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作者:Zang, Yi; Shi, Jingjing; Zhao, Guanguan; Tang, Bixi; Liu, Mingliang; Yao, Benqiang; Wang, Gaihong; Pan, Hualing; Yang, Shengsheng; Deng, Rong; Zhao, Yishuang; Zhang, Zhenwei; Guo, Hao-Ran; Sun, Dan-Dan; Wang, Hanlin; Gao, Lixin; Yu, Jinghua; Diao, Xingxing; Li, Yong; Li, Jia; Xu, H. Eric
作者单位:Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Lin Gang Laboratory; Central South University; Xiamen University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Jiao Tong University
摘要:Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation tha...
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作者:Canepa, Jacob; Ruiz-Arroyo, Victor M.; Schlamowitz, Netanya S.; Nam, Yunsun
作者单位:University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
摘要:Specific deposition of RNA modifications is important for regulating gene expression1,2. 5-Methylcytosine (m5C) is a common epitranscriptomic modification, and NSUN2 is a key enzyme responsible for m5C methylation of various types of RNA. Dysregulation of NSUN2 is associated with numerous diseases, including cancers and neurological disorders3. The versatility of NSUN2 complicates our understanding of its substrate specificity and molecular roles in biology and disease. Here we show how NSUN2 ...
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作者:Collins, Katherine M.; Zhang, Cedegao E.; Wong, Lionel; Barba da Costa, Mauricio; Todd, Graham; Weller, Adrian; Cheyette, Samuel J.; Griffiths, Thomas L.; Tenenbaum, Joshua B.
作者单位:Massachusetts Institute of Technology (MIT); Princeton University; University of Cambridge; Stanford University; New York University; Alan Turing Institute
摘要:Games have long been a microcosm for studying planning and reasoning in both natural and artificial intelligence, often focusing on expert-level or even super-human play1, 2, 3, 4, 5-6. But real life also pushes human intelligence along a different frontier, requiring people to flexibly navigate decision-making problems that they have never thought about before. Here we use novice gameplay to study how people reason about new problem settings. Through a series of large-scale behavioural studie...
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作者:Nasari, Hadiseh; Moussa, Hady; Kasahara, Yoshiaki; Thielens, Arno; Alu, Andrea
作者单位:City University of New York (CUNY) System; City University of New York (CUNY) System; City College of New York (CUNY); City University of New York (CUNY) System
摘要:Time-driven systems provide a framework for controlling waves through spatio-temporal modulation, which enables the synthesis of effective motion without mechanical displacement1, 2, 3, 4, 5, 6-7. Within this framework, travelling-wave modulations can emulate moving media and give rise to phenomena such as Doppler-induced non-reciprocity8, 9-10. A related effect is the extraction of energy from rotating media, which has been theoretically predicted to occur when waves experience sufficiently l...
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作者:Shi, Yiting; Yang, Shuhua
作者单位:China Agricultural University
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作者:Chen, Edward
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作者:Vasilakos, Petros N.; Upadhyay, Abhishek; Manousakas, Manousos I.; Alastuey, Andres; Allan, James D.; Alves, Celia A.; Bergmans, Benjamin; Brem, Benjamin T.; Castillo, Sonia; Christoudias, Theodoros; Colombi, Cristina; Conil, Sebastien; Dzepina, Katja; Eichler, Anja; Eleftheriadis, Konstantinos; Favez, Olivier; Flynn, Michael; Glojek, Kristina; Grange, Stuart K.; Green, David C.; Hueglin, Christoph; Jaffrezo, Jean-Luc; Jenk, Theo M.; Jiang, Jianhui; Krymova, Ekaterina; Lucarelli, Franco; Makoric, Petra; Massabo, Dario; Mihalopoulos, Nikolaos; Mocnik, Grisa; Modini, Robin L.; Mohr, Claudia; Naccarato, Attilio; Pokorna, Petra; Prati, Paolo; Probst-Hensch, Nicole; Prevot, Andre S. H.; Querol, Xavier; Reche, Cristina; de la Rosa, Jesus D.; Scerri, Mark M.; Sciare, Jean; Sigl, Michael; Tremper, Anja H.; Traversi, Rita; Banos, Daniel Trejo; Tsagkaraki, Maria; Uzu, Gaelle; Vecchi, Roberta; Via, Marta; de Hoogh, Kees; El-Haddad, Imad; Daellenbach, Kaspar R.
作者单位:Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigacion y Desarrollo Pascual Vila (CID-CSIC); CSIC - Instituto de Diagnostico Ambiental y Estudios del Agua (IDAEA); University of Manchester; University of Manchester; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC National Centre for Atmospheric Science; Universidade de Aveiro; Universidad de Jaen; University of Granada; Universidad de Cordoba; Instituto Interuniversitario de Investigacion del Sistema Tierra en Andalucia; University of Nova Gorica; University of Bern; Institut National de l'Environnement Industriel et des Risques (INERIS); Swiss Federal Institutes of Technology Domain; Swiss Federal Laboratories for Materials Science & Technology (EMPA); University of Bern; Imperial College London; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); East China Normal University; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Florence; Istituto Nazionale di Fisica Nucleare (INFN); University of Nova Gorica; University of Genoa; University of Crete; National Observatory of Athens; University of Calabria; Czech Academy of Sciences; Institute of Chemical Process Fundamentals of the Czech Academy of Sciences; University of Basel; Swiss Tropical & Public Health Institute; University of Basel; University of Milan
摘要:Mineral desert dust is a major contributor to total atmospheric particulate matter1. Desert dust outbreaks degrade air quality and can pose adverse health effects2, including asthma exacerbation3 and increased mortality4. At some European locations, there has been a rise in the intensity and frequency of transported dust outbreaks from deserts in recent decades5, 6, 7, 8-9. However, it remains unclear whether this increase is consistent across Europe and whether desertification and aridity or ...
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作者:Castelvecchi, Davide
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作者:Urnov, Fyodor
作者单位:University of California System; University of California Berkeley
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作者:[Anonymous]