longitudinal relationship between being praised for prosocial behavior and depressive symptoms in adolescents.MethodsIn Tokyo Teen Cohort study (TTC), an ongoing prospective population-based cohort study, we collected 3,171 adolescents' data on self-reported experiences of being praised for prosocial behavior, depressive symptoms, and caregiver-evaluated prosocial behavior. Ten-year-old children were asked to freely describe answers to the question “What are you praised for?”. Only children who clearly answered that they were praised for their prosocial behavior were designated the “prosocial praise group.” The degree of depression at ages 10 and 12 was measured with the Short Mood and Feelings Questionnaire (SMFQ), a self-report questionnaire about depression. Objective prosocial behavior of the 10 year-old children was assessed by the Strength and Difficulty Questionnaire (SDQ). Multiple linear regression analysis was performed using the SMFQ score at age 12 as the objective variable and being praised for prosocial behavior as the main explanatory variable, and the SMFQ score at age 10 and the objective prosocial behavior at age 10 were included as confounders.ResultsDepressive symptoms (SMFQ scores) in the “prosocial praise group” were significantly lower than those in the other group both at age 10 (4.3 ± 4.4 vs. 4.9 ± 4.6, p < 0.001) and at age 12 (3.4 ± 4.2 vs. 4.0 ± 4.6, p < 0.01). In the single regression analysis, the children who reported being praised for prosocial behavior at age 10 had significantly lower depressive symptoms at age 12 (partial regression variable: −0.57, 95% confidence interval (CI) [−0.96, −0.17]). This association remained significant after adjusting for confounders, including baseline depressive symptoms (partial regression variable: −0.44, 95% CI [−0.80, −0.08]). Prosocial behavior alone was not associated with depressive symptoms.ConclusionsBeing praised for prosocial behavior rather than objective prosocial behavior at 10 years of age predicted lower depressive symptoms 2 years later. Praise for adolescents' prosocial behavior can be encouraged to prevent depression

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