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37th International Cosmic Ray Conference, ICRC 2021

作者： Kobayshi, Yukiho Sanchez, David Abe, H. Aguasca, A. Agudo, I. Antonelli, L.A. Aramo, C. Armstrong, T. Artero, M. Asano, K. Ashkar, H. Aubert, P. Baktash, A. Bamba, A. Baquero Larriva, A. Baroncelli, L. Barres de Almeida, U. Barrio, J.A. Batkovic, I. Becerra González, J. Bernardos, M.I. Berti, A. Biederbeck, N. Bigongiari, C. Blanch, O. Bonnoli, G. Bordas, P. Bose, D. Bulgarelli, A. Burelli, I. Buscemi, M. Cardillo, M. Caroff, S. Carosi, A. Cassol, F. Cerruti, M. Chai, Y. Cheng, K. Chikawa, M. Chytka, L. Contreras, J.L. Cortina, J. Costantini, H. Dalchenko, M. De Angelis, A. de Bony de Lavergne, M. Deleglise, G. Delgado, C. Delgado Mengual, J. della Volpe, D. Depaoli, D. Di Pierro, F. Di Venere, L. Díaz, C. Dominik, R.M. Dominis Prester, D. Donini, A. Dorner, D. Doro, M. Elsässer, D. Emery, G. Escudero, J. Fiasson, A. Foffano, L. Fonseca, M.V. Freixas Coromina, L. Fukami, S. Fukazawa, Y. Garcia, E. Garcia López, R. Giglietto, N. Giordano, F. Gliwny, P. Godinovic, N. Green, D. Grespan, P. Gunji, S. Hackfeld, J. Hadasch, D. Hahn, A. Hassan, T. Hayashi, K. Heckmann, L. Heller, M. Herrera Llorente, J. Hirotani, K. Hoffmann, D. Horns, D. Houles, J. Hrabovsky, M. Hrupec, D. Hui, D. Hütten, M. Inada, T. Inome, Y. Iori, M. Ishio, K. Iwamura, Y. Jacquemont, M. Jimenez Martinez, I. Jouvin, L. Jurysek, J. Kagaya, M. Karas, V. Katagiri, H. Kataoka, J. Kerszberg, D. Kobayashi, Y. Kong, A. Kubo, H. Kushida, J. Lamanna, G. Lamastra, A. Le Flour, T. Longo, F. López-Coto, R. López-Moya, M. López-Oramas, A. Luque-Escamilla, P.L. Majumdar, P. Makariev, M. Mandat, D. Manganaro, M. Mannheim, K. Mariotti, M. Marquez, P. Marsella, G. Martí, J. Martinez, O. Martínez, G. Martínez, M. Marusevec, P. Mas, A. Maurin, G. Mazin, D. Mestre Guillen, E. Micanovic, S. Miceli, D. Miener, T. Miranda, J.M. Miranda, L.D.M. Mirzoyan, R. Mizuno, T. Molina, E. Montaruli, T. Monteiro, I. Moralejo, A. Morcuende, D. Moretti, E. Morselli, A. Mrakovcic, K. Murase, K. Nagai, A. LAPP Université de Savoie Mont-Blanc CNRS/IN2P3 Annecy74941 France Institute for Cosmic Ray Research The University of Tokyo Kashiwa Japan Institute for Cosmic Ray Research University of Tokyo Japan Departament de Física Quàntica i Astrofísica Institut de Ciències del Cosmos Universitat de Barcelona IEEC-UB Spain Instituto de Astrofísica de Andalucía CSIC INAF - Osservatorio Astronomico di Roma Italy INFN Sezione di Napoli Italy Aix Marseille Univ CNRS/IN2P3 CPPM France The Barcelona Institute of Science and Technology Spain IRFU CEA Université Paris-Saclay France LAPP Univ. Grenoble Alpes Univ. Savoie Mont Blanc CNRS/IN2P3 Annecy France Universität Hamburg Institut für Experimentalphysik Germany Graduate School of Science University of Tokyo Japan EMFTEL department IPARCOS Universidad Complutense de Madrid Spain INAF - Osservatorio di Astrofisica Scienza dello Spazio di Bologna Italy Centro Brasileiro de Pesquisas Físicas Brazil INFN Sezione di Padova Università degli Studi di Padova Italy Instituto de Astrofísica de Canarias Departamento de Astrofísica Universidad de La Laguna Spain Max-Planck-Institut für Physik Germany Department of Physics TU Dortmund University Germany Saha Institute of Nuclear Physics INFN Sezione di Trieste Università degli Studi di Udine Italy INFN Sezione di Catania Italy Italy University of Geneva Département de Physique Nucléaire et Corpusculaire Switzerland Palacky University Olomouc Faculty of Science Czech Republic CIEMAT Port d'Informació Científica INFN Sezione di Torino Italy Dipartimento di Fisica Universitá degli Studi di Torino Italy INFN Sezione di Bari Università di Bari Italy University of Rijeka Department of Physics Croatia Institute for Theoretical Physics and Astrophysics Universität Würzburg Germany Physics Program Graduate School of Advanced Science and Engineering Hiroshima University Japan INFN Sezione di Bari Politecnico di Bari Italy Faculty of Physics and Applied Informatics University of L

The recent detection of a very high energy (VHE) emission from Gamma-Ray Bursts (GRBs) above 100 GeV performed by the MAGIC and H.E.S.S. collaborations, has represented a significant, long-awaited result for the VHE astrophysics community. Although these results' scientific impact has not yet been fully exploited, the possibility to detect VHE gamma-ray signals from GRBs has always been considered crucial for clarifying the poorly known physics of these objects. Furthermore, the discovery of high-energy neutrinos and gravitational waves associated with astrophysical sources have definitively opened the era of multi-messenger astrophysics, providing unique insights into the physics of extreme cosmic accelerators. In the near future, the Cherenkov Telescope Array (CTA) will play a major role in these observations. Within this framework, the Large Size Telescopes (LSTs) will be the instruments best suited to significantly impact on short time-scale transients follow-up thanks to their fast slewing and large effective area. The observations of the early emission phase of a wide range of transient events with good sensitivity below 100 GeV will allow us to open new opportunities for time-domain astrophysics in an energy range not affected by selective absorption processes typical of other wavelengths. In this contribution, we will report about the observational program and first transients follow-up observations performed by the LST-1 telescope currently in its commissioning phase on La Palma, Canary Islands, the CTA northern hemisphere site. © Copyright owned by the author(s) under the terms of the Creative Commons.

关键词： Telescopes

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Learn-Morph-Infer: a new way of solving the inverse problem for brain tumor modeling

arXiv

引用

arXiv 2021年

作者： Ezhov, Ivan Scibilia, Kevin Franitza, Katharina Steinbauer, Felix Shit, Suprosanna Zimmer, Lucas Lipkova, Jana Kofler, Florian Paetzold, Johannes Canalini, Luca Waldmannstetter, Diana Menten, Martin J. Metz, Marie Wiestler, Benedikt Menze, Bjoern Department of Informatics TUM Munich Germany TranslaTUM - Central Institute for Translational Cancer Research TUM Munich Germany Department of Mechanical Engineering TUM Munich Germany Department of Quantitative Biomedicine UZH Zurich Switzerland Department of Pathology Brigham and Women’s Hospital Harvard Medical School BostonMA United States Broad Institute of Harvard MIT CambridgeMA United States Data Science Program Dana-Farber Cancer Institute BostonMA United States Fraunhofer MEVIS Bremen Germany Neuroradiology Department of Klinikum Rechts der Isar TUM Munich Germany

Current treatment planning of patients diagnosed with a brain tumor, such as glioma, could significantly benefit by accessing the spatial distribution of tumor cell concentration. Existing diagnostic modalities, e.g. magnetic resonance imaging (MRI), contrast sufficiently well areas of high cell density. In gliomas, however, they do not portray areas of low cell concentration, which can often serve as a source for the secondary appearance of the tumor after treatment. To estimate tumor cell densities beyond the visible boundaries of the lesion, numerical simulations of tumor growth could complement imaging information by providing estimates of full spatial distributions of tumor cells. Over recent years a corpus of literature on medical image-based tumor modeling was published. It includes different mathematical formalisms describing the forward tumor growth model. Alongside, various parametric inference schemes were developed to perform an efficient tumor model personalization, i.e. solving the inverse problem. However, the unifying drawback of all existing approaches is the time complexity of the model personalization which prohibits a potential integration of the modeling into clinical settings. In this work, we introduce a deep learning based methodology for inferring the patient-specific spatial distribution of brain tumors from T1Gd and FLAIR MRI medical scans. Coined as Learn-Morph-Infer, the method achieves real-time performance in the order of minutes on widely available hardware and the compute time is stable across tumor models of different complexity, such as reaction-diffusion and reaction-advection-diffusion models. We believe the proposed inverse solution approach not only bridges the way for clinical translation of brain tumor personalization but can also be adopted to other scientific and engineering domains. Copyright © 2021, The Authors. All rights reserved.

关键词： Magnetic resonance imaging

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Seebeck coefficient in a cuprate superconductor: Particle-hole asymmetry in the strange metal phase and Fermi surface transformation in the pseudogap phase

arXiv

引用

arXiv 2021年

作者： Gourgout, A. Grissonnanche, G. Laliberté, F. Ataei, A. Chen, L. Verret, S. Zhou, J.-S. Mravlje, J. Georges, A. Doiron-Leyraud, N. Taillefer, Louis Institut Quantique Département de physique and RQMP Université de Sherbrooke SherbrookeQC Canada Laboratory of Atomic and Solid State Physics Cornell University IthacaNY United States Kavli Institute at Cornell for Nanoscale Science IthacaNY United States Materials Science and Engineering Program/Mechanical Engineering University of Texas - Austin AustinTX United States Department of Theoretical Physics Institute Jožef Stefan Ljubljana Slovenia Collège de France 11 place Marcelin Berthelot Paris France Center for Computational Quantum Physics Flatiron Institute New YorkNY United States CPHT CNRS Ecole Polytechnique IP Paris Palaiseau France DQMP Université de Genève Geneva Switzerland Canadian Institute for Advanced Research TorontoON Canada

We report measurements of the Seebeck effect in both the ab plane (Sa) and along the c axis (Sc) of the cuprate superconductor La1:6-xNd0:4SrxCuO4(Nd-LSCO), performed in magnetic fields large enough to suppress superconductivity down to low temperature. We use the Seebeck coefficient as a probe of the particle-hole asymmetry of the electronic structure across the pseudogap critical doping p∗ = 0:23. Outside the pseudogap phase, at p = 0:24 > p∗, we observe a positive and essentially isotropic Seebeck coefficient as T → 0. That S > 0 at p = 0:24 is at odds with expectations given the electronic band structure of Nd-LSCO above p∗ and its known electron-like Fermi surface. We can reconcile this observation by invoking an energy-dependent scattering rate with a particle-hole asymmetry, possibly rooted in the non-Fermi liquid nature of cuprates just above p∗. Inside the pseudogap phase, for p Copyright © 2021, The Authors. All rights reserved.

关键词： Electronic structure

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EMPRESS. XII. Statistics on the Dynamics and Gas Mass Fraction of Extremely-Metal Poor Galaxies

arXiv

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arXiv 2023年

作者： Xu, Yi Ouchi, Masami Isobe, Yuki Nakajima, Kimihiko Ozaki, Shinobu Bouché, Nicolas F. Wise, John H. Emsellem, Eric Kusakabe, Haruka Hattori, Takashi Nagao, Tohru Chiaki, Gen Fukushima, Hajime Harikane, Yuichi Hayashi, Kohei Hirai, Yutaka Kim, Ji Hoon Maseda, Michael V. Nagamine, Kentaro Shibuya, Takatoshi Sugahara, Yuma Yajima, Hidenobu Aoyama, Shohei Fujimoto, Seiji Fukushima, Keita Hatano, Shun Inoue, Akio K. Ishigaki, Tsuyoshi Kawasaki, Masahiro Kojima, Takashi Komiyama, Yutaka Koyama, Shuhei Koyama, Yusei Lee, Chien-Hsiu Matsumoto, Akinori Mawatari, Ken Moriya, Takashi J. Motohara, Kentaro Murai, Kai Nishigaki, Moka Onodera, Masato Ono, Yoshiaki Rauch, Michael Saito, Tomoki Sasaki, Rin Suzuki, Akihiro Takeuchi, Tsutomu T. Umeda, Hiroya Umemura, Masayuki Watanabe, Kuria Yabe, Kiyoto Zhang, Yechi Institute for Cosmic Ray Research The University of Tokyo 5-1-5 Kashiwanoha Chiba Kashiwa277-8582 Japan Department of Astronomy Graduate School of Science The University of Tokyo 7-3-1 Hongo Bunkyo Tokyo113-0033 Japan National Astronomical Observatory of Japan 2-21-1 Osawa Mitaka Tokyo181-8588 Japan University of Tokyo Chiba Kashiwa277-8583 Japan Department of Physics Graduate School of Science The University of Tokyo 7-3-1 Hongo Bunkyo Tokyo113-0033 Japan Univ Lyon Univ Lyon1 ENS de Lyon CNRS Centre de Recherche Astrophysique de Lyon UMR5574 Saint-Genis-LavalF-69230 France Center for Relativistic Astrophysics School of Physics Georgia Institute of Technology AtlantaGA30332 United States European Southern Observatory Karl-Schwarzschild-Straße 2 Garching85748 Germany Observatoire de Genéve Université de Genéve 51 Ch. des Maillettes Versoix1290 Switzerland 650 North A’ohoku Place HiloHI96720 United States Research Center for Space and Cosmic Evolution Ehime University Bunkyo-cho 2-5 Ehime Matsuyama790-8577 Japan Center for Computational Sciences University of Tsukuba Ten-nodai 1-1-1 Tsukuba Ibaraki305-8577 Japan Department of Physics and Astronomy University College London Gower Street LondonWC1E 6BT United Kingdom National Institute of Technology Ichinoseki College Hagisho Ichinoseki021-8511 Japan Astronomical Institute Tohoku University 6-3 Aoba Aramaki Aoba-ku Miyagi Sendai980-8578 Japan Department of Physics and Astronomy University of Notre Dame 225 Nieuwland Science Hall Notre DameIN46556 United States Astronomy Program Department of Physics and Astronomy Seoul National University 1 Gwanak-ro Gwanak-gu Seoul08826 Korea Republic of SNU Astronomy Research Center Seoul National University 1 Gwanak-ro Gwanak-gu Seoul08826 Korea Republic of Department of Astronomy University of Wisconsin-Madison 475 N. Charter Street MadisonWI53706 United States Theoretical Astrophysics Department of Earth & Space S

We present demography of the dynamics and gas-mass fraction of 33 extremely metal-poor galaxies (EMPGs) with metallicities of 0.015 − 0.195 Zo and low stellar masses of 104 − 108 Mo in the local universe. We conduct deep optical integral-field spectroscopy (IFS) for the low-mass EMPGs with the medium high resolution (R = 7500) grism of the 8m-Subaru FOCAS IFU instrument by the EMPRESS 3D survey, and investigate Hα emission of the EMPGs. Exploiting the resolution high enough for the low-mass galaxies, we derive gas dynamics with the Hα lines by the fitting of 3-dimensional disk models. We obtain an average maximum rotation velocity (vrot) of 15 ± 3 km s−1 and an average intrinsic velocity dispersion (σ0) of 27 ± 10 km s−1 for 15 spatially resolved EMPGs out of the 33 EMPGs, and find that all of the 15 EMPGs have vrot/σ0 rot/σ0 with the decreasing stellar mass and metallicity. We derive the gas mass fraction (fgas) for all of the 33 EMPGs, and find no clear dependence on stellar mass and metallicity. These vrot/σ0 and fgas trends should be compared with young high-z galaxies observed by the forthcoming JWST IFS programs to understand the physical origins of the EMPGs in the local universe. © 2023, CC BY.

关键词： Galaxies

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Advancing the Use of Longitudinal Electronic Health Records: Tutorial for Uncovering Real-World Evidence in Chronic Disease Outcomes

引用

Journal of Medical Internet Research 2025年第1期27卷 e71873页

作者： Huang, Feiqing Hou, Jue Zhou, Ningxuan Greco, Kimberly Lin, Chenyu Sweet, Sara Morini Wen, Jun Shen, Lechen Gonzalez, Nicolas Zhang, Sinian Liao, Katherine P. Cai, Tianrun Xia, Zongqi Bourgeois, Florence T. Cai, Tianxi Department of Biostatistics Harvard T.H. Chan School of Public Health Boston MA United States Harvard-MIT Center for Regulatory Science Harvard Medical School Boston MA United States Division of Biostatistics and Health Data Science School of Public Health University of Minnesota Minneapolis MN United States Department of Biomedical Informatics Harvard Medical School Boston MA United States Department of Engineering University of Toronto Toronto ON Canada Division of Rheumatology Inflammation and Immunity Brigham and Women's Hospital Boston MA United States Department of Neurology University of Pittsburgh Pittsburgh PA United States Computational Health Informatics Program (CHIP) Boston Children's Hospital Boston MA United States Department of Pediatrics Harvard Medical School Boston MA United States

Managing chronic diseases requires ongoing monitoring of disease activity and therapeutic responses to optimize treatment plans. With the growing availability of disease-modifying therapies, it is crucial to investigate comparative effectiveness and long-term outcomes beyond those available from randomized clinical trials. We introduce a comprehensive pipeline for generating reproducible and generalizable real-world evidence on disease outcomes by leveraging electronic health record data. The pipeline first generates scalable disease outcomes by linking electronic health record data with registry data containing a small sample of labeled outcomes. It then applies causal analysis using these scalable outcomes to evaluate therapies for chronic diseases. The implementation of the pipeline is illustrated in a case study based on multiple sclerosis. Our approach addresses challenges in real-world evidence generation for disease activity of chronic conditions, specifically the lack of direct observations on key outcomes and biases arising from imperfect or incomplete data. We present advanced machine learning techniques such as semisupervised and ensemble methods to impute missing outcome data, further incorporating steps for calibrated causal analyses and bias correction. ©Feiqing Huang, Jue Hou, Ningxuan Zhou, Kimberly Greco, Chenyu Lin, Sara Morini Sweet, Jun Wen, Lechen Shen, Nicolas Gonzalez, Sinian Zhang, Katherine P Liao, Tianrun Cai, Zongqi Xia, Florence T Bourgeois, Tianxi Cai.

关键词： calibration causal inference chronic disease outcomes data imputation electronic health records longitudinal disease activity machine learning real-world evidence

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Revealing rejuvenated disorder states towards crystallization in a supercooled metallic glass-forming liquid

arXiv

引用

arXiv 2020年

作者： Song, Wen-Xiong Yang, Yong Wang, Weihua Guan, Pengfei State Key Laboratory of Functional Materials for Informatics Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences Shanghai200050 China Beijing Computational Science Research Center Beijing100193 China Department of Mechanical and Biomedical Engineering City University of Hong Kong Kowloon Hong Kong Institute of Physics Chinese Academy of Sciences Beijing100190 China

We report a metadynamics simulation study of crystallization in a deep undercooled metallic glass-forming liquid by developing appropriate collective variables. Through a combined analysis of free energy surface (FES) and atomic-level behaviors, a picture of an abnormal-endothermic crystallization process is revealed: rejuvenated disorder states with less local fivefold-symmetry and fast dynamics form firstly by changing the local chemical order around Cu atoms, which then act as the precursor for the nucleation of well-ordered crystallites. This process reflects a complex energy landscape with well-separated glassy and crystal basins, giving rise to the direct evidence of intrinsic frustration against crystallization in deep undercooled metallic glass forming liquids. Moreover, the rejuvenated disorder states with distinct physical behaviors offer great opportunities to tailor the performances of metallic glass by controlling the thermal history of a metallic melt. Copyright © 2020, The Authors. All rights reserved.

关键词： Metallic glass

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Disability in space - What ESA should have aimed for

arXiv

引用

arXiv 2021年

作者： Heinicke, Christiane Kaczmarzyk, Marcin Tannert, Benjamin Wasniowski, Aleksander Perycz, Malgorzata Schöning, Johannes Am Fallturm 2 Bremen28359 Germany Rzeszow University of Technology The Faculty of Civil and Environmental Engineering and Architecture Department of Building Engineering Poznańska Street 2 Rzeszow35-084 Poland Hochschule Bremen - City University of Applied Science Applied Media Informatics Flughafenallee 10 Bremen28199 Germany Space Is More ul. Mikulskiego 17 Wroclaw52-420 Poland Institute of Computer Science Polish Academy of Sciences Department of Artificial Intelligence Lab of Computational Biology Jana Kazimierza 5 st. Warsaw01-248 Poland University of Bremen Human-Computer Interaction Bibliothekstraße 5 Bremen28359 Germany

With announcing their "Parastronaut Feasibility Project", the European Space Agency ESA promises to make every reasonable effort to send astronauts with disability to space. This could spark hope in the 15% of all people who live with some form of disability. However, the fine-print of the announcement sets overly tight boundaries to "acceptable" disabilities, allowing only malformations that are expected to have a positive impact on the parastronaut's performance in space. By doing so, ESA is following decade-old traditions in space flight, with some inclusion for the sake of inclusion and public opinion. Instead of accommodating people with disabilities, ESA should send a strong signal for inclusion and truly challenge people with disabilities so they can and will tease out the best of their qualities. © 2021, CC BY.

关键词： Manned space flight

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Correction: The genome of the soybean cyst nematode (Heterodera glycines) reveals complex patterns of duplications involved in the evolution of parasitism genes

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BMC genomics 2024年第1期25卷 537页

作者： Rick Masonbrink Tom R Maier Usha Muppirala Arun S Seetharam Etienne Lord Parijat S Juvale Jeremy Schmutz Nathan T Johnson Dmitry Korkin Melissa G Mitchum Benjamin Mimee Sebastian Eves-van den Akker Matthew Hudson Andrew J Severin Thomas J Baum Department of Plant Pathology Iowa State University Ames IA USA. Genome Informatics Facility Iowa State University Ames IA USA. Agriculture and Agri-Food Canada Saint-Jean-sur-Richelieu QC Canada. Department of Energy Joint Genome Institute Walnut Creek CA USA. HudsonAlpha Institute for Biotechnology Huntsville AL USA. Bioinformatics and Computational Biology Program Worcester Polytechnic Institute Worcester MA USA. Department of Computer Science Worcester Polytechnic Institute Worcester MA USA. Division of Plant Sciences University of Missouri Columbia MO USA. Department of Plant Sciences University of Cambridge Cambridge UK. Department of Crop Sciences University of Illinois Urbana IL USA. Genome Informatics Facility Iowa State University Ames IA USA. severin@iastate.edu.

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Rewriting regulatory DNA to dissect and reprogram gene expression

引用

Cell 2025年第12期188卷 3349-3366.e23,26页

作者： Martyn, Gabriella E. Montgomery, Michael T. Jones, Hank Guo, Katherine Doughty, Benjamin R. Linder, Johannes Bisht, Deepa Xia, Fan Cai, Xiangmeng S. Chen, Ziwei Cochran, Kelly Lawrence, Kathryn A. Munson, Glen Pampari, Anusri Fulco, Charles P. Sahni, Nidhi Kelley, David R. Lander, Eric S. Kundaje, Anshul Engreitz, Jesse M. Department of Genetics Stanford University School of Medicine Stanford 94305 CA United States Basic Science and Engineering Initiative Stanford Children's Health Betty Irene Moore Children's Heart Center Stanford 94305 CA United States Calico Life Sciences LLC South San Francisco 94080 CA United States Department of Genitourinary Medical Oncology Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston 77030 TX United States Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston 77030 TX United States Department of Epigenetics and Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Houston 77230 TX United States Department of Bioengineering Stanford University Stanford 94305 CA United States Department of Computer Science Stanford University Stanford 94305 CA United States Novo Nordisk Foundation Center for Genomic Mechanisms of Disease Broad Institute of MIT and Harvard Cambridge 02142 MA United States Gene Regulation Observatory Broad Institute of MIT and Harvard Cambridge 02142 MA United States Broad Institute of MIT and Harvard Cambridge 02142 MA United States Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Houston 77230 TX United States Quantitative and Computational Biosciences Program Baylor College of Medicine Houston 77030 TX United States Department of Biology MIT Cambridge 02139 MA United States Department of Systems Biology Harvard Medical School Boston 02115 MA United States Stanford Cardiovascular Institute Stanford University Stanford 94305 CA United States

Regulatory DNA provides a platform for transcription factor binding to encode cell-type-specific patterns of gene expression. However, the effects and programmability of regulatory DNA sequences remain difficult to map or predict. Here, we develop variant effects from flow-sorting experiments with CRISPR targeting screens (Variant-EFFECTS) to introduce hundreds of designed edits to endogenous regulatory DNA and quantify their effects on gene expression. We systematically dissect and reprogram 3 regulatory elements for 2 genes in 2 cell types. These data reveal endogenous binding sites with effects specific to genomic context, transcription factor motifs with cell-type-specific activities, and limitations of computational models for predicting the effect sizes of variants. We identify small edits that can tune gene expression over a large dynamic range, suggesting new possibilities for prime-editing-based therapeutics targeting regulatory DNA. Variant-EFFECTS provides a generalizable tool to dissect regulatory DNA and to identify genome editing reagents that tune gene expression in an endogenous context. © 2025 Elsevier Inc.

关键词： CRISPR enhancers gene regulation high-throughput screening non-coding variants predictive models prime editing RNA FlowFISH sequence design transcription factors

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Continuous black-box optimization with quantum annealing and random subspace coding

arXiv

引用

arXiv 2021年

作者： Izawa, Syun Kitai, Koki Tanaka, Shu Tamura, Ryo Tsuda, Koji Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo Kashiwa277-8561 Japan Department of Mechanical Engineering University of Tokyo Tokyo113-8654 Japan Department of Applied Physics and Physico-Informatics Keio University Yokohama223-8522 Japan Green Computing System Research Organization Waseda University Tokyo162-0042 Japan International Center for Materials Nanoarchitectonics National Institute for Materials Science Tsukuba305-0047 Japan Research and Services Division of Materials Data and Integrated System National Institute for Materials Science Tsukuba305-0047 Japan RIKEN Center for Advanced Intelligence Project Tokyo103-0027 Japan

A black-box optimization algorithm such as Bayesian optimization finds extremum of an unknown function by alternating inference of the underlying function and optimization of an acquisition function. In a high-dimensional space, such algorithms perform poorly due to the difficulty of acquisition function optimization. Herein, we apply quantum annealing (QA) to overcome the difficulty in the continuous black-box optimization. As QA specializes in optimization of binary problems, a continuous vector has to be encoded to binary, and the solution of QA has to be translated back. Our method has the following three parts: 1) Random subspace coding based on axis-parallel hyperrectangles from continuous vector to binary vector. 2) A quadratic unconstrained binary optimization (QUBO) defined by acquisition function based on nonnegative-weighted linear regression model which is solved by QA. 3) A penalization scheme to ensure that the QA solution can be translated back. It is shown in benchmark tests that its performance using D-Wave AdvantageTM quantum annealer is competitive with a state-of-the-art method based on the Gaussian process in high-dimensional problems. Our method may open up a new possibility of quantum annealing and other QUBO solvers including quantum approximate optimization algorithm (QAOA) using a gated-quantum computers, and expand its range of application to continuous-valued problems. © 2021, CC BY.

关键词： Annealing

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