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In silico identification of a novel Cdc2-like kinase 2 (CLK2) inhibitor in triple negative breast cancer

Protein science 2024年第6期33卷 e5004-e5004页

作者： Huang, Cheng-Chiao Hsu, Chia-Ming Chao, Min-Wu Hsu, Kai-Cheng Lin, Tony Eight Yen, Shih-Chung Tu, Huang-Ju Pan, Shiow-Lin Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Division of General Surgery Department of Surgery Taipei Medical University Hospital Taipei Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Institute of Biopharmaceutical Sciences College of Medicine National Sun Yat-sen University Kaohsiung Taiwan The Doctoral Program of Clinical and Experimental Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan TMU Research Center of Drug Discovery Taipei Medical University Taipei Taiwan Warshel Institute for Computational Biology The Chinese University of Hong Kong (Shenzhen) Guangdong Shenzhen China

Dysregulation of RNA splicing processes is intricately linked to tumorigenesis in various cancers, especially breast cancer. Cdc2-like kinase 2 (CLK2), an oncogenic RNA-splicing kinase pivotal in breast cancer, plays a significant role, particularly in the context of triple-negative breast cancer (TNBC), a subtype marked by substantial medical challenges due to its low survival rates. In this study, we employed a structure-based virtual screening (SBVS) method to identify potential CLK2 inhibitors with novel chemical structures for treating TNBC. Compound 670551 emerged as a novel CLK2 inhibitor with a 50% inhibitory concentration (IC₅₀) value of 619.7 nM. Importantly, Compound 670551 exhibited high selectivity for CLK2 over other protein kinases. Functionally, this compound significantly reduced the survival and proliferation of TNBC cells. Results from a cell-based assay demonstrated that this inhibitor led to a decrease in RNA splicing proteins, such as SRSF4 and SRSF6, resulting in cell apoptosis. In summary, we identified a novel CLK2 inhibitor as a promising potential treatment for TNBC therapy. © 2024 The Authors. Protein science published by Wiley Periodicals LLC on behalf of The Protein Society.

关键词： CLK2 drug discovery kinase inhibitor structure-based virtual screening triple-negative breast cancer

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GW190521 as a black-hole merger coincident with the ZTF19abanrhr flare

arXiv

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arXiv 2021年

作者： Bustillo, Juan Calderón Leong, Samson H.W. Chandra, Koustav McKernan, Barry Ford, K.E.S. Instituto Galego de Física de Altas Enerxías Universidade de Santiago de Compostela Galicia Santiago de Compostela15782 Spain Department of Physics The Chinese University of Hong Kong N.T. Shatin Hong Kong Department of Physics Indian Institute of Technology Bombay Powai Maharashtra Mumbai400076 India Department of Science CUNY-BMCC 199 Chambers St. New YorkNY10007 United States Department of Astrophysics American Museum of Natural History Central Park West New YorkNY10028 United States Physics Program The Graduate Center CUNY New YorkNY10016 United States Center for Computational Astrophysics Flatiron Institute New YorkNY10010 United States

We present an analysis that reconciles the gravitational wave signal GW190521 observed by the Advanced LIGO and Advanced Virgo detectors with the electromagnetic flare ZTF19abanrhr observed by the Zwicky Transient Facility. We analyze GW190521 under a mass-ratio prior uniform in Q ∈ [1, 4] using the state-of-the-art waveform model for black-hole mergers NRSur7dq4. We find a 90% credible region for the black-hole masses extending far outside what originally reported by [1], where our maximum likelihood masses reside. We find a 15% probability that both black holes avoid the pair-instability supernova gap. We infer a three-dimensional sky-location highly consistent with ZTF19abanrhr, obtaining an odds-ratio OC/R = 72: 1 that strongly favors the hypothesis of a true coincidence over a random one. Combining this event with the neutron-star merger GW170817, we estimate a Hubble constant H0 = 72.1-6.4+10.6km s-1 Mpc-1 at the 68% credible level. Copyright © 2021, The Authors. All rights reserved.

关键词： Merging

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Is there any linkage between interstellar aldehyde and alcohol?

arXiv

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arXiv 2021年

作者： Mondal, Suman Kumar Gorai, Prasanta Sil, Milan Ghosh, Rana Etim, Emmanuel E. Chakrabarti, Sandip K. Shimonishi, Takashi Nakatani, Naoki Furuya, Kenji Tan, Jonathan C. Das, Ankan Indian Centre for Space Physics 43 Chalantika Garia Station Road Kolkata700084 India Department of Space Earth and Environment Chalmers University of Technology GothenburgSE-412 96 Sweden Department of Chemical Sciences Federal University Wukari Katsina-Ala Road P.M.B. 1020 Taraba State Wukari Nigeria Center for Transdisciplinary Research Niigata University Nishi-ku Niigata950-2181 Japan Environmental Science Program Department of Science Faculty of Science Niigata University Nishi-ku Niigata950-2181 Japan Institute for Catalysis Hokkaido University N21W10 Kita-ku Hokkaido Sapporo001-0021 Japan Center for Computational Sciences University of Tsukuba Tsukuba305-8577 Japan Department of Astronomy University of Virginia CharlottesvilleVA22904 United States Department of Chemistry Graduate School of Science and Engineering Tokyo Metropolitan University 1-1 Minami-Osawa Hachioji Tokyo192-0397 Japan National Astronomical Observatory of Japan Tokyo181-8588 Japan

It is speculated that there might be some linkage between interstellar aldehydes and their corresponding alcohols. Here, an observational study and astrochemical modeling are coupled together to illustrate the connection between them. The ALMA cycle 4 data of a hot molecular core, G10.47+0.03 is utilized for this study. Various aldehydes (acetaldehyde, propanal, and glycolaldehyde), alcohols (methanol and ethylene glycol), and a ketone (acetone) are identified in this source. The excitation temperatures and the column densities of these species were derived via the rotation diagram method assuming LTE conditions. An extensive investigation is carried out to understand the formation of these species. Six pairs of aldehyde-alcohol: i) methanal and methanol;ii) ethanal and ethanol;iii) propanal and 1-propanol;iv) propenal and allyl alcohol;v) propynal and propar gyl alcohol;vi) glycolaldehyde and ethylene glycol;vii) along with one pair of ketone-alcohol (acetone and isopropanol) and viii) ketene-alcohol (ethenone and vinyl alcohol) are considered for this study. Two succes sive hydrogenation reactions in the ice phase are examined to form these alcohols from aldehydes, ketone, and ketene, respectively. Quantum chemical methods are extensively executed to review the ice phase formation route and the kinetics of these species. Based on the obtained kinetic data, astrochemical modeling is employed to derive the abundances of these aldehydes, alcohols, ketone, and ketene in this source. It is seen that our model could successfully explain the observed abundances of various species in this hot molecular core. Copyright © 2021, The Authors. All rights reserved.

关键词： Acetone

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MoSi2N4single-layer: A novel two-dimensional material with outstanding mechanical, thermal, electronic, optical, and photocatalytic properties

arXiv

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arXiv 2020年

作者： Bafekry, A. Faraji, M. Hoat, Do M. Fadlallah, M.M. Shahrokhi, M. Shojaei, F. Gogova, D. Ghergherehchi, M. Department of Physics University of Guilan Rasht41335-1914 Iran Department of Physics University of Antwerp Groenenborgerlaan 171 AntwerpB-2020 Belgium Micro and Nanotechnology Graduate Program TOBB University of Economics and Technology Sogutozu Caddesi No 43 Sogutozu Ankara06560 Turkey Computational Laboratory for Advanced Materials and Structures Advanced Institute of Materials Science Ton Duc Thang University Ho Chi Minh City Viet Nam Department of Physics Faculty of Science Benha University Benha13518 Egypt University Lyon ENS de Lyon CNRS Universit Claude Bernard Lyon 1 Laboratoire de Chimie UMR 5182 LyonF-69342 France Department of Chemistry Faculty of Sciences Persian Gulf University Bushehr75169 Iran Department of Physics University of Oslo P.O. Box 1048 Blindern Oslo Norway College of Electronic and Electrical Engineering Sungkyun Kwan University Suwon Korea Republic of

Very recently, the two-dimensional (2D) form of MoSi2N4has been successfully fabricated [Hong et al., Sci. 369, 670 (2020)]. Motivated by theses recent experimental results, herein we investigate the structural, mechanical, thermal, electronic, optical and photocatalytic properties using hybrid density functional theory (HSE06-DFT). Phonon band dispersion calculations reveal the dynamical stability of MoSi2N4monolayer structure. Furthermore, the mechanical study confirms the stability of MoSi2N4monolayer. As compared to the corresponding value of graphene, we find the Young's modulus decreases by ∼ 30% while the Poisson's ratio increases by ∼ 30%. In addition, its work function is very similar to that of phosphorene and MoS2 monolayers. The electronic structure investigation shows the MoSi2N4monolayer is an indirect bandgap semiconductor. We have determined the bandgap using the HSE06 (GGA) is 2.35 (1.79) eV, which is an overestimated (underestimated) value of the experimental bandgap (1.99 eV). The thermoelectric study shows a good thermoelectric performance of the MoSi2N4monolayer with a figure of merit slightly larger than unity at high temperatures. The optical analysis using the RPA method constructed over HSE06 shows that the first absorption peak of the MoSi2N4monolayer for in-plane polarization is located in the visible range of spectrum, i.e. it is a promising candidate for advancing optoelectronic nanodevices. The photocatalytic study indicates the MoSi2N4monloayer can be a promising photocatalyst for water splitting as well as and CO2 reduction. In summary, the fascinating MoSi2N4monloayer is a promising 2D material in many applications due to its unique physical properties. Copyright © 2020, The Authors. All rights reserved.

关键词： Molybdenum compounds

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The bulk van der Waals layered magnet CrSBr is a quasi-1D material

arXiv

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arXiv 2022年

作者： Klein, Julian Pingault, Benjamin Florian, Matthias Heißenbüttel, Marie-Christin Steinhoff, Alexander Song, Zhigang Torres, Kierstin Dirnberger, Florian Curtis, Jonathan B. Weile, Mads Penn, Aubrey Deilmann, Thorsten Dana, Rami Bushati, Rezlind Quan, Jiamin Luxa, Jan Sofer, Zdenek Alù, Andrea Menon, Vinod M. Wurstbauer, Ursula Rohlfing, Michael Narang, Prineha Lončar, Marko Ross, Frances M. Department of Materials Science and Engineering Massachusetts Institute of Technology CambridgeMA02139 United States John A. Paulson School of Engineering and Applied Sciences Harvard University CambridgeMA02138 United States QuTech Delft University of Technology Delft2600 GA Netherlands Department of Electrical and Computer Engineering Department of Physics University of Michigan Ann ArborMI48109 United States Institut für Festkörpertheorie Westfälische Wilhelms-Universität Münster Münster48149 Germany Institut für Theoretische Physik Universität Bremen P.O. Box 330 440 Bremen28334 Germany Bremen Center for Computational Materials Science University of Bremen Bremen28359 Germany Department of Physics City College of New York New YorkNY10031 United States College of Letters and Science UCLA Los AngelesCA90095 United States Department of Physics Technical University of Denmark Kgs. LyngbyDK-2800 Denmark MIT.nano Massachusetts Institute of Technology CambridgeMA02139 United States Department of Physics The Graduate Center City University of New York New YorkNY10016 United States Photonics Initiative CUNY Advanced Science Research Center New YorkNY10031 United States Physics Program Graduate Center City University of New York New YorkNY10026 United States Department of Inorganic Chemistry University of Chemistry and Technology Prague Technická 5 Prague 6166 28 Czech Republic Institute of Physics Center for Nanotechnology University of Münster Münster48149 Germany

Correlated quantum phenomena in one-dimensional (1D) systems that exhibit competing electronic and magnetic order are of strong interest for studying fundamental interactions and excitations, such as Tomonaga-Luttinger liquids and topological orders and defects with properties completely different from the quasiparticles expected in their higher-dimensional counterparts. However, clean 1D electronic systems are difficult to realize experimentally, particularly magnetically ordered systems. Here, we show that the van der Waals layered magnetic semiconductor CrSBr behaves like a quasi-1D material embedded in a magnetically ordered environment. The strong 1D electronic character originates from the Cr-S chains and the combination of weak interlayer hybridization and anisotropy in effective mass and dielectric screening with an effective electron mass ratio of meX/meY ∼ 50. This extreme anisotropy experimentally manifests in strong electron-phonon and exciton-phonon interactions, a Peierls-like structural instability and a Fano resonance from a van Hove singularity of similar strength of metallic carbon nanotubes. Moreover, due to the reduced dimensionality and interlayer coupling, CrSBr hosts spectrally narrow (1 meV) excitons of high binding energy and oscillator strength that inherit the 1D character. Overall, CrSBr is best understood as a stack of weakly hybridized monolayers and appears to be an experimentally attractive candidate for the study of exotic exciton and 1D correlated many-body physics in the presence of magnetic order. Copyright © 2022, The Authors. All rights reserved.

关键词： Excitons

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Democratising Knowledge Representation with BioCypher

arXiv

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arXiv 2022年

作者： Lobentanzer, Sebastian Aloy, Patrick Baumbach, Jan Bohar, Balazs Charoentong, Pornpimol Danhauser, Katharina Doğan, Tunca Dreo, Johann Dunham, Ian Fernandez-Torras, Adrià Gyori, Benjamin M. Hartung, Michael Hoyt, Charles Tapley Klein, Christoph Korcsmaros, Tamas Maier, Andreas Mann, Matthias Ochoa, David Pareja-Lorente, Elena Popp, Ferdinand Preusse, Martin Probul, Niklas Schwikowski, Benno Sen, Bünyamin Strauss, Maximilian T. Turei, Denes Ulusoy, Erva Heidrun Wodke, Judith Andrea Saez-Rodriguez, Julio Heidelberg University Faculty of Medicine Heidelberg University Hospital Institute for Computational Biomedicine Bioquant Heidelberg Germany The Barcelona Institute of Science and Technology Catalonia Barcelona Spain Catalonia Barcelona Spain Institute for Computational Systems Biology University of Hamburg Germany Earlham Institute Norwich United Kingdom Biological Research Centre Szeged Hungary Heidelberg University Im Neuenheimer Feld 267 Heidelberg69120 Germany Im Neuenheimer Feld 460 Heidelberg69120 Germany Department of Pediatrics Dr. von Hauner Children’s Hospital University Hospital LMU Munich Germany Biological Data Science Lab Department of Computer Engineering Hacettepe University Ankara Turkey Department of Bioinformatics Graduate School of Health Sciences Hacettepe University Ankara Turkey Computational Systems Biomedicine Lab Department of Computational Biology Institut Pasteur Université Paris Cité Paris France Bioinformatics and Biostatistics Hub Institut Pasteur Université Paris Cité Paris France Wellcome Genome Campus Cambridgeshire HinxtonCB10 1SD United Kingdom Open Targets Wellcome Genome Campus Cambridgeshire HinxtonCB10 1SD United Kingdom Laboratory of Systems Pharmacology Harvard Medical School Boston United States Imperial College London London United Kingdom Quadram Institute Bioscience Norwich United Kingdom Proteomics Program Novo Nordisk Foundation Centre for Protein Research University of Copenhagen Copenhagen Denmark Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry Martinsried Germany Im Neuenheimer Feld 460 Heidelberg69120 Germany Neuherberg Germany Medical Informatics Laboratory University Medicine Greifswald Germany

Standardising the representation of biomedical knowledge among all researchers is an insurmountable task, hindering the effectiveness of many computational methods. To facilitate harmonisation and interoperability despite this fundamental challenge, we propose to standardise the framework of knowledge graph creation instead. We implement this standardisation in BioCypher, a FAIR (findable, accessible, interoperable, reusable) framework to transparently build biomedical knowledge graphs while preserving provenances of the source data. Mapping the knowledge onto biomedical ontologies helps to balance the needs for harmonisation, human and machine readability, and ease of use and accessibility to nonspecialist researchers. We demonstrate the usefulness of this framework on a variety of use cases, from maintenance of task-specific knowledge stores, to interoperability between biomedical domains, to on-demand building of task-specific knowledge graphs for federated learning. BioCypher (https://***) frees up valuable developer time;we encourage further development and usage by the community. © 2022, CC BY-NC-ND.

关键词： Ontology

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Orbital migration of interacting stellar mass black holes in disks around supermassive black holes

arXiv

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arXiv 2018年

作者： Secunda, Amy Bellovary, Jillian Low, Mordecai-Mark Mac Ford, K.E. Saavik McKernan, Barry Leigh, Nathan Lyra, Wladimir Department of Astrophysics American Museum of Natural History Central Park West at 79th Street New YorkNY10024 United States Department of Physics Queensborough Community College BaysideNY11364 United States Department of Science Borough of Manhattan Community College City University of New York New YorkNY10007 United States Physics Program Graduate Center CUNY New YorkNY10016 United States Department of Physics and Astronomy Stony Brook University Stony BrookNY11794-3800 United States Center for Computational Astrophysics Flatiron Institute New YorkNY10010 United States Department of Physics and Astronomy California State University Northridge 18111 Nordhoff Street NorthridgeCA91330 United States Jet Propulsion Laboratory California Institute of Technology 4800 Oak Grove Drive PasadenaCA91109 United States

The merger rate of stellar mass black holes binaries (sBHBs) inferred by the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) suggests the need for an efficient source of sBHB formation. Active galactic nucleus (AGN) disks are a promising location for the formation of these sBHBs, as well as binaries of other compact objects, because of powerful torques exerted by the gas disk. These gas torques cause orbiting compact objects to migrate towards regions in the disk where inward and outward torques cancel, known as migration traps. We simulate the migration of stellar mass black holes (sBHs) in an analytically modeled AGN disk using an augmented N-body code that includes migration torques, a stochastic gravitational force exerted by turbulent density fluctuations in the disk, and inclination and eccentricity dampening produced by passages through the gas disk, in addition to the standard gravitational forces between objects. We find that sBHBs form rapidly in the disk as sBHs migrate towards the migration trap. These sBHBs are likely to subsequently merge on short time-scales. The process continues, leading to the build up of a population of over-massive sBHs. sBHBs that form in AGN disks could contribute significantly to the sBHB merger rate inferred by LIGO. Copyright © 2018, The Authors. All rights reserved.

关键词： Merging

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A light in the dark: searching for electromagnetic counterparts to black hole-black hole mergers in LIGO/Virgo O3 with the Zwicky Transient Facility

arXiv

引用

arXiv 2022年

作者： Graham, Matthew J. McKernan, Barry Ford, K.E. Saavik Stern, Daniel Djorgovski, S.G. Coughlin, Michael Burdge, Kevin B. Bellm, Eric C. Helou, George Mahabal, Ashish A. Masci, Frank J. Purdum, Josiah Rosnet, Philippe Rusholme, Ben California Institute of Technology 1200 E. California Blvd PasadenaCA91125 United States Department of Science CUNY Borough of Manhattan Community College 199 Chambers Street New YorkNY10007 United States Department of Astrophysics American Museum of Natural History Central Park West New YorkNY10028 United States Physics Program CUNY Graduate Center 365 5th Avenue New YorkNY10016 United States Center for Computational Astrophysics Flatiron Institute New YorkNY10010 United States Jet Propulsion Laboratory California Institute of Technology 4800 Oak Grove Drive PasadenaCA91109 United States School of Physics and Astronomy University of Minnesota MinneapolisMN55455 United States Department of Physics Massachusetts Institute of Technology CambridgeMA02139 United States Kavli Institute for Astrophysics and Space Research Massachusetts Institute of Technology CambridgeMA02139 United States DIRAC Institute Department of Astronomy University of Washington 3910 15th Avenue NE SeattleWA98195 United States IPAC California Institute of Technology 1200 E. California Blvd PasadenaCA91125 United States Division of Physics Mathematics and Astronomy California Institute of Technology PasadenaCA91125 United States Center for Data Driven Discovery California Institute of Technology PasadenaCA91125 United States Caltech Optical Observatories California Institute of Technology PasadenaCA91125 United States Université Clermont Auvergne CNRS IN2P3 LPC Clermont-FerrandF-63000 France

The accretion disks of active galactic nuclei (AGN) are promising locations for the merger of compact objects detected by gravitational wave (GW) observatories. Embedded within a baryon-rich, high density environment, mergers within AGN are the only GW channel where an electromagnetic (EM) counterpart must occur (whether detectable or not). Considering AGN with unusual flaring activity observed by the Zwicky Transient Facility (ZTF), we describe a search for candidate EM counterparts to binary black hole (BBH) mergers detected by LIGO/Virgo in O3. After removing probable false positives, we find nine candidate counterparts to BBH mergers during O3 (seven in O3a, two in O3b) with a p-value of 0.0019. Based on ZTF sky coverage, AGN geometry, and merger geometry, we expect ≈ 3(NBBH/83)(fAGN/0.5) potentially detectable EM counterparts from O3, where NBBH is the total number of observed BBH mergers and fAGN is the fraction originating in AGN. Further modeling of breakout and flaring phenomena in AGN disks is required to reduce our false positive rate. Two of the events are also associated with mergers with total masses > 100M☉, which is the expected rate for O3 if hierarchical (large mass) mergers occur in the AGN channel. Candidate EM counterparts in future GW observing runs can be better constrained by coverage of the Southern sky as well as spectral monitoring of unusual AGN flaring events in LIGO/Virgo alert volumes. A future set of reliable AGN EM counterparts to BBH mergers will yield an independent means of measuring cosmic expansion (H0) as a function of redshift. © 2022, CC BY.

关键词： Gravity waves

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Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (vol 613, pg 169, 2023)

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NATURE 2023年第7949期614卷 E45-E45页

作者： Moiseeva, Victoria Cisneros, Andres Sica, Valentina Deryagin, Oleg Lai, Yiwei Jung, Sascha Andres, Eva An, Juan Segales, Jessica Ortet, Laura Lukesova, Vera Volpe, Giacomo Benguria, Alberto Dopazo, Ana Benitah, Salvador Aznar Urano, Yasuteru del Sol, Antonio Esteban, Miguel A. A. Ohkawa, Yasuyuki Serrano, Antonio L. L. Perdiguero, Eusebio Munoz-Canoves, Pura Department of Medicine and Life Sciences Pompeu Fabra University Barcelona Spain CIBERNED Barcelona Spain Altos labs Inc San Diego CA USA ICREA Barcelona Spain Cardiovascular Regeneration Program CNIC Centro Nacional de Investigaciones Cardiovasculares Madrid Spain Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China Key Laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China University of Science and Technology of China Hefei China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou China CIC bioGUNE-BRTA (Basque Research and Technology Alliance) Bizkaia Technology Park Derio Spain Computational Biology Group Luxembourg Centre for Systems Biomedicine University of Luxembourg Esch-sur-Alzette Luxembourg IKERBASQUE Basque Foundation for Science Bilbao Spain Genomic Unit Centro Nacional de Investigaciones Cardiovasculares and CIBERCV Madrid Spain Institute for Research in Biomedicine and BIST Barcelona Spain Laboratory of Chemistry & Biology Graduate School of Pharmaceutical Sciences and School of Medicine The University of Tokyo Tokyo Japan Division of Transcriptomics. Medical Institute of Bioregulation Kyushu University Fukuoka Japan

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Search for Continuous Gravitational Waves from Known Pulsars in the First Part of the Fourth LIGO-Virgo-KAGRA Observing Run

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Astrophysical Journal 2025年第2期983卷 99-99页

作者： Abac, A.G. Abbott, R. Abouelfettouh, I. Acernese, F. Ackley, K. Adhicary, S. Adhikari, N. Adhikari, R.X. Adkins, V.K. Agarwal, D. Agathos, M. Aghaei Abchouyeh, M. Aguiar, O.D. Aguilar, I. Aiello, L. Ain, A. Ajith, P. Akutsu, T. Albanesi, S. Alfaidi, R.A. Al-Jodah, A. Alléné, C. Allocca, A. Al-Shammari, S. Altin, P.A. Alvarez-Lopez, S. Amato, A. Amez-Droz, L. Amorosi, A. Amra, C. Ananyeva, A. Anderson, S.B. Anderson, W.G. Andia, M. Ando, M. Andrade, T. Andres, N. Andrés-Carcasona, M. Andrić, T. Anglin, J. Ansoldi, S. Antelis, J.M. Antier, S. Aoumi, M. Appavuravther, E.Z. Appert, S. Apple, S.K. Arai, K. Araya, A. Araya, M.C. Areeda, J.S. Argianas, L. Aritomi, N. Armato, F. Arnaud, N. Arogeti, M. Aronson, S.M. Ashton, G. Aso, Y. Assiduo, M. Assis de Souza Melo, S. Aston, S.M. Astone, P. Attadio, F. Aubin, F. AultONeal, K. Avallone, G. Babak, S. Badaracco, F. Badger, C. Bae, S. Bagnasco, S. Bagui, E. Baier, J.G. Baiotti, L. Bajpai, R. Baka, T. Ball, M. Ballardin, G. Ballmer, S.W. Banagiri, S. Banerjee, B. Bankar, D. Baral, P. Barayoga, J.C. Barish, B.C. Barker, D. Barneo, P. Barone, F. Barr, B. Barsotti, L. Barsuglia, M. Barta, D. Bartoletti, A.M. Barton, M.A. Bartos, I. Basak, S. Basalaev, A. Bassiri, R. Basti, A. Bates, D.E. Bawaj, M. Baxi, P. Bayley, J.C. Baylor, A.C. Baynard, P.A. Bazzan, M. Bedakihale, V.M. Beirnaert, F. Bejger, M. Belardinelli, D. Bell, A.S. Benedetto, V. Benoit, W. Bentley, J.D. Ben Yaala, M. Bera, S. Berbel, M. Bergamin, F. Berger, B.K. Bernuzzi, S. Beroiz, M. Bersanetti, D. Bertolini, A. Betzwieser, J. Beveridge, D. Bevins, N. Bhandare, R. Bhardwaj, U. Bhatt, R. Bhattacharjee, D. Bhaumik, S. Bhowmick, S. Bianchi, A. Bilenko, I.A. Billingsley, G. Binetti, A. Bini, S. Birnholtz, O. Biscoveanu, S. Bisht, A. Bitossi, M. Bizouard, M.-A. Blackburn, J.K. Blagg, L.A. Blair, C.D. Blair, D.G. Bobba, F. Bode, N. Boileau, G. Boldrini, M. Bolingbroke, G.N. Bolliand, A. Bonavena, L.D. Bondarescu, R. Bondu, F. Bonilla, E. Bonilla, M.S. Bonino, A. Bonnand, R. Booker, P. Borchers, A. Boschi, V. Bose, S. Boss Max Planck Institute for Gravitational Physics (Albert Einstein Institute) Potsdam D-14476 Germany LIGO Laboratory California Institute of Technology Pasadena 91125 CA United States LIGO Hanford Observatory Richland 99352 WA United States Dipartimento di Farmacia Università di Salerno Fisciano Salerno I-84084 Italy INFN Sezione di Napoli Napoli I-80126 Italy University of Warwick Coventry CV 47AL United Kingdom The Pennsylvania State University University Park 16802 PA United States University of Wisconsin-Milwaukee Milwaukee 53201 WI United States Louisiana State University Baton Rouge 70803 LA United States Université Catholique de Louvain Louvain-la-Neuve B-1348 Belgium Inter-University Centre for Astronomy and Astrophysics Pune 411007 India Queen Mary University of London London E1 4NS United Kingdom Department of Physics and Astronomy Sejong University 209 Neungdong-ro Gwangjin-gu Seoul 143-747 South Korea Instituto Nacional de Pesquisas Espaciais São José dos Campos São Paulo 12227-010 Brazil Stanford University Stanford 94305 CA United States Università di Roma Tor Vergata Roma I-00133 Italy INFN Sezione di Roma Tor Vergata Roma I-00133 Italy Cardiff University Cardiff CF24 3AA United Kingdom Universiteit Antwerpen Antwerpen 2000 Belgium International Centre for Theoretical Sciences Tata Institute of Fundamental Research Bengaluru 560089 India Gravitational Wave Science Project National Astronomical Observatory of Japan 2-21-1 Osawa Mitaka City Tokyo 181-8588 Japan Advanced Technology Center National Astronomical Observatory of Japan 2-21-1 Osawa Mitaka City Tokyo 181-8588 Japan INFN Sezione di Torino Torino I-10125 Italy Theoretisch-Physikalisches Institut Friedrich-Schiller-Universität Jena Jena D-07743 Germany Dipartimento di Fisica Università degli Studi di Torino Torino I-10125 Italy SUPA University of Glasgow Glasgow G12 8QQ United Kingdom OzGrav University of Western Australia Crawley 6009 WA

Continuous gravitational waves (CWs) emission from neutron stars carries information about their internal structure and equation of state, and it can provide tests of general relativity. We present a search for CWs from a set of 45 known pulsars in the first part of the fourth LIGO-Virgo-KAGRA observing run, known as O4a. We conducted a targeted search for each pulsar using three independent analysis methods considering single-harmonic and dual-harmonic emission models. We find no evidence of a CW signal in O4a data for both models and set upper limits on the signal amplitude and on the ellipticity, which quantifies the asymmetry in the neutron star mass distribution. For the single-harmonic emission model, 29 targets have the upper limit on the amplitude below the theoretical spin-down limit. The lowest upper limit on the amplitude is 6.4 × 10^-27 for the young energetic pulsar J0537-6910, while the lowest constraint on the ellipticity is 8.8 × 10^-9 for the bright nearby millisecond pulsar J0437-4715. Additionally, for a subset of 16 targets, we performed a narrowband search that is more robust regarding the emission model, with no evidence of a signal. We also found no evidence of nonstandard polarizations as predicted by the Brans-Dicke theory. © 2025. The Author(s). Published by the American Astronomical Society.

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