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Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

science (New York, N.Y.) 2025年第6734期387卷 eadp4753页

作者： Liu, Hongbo Abedini, Amin Ha, Eunji Ma, Ziyuan Sheng, Xin Dumoulin, Bernhard Qiu, Chengxiang Aranyi, Tamas Li, Shen Dittrich, Nicole Chen, Hua-Chang Tao, Ran Tarng, Der-Cherng Hsieh, Feng-Jen Chen, Shih-Ann Yang, Shun-Fa Lee, Mei-Yueh Kwok, Pui-Yan Wu, Jer-Yuarn Chen, Chien-Hsiun Khan, Atlas Limdi, Nita A. Wei, Wei-Qi Walunas, Theresa L. Karlson, Elizabeth W. Kenny, Eimear E. Luo, Yuan Kottyan, Leah Connolly, John J. Jarvik, Gail P. Weng, Chunhua Shang, Ning Cole, Joanne B. Mercader, Josep M. Mandla, Ravi Majarian, Timothy D. Florez, Jose C. Haas, Mary E. Lotta, Luca A. Drivas, Theodore G. Vy, Ha My T Nadkarni, Girish N. Wiley, Laura K. Wilson, Melissa P. Gignoux, Christopher R. Rasheed, Humaira Thomas, Laurent F. Åsvold, Bjørn Olav Brumpton, Ben M. Hallan, Stein I. Hveem, Kristian Zheng, Jie Hellwege, Jacklyn N. Zawistowski, Matthew Zöllner, Sebastian Franceschini, Nora Hu, Hailong Zhou, Jianfu Kiryluk, Krzysztof Ritchie, Marylyn D. Palmer, Matthew Edwards, Todd L. Voight, Benjamin F. Hung, Adriana M. Susztak, Katalin Department of Medicine Renal Electrolyte and Hypertension Division University of Pennsylvania Philadelphia PA United States Institute of Diabetes Obesity and Metabolism University of Pennsylvania Philadelphia PA United States Department of Genetics University of Pennsylvania Philadelphia PA United States Penn-CHOP Kidney Innovation Center University of Pennsylvania Philadelphia PA United States Liangzhu Laboratory Zhejiang University 1369 West Wenyi Road Hangzhou Zhejiang China Department of Nephrology Children' Hospital Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang China Institute of Molecular Life Sciences HUN-REN Research Center for Natural Sciences Budapest Hungary Department of Molecular Biology Semmelweis University Budapest Hungary Department of Medicine Federal University of São Paulo São Paulo Brazil Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN United States Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Division of Nephrology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Institute of Biomedical Sciences Academia Sinica ROC Taipei Taiwan Cardiovascular Center Taichung Veterans General Hospital Taichung Taiwan ROC National Chung Hsing University Taichung Taiwan ROC Heart Rhythm Center Division of Cardiology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Department of Internal Medicine College of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan ROC Division of Endocrinology and Metabolism Department of Internal Medicine Kaohsiung Medical Universit

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

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Tailoring magnetism in self-intercalated Cr1+δTe2 epitaxial films

arXiv

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arXiv 2020年

作者： Fujisawa, Y. Pardo-Almanza, M. Garland, J. Yamagami, K. Zhu, X. Chen, X. Araki, K. Takeda, T. Kobayashi, M. Takeda, Y. Hsu, C.H. Chuang, F.C. Laskowski, R. Khoo, K.H. Soumyanarayanan, A. Okada, Yoshinori Okinawa904-0495 Japan Applied Physics & Mathematics Department Northeastern University BostonMA02115 United States Institute of Materials Research and Engineering Agency for Science Technology and Research Singapore138634 Singapore Department of Electrical Engineering and Information Systems University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo113-8656 Japan Center for Spintronics Research Network University of Tokyo 7-3-1 Hongo Bunkyo-ku Tokyo113-8656 Japan Condensed Matter Science Division Quantum Beam Science Directorate Japan Atomic Energy Agency 1-1-1 Kouto Sayo-cho Sayo-gunHyogo679-5148 Japan Department of Physics National Sun Yat-sen University Kaohsiung80424 Taiwan Institute of High Performance Computing Agency for Science Technology and Research 138632 Singapore Department of Physics National University of Singapore 117551 Singapore

Magnetic transition metal dichalcogenide (TMD) films have recently emerged as promising candidates to host novel magnetic phases relevant to next-generation spintronic devices. However, systematic control of the magnetization orientation, or anisotropy, and its thermal stability, characterized by Curie temperature (Tc) – remains to be achieved in such films. Here we present self-intercalated epitaxial Cr1+δTe2 films as a platform for achieving systematic/smooth magnetic tailoring in TMD films. Using a molecular beam epitaxy (MBE) based technique, we have realized epitaxial Cr1+δTe2 films with smoothly tunable δ over a wide range (0.33-0.82), while maintaining NiAs-type crystal structure. With increasing δ, we found monotonic enhancement of Tc from 160 to 350 K, and the rotation of magnetic anisotropy from out-of-plane to in-plane easy axis configuration for fixed film thickness. Contributions from conventional dipolar and orbital moment terms are insufficient to explain the observed evolution of magnetic behavior with δ. Instead, ab initio calculations suggest that the emergence of antiferromagnetic interactions with δ, and its interplay with conventional ferromagnetism, may play a key role in the observed trends. To our knowledge, this constitutes the first demonstration of tunable Tc and magnetic anisotropy across room temperature in TMD films, and paves the way for engineering novel magnetic phases for spintronic applications. Copyright © 2020, The Authors. All rights reserved.

关键词： Transition metals

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Correction: Additive-mediated intercalation and surface modification of MXenes

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Chemical Society reviews 2022年第8期51卷 3314页

作者： Jing Zou Jing Wu Yizhou Wang Fengxia Deng Jizhou Jiang Yizhou Zhang Song Liu Neng Li Han Zhang Jiaguo Yu Tianyou Zhai Husam N Alshareef School of Environmental Ecology and Biological Engineering School of Chemistry and Environmental Engineering Key Laboratory of Green Chemical Engineering Process of Ministry of Education Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education Wuhan Institute of Technology Wuhan Hubei 430205 P. R. China. 027wit@***. Key Laboratory of Rare Mineral Ministry of Natural Resources Geological Experimental Testing Center of Hubei Province Wuhan Hubei 430034 P. R. China. Physical Science and Engineering Division Materials Science & Engineering King Abdullah University of Science and Technology (KAUST) Thuwal 23955-6900 Kingdom of Saudi Arabia. husam.alshareef@kaust.edu.sa. State Key Laboratory of Urban Water Resources and Environment School of Environment Harbin Institute of Technology Harbin 150090 P. R. China. Institute of Advanced Materials and Flexible Electronics (IAMFE) School of Chemistry and Materials Science Nanjing University of Information Science & Technology Nanjing 210044 P. R. China. yizhou.zhang@***. Key Laboratory for Organic Electronics & Information Displays and Institute of Advanced Materials Nanjing University of Posts and Telecommunications Nanjing 210023 P. R. China. Institute of Chemical Biology and Nanomedicine (ICBN) State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical Engineering Hunan University Changsha 410082 P. R. China. State Key Laboratory of Advanced Technology for Materials Synthesis and Processing State Key Laboratory of Silicate Materials for Architectures Wuhan University of Technology Wuhan Hubei 430070 P. R. China. Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics and Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province Shenzhen University Shenzhen 518060 P. R. China. State Key Laboratory of Material Processing and Die & Mould Technology School of Materials Science and Engineering H

Correction for 'Additive-mediated intercalation and surface modification of MXenes' by Jing Zou , , 2022, DOI: 10.1039/d0cs01487g.

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Polarization-Orthogonal Nondegenerate Plasmonic Higher-Order Topological States

arXiv

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arXiv 2021年

作者： Li, Yuanzhen Xu, Su Zhang, Zijian Yang, Yumeng Xie, Xinrong Ye, Wenzheng Liu, Feng Xue, Haoran Jing, Liqiao Wang, Zuojia Chen, Qi-Dai Sun, Hong-Bo Li, Erping Chen, Hongsheng Gao, Fei Interdisciplinary Center for Quantum Information State Key Laboratory of Extreme Photonics and Instrumentation ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang University Hangzhou310027 China International Joint Innovation Center The Electromagnetics Academy Zhejiang University Zhejiang University Haining314400 China State Key Laboratory of Integrated Optoelectronics College of Electronic Science and Engineering Jilin University 2699 Qianjin Street Changchun130012 China Division of Physics and Applied Physics School of Physical and Mathematical Sciences Nanyang Technological University Singapore637371 Singapore State Key Laboratory of Precision Measurement Technology and Instruments Department of Precision Instrument Tsinghua University Haidian Beijing100084 China Key Lab. of Advanced Micro/Nano Electronic Devices & Smart Systems of Zhejiang Jinhua Institute of Zhejiang University Zhejiang University Jinhua321099 China Shaoxing Institute of Zhejiang University Zhejiang University Shaoxing312000 China

Photonic topological states, providing light-manipulation approaches in robust manners, have attracted intense attention. Connecting photonic topological states with far-field degrees of freedom (DoFs) has given rise to fruitful phenomena. Recently emerged higher-order topological insulators (HOTIs), hosting boundary states two or more dimensions lower than those of bulk, offer new paradigms to localize/transport light topologically in extended dimensionalities. However, photonic HOTIs have not been related to DoFs of radiation fields yet. Here, we report the observation of polarization-orthogonal second-order topological corner states at different frequencies on a designer-plasmonic Kagome metasurface in the far field. Such phenomenon stands on two mechanisms, i.e., projecting the far-field polarizations to the intrinsic parity DoFs of lattice modes and the parity splitting of the plasmonic corner states in spectra. We theoretically and numerically show that the parity splitting originates from the underlying inter-orbital coupling. Both near-field and far-field experiments verify the polarization-orthogonal nondegenerate second-order topological corner states. These results promise applications in robust optical single photon emitters and multiplexed photonic devices. Copyright © 2021, The Authors. All rights reserved.

关键词： Polarization

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Itinerant ferromagnetism mediated by giant spin polarization of metallic ligand band in van der Waals magnet Fe5GeTe2

arXiv

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arXiv 2021年

作者： Yamagami, K. Fujisawa, Y. Driesen, B. Hsu, C.H. Kawaguchi, K. Tanaka, H. Kondo, T. Zhang, Y. Wadati, H. Araki, K. Takeda, T. Takeda, Y. Muro, T. Chuang, F.C. Niimi, Y. Kuroda, K. Kobayashi, M. Okada, Yoshinori Okinawa Institute of Science and Technology Graduate University Tancha Onna-son Kunigami-gunOkinawa904-0495 Japan Institute for Solid State Physics The University of Tokyo Kashiwa277-8581 Japan Department of Physics National Sun Yat-sen University Kaohsiung80424 Taiwan Institute of High Energy Physics Chinese Academy of Sciences Shijingshan District Beijing100049 China Graduate School of Material Science University of Hyogo AkoHyogo678-1297 Japan Department of Electrical Engineering and Information Systems Graduate School of Engineering University of Tokyo Japan Materials Sciences Research Center Japan Atomic Energy Agency 1-1-1 Kouto Sayo-cho Sayo-gunHyogo679-5148 Japan 1-1-1 Kouto SayoHyogo679-5198 Japan Department of Physics National Tsing Hua University Hsinchu30013 Taiwan Physics Division National Center for Theoretical Sciences Hsinchu30013 Taiwan Department of Physics Graduate School of Science Osaka University Japan Center for Spintronics Research Network The University of Tokyo Hongo Bunkyo-kuTokyo113-8656 Japan

We investigate near-Fermi-energy (EF) element-specific electronic and spin states of ferromagnetic van der Waals (vdW) metal Fe5GeTe2. The soft x-ray angle-resolved photoemission spectroscopy (SX-ARPES) measurement provides spectroscopic evidence of localized Fe 3d band. We also find prominent hybridization between the localized Fe 3d band and the delocalized Ge/Te p bands. This picture is strongly supported from direct observation of the remarkable spin polarization of the ligand p bands near EF, using x-ray magnetic circular dichroism (XMCD) measurements. The strength of XMCD signal from ligand element Te shows the highest value, as far as we recognize, among literature reporting finite XMCD signal for none-magnetic element in any systems. Combining SX-ARPES and elemental selective XMCD measurements, we collectively point an important role of giant spin polarization of the delocalized ligand Te states for realizing itinerant long-range ferromagnetism in Fe5GeTe2. Our finding provides a fundamental elemental selective view-point for understanding mechanism of itinerant ferromagnetism in low dimensional compounds, which also leads insight for designing exotic magnetic states by interfacial band engineering in heterostructures. © 2021, CC BY.

关键词： Ligands

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散寒化湿颗粒及其活性成分对新冠病毒肺炎的抗病毒和抗炎作用（英文）

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Engineering 2024年第12期 159-172页

作者：田传玺刘航王倩赵金悦姚晨思姚艳丰张旭马钦海王维皓周严严王梦晓师晓萌李香艳王杉杨映映苟筱雯周丽娟赵旌屹万砺李佳芮 Stefanie Tiefenbacher 高军涛 Rudolf Bauer 李敏仝小林 Institute of Metabolic Diseases Guang’anmen Hospital China Academy of Chinese Medical Sciences Graduate School Beijing University of Chinese Medicine Center for Biosafety Mega-Science Wuhan Institute of Virology Chinese Academy of Sciences State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Graduate School Changchun University of Chinese Medicine Department of Endocrinology The First Affiliated Hospital of Zhejiang Chinese Medicine University Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences College of Pharmacy Hebei Medical University State Key Laboratory of Respiratory Disease&National Clinical Research Center for Respiratory Disease&Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University National Center for Integrative Medicine China-Japan Friendship Hospital Institute of Pharmaceutical Sciences University of Graz Institute for TCM-X MOE Key Laboratory of Bioinformatics/Bioinformatics Division Beijing National Research Center for Information Science and Technology Center for Synthetic&Systems Biology Tsinghua University Molecular Biology Laboratory Guang’anmen Hospital China Academy of Chinese Medical Sciences

Sanhan Huashi formula（SHHS）, a traditional Chinese medicine（TCM）, has shown significant therapeutic effects on coronavirus disease 2019（COVID-19） in clinical settings. However, its specific mechanism and components still require further clarification. In vitro experiments with Vero-E6 cells infected with severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） demonstrated that SHHS effectively inhibited viral invasion and proliferation. Complementary in vivo experiments using K18-human angiotensin converting enzyme 2（hACE2） mice exposed to virus-like particles（VLPs） further confirmed that SHHS impeded SARS-CoV-2 entry. Although SHHS did not demonstrate direct antiviral effects in K18-hACE2 mice challenged with SARS-CoV-2, it significantly alleviated pathological damage and decreased the expression of chemokines such as C–C motif ligand（CCL）-2, CCL-3, C–X–C motif ligand（CXCL）-1,CXCL-6, CXCL-9, CXCL-10, and CXCL-11 in the lungs, suggesting that SHHS exerts immunomodulatory and anti-inflammatory effects via the CCL-2–CXCL axis. Additional research using a lipopolysaccharide（LPS）-induced acute lung injury（ALI） and RAW264.7 cell model validated the ability of SHHS to reduce the levels of inflammatory biomarkers, including interleukin（IL）-1β, IL-6, and tumor necrosis factor-α（TNF-α）. Using advanced analytical techniques such as ultrahigh-performance liquid chromatography coupled with linear trap quadrupole Orbitrap mass spectrometry（UHPLC-LTQ-Orbitrap-MS） and surface plasmon resonance（SPR）, nodakenin was identified as a potent antiviral component of SHHS that targets the 3C-like protease(3CLpro), a finding supported by the hydrogen–deuterium exchange mass spectrometry（HDX-MS） and molecular docking analyses. Furthermore, nodakenin demonstrated a significant antiviral effect, reducing the viral load by more than 66%. This investigation reveals that SHHS can combat COVID-19 by inhibiting viral invasion and promoting anti-inflammatory effects.

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Eye tracking: empirical foundations for a minimal reporting guideline

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Behavior research methods 2023年第1期55卷 364-416页

作者： Kenneth Holmqvist Saga Lee Örbom Ignace T C Hooge Diederick C Niehorster Robert G Alexander Richard Andersson Jeroen S Benjamins Pieter Blignaut Anne-Marie Brouwer Lewis L Chuang Kirsten A Dalrymple Denis Drieghe Matt J Dunn Ulrich Ettinger Susann Fiedler Tom Foulsham Jos N van der Geest Dan Witzner Hansen Samuel B Hutton Enkelejda Kasneci Alan Kingstone Paul C Knox Ellen M Kok Helena Lee Joy Yeonjoo Lee Jukka M Leppänen Stephen Macknik Päivi Majaranta Susana Martinez-Conde Antje Nuthmann Marcus Nyström Jacob L Orquin Jorge Otero-Millan Soon Young Park Stanislav Popelka Frank Proudlock Frank Renkewitz Austin Roorda Michael Schulte-Mecklenbeck Bonita Sharif Frederick Shic Mark Shovman Mervyn G Thomas Ward Venrooij Raimondas Zemblys Roy S Hessels Department of Psychology Nicolaus Copernicus University Torun Poland. kenneth.holmqvist@ur.de. Department of Computer Science and Informatics University of the Free State Bloemfontein South Africa. kenneth.holmqvist@ur.de. Department of Psychology Regensburg University Regensburg Germany. kenneth.holmqvist@ur.de. Department of Psychology Regensburg University Regensburg Germany. Experimental Psychology Helmholtz Institute Utrecht University Utrecht The Netherlands. Lund University Humanities Lab and Department of Psychology Lund University Lund Sweden. Department of Ophthalmology SUNY Downstate Health Sciences University Brooklyn NY USA. Tobii Pro AB Danderyd Sweden. Social Health and Organizational Psychology Utrecht University Utrecht The Netherlands. Department of Computer Science and Informatics University of the Free State Bloemfontein South Africa. TNO Soesterberg The Netherlands. Department of Ergonomics Leibniz Institute for Working Environments and Human Factors Dortmund Germany. Institute of Informatics LMU Munich Munich Germany. Institute of Child Development University of Minnesota Minneapolis USA. School of Psychology University of Southampton Southampton UK. School of Optometry and Vision Sciences Cardiff University Cardiff UK. Department of Psychology University of Bonn Bonn Germany. Vienna University of Economics and Business Vienna Austria. Department of Psychology University of Essex Essex UK. Department of Neuroscience Erasmus MC Rotterdam The Netherlands. Machine Learning Group Department of Computer Science IT University of Copenhagen Copenhagen Denmark. SR Research Ltd Ottawa Canada. Human-Computer Interaction University of Tübingen Tübingen Germany. University of British Columbia Columbia Canada. Department of Eye and Vision Science Institute of Life Course and Medical Sciences University of Liverpool Liverpool UK. Department of Education and Pedagogy Division Education Faculty of Social and Behavioral Sciences Ut

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

关键词： Data quality Eye movements Eye tracking Replicability Reporting guidelines Reporting practices Reporting standards Reproducibility

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Distributed multi-objective scheduling of power consumption for smart buildings

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Energy Informatics 2019年第1期2卷 28-28页

作者： Nebel-Wenner, Marvin Reinhold, Christian Wille, Farina Nieße, Astrid Sonnenschein, Michael OFFIS - Institute for Information Technology R&D Division Energy Escherweg 2 Oldenburg26121 Germany Technische Universität Braunschweig Institute for High Voltage Technology and Electrical Power Systems - elenia Schleinitzstraße 23 Braunschweig38106 Germany Technische Universität Braunschweig Institute of Psychology Division of Research Methods and Biopsychology - IPMB Spielmannstraße 19 Braunschweig38106 Germany Leibniz Universität Hannover Faculty for Electrical Engineering and Computer Science Group Energy Informatics Appelstr. 9a Hannover30167 Germany

Load management of electrical devices in residential buildings can be applied with different goals in the power grid, such as the cost optimization regarding variable electricity prices, peak load reduction or the minimization of behavioral efforts for users due to load shifting. A cooperative multi-objective optimization of consumers and generators of power has the potential to solve the simultaneity problem of power consumption and optimize the power supply from the superposed grid regarding different goals. In this paper, we present a multi-criteria extension of a distributed cooperative load management technique in smart grids based on a multi-agent framework. As a data basis, we use feasible power consumption and production schedules of buildings, which have been derived from simulations of a building model and have already been optimized with regard to self-consumption. We show that the flexibilities of smart buildings can be used to pursue different targets and display the advantage of integrating various goals into one optimization process. © 2019, The Author(s).

关键词： Multiobjective optimization

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Discovery and affinity maturation of antibody fragments from an unfavorably enriched phage display selection by deep sequencing and machine learning

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Journal of Bioscience and Bioengineering 2025年

作者： Kawada, Sakiya Kurumida, Yoichi Ito, Tomoyuki Nguyen, Thuy Duong Nishi, Hafumi Nakazawa, Hikaru Saito, Yutaka Kameda, Tomoshi Tsuda, Koji Umetsu, Mitsuo Department of Biomolecular Engineering of Engineering Tohoku University 6-6-11 Aoba Aramaki Aoba-ku Sendai 980-8579 Japan Department of Data Science School of Frontier Engineering Kitasato University 1-15-1 Kitazato Minami-ku Kanagawa Sagamihara 252-0373 Japan Artificial Intelligence Research Center National Institute of Advanced Industrial Science and Technology (AIST) 2-4-7 Aomi Koto-ku Tokyo 135-0064 Japan Department of Applied Information Sciences of Information Sciences Tohoku University 6-3-09 Aoba Aramaki Aoba-ku Sendai 980-8579 Japan Tohoku Medical Megabank Organization Tohoku University 2-1 Seiryo-machi Aoba-ku Sendai 980-8573 Japan Faculty of Core Research Ochanomizu University 2-1-1 Ohtsuka Bunkyo-ku Tokyo 112-8610 Japan Department of Computational Biology and Medical Sciences of Frontier Sciences The University of Tokyo 5-1-5 Kashiwanoha Chiba Kashiwa 277-8561 Japan Center for Advanced Intelligence Project RIKEN 1-4-1 Nihombashi Chuo-ku Tokyo 103-0027 Japan Research and Services Division of Materials Data and Integrated Systems National Institute for Materials Science 1-2-1 Sengen Tsukuba Ibaraki 305-0047 Japan

Phage display selection has been used for directed evolution of antibody fragments. However, variants with binding affinity cannot be always identified due to undesirable enrichment of target-unrelated variants in the biopanning process. Here, our goal was to obtain functional variants by deep sequencing and machine learning from a phage display library where functional variants were not appropriately enriched. Deep sequencing of the previously biopanned pools revealed that amplification bias might have prevented the enrichment of target-binding phages. We performed a sequence similarity search based on the deep sequencing analysis so that the influence of bias was decreased, leading to discovery of a variant with binding affinity, which could not be discovered by a conventional screening method alone. We applied machine learning to the deep sequencing data;the machine learning proposed effective mutations for increasing affinity, allowing us to identify a variant with improved affinity (EC50 = 3.46 μM). In summary, we present the possibility of obtaining functional variants even from unfavorably enriched phage libraries by using deep sequencing and machine learning. © 2025 The Society for Biotechnology, Japan

关键词： Clustering analysis Deep sequencing Galectin-3 Machine learning Phage display VHH

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Near-Optimal Online Motion Planning of Connected and Automated Vehicles at a Signal-Free and Lane-Free Intersection

Near-Optimal Online Motion Planning of Connected and Automat...

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2018 IEEE Intelligent Vehicles Symposium, IV 2018

作者： Li, Bai Zhang, Youmin Zhang, Yue Jia, Ning Ge, Yuming Shaanxi Key Laboratory of Complex System Control and Intelligent Information Processing Xi'An University of Technology Xi'an710048 China College of Control Science and Engineering Zhejiang University Hangzhou310027 China Department of Mechanical Industrial and Aerospace Engineering Concordia Institute of Aerospace Design and Innovation Concordia University Montreal Canada Division of Systems Engineering Center for Information and Systems Engineering Boston University BostonMA02215 United States Institute of Systems Engineering Tianjin University Tianjin300072 China China Academy of Information and Communications Technology Beijing100191 China

ISBN: (纸本)9781538644522

In this paper, we propose a cooperative motion planning method for a group of connected and automated vehicles (CAVs) crossing a lane-free intersection without using explicit traffic signaling. This multi-vehicle motion planning task is formulated as a centralized optimal control problem. However, the solution to this optimal control problem is numerically intractable due to the high dimensionality of the collision-avoidance constraints and the nonlinearity of the vehicle kinematics. A two-stage strategy is proposed for generating online solutions: at Stage 1, the CAVs are requested to reach a standard formation before entering the intersection;at Stage 2, the vehicles cross the intersection. As the motion planning sub-problem at Stage 2 begins with a standard configuration, the optimal solution to this standard sub-problem can be computed offline in advance and applied online directly. On the other hand, the formation reconfiguration sub-problem at Stage 1 is easy to solve online. Through dividing the entire dynamic process into two periods, the difficulties in the original optimal control problem are significantly reduced so that the real-time performance is achieved. © 2018 IEEE.

关键词： Motion planning

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