153 results on '"Yamada, Ryo"'
Search Results
2. Visualization of the landscape of the read alignment shape of ATAC‐seq data using Hellinger distance metric.
- Author
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Cheng, Jian Hao, Zheng, Cheng, Yamada, Ryo, and Okada, Daigo
- Subjects
GENE expression ,DATA visualization ,NUCLEOTIDE sequencing ,INFORMATION theory ,DISTRIBUTION (Probability theory) ,PROMOTERS (Genetics) - Abstract
Assay for Transposase‐Accessible Chromatin using high‐throughput sequencing (ATAC‐seq) is the popular technique using next‐generation sequencing to measure chromatin accessibility and identify open chromatin regions. While read alignment shape information of next‐generation sequencing data with intensity information has been used in various bioinformatics methods, few studies have focused on pure shape information alone. In this study, we investigated what types of ATAC‐seq read alignment shapes are observed for the promoter region and whether the pure shape information was related or unrelated to other gene features. We introduced a novel concept and pipeline for handling the pure shape information of NGS data as probability distributions and quantifying their dissimilarities by information theory. Based on this concept, we demonstrate that the pure shape information of ATAC‐seq data is correlated with chromatin openness and some gene characteristics. On the other hand, it is suggested that the pure information of ATAC‐seq read alignment shape is unlikely to contain additional information to explain differences in RNA expression. Our study suggests that viewing the read alignment shape of NGS data as probability distributions enables us to capture the characteristics of the genome‐wide landscape of such data in a non‐parametric manner. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Ostwald ripening under temperature gradient: A phase-field study.
- Author
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Yamada, Ryo, Inubushi, Haruki, and Ohno, Munekazu
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OSTWALD ripening ,PARTICLE size distribution ,CONCENTRATION gradient ,HIGH temperatures ,LOW temperatures - Abstract
Ostwald ripening under a temperature gradient in binary model alloys is investigated using a quantitative phase-field model. The simulations show that a cube of average radius of a second-phase particle is proportional to time, and the particle size distribution shows self-similarity in a steady state, as with a uniform temperature field. It is found that the growth rate of particles under a temperature gradient is faster than that in the isothermal case, and the steady-state particle size distribution depends on the magnitude of the temperature gradient. Furthermore, the second-phase particles migrate from low temperature regions to high temperature regions when a non-uniform temperature field is applied. The migration velocity of particles, averaged over the whole system, increases with the magnitude of the temperature gradient. On the other hand, the velocity of each particle is not relevant to particle size. Hence, the particle migration is entirely ascribed to the diffusion flux driven by the concentration gradient originating from the temperature dependence of solute solubility. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Magnetoresistance originated from the Au/S interface in Au/1,6-hexanedithiol/Au single-molecule junctions at room temperature.
- Author
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Andika, Rachmat, Yamada, Ryo, and Tada, Hirokazu
- Abstract
We report a magnetic response of Au/1,6-hexanedithiol/Au single-molecule junctions at room temperature using a mechanically controllable break junction method. The electrical resistance of the junction was found to increase up to 5.5% under a magnetic field. This phenomenon could originate from the unpaired charge at the Au/S interface. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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5. Robot‐assisted total remnant gastrectomy for interposed jejunal pouch dysfunction 25 years after proximal gastrectomy for gastric cancer: A case report.
- Author
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Uemura, Sunao, Yamai, Hiromichi, Onishi, Kazuhisa, Chikamori, Fumio, Yoshida, Mitsuteru, Hokimoto, Norihiro, Matsuoka, Hisashi, Iwabu, Jun, Ueta, Koji, Yamada, Ryo, Mizobuchi, Kai, Marui, Akira, and Tanida, Nobuyuki
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STOMACH cancer ,GASTRECTOMY ,SURGICAL robots ,FOOD consumption ,COMPUTED tomography - Abstract
Proximal gastrectomy (PG) in combination with jejunal pouch interposition is a technique aimed at improving the postoperative dietary outcomes; however, some cases are reported to require surgical intervention owing to difficulty of food intake caused by pouch dysfunction. Herein, we present a case of robot‐assisted surgery for interposed jejunal pouch (IJP) dysfunction in a 79‐year‐old male, occurring 25 years after the initial PG for gastric cancer. The patient had chronic anorexia for 2 years and was treated with medications and dietary guidance; however, 3 months prior to admission his quality of life had reduced, owing to worsening symptoms. The patient was diagnosed with pouch dysfunction due to extremely dilated IJP identified using computed tomography and underwent robot‐assisted total remnant gastrectomy (RATRG) with IJP resection. After an uneventful course of intraoperative and postoperative treatment, he was discharged with sufficient food intake on postoperative day 9. RATRG can, thus, be considered in patients with IJP dysfunction after PG. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
6. Reservoir computing with the electrochemical formation and reduction of gold oxide in aqueous solutions with a three-electrode electrochemical setup.
- Author
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Yamada, Ryo, Watanabe, Shuto, and Tada, Hirokazu
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- 2023
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7. Data-driven identification and classification of nonlinear aging patterns reveals the landscape of associations between DNA methylation and aging.
- Author
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Okada, Daigo, Cheng, Jian Hao, Zheng, Cheng, Kumaki, Tatsuro, and Yamada, Ryo
- Abstract
Background: Aging affects the incidence of diseases such as cancer and dementia, so the development of biomarkers for aging is an important research topic in medical science. While such biomarkers have been mainly identified based on the assumption of a linear relationship between phenotypic parameters, including molecular markers, and chronological age, numerous nonlinear changes between markers and aging have been identified. However, the overall landscape of the patterns in nonlinear changes that exist in aging is unknown. Result: We propose a novel computational method, Data-driven Identification and Classification of Nonlinear Aging Patterns (DICNAP), that is based on functional data analysis to identify biomarkers for aging and potential patterns of change during aging in a data-driven manner. We applied the proposed method to large-scale, public DNA methylation data to explore the potential patterns of age-related changes in methylation intensity. The results showed that not only linear, but also nonlinear changes in DNA methylation patterns exist. A monotonous demethylation pattern during aging, with its rate decreasing at around age 60, was identified as the candidate stable nonlinear pattern. We also analyzed the age-related changes in methylation variability. The results showed that the variability of methylation intensity tends to increase with age at age-associated sites. The representative variability pattern is a monotonically increasing pattern that accelerates after middle age. Conclusion: DICNAP was able to identify the potential patterns of the changes in the landscape of DNA methylation during aging. It contributes to an improvement in our theoretical understanding of the aging process. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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8. Design and implementation of a hybrid cloud system for large-scale human genomic research.
- Author
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Nagasaki, Masao, Sekiya, Yayoi, Asakura, Akihiro, Teraoka, Ryo, Otokozawa, Ryoko, Hashimoto, Hiroki, Kawaguchi, Takahisa, Fukazawa, Keiichiro, Inadomi, Yuichi, Murata, Ken T., Ohkawa, Yasuyuki, Yamaguchi, Izumi, Mizuhara, Takamichi, Tokunaga, Katsushi, Sekiya, Yuji, Hanawa, Toshihiro, Yamada, Ryo, and Matsuda, Fumihiko
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HYBRID cloud computing ,DEEP learning ,SUPERCOMPUTERS ,GRAPHICS processing units ,HUMAN experimentation ,CLOUD computing ,IMAGE analysis - Abstract
In the field of genomic medical research, the amount of large-scale information continues to increase due to advances in measurement technologies, such as high-performance sequencing and spatial omics, as well as the progress made in genomic cohort studies involving more than one million individuals. Therefore, researchers require more computational resources to analyze this information. Here, we introduce a hybrid cloud system consisting of an on-premise supercomputer, science cloud, and public cloud at the Kyoto University Center for Genomic Medicine in Japan as a solution. This system can flexibly handle various heterogeneous computational resource-demanding bioinformatics tools while scaling the computational capacity. In the hybrid cloud system, we demonstrate the way to properly perform joint genotyping of whole-genome sequencing data for a large population of 11,238, which can be a bottleneck in sequencing data analysis. This system can be one of the reference implementations when dealing with large amounts of genomic medical data in research centers and organizations. Genomics: Designing and deploying a hybrid cloud computing system Researchers in Japan have set up a hybrid cloud computing system for genomic analysis. A team headed by Masao Nagasaki of Kyoto University has designed and developed a scalable bioinformatics system and demonstrated its effectiveness by analyzing over 11,000 human genome sequences. The system combines local computing resources with supercomputers at Japanese universities and cloud computing from Amazon Web Services. The analysis pipelines were designed to be distributed across multiple sites while also ensuring reproducibility. Computing resources can be added as needed, for example, nodes based on graphics processing unit could be added for workflows that rely on deep learning, such as analysis of pathology images. This hybrid cloud computing platform not only provides a tool for researchers in Japan but also serves as a reference point for designing similar systems in other institutes or countries. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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9. Time evolution of interface shape distribution of equiaxed dendrite: A phase-field study.
- Author
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Ohno, Munekazu, Kudo, Mikihiro, Kim, Geunwoo, Yamada, Ryo, Shibuta, Yasushi, and Takaki, Tomohiro
- Published
- 2023
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10. Tri-Directional Loading Tests on Reinforced Concrete Shear Walls.
- Author
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Yamada, Ryo, Tani, Masanori, and Nishiyama, Minehiro
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REINFORCED concrete testing ,CONCRETE walls ,AXIAL loads ,SHEARING force ,LATERAL loads ,CONCRETE columns - Abstract
This paper reports loading tests conducted to investigate the effect of tri-directional seismic force on the shear capacity of reinforced concrete (RC) shear walls. The experimental parameters were the magnitude of out-of-plane deformation and axial load condition. All specimens reached the in-plane maximum load capacity at approximately Rx = 0.50%. The maximum value of the average shear stress divided by the tensile strength of concrete decreased by 12.1 to 18.2% with increasing difference between axial compressive force and tensile force. The minimum safety margin was 1.07 attained for the specimen subjected to out-of-plane lateral load and varying axial load acting simultaneously, while that of the specimen subjected to only in-plane lateral load under constant axial load was 1.50. The safety margin was defined as the ratio of the maximum load capacity obtained experimentally to the calculated capacity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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11. A simple proteinuria-based risk score predicts contrast-associated acute kidney injury after percutaneous coronary intervention.
- Author
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Fujiwara, Wakaya, Ishii, Hideki, Sobue, Yoshihiro, Shimizu, Shinya, Ishiguro, Tomoya, Yamada, Ryo, Ueda, Sayano, Nishimura, Hideto, Niwa, Yudai, Miyazaki, Akane, Miyagi, Wataru, Takahara, Shuhei, Naruse, Hiroyuki, Ishii, Junichi, Kiyono, Ken, Watanabe, Eiichi, and Izawa, Hideo
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PERCUTANEOUS coronary intervention ,ACUTE kidney failure ,DISEASE risk factors ,CORONARY arteries ,KIDNEY diseases ,LOGISTIC regression analysis - Abstract
Contrast-associated acute kidney injury (CA-AKI) is a complication of percutaneous coronary intervention (PCI). Because proteinuria is a sentinel marker of renal dysfunction, we assessed its role in predicting CA-AKI in patients undergoing PCI. A total of 1,254 patients undergoing PCI were randomly assigned to a derivation (n = 840) and validation (n = 414) dataset. We identified the independent predictors of CA-AKI where CA-AKI was defined by the new criteria issued in 2020, by a multivariate logistic regression in the derivation dataset. We created a risk score from the remaining predictors. The discrimination and calibration of the risk score in the validation dataset were assessed by the area under the receiver-operating characteristic curves (AUC) and Hosmer–Lemeshow test, respectively. A total of 64 (5.1%) patients developed CA-AKI. The 3 variables of the risk score were emergency procedures, serum creatinine, and proteinuria, which were assigned 1 point each based on the correlation coefficient. The risk score demonstrated a good discriminative power (AUC 0.789, 95% CI 0.766–0.912) and significant calibration. It was strongly associated with the onset of CA-AKI (Cochran-Armitage test, p < 0.0001). Our risk score that included proteinuria was simple to obtain and calculate, and may be useful in assessing the CA-AKI risk before PCI. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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12. Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma.
- Author
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Takehana, Keiichi, Sakamoto, Ryo, Fujimoto, Koji, Matsuo, Yukinori, Nakajima, Naoki, Yoshizawa, Akihiko, Menju, Toshi, Nakamura, Mitsuhiro, Yamada, Ryo, Mizowaki, Takashi, and Nakamoto, Yuji
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RADIOMICS ,COMPUTED tomography ,LUNGS ,ADENOCARCINOMA ,MACHINE learning ,PROGNOSIS - Abstract
The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans.
- Author
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Okada, Daigo, Okamoto, Yosuke, Io, Toshiro, Oka, Miho, Kobayashi, Daiki, Ito, Suzuka, Yamada, Ryo, Ishii, Kuniaki, and Ono, Kyoichi
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HEART ,TRANSCRIPTOMES ,SINOATRIAL node ,HEART atrium ,GENE expression ,COMPARATIVE studies ,TRANSCRIPTION factors ,MICE - Abstract
The heart is a significant organ in mammalian life, and the heartbeat mechanism has been an essential focus of science. However, few studies have focused on species differences. Accordingly, challenges remain in studying genes that have universal functions across species and genes that determine species differences. Here, we analyzed transcriptome data in mouse, rat, and human atria, ventricles, and sinoatrial nodes (SA) obtained from different platforms and compared them by calculating specificity measure (SPM) values in consideration of species differences. Among the three heart regions, the species differences in SA were the greatest, and we searched for genes that determined the essential characteristics of SA, which was SHOX2 in our criteria. The SPM value of SHOX2 was prominently high across species. Similarly, by calculating SPM values, we identified 3 atrial-specific, 11 ventricular-specific, and 17 SA-specific markers. Ontology analysis identified 70 cardiac region- and species-specific ontologies. These results suggest that reanalyzing existing data by calculating SPM values may identify novel tissue-specific genes and species-dependent gene expression. This study identified the importance of SHOX2 as an SA-specific transcription factor, a novel cardiac regional marker, and species-dependent ontologies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Comparison of the prognosis of the remaining teeth between implant‐supported fixed prostheses and removable partial dentures in partially edentulous patients: A retrospective study.
- Author
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Yamada, Ryo, Nogawa, Toshifumi, Takayama, Yoshiyuki, Iwata, Kai, Saito, Masayasu, and Yokoyama, Atsuro
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REMOVABLE partial dentures ,TOOTH loss ,EDENTULOUS mouth ,TEETH ,PROSTHETICS ,PROGNOSIS - Abstract
Background: There have been several reports about the prognosis of teeth adjacent to edentulous spaces for implant‐supported fixed prostheses (ISFPs) and removable partial dentures (RPDs). However, there are few reports about the prognosis of the other remaining teeth comparing ISFPs with RPDs. Purpose: The aim of this study was to evaluate and compare the prognosis of the remaining teeth for ISFPs and RPDs in terms of survival and complication‐free rates. Methods: Subjects were partially edentulous patients with ISFPs or RPDs inserted in 2003–2016. Teeth adjacent to edentulous spaces (A‐teeth), teeth not adjacent to edentulous spaces (R‐teeth), and teeth opposing edentulous spaces (O‐teeth) were investigated. The endpoints were tooth extraction and complications. A multivariate cox regression model was used to estimate the risk factors for survival of the investigated teeth. Results: A total of 233 (ISFP: 89, RPD: 144) patients were included in the statistical analyses. An IFSP prosthesis, when compared to an RPD prosthesis did not significantly decrease the tooth loss rate for A‐teeth (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.30–1.92), for R‐teeth (HR: 0.54; 95% CI: 0.28–1.05), or for O‐teeth (HR: 0.45; 95% CI: 0.10–2.09). Conclusions: In partially edentulous spaces, the difference between ISFPs and RPDs does not affect the prognosis of teeth adjacent to edentulous spaces, teeth not adjacent to edentulous spaces, and teeth opposing edentulous spaces. Namely, our findings suggest that it depends largely on the tooth type, jaw, endodontic therapy performed, not on the type of prostheses. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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15. Cell population‐based framework of genetic epidemiology in the single‐cell omics era.
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Okada, Daigo, Zheng, Cheng, Cheng, Jian Hao, and Yamada, Ryo
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GENETIC epidemiology ,GENETIC models ,SYSTEMS biology ,GENETIC variation ,FEATURE extraction - Abstract
Genetic epidemiology is a rapidly advancing field due to the recent availability of large amounts of omics data. In recent years, it has become possible to obtain omics information at the single‐cell level, so genetic epidemiological models need to be updated to integrate with single‐cell expression data. In this perspective paper, we propose a cell population‐based framework for genetic epidemiology in the single‐cell era. In this framework, genetic diversity influences phenotypic diversity through the diversity of cell population profiles, which are defined as high‐dimensional probability distributions of the state spaces of biomolecules of each omics layer. We discuss how biomolecular experimental measurement data can capture the different properties of this distribution. In particular, single‐cell data constitute a sample from this population distribution where only some coordinate values are observable. From a data analysis standpoint, we introduce methodology for feature extraction from cell population profiles. Finally, we discuss how this framework can be applied not only to genetic epidemiology but also to systems biology. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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16. Impact of heart failure severity on bone mineral density among older patients with heart failure.
- Author
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Kono, Yuji, Izawa, Hideo, Aoyagi, Yoichiro, Yamada, Ryo, Ishiguro, Tomoya, Yoshinaga, Masataka, Okumura, Satoshi, Fujiwara, Wakaya, Hayashi, Mutsuharu, and Otaka, Yohei
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BONE density ,OLDER patients ,HEART failure patients ,HEART failure ,MULTIPLE regression analysis ,BIVARIATE analysis - Abstract
The study aimed to identify factors related to bone mineral density (BMD) among older patients with heart failure (HF). A total of 70 consecutive patients with HF aged 65 years or older who were admitted to an acute hospital due to worsening condition were enrolled before discharge. BMD of the femoral neck was evaluated using the DEXA method. Physical function, as well as echocardiographic and laboratory findings including biomarker of HF severity were collected. Bivariate and multiple regression analyses were employed to determine the association between BMD and the clinical variables. Bivariate analysis determined that age, grip strength, walking speed, serum albumin, and N-terminal pro B-type natriuretic peptide (NT-proBNP) were significantly correlated with BMD (P < 0.01), whereas other clinical parameters were not. The multiple regression analysis identified NT-proBNP as an independent related factor for BMD after adjusting with confounding clinical variables. NT-proBNP was independently related to BMD among older patients with HF. Our results suggest the inclusion of bone fracture prevention strategies in disease management programs, especially for older patients with HF. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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17. Intrinsic defect formation and the effect of transition metal doping on transport properties in a ductile thermoelectric material α-Ag2S: a first-principles study.
- Author
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Ngoc Nam, Ho, Yamada, Ryo, Okumura, Haruki, Nguyen, Tien Quang, Suzuki, Katsuhiro, Shinya, Hikari, Masago, Akira, Fukushima, Tetsuya, and Sato, Kazunori
- Abstract
In this paper, the electronic structure and transport properties of a ductile thermoelectric material α-Ag
2 S are examined using first-principles calculations combined with the Boltzmann transport equation within a constant relaxation-time approximation. The use of the exchange–correlation functional SCAN + rVV10 successfully describes the geometric and electronic structure of α-Ag2 S with a direct bandgap value of 0.99 eV, which is consistent with the previous experimental observations. Based on the calculations of the formation energy of typical intrinsic defects, it is found that intrinsic defect formation greatly affects the conductivity of the system where silver vacancy and interstitial silver act as p-type and n-type defects, respectively. Large Seebeck coefficients at room-temperature, of around −760 μV K−1 for n-type and 1400 μV K−1 for p-type, are realized. It is also suggested that the doping of fully filled d-block elements such as Cu and Au not only maintained the Seebeck coefficients at high values but also improved electrical conductivity by more than 1.4 times, leading to the improvement of the power factor by up to 40% compared to the non-doped sample at low carrier concentration. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Single‐Molecule Conductance of a π‐Hybridized Tripodal Anchor while Maintaining Electronic Communication.
- Author
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Ohto, Tatsuhiko, Tashiro, Aya, Seo, Takuji, Kawaguchi, Nana, Numai, Yuichi, Tokumoto, Junpei, Yamaguchi, Soichiro, Yamada, Ryo, Tada, Hirokazu, Aso, Yoshio, and Ie, Yutaka
- Published
- 2021
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19. A High‐Power Dielectric Biconical Antenna for Treatment of Subcutaneous Targets.
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Xiao, Shu, Zou, Xianbing, Huynh, Khiem, Yamada, Ryo, Petrella, Ross, Bani Hani, Maisoun, and Beebe, Stephen
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- 2020
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20. Electrical conductance measurement of HgII-mediated DNA duplex in buffered aqueous solution.
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Yamada, Ryo, Nomura, Issei, Yamaguchi, Yuki, Matsuda, Yosuke, Hattori, Yoshikazu, Tada, Hirokazu, Ono, Akira, and Tanaka, Yoshiyuki
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AQUEOUS solutions ,SINGLE-stranded DNA ,DNA ,SCANNING tunneling microscopy - Abstract
Electrical properties of metal-mediated DNA duplexes (metallo-DNA) have been of particular interest because of their potential applications in DNA-based nanoelectronics. We prepared Hg
II -mediated DNA duplex with NH2 anchors and measured the electrical conductance of single-molecule metallo-DNA via scanning tunneling microscopy-based break junction method in the buffered solution. Three conductance values were observed that may correspond to different conformations of the metallo-DNA molecule bridged over metallic electrodes. [ABSTRACT FROM AUTHOR]- Published
- 2020
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21. Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson.
- Author
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Hosoda, Yoshikatsu, Miyake, Masahiro, Meguro, Akira, Tabara, Yasuharu, Iwai, Sachiko, Ueda-Arakawa, Naoko, Nakano, Eri, Mori, Yuki, Yoshikawa, Munemitsu, Nakanishi, Hideo, Khor, Chiea-Chuen, Saw, Seang-Mei, Yamada, Ryo, Matsuda, Fumihiko, Cheng, Ching-Yu, Mizuki, Nobuhisa, Tsujikawa, Akitaka, Yamashiro, Kenji, Kawaguchi, Takahisa, and Setoh, Kazuya
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KERATOCONUS ,ARTIFICIAL intelligence ,GENOMES ,COMPUTER systems ,CORNEAL transplantation - Abstract
Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10
−13 ), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development. Yoshikatsu Hosoda et al. study the genetic basis for central corneal thickness (CCT) that is associated with keratoconus. They identify two susceptibility loci, STON2 rs2371597 and SMAD3 rs12913547, using two-step genome-wide association study (GWAS) and predictive analysis with IBM's Watson question answering computer system, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
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22. Predicting the treatment response of certolizumab for individual adult patients with rheumatoid arthritis: protocol for an individual participant data meta-analysis.
- Author
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Luo, Yan, Chalkou, Konstantina, Yamada, Ryo, Funada, Satoshi, Salanti, Georgia, and Furukawa, Toshi A.
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RHEUMATOID arthritis ,CLINICAL trial registries ,CORPORATE websites ,TREATMENT effectiveness ,EXPERIMENTAL arthritis ,RANDOMIZED controlled trials - Abstract
Background: A model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA). Methods: We will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical, and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage 1 risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags. Discussion: This is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients. Systematic review registration: PROSPERO registration number pending (ID#157595). [ABSTRACT FROM AUTHOR]
- Published
- 2020
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23. Origin of the phase separation into B2 and L21 ordered phases in X–Al–Ti (X: Fe, Co, and Ni) alloys based on the first-principles cluster variation method.
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Yamada, Ryo and Mohri, Tetsuo
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- 2020
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24. Mechanical switching of current–voltage characteristics in spiropyran single-molecule junctions.
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Tamaki, Takashi, Minode, Keigo, Numai, Yuichi, Ohto, Tatsuhiko, Yamada, Ryo, Masai, Hiroshi, Tada, Hirokazu, and Terao, Jun
- Published
- 2020
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25. Decomposition of a set of distributions in extended exponential family form for distinguishing multiple oligo-dimensional marker expression profiles of single-cell populations and visualizing their dynamics.
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Okada, Daigo and Yamada, Ryo
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POPULATION dynamics ,EXPONENTIAL families (Statistics) ,EPIDERMAL growth factor ,EXTENDED families ,CELL populations ,MAMMARY glands ,CELL aggregation - Abstract
Single-cell expression analysis is an effective tool for studying the dynamics of cell population profiles. However, the majority of statistical methods are applied to individual profiles and the methods for comparing multiple profiles simultaneously are limited. In this study, we propose a nonparametric statistical method, called Decomposition into Extended Exponential Family (DEEF), that embeds a set of single-cell expression profiles of several markers into a low-dimensional space and identifies the principal distributions that describe their heterogeneity. We demonstrate that DEEF can appropriately decompose and embed sets of theoretical probability distributions. We then apply DEEF to a cytometry dataset to examine the effects of epidermal growth factor stimulation on an adult human mammary gland. It is shown that DEEF can describe the complex dynamics of cell population profiles using two parameters and visualize them as a trajectory. The two parameters identified the principal patterns of the cell population profile without prior biological assumptions. As a further application, we perform a dimensionality reduction and a time series reconstruction. DEEF can reconstruct the distributions based on the top coordinates, which enables the creation of an artificial dataset based on an actual single-cell expression dataset. Using the coordinate system assigned by DEEF, it is possible to analyze the relationship between the attributes of the distribution sample and the features or shape of the distribution using conventional data mining methods. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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26. Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients.
- Author
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Kono, Yuji, Izawa, Hideo, Aoyagi, Yoichiro, Ishikawa, Ayako, Sugiura, Tsubasa, Mori, Etsuko, Yanohara, Ryuzo, Ishiguro, Tomoya, Yamada, Ryo, Okumura, Satoshi, Fujiwara, Wakaya, Hayashi, Mutsuharu, and Saitoh, Eiichi
- Subjects
HEART failure patients ,PATIENT readmissions ,PROPORTIONAL hazards models ,LOG-rank test - Abstract
The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan–Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan–Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
27. A Geometry-Based Multiple Testing Correction for Contingency Tables by Truncated Normal Distribution.
- Author
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Basak, Tapati, Nagashima, Kazuhisa, Kajimoto, Satoshi, Kawaguchi, Takahisa, Tabara, Yasuharu, Matsuda, Fumihiko, and Yamada, Ryo
- Abstract
Inference procedure is a critical step of experimental researches to draw scientific conclusions especially in multiple testing. The false positive rate increases unless the unadjusted marginal p-values are corrected. Therefore, a multiple testing correction is necessary to adjust the p-values based on the number of tests to control type I error. We propose a multiple testing correction of MAX-test for a contingency table, where multiple χ
2 -tests are applied based on a truncated normal distribution (TND) estimation method by Botev. The table and tests are defined geometrically by contour hyperplanes in the degrees of freedom (df) dimensional space. A linear algebraic method called spherization transforms the shape of the space, defined by the contour hyperplanes of the distribution of tables sharing the same marginal counts. So, the stochastic distributions of these tables are transformed into a standard multivariate normal distribution in df-dimensional space. Geometrically, the p-value is defined by a convex polytope consisted of truncating hyperplanes of test's contour lines in df-dimensional space. The TND approach of the Botev method was used to estimate the corrected p. Finally, the features of our approach were extracted using a real GWAS data. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
28. Three site molecular orbital controlled single-molecule rectifiers based on perpendicularly linked porphyrin–imide dyads.
- Author
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Handayani, Murni, Tanaka, Hirofumi, Katayose, Shinichi, Ohto, Tatsuhiko, Chen, Zhijin, Yamada, Ryo, Tada, Hirokazu, and Ogawa, Takuji
- Published
- 2019
- Full Text
- View/download PDF
29. Low-temperature atomistic spin relaxation and non-equilibrium intensive properties using steepest-entropy-ascent quantum-inspired thermodynamics modeling.
- Author
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Yamada, Ryo, Spakovsky, Michael R von, and Jr, William T Reynolds
- Published
- 2019
- Full Text
- View/download PDF
30. Operation of a transformerless three‐phase PV inverter using multiple bidirectional choppers.
- Author
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Yamada, Ryo and Hagiwara, Makoto
- Subjects
SOLAR cells ,INTEGRATED software ,BUILDING-integrated photovoltaic systems ,COMPUTER simulation ,MAXIMUM power point trackers ,ELECTRIC capacity ,LEAKAGE - Abstract
A 50‐kW class three‐phase photovoltaic (PV) inverter typically applies a transformerless circuit configuration due to its high efficiency and small volume/size. On the other hand, the conventional PV inverter may suffer from the deterioration of solar panels due to a dc leakage current flowing through the stray capacitance of the solar panels. To solve this problem, this paper presents a transformerless three‐phase PV inverter consisting of multiple bidirectional choppers, which prevents the dc leakage current by maintaining a negative PV array voltage with respect to the ground potential to a dc voltage that is zero or higher. In addition, the size/volume of an ac filter can be reduced by applying the so‐called phase‐shifted PWM to the inverter. In this paper, the operating principles and control method of the inverter are discussed and the validity of the control method is verified by performing computer simulation using the "PSCAD/EMTDC" software package and conducting experiments using a 150‐V downscaled model. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
31. Two-dimensional binary-coded coordinate markers for fabricating nanodevices.
- Author
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Redhyka, Grace Gita, Hanamura, Yuki, Yamada, Ryo, and Tada, Hirokazu
- Abstract
A marker system based on the binary translation of two-dimensional coordinate numbers was developed to facilitate the positional determination of individual nanomaterial adsorbed randomly on a substrate. The design of the coordinate markers enabled simple calculations of the position of the selected individual nanomaterial from an atomic force microscope image. This position information was used to fabricate metal contact structures for the selected nanomaterial. We demonstrated that the coordinate markers were successfully used to prepare field-effect transistors with a thin bundle of single-walled carbon nanotubes. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
32. One-stage operation for superficialization of native radio-cephalic fistula in obese patients.
- Author
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Okawa, Takao, Murakami, Masaaki, Yamada, Ryo, Tanaka, Satoshi, Mori, Kiyoshi, and Mori, Noriko
- Published
- 2019
- Full Text
- View/download PDF
33. Single-molecule rectifiers based on voltage-dependent deformation of molecular orbitals in carbazole oligomers.
- Author
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Yamada, Ryo, Albrecht, Ken, Ohto, Tatsuhiko, Minode, Keigo, Yamamoto, Kimihisa, and Tada, Hirokazu
- Published
- 2018
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34. Dynamic Birefringence and Mechanical Loss Spectra of Crystalline Polymers.
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Yamada, Ryo and Stein, R. S.
- Published
- 1965
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- View/download PDF
35. Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow.
- Author
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Abe, Shinya, Asahi, Takuma, Hara, Takahiro, Cui, Guangwei, Shimba, Akihiro, Tani-ichi, Shizue, Yamada, Kohei, Miyazaki, Kazuko, Miyachi, Hitoshi, Kitano, Satsuki, Nakamura, Naotoshi, Kikuta, Junichi, Vandenbon, Alexis, Miyazaki, Masaki, Yamada, Ryo, Ohteki, Toshiaki, Ishii, Masaru, Sexl, Veronika, Nagasawa, Takashi, and Ikuta, Koichi
- Abstract
Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response. [Display omitted] • NK cell development in bone marrow depends on IL-15 produced by myeloid cells • Developing NK cells are localized in bone marrow in scattered and clustered manners • Scattered NK cells need CXCR4, while clustered NK cells overlap with myeloid cells Abe et al. demonstrate the dependence of natural killer (NK) cell development on myeloid cell-derived interleukin-15 in the bone marrow. Using NK cell reporter mice, they identify scattered and clustered localization of NK cells. Scattered NK cells require CXCR4 expression, whereas clustered NK cells overlap with accumulations of myeloid cells. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
36. Cross-Sectional Epidemiological Analysis of the Nagahama Study for Correlates of Overactive Bladder: Genetic and Environmental Considerations.
- Author
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Funada, Satoshi, Kawaguchi, Takahisa, Terada, Naoki, Negoro, Hiromitsu, Tabara, Yasuharu, Kosugi, Shinji, Yamada, Ryo, Nakayama, Takeo, Akamatsu, Shusuke, Yoshimura, Koji, Matsuda, Fumihiko, and Ogawa, Osamu
- Published
- 2018
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- View/download PDF
37. Methods to Determine Electrical Conductance of Single-Molecule Junctions.
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Yamada, Ryo
- Published
- 2016
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- View/download PDF
38. Highly Luminescent 2D-Type Slab Crystals Based on a Molecular Charge-Transfer Complex as Promising Organic Light-Emitting Transistor Materials.
- Author
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Park, Sang Kyu, Kim, Jin Hong, Ohto, Tatsuhiko, Yamada, Ryo, Jones, Andrew O. F., Whang, Dong Ryeol, Cho, Illhun, Oh, Sangyoon, Hong, Seung Hwa, Kwon, Ji Eon, Kim, Jong H., Olivier, Yoann, Fischer, Roland, Resel, Roland, Gierschner, Johannes, Tada, Hirokazu, and Park, Soo Young
- Published
- 2017
- Full Text
- View/download PDF
39. Analysis of Single Molecule Conductance of Heterogeneous Porphyrin Arrays by Partial Transmission Probabilities.
- Author
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Tamaki, Takashi, Ohto, Tatsuhiko, Yamada, Ryo, Tada, Hirokazu, and Ogawa, Takuji
- Abstract
Abstract: Single molecule conductance (SMC) of a series of porphyrin derivatives, whose porphyrin units are connected through a phenylene bridge that have one or two thiolate end groups, was measured by a scanning tunneling microscopic break junction (STM‐BJ) technique. The observed conductance values were analyzed by partial transmission probabilities (T
i ) for the molecular parts using the equation G=G0 ∏ i N T i . Unique combination of Ti was obtained, which indicates the validity of this analysis. By the analysis, the free‐base porphyrin ring interacting with the gold electrode was found to show a greater transmission probability Tpor‐Au than that of the bridge between thiolate and the gold electrode (TS‐Au ). [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
40. HLA-HD: An accurate HLA typing algorithm for next-generation sequencing data.
- Author
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Kawaguchi, Shuji, Higasa, Koichiro, Shimizu, Masakazu, Yamada, Ryo, and Matsuda, Fumihiko
- Abstract
The accurate typing of human leukocyte antigen ( HLA) alleles is critical for a variety of medical applications, such as genomic studies of multifactorial diseases, including immune system and inflammation-related disorders, and donor selection in organ transplantation and regenerative medicine. Here, we developed a new algorithm for determining HLA alleles using next-generation sequencing (NGS) results. The method consists of constructing an extensive dictionary of HLA alleles, precise mapping of the NGS reads, and calculating a score based on weighted read counts to select the most suitable pair of alleles. The developed algorithm compares the score of all allele pairs, taking into account variation not only in the domain for antigen presentation (G-DOMAIN), but also outside this domain. Using this method, HLA alleles could be determined with 6-digit precision. We showed that our method was more accurate than other NGS-based methods and revealed limitations of the conventional HLA typing technologies. Furthermore, we determined the complete genomic sequence of an HLA-A-like-pseudogene when we assembled NGS reads that had caused arguable typing, and found its identity with HLA-Y*02:01. The accuracy of the HLA-A allele typing was improved after the HLA-Y*02:01 sequence was included in the HLA allele dictionary. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
41. A burden of rare variants in BMPR2 and KCNK3 contributes to a risk of familial pulmonary arterial hypertension.
- Author
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Koichiro Higasa, Aiko Ogawa, Chikashi Terao, Masakazu Shimizu, Shinji Kosugi, Ryo Yamada, Hiroshi Date, Hiromi Matsubara, Fumihiko Matsuda, Higasa, Koichiro, Ogawa, Aiko, Terao, Chikashi, Shimizu, Masakazu, Kosugi, Shinji, Yamada, Ryo, Date, Hiroshi, Matsubara, Hiromi, and Matsuda, Fumihiko
- Subjects
PULMONARY hypertension ,LUNG diseases ,BLOOD circulation disorders ,CARDIOVASCULAR diseases ,BLOOD pressure ,NUCLEOTIDE sequencing ,POTASSIUM channels ,GENETIC testing ,CELL receptors ,DISEASE susceptibility ,FAMILY health ,NERVE tissue proteins - Abstract
Background: Pulmonary arterial hypertension (PAH) is a severe lung disease with only few effective treatments available. Familial cases of PAH are usually recognized as an autosomal dominant disease, but incomplete penetrance of the disease makes it difficult to identify pathogenic variants in accordance with a Mendelian pattern of inheritance.Methods: To elucidate the complex genetic basis of PAH, we obtained whole exome- or genome-sequencing data of 17 subjects from 9 families with heritable PAH and applied gene-based association analysis with 9 index patients and 300 PAH-free controls.Results: A burden of rare variants in BMPR2 significantly contributed to the risk of the disease (p = 6.0 × 10-8). Eight of nine families carried four previously reported single nucleotide variants and four novel insertion/deletion variants in the gene. One of the novel variants was a large 6.5 kilobase-deletion. In the remaining one family, the patient carried a pathogenic variant in a member of potassium channels, KCNK3, which was the first replicative finding of channelopathy in an Asian population.Conclusions: The variety of rare pathogenic variants suggests that gene-based association analysis using genome-wide sequencing data from increased number of samples is essential to tracing the genetic heterogeneity and developing an appropriate panel for genetic testing. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
42. Combined association of clinical and lifestyle factors with non-restorative sleep: The Nagahama Study.
- Author
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Matsumoto, Takeshi, Tabara, Yasuharu, Murase, Kimihiko, Takahashi, Yoshimitsu, Setoh, Kazuya, Kawaguchi, Takahisa, Muro, Shigeo, Kadotani, Hiroshi, Kosugi, Shinji, Sekine, Akihiro, Yamada, Ryo, Nakayama, Takeo, Mishima, Michiaki, Matsuda, Fumihiko, and Chin, Kazuo
- Subjects
LIFESTYLES & health ,CARDIOVASCULAR system ,HEALTH ,SLEEP ,GASTROESOPHAGEAL reflux ,DISEASES - Abstract
Background: Non-restorative sleep (NRS) was suggested to be associated with cardiovascular outcomes. However, causative factors for NRS have not been fully elucidated. This study aimed to clarify factors and their relationships with NRS to better understand the clinical and epidemiological implications of NRS and to develop a score that can objectively evaluate NRS status. Methods: Study subjects consisted of 9,788 community residents (age 53.6 ± 13.4 y). Subjective NRS as well as possible clinical and lifestyle factors for NRS were investigated by questionnaires. Other clinical parameters were obtained from personal records of information obtained at the baseline examination. Results: A total of 3,261 participants complained of NRS. Factors independently associated with subjective NRS were younger age (odds ratio = 1.43), use of a hypnotic drug (2.04), irregular sleep schedule (2.02), short sleep duration (<5 h, 11.7; 5–6 h, 4.81; 6–7 h, 2.40), frequent sleepiness (2.33), routine stress (4.63), no habitual exercise (1.61), nocturia symptoms (1.43), symptoms of gastroesophageal reflux disease (1.44), and depression (1.46) (all P <0.001). The NRS score comprised of these 10 factors was linearly associated with the frequency of subjective NRS (P
trend <0.001). Frequency of individuals with a high NRS score was greater in women (52.3%) than in men (42.1%, P<0.001), while no clear association was observed with common risk factors for cardiovascular diseases. Conclusions: NRS was a phenomenon representing various clinical and lifestyle features. Careful attention should be paid to individuals with a high NRS score who might be at risk for mental fatigue and have unfavorable lifestyle factors. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
43. A position estimation method based on position fingerprint using directional antennas.
- Author
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Yamada, Ryo, Iwai, Hisato, and Sasaoka, Hideichi
- Published
- 2015
44. Pairwise Kinship Analysis by the Index of Chromosome Sharing Using High-Density Single Nucleotide Polymorphisms.
- Author
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Morimoto, Chie, Manabe, Sho, Kawaguchi, Takahisa, Kawai, Chihiro, Fujimoto, Shuntaro, Hamano, Yuya, Yamada, Ryo, Matsuda, Fumihiko, and Tamaki, Keiji
- Subjects
SINGLE nucleotide polymorphisms ,CHROMOSOMES ,FORENSIC genetics ,LINKAGE disequilibrium ,GENE frequency - Abstract
We developed a new approach for pairwise kinship analysis in forensic genetics based on chromosomal sharing between two individuals. Here, we defined “index of chromosome sharing” (ICS) calculated using 174,254 single nucleotide polymorphism (SNP) loci typed by SNP microarray and genetic length of the shared segments from the genotypes of two individuals. To investigate the expected ICS distributions from first- to fifth-degree relatives and unrelated pairs, we used computationally generated genotypes to consider the effect of linkage disequilibrium and recombination. The distributions were used for probabilistic evaluation of the pairwise kinship analysis, such as likelihood ratio (LR) or posterior probability, without allele frequencies and haplotype frequencies. Using our method, all actual sample pairs from volunteers showed significantly high LR values (i.e., ≥ 10
8 ); therefore, we can distinguish distant relationships (up to the fifth-degree) from unrelated pairs based on LR. Moreover, we can determine accurate degrees of kinship in up to third-degree relationships with a probability of > 80% using the criterion of posterior probability ≥ 0.90, even if the kinship of the pair is totally unpredictable. This approach greatly improves pairwise kinship analysis of distant relationships, specifically in cases involving identification of disaster victims or missing persons. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
45. Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice.
- Author
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Akari Suzuki, Yuta Kochi, Hirofumi Shoda, Yu Seri, Keishi Fujio, Tetsuji Sawada, Ryo Yamada, Kazuhiko Yamamoto, Suzuki, Akari, Kochi, Yuta, Shoda, Hirofumi, Seri, Yu, Fujio, Keishi, Sawada, Tetsuji, Yamada, Ryo, and Yamamoto, Kazuhiko
- Subjects
GENETICS of rheumatoid arthritis ,GENOMICS ,GENE expression ,IMMUNOHISTOCHEMISTRY ,SEVERITY of illness index ,AMINO acid metabolism ,AMINO acids ,ANIMAL experimentation ,ARTHRITIS ,AUTOANTIBODIES ,AUTOIMMUNE diseases ,COLLAGEN ,CYTOKINES ,DISEASE susceptibility ,ENZYME-linked immunosorbent assay ,HYDROLASES ,MICE ,RHEUMATOID arthritis ,TUMOR necrosis factors ,DISEASE progression ,SEQUENCE analysis - Abstract
Background: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates. The aim of this study was to evaluate the importance of the PADI4 gene in the progression of RA.Methods: We generated Padi4 knockout (Padi4(-/-)) DBA1J mice. The Padi4(-/-) DBA1J and wild-type mice were immunized with bovine type II collagen (CII) to develop collagen-induced arthritis (CIA). The expression of various inflammatory cytokines and Padi genes in immune cells was detected by the real-time TaqMan assay. Cytokine concentrations in sera were measured by enzyme-linked immunosorbent assays. Localization of the PAD4 and PAD2 proteins was indicated by immunohistochemistry.Results: We demonstrated that the clinical disease score was significantly decreased in the Padi4(-/-) mice and Padi4 expression was induced by CII immunization. In the Padi4(-/-) mice, serum anti-type II collagen (CII) immunoglobulin M (IgM), IgG, and inflammatory cytokine levels were significantly decreased compared with those in the wild-type mice. Padi2 expression was induced in the immune cells of the Padi4(-/-) mice as a compensation for the defect in Padi4.Conclusions: Padi4 affected disease severity in the CIA mice and was involved in the enhancement of the collagen-initiated inflammatory responses. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
46. Thermoelectricity at the molecular scale: a large Seebeck effect in endohedral metallofullerenes.
- Author
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Lee, See Kei, Buerkle, Marius, Yamada, Ryo, Asai, Yoshihiro, and Tada, Hirokazu
- Published
- 2015
- Full Text
- View/download PDF
47. Knee Pain and Low Back Pain Additively Disturb Sleep in the General Population: A Cross-Sectional Analysis of the Nagahama Study.
- Author
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Murase, Kimihiko, Tabara, Yasuharu, Ito, Hiromu, Kobayashi, Masahiko, Takahashi, Yoshimitsu, Setoh, Kazuya, Kawaguchi, Takahisa, Muro, Shigeo, Kadotani, Hiroshi, Kosugi, Shinji, Sekine, Akihiro, Yamada, Ryo, Nakayama, Takeo, Mishima, Michiaki, Matsuda, Shuichi, Matsuda, Fumihiko, and Chin, Kazuo
- Subjects
KNEE pain ,BACKACHE diagnosis ,HEALTH ,SLEEP ,POPULATION health ,ORTHOPEDICS ,CROSS-sectional method ,DIAGNOSIS - Abstract
Introduction: Association of knee and low back pain with sleep disturbance is poorly understood. We aimed to clarify the independent and combined effects of these orthopedic symptoms on sleep in a large-scale general population. Methods: Cross-sectional data about sleep and knee/low back pain were collected for 9,611 community residents (53±14 years old) by a structured questionnaire. Sleep duration less than 6 h/d was defined as short sleep. Sleep quality and the presence of knee and low back pain were evaluated by dichotomous questions. Subjects who complained about knee or low back pains were graded by tertiles of a numerical response scale (NRS) score and a Roland-Morris disability questionnaire (RDQ) score respectively. Multivariate regression analyses were performed to determine the correlates of short sleep duration and poor sleep quality. Results: Frequency of participants who complained of the orthopedic symptoms was as follows; knee pain, 29.0%; low back pain, 42.0% and both knee and low back pain 17.6%. Both knee and low back pain were significantly and independently associated with short sleep duration (knee pain: odds ratio (OR) = 1.19, p<0.01; low back pain: OR = 1.13, p = 0.01) and poor sleep quality (knee pain: OR = 1.22, p<0.01; low back pain; OR = 1.57, p<0.01). The group in the highest tertile of the NRS or RDQ score had the highest risk for short sleep duration and poor sleep quality except for the relationship between the highest tertile of the RDQ score and short sleep duration.(the highest tertile of the NRS: OR for short sleep duration = 1.31, p<0.01; OR for poor sleep quality = 1.47, p<0.01; the highest tertile of the RDQ: OR for short sleep duration = 1.11, p = 0.12; OR for poor sleep quality = 1.81, p<0.01) Further, coincident knee and low back pain raised the odds ratios for short sleep duration (either of knee or low back pain: OR = 1.10, p = 0.06; both knee and low back pain: OR = 1.40, p<0.01) and poor sleep quality (either of knee or low back pain: OR = 1.61, p<0.01; both knee and low back pain: OR = 2.17, p<0.01). Conclusion: Knee and low back pains were independently associated with short sleep duration and poor sleep quality. Further, they additively increased the correlation with these sleep problems in the general population. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
48. Exploring the origin and limitations of kidney regeneration.
- Author
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Endo, Tomomi, Nakamura, Jin, Sato, Yuki, Asada, Misako, Yamada, Ryo, Takase, Masayuki, Takaori, Koji, Oguchi, Akiko, Iguchi, Taku, Higashi, Atsuko Y, Ohbayashi, Tetsuya, Nakamura, Tomoyuki, Muso, Eri, Kimura, Takeshi, and Yanagita, Motoko
- Abstract
Epidemiological findings indicate that acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD), although the molecular mechanism remains unclear. Genetic fate mapping demonstrated that nephrons, functional units in the kidney, are repaired by surviving nephrons after AKI. However, the cell population that repairs damaged nephrons and their repair capacity limitations remain controversial. To answer these questions, we generated a new transgenic mouse strain in which mature proximal tubules, the segment predominantly damaged during AKI, could be genetically labelled at desired time points. Using this strain, massive proliferation of mature proximal tubules is observed during repair, with no dilution of the genetic label after the repair process, demonstrating that proximal tubules are repaired mainly by their own proliferation. Furthermore, acute tubular injury caused significant shortening of proximal tubules associated with interstitial fibrosis, suggesting that proximal tubules have a limited capacity to repair. Understanding the mechanism of this limitation might clarify the mechanism of the AKI-to-CKD continuum. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
49. Association Between Antinuclear Antibodies and the HLA Class II Locus and Heterogeneous Characteristics of Staining Patterns: The Nagahama Study.
- Author
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Terao, Chikashi, Ohmura, Koichiro, Yamada, Ryo, Kawaguchi, Takahisa, Shimizu, Masakazu, Tabara, Yasuharu, Takahashi, Meiko, Setoh, Kazuya, Nakayama, Takeo, Kosugi, Shinji, Sekine, Akihiro, Matsuda, Fumihiko, and Mimori, Tsuneyo
- Subjects
SYSTEMIC lupus erythematosus diagnosis ,ACADEMIC medical centers ,ARTHRITIS ,AUTOANTIBODIES ,DNA ,FLUORESCENT antibody technique ,GENOMES ,LONGITUDINAL method ,RHEUMATOLOGY ,STAINS & staining (Microscopy) ,HLA-B27 antigen ,DATA analysis - Abstract
Objective While antinuclear antibodies (ANAs) are observed in healthy populations as well as in patients with autoimmune diseases such as systemic lupus erythematosus (SLE), the detailed genetic background of ANAs has remained unclear. We undertook this study to identify the genetic determinants of ANAs in the general population in order to elucidate the underlying mechanisms of ANA production and to distinguish disease susceptibility genes from ANA production genes. Methods A total of 9,575 Japanese volunteers were registered, and their ANA levels were quantified using indirect immunofluorescence to analyze correlates of ANA positivity. Genetic studies were performed using 7,148 of the 9,575 subjects. We performed a genome-wide association study using 3,185 subjects genotyped for 303,506 single-nucleotide polymorphisms (SNPs), followed by a replication study of 3,963 subjects. HLA-DRB1 and HLA-DQB1 alleles were imputed, and associations between ANA positivity and the SNPs or the HLA alleles associated with SLE were analyzed. Results Female sex and old age were associated with ANA positivity, except for the nucleolar pattern. The T allele of rs2395185 in the HLA locus, which was in moderate linkage disequilibrium with HLA-DRB1*0405, was significantly associated with ANA positivity ( P = 1.3 × 10
−11 ). The T allele of rs2395185 displayed increasing effects on the frequency of speckled and homogeneous patterns ( P = 7.5 × 10−12 and P = 2.2 × 10−11 , respectively) but decreasing effects on the frequency of the nucleolar pattern ( P = 0.0045). The 7 SNPs and 4 HLA-DRB1 alleles associated with SLE did not display strong associations with ANA positivity. Conclusion SNP rs2395185 linked with HLA-DRB1*0405 is a genetic determinant of ANA production in the Japanese population. Overlapping of loci for susceptibility to SLE and to ANA positivity was limited. The nucleolar pattern showed different associations from other staining patterns, both with correlates of ANA positivity and with the HLA locus. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
50. Association of serum-free fatty acid level with reduced reflection pressure wave magnitude and central blood pressure: the Nagahama study.
- Author
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Tabara, Yasuharu, Takahashi, Yoshimitsu, Kawaguchi, Takahisa, Setoh, Kazuya, Terao, Chikashi, Yamada, Ryo, Kosugi, Shinji, Sekine, Akihiro, Nakayama, Takeo, Matsuda, Fumihiko, and Nagahama Study Group
- Published
- 2014
- Full Text
- View/download PDF
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