July 5, 2016 u vol. 113 u no. 27 From the Cover 7308 Finding causality in Big Data E3901 Treating inflammation-driven fibrosis 7403 Interactions between liquid droplets on solids 7667 Role of plant photoreceptors Contents THIS WEEK IN PNAS 7285 In This Issue Cover image: Societies now collect immense amounts of data from both LETTERS (ONLINE ONLY) controlled experiments and natural E3811 Avoid the hard problem: Employment of mental simulation for prediction is observations such as activity on the already a crucial step World Wide Web. Pictured is a Malte Schilling and Holk Cruse visualization of one possible archive of E3812 Consciousness explained or consciousness redefined? data in network form. Such databases Shelley Anne Adamo are analyzed and used for scientific, business, and health purposes. Effective E3813 Insects cannot tell us anything about subjective experience or the origin use of these large databases of of consciousness information, collectively termed Big Brian Key, Robert Arlinghaus, and Howard I. Browman Data, requires identifying the causal E3814 Reply to Adamo, Key et al., and Schilling and Cruse: Crawling around the hard forces behind patterns in the data. Such problem of consciousness an effort was the focus of the Sackler Colin Klein and Andrew B. Barron Colloquium on Drawing Causal Inference from Big Data. See the OPINION—Leading scientists discuss current issues Introduction to the Colloquium papers by Richard M. Shiffrin on pages 7308– 7287 In the wake of Paris Agreement, scientists must embrace new directions for 7309. Image courtesy of Alexander climate change research Vasilyev/Shutterstock. Olivier Boucher, Valentin Bellassen, He´le`ne Benveniste, Philippe Ciais, Patrick Criqui, Ce´line Guivarch, Herve´ Le Treut, Sandrine Mathy, and Roland Se´fe´rian COMMENTARIES 7291 Strategies to overcome the hurdles to treat fibrosis, a major unmet clinical need Jagdeep Nanchahal and Boris Hinz See companion article on page E3901 7294 Role reversal: Liquid “Cheerios” on a solid sense each other Anand Jagota See companion article on page 7403 7296 Unraveling the mystery of the ring: Tracking heme dynamics in living cells Margaret C. Carpenter and Amy E. Palmer See companion article on page 7539 7298 Multifaceted role of E-cadherin in hepatitis C virus infection and pathogenesis Che C. Colpitts, Joachim Lupberger, and Thomas F. Baumert See companion article on page 7620 7301 Plants wait for the lights to change to red Paul F. Devlin See companion article on page 7667 Free online through the PNAS open access option. PNAS u July 5, 2016 u vol. 113 u no. 27 u iii–viii Downloaded by guest on September 24, 2021 PNAS PLUS PHYSICAL SCIENCES 7304 Significance Statements APPLIED PHYSICAL SCIENCES Brief statements written by the authors about the significance of 7399 Electrorheology leads to healthier and their papers. tastier chocolate Rongjia Tao, Hong Tang, Kazi Tawhid-Al-Islam, Enpeng Du, ARTHUR M. SACKLER COLLOQUIUM ON DRAWING and Jeongyoo Kim CAUSAL INFERENCE FROM BIG DATA 7403 Liquid drops attract or repel by the inverted Cheerios effect INTRODUCTION Stefan Karpitschka, Anupam Pandey, Luuk A. Lubbers, Joost H. 7308 Drawing causal inference from Big Data Weijs, Lorenzo Botto, Siddhartha Das, Bruno Andreotti, Richard M. Shiffrin and Jacco H. Snoeijer See Commentary on page 7294 COLLOQUIUM PAPERS + − 7491 A macroscopic H and Cl ions pump via 7310 Causal inference in economics and marketing reconstitution of EcClC membrane proteins Hal R. Varian in lipidic cubic mesophases 7316 Estimating peer effects in networks with peer Chiara Speziale, Livia Salvati Manni, Cristina Manatschal, encouragement designs Ehud M. Landau, and Raffaele Mezzenga Dean Eckles, Rene´ F. Kizilcec, and Eytan Bakshy 7323 Quantity discounts on a virtual good: The results CHEMISTRY of a massive pricing experiment at King 7408 Metallurgically lithiated SiO anode with high capacity Digital Entertainment x and ambient air compatibility Steven D. Levitt, John A. List, Susanne Neckermann, Jie Zhao, Hyun-Wook Lee, Jie Sun, Kai Yan, Yayuan and David Nelson Liu, Wei Liu, Zhenda Lu, Dingchang Lin, Guangmin Zhou, 7329 Characterizing treatment pathways at scale using the and Yi Cui OHDSI network 7414 Two-dimensional polyaniline (C3N) from carbonized George Hripcsak, Patrick B. Ryan, Jon D. Duke, Nigam H. organic single crystals in solid state Shah, Rae Woong Park, Vojtech Huser, Marc A. Suchard, Javeed Mahmood, Eun Kwang Lee, Minbok Jung, Martijn J. Schuemie, Frank J. DeFalco, Adler Perotte, Dongbin Shin, Hyun-Jung Choi, Jeong-Min Seo, Juan M. Banda, Christian G. Reich, Lisa M. Schilling, Sun-Min Jung, Dongwook Kim, Feng Li, Myoung Soo Michael E. Matheny, Daniella Meeker, Nicole Pratt, Lah, Noejung Park, Hyung-Joon Shin, Joon Hak Oh, and David Madigan and Jong-Beom Baek 7337 Inferring cortical function in the mouse visual system 7420 Multiscale simulations reveal key features of the through large-scale systems neuroscience proton-pumping mechanism in cytochrome Michael Hawrylycz, Costas Anastassiou, Anton Arkhipov, Jim c oxidase Berg, Michael Buice, Nicholas Cain, Nathan W. Gouwens, Sergey Gratiy, Ramakrishnan Iyer, Jung Hoon Lee, Stefan Ruibin Liang, Jessica M. J. Swanson, Yuxing Peng, Ma˚rten Mihalas, Catalin Mitelut, Shawn Olsen, R. Clay Reid, Corinne Wikstro¨m, and Gregory A. Voth Teeter, Saskia de Vries, Jack Waters, Hongkui Zeng, Christof Koch, and MindScope COMPUTER SCIENCES 7345 Causal inference and the data-fusion problem 7310 Causal inference in economics and marketing Elias Bareinboim and Judea Pearl Hal R. Varian 7353 Recursive partitioning for heterogeneous 7345 Causal inference and the data-fusion problem causal effects Elias Bareinboim and Judea Pearl Susan Athey and Guido Imbens 7391 Modeling confounding by half-sibling regression 7361 Methods for causal inference from gene perturbation Bernhard Scho¨lkopf, David W. Hogg, Dun Wang, experiments and validation Daniel Foreman-Mackey, Dominik Janzing, Carl-Johann Nicolai Meinshausen, Alain Hauser, Joris M. Mooij, Jonas Peters, Simon-Gabriel, and Jonas Peters Philip Versteeg, and Peter Bu¨hlmann 7369 Improving massive experiments with threshold blocking EARTH, ATMOSPHERIC, AND PLANETARY SCIENCES Michael J. Higgins, Fredrik Savje, and Jasjeet S. Sekhon ¨ 7426 Relative influence of meteorological conditions 7377 Linear mixed model for heritability estimation that and aerosols on the lifetime of mesoscale explicitly addresses environmental variation convective systems David Heckerman, Deepti Gurdasani, Carl Kadie, Cristina Sudip Chakraborty, Rong Fu, Steven T. Massie, Pomilla, Tommy Carstensen, Hilary Martin, Kenneth and Graeme Stephens Ekoru, Rebecca N. Nsubuga, Gerald Ssenyomo, Anatoli Kamali, Pontiano Kaleebu, Christian Widmer, 7432 Multiple sulfur-isotope signatures in Archean sulfates and Manjinder S. Sandhu and their implications for the chemistry and dynamics of the early atmosphere 7383 Lasso adjustments of treatment effect estimates in E´lodie Muller, Pascal Philippot, Claire Rollion-Bard, randomized experiments and Pierre Cartigny Adam Bloniarz, Hanzhong Liu, Cun-Hui Zhang, Jasjeet S. Sekhon, and Bin Yu 7391 Modeling confounding by half-sibling regression PHYSICS Bernhard Scho¨lkopf, David W. Hogg, Dun Wang, 7438 Elementary quantum mechanics of the neutron with an Daniel Foreman-Mackey, Dominik Janzing, Carl-Johann electric dipole moment Simon-Gabriel, and Jonas Peters Gordon Baym and D. H. Beck iv u www.pnas.org Contents Downloaded by guest on September 24, 2021 STATISTICS 7470 Placebo effects in cognitive training 7316 Estimating peer effects in networks with peer Cyrus K. Foroughi, Samuel S. Monfort, Martin Paczynski, encouragement designs Patrick E. McKnight, and P. M. Greenwood Dean Eckles, Rene´ F. Kizilcec, and Eytan Bakshy 7475 The base rate principle and the fairness principle in 7353 Recursive partitioning for heterogeneous social judgment causal effects Jack Cao and Mahzarin R. Banaji Susan Athey and Guido Imbens SOCIAL SCIENCES 7361 Methods for causal inference from gene perturbation experiments and validation 7316 Estimating peer effects in networks with peer Nicolai Meinshausen, Alain Hauser, Joris M. Mooij, Jonas Peters, encouragement designs Philip Versteeg, and Peter Bu¨hlmann Dean Eckles, Rene´ F. Kizilcec, and Eytan Bakshy 7369 Improving massive experiments with threshold blocking 7353 Recursive partitioning for heterogeneous Michael J. Higgins, Fredrik Sa¨vje, and Jasjeet S. Sekhon causal effects Susan Athey and Guido Imbens 7377 Linear mixed model for heritability estimation that explicitly addresses environmental variation 7383 Lasso adjustments of treatment effect estimates in David Heckerman, Deepti Gurdasani, Carl Kadie, Cristina randomized experiments Pomilla, Tommy Carstensen, Hilary Martin, Kenneth Adam Bloniarz, Hanzhong Liu, Cun-Hui Zhang, Jasjeet S. Ekoru, Rebecca N. Nsubuga, Gerald Ssenyomo, Sekhon, and Bin Yu Anatoli Kamali, Pontiano Kaleebu, Christian Widmer, 7481 Increasing instruction time in school does and Manjinder S. Sandhu increase learning 7383 Lasso adjustments of treatment effect estimates in Simon Calmar Andersen, Maria Knoth Humlum, randomized experiments and Anne Brink Nandrup Adam Bloniarz, Hanzhong Liu, Cun-Hui Zhang, Jasjeet S. Sekhon, and Bin Yu SUSTAINABILITY SCIENCE 7575 Global threat to agriculture from invasive species Dean R. Paini, Andy W. Sheppard, David C. Cook, Paul J. De Barro, Susan P. Worner, and Matthew B. Thomas SOCIAL SCIENCES ANTHROPOLOGY 7443 Geospatial modeling approach to monument BIOLOGICAL SCIENCES construction using