Numerical study of air-entraining and submerged vortices in a pump sump

Numerical detection of harmful vortices in pump sumps, such as an air-entraining vortex (AEV) and a submerged vortex (SMV), is crucially important to develop the drain pump machinery. We performed numerical simulations of the benchmark experiments of the pump sump conducted by Matsui et al. (2006 and 2016) using the OpenFOAM and compared the simulation results with the experimental data considering the effects of turbulence model, grid density and detection method of the vortices. We studied the threshold of the gas-liquid volume fraction of the VOF method and the second invariant of velocity gradient tensor to identify AEV and SMV. The methods proposed in the present paper were found to be very effective for the detection of the vortices, and the simulation results by RANS with the SST k-omega model successfully reproduced the experimental data. LES with the Smagorinsky model, however, was sensitive to the grid system and difficult to reproduce the experimental data even for the finest grid system having 3.7 million cells in the present study

Coexistence of muscle atrophy and high subcutaneous adipose tissue radiodensity predicts poor prognosis in hepatocellular carcinoma

IntroductionWe aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC).MethodsIn this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis.ResultsA total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child–Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan–Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child–Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis.ConclusionMuscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes

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

Robust Moth-Inspired Algorithm for Odor Source Localization Using Multimodal Information

Odor-source localization, by which one finds the source of an odor by detecting the odor itself, is an important ability to possess in order to search for leaking gases, explosives, and disaster survivors. Although many animals possess this ability, research on implementing olfaction in robotics is still developing. We developed a novel algorithm that enables a robot to localize an odor source indoors and outdoors by taking inspiration from the adult male silk moth, which we used as the target organism. We measured the female-localization behavior of the silk moth by using a virtual reality (VR) system to obtain the relationship between multiple sensory stimuli and behavior during the localization behavior. The results showed that there were two types of search active and inactive depending on the direction of odor and wind detection. In an active search, the silk moth moved faster as the odor-detection frequency increased, whereas in the inactive search, they always moved slower under all odor-detection frequencies. This phenomenon was constructed as a robust moth-inspired (RMI) algorithm and implemented on a ground-running robot. Experiments on odor-source localization in three environments with different degrees of environmental complexity showed that the RMI algorithm has the best localization performance among conventional moth-inspired algorithms. Analysis of the trajectories showed that the robot could move smoothly through the odor plume even when the environment became more complex. This indicates that switching and modulating behavior based on the direction of odor and wind detection contributes to the adaptability and robustness of odor-source localization

Robust Moth-Inspired Algorithm for Odor Source Localization Using Multimodal Information

Odor-source localization, by which one finds the source of an odor by detecting the odor itself, is an important ability to possess in order to search for leaking gases, explosives, and disaster survivors. Although many animals possess this ability, research on implementing olfaction in robotics is still developing. We developed a novel algorithm that enables a robot to localize an odor source indoors and outdoors by taking inspiration from the adult male silk moth, which we used as the target organism. We measured the female-localization behavior of the silk moth by using a virtual reality (VR) system to obtain the relationship between multiple sensory stimuli and behavior during the localization behavior. The results showed that there were two types of search active and inactive depending on the direction of odor and wind detection. In an active search, the silk moth moved faster as the odor-detection frequency increased, whereas in the inactive search, they always moved slower under all odor-detection frequencies. This phenomenon was constructed as a robust moth-inspired (RMI) algorithm and implemented on a ground-running robot. Experiments on odor-source localization in three environments with different degrees of environmental complexity showed that the RMI algorithm has the best localization performance among conventional moth-inspired algorithms. Analysis of the trajectories showed that the robot could move smoothly through the odor plume even when the environment became more complex. This indicates that switching and modulating behavior based on the direction of odor and wind detection contributes to the adaptability and robustness of odor-source localization

Characterization of the multimeric structure of poly(A)-binding protein on a poly(A) tail

Abstract Eukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates translation and mRNA metabolism by binding to regulatory proteins. To understand functional mechanism of the regulatory proteins, it is necessary to reveal how multiple molecules of PABPC1 exist on poly(A). Here, we characterize the structure of the multiple molecules of PABPC1 on poly(A), by using transmission electron microscopy (TEM), chemical cross-linking, and NMR spectroscopy. The TEM images and chemical cross-linking results indicate that multiple PABPC1 molecules form a wormlike structure in the PABPC1-poly(A) complex, in which the PABPC1 molecules are linearly arrayed. NMR and cross-linking analyses indicate that PABPC1 forms a multimer by binding to the neighbouring PABPC1 molecules via interactions between the RNA recognition motif (RRM) 2 in one molecule and the middle portion of the linker region of another molecule. A PABPC1 mutant lacking the interaction site in the linker, which possesses an impaired ability to form the multimer, reduced the in vitro translation activity, suggesting the importance of PABPC1 multimer formation in the translation process. We therefore propose a model of the PABPC1 multimer that provides clues to comprehensively understand the regulation mechanism of mRNA translation

Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy

A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates beta 1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)-or progesterone receptor (PgR)positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses