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Internal state dynamics shape brainwide activity and foraging behaviour 期刊论文
NATURE, 2020, 577 (7789) : 239-+
作者:  Marques, Joao C.;  Li, Meng;  Schaak, Diane;  Robson, Drew N.;  Li, Jennifer M.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

The brain has persistent internal states that can modulate every aspect of an animal'  s mental experience(1-4). In complex tasks such as foraging, the internal state is dynamic(5-8). Caenorhabditis elegans alternate between local search and global dispersal(5). Rodents and primates exhibit trade-offs between exploitation and exploration(6,7). However, fundamental questions remain about how persistent states are maintained in the brain, which upstream networks drive state transitions and how state-encoding neurons exert neuromodulatory effects on sensory perception and decision-making to govern appropriate behaviour. Here, using tracking microscopy to monitor whole-brain neuronal activity at cellular resolution in freely moving zebrafish larvae(9), we show that zebrafish spontaneously alternate between two persistent internal states during foraging for live prey (Paramecia). In the exploitation state, the animal inhibits locomotion and promotes hunting, generating small, localized trajectories. In the exploration state, the animal promotes locomotion and suppresses hunting, generating long-ranging trajectories that enhance spatial dispersion. We uncover a dorsal raphe subpopulation with persistent activity that robustly encodes the exploitation state. The exploitation-state-encoding neurons, together with a multimodal trigger network that is associated with state transitions, form a stochastically activated nonlinear dynamical system. The activity of this oscillatory network correlates with a global retuning of sensorimotor transformations during foraging that leads to marked changes in both the motivation to hunt for prey and the accuracy of motor sequences during hunting. This work reveals an important hidden variable that shapes the temporal structure of motivation and decision-making.


  
Accelerated discovery of CO2 electrocatalysts using active machine learning 期刊论文
NATURE, 2020, 581 (7807) : 178-+
作者:  Lan, Jun;  Ge, Jiwan;  Yu, Jinfang;  Shan, Sisi;  Zhou, Huan;  Fan, Shilong;  Zhang, Qi;  Shi, Xuanling;  Wang, Qisheng;  Zhang, Linqi;  Wang, Xinquan
收藏  |  浏览/下载:88/0  |  提交时间:2020/07/03

The rapid increase in global energy demand and the need to replace carbon dioxide (CO2)-emitting fossil fuels with renewable sources have driven interest in chemical storage of intermittent solar and wind energy(1,2). Particularly attractive is the electrochemical reduction of CO2 to chemical feedstocks, which uses both CO2 and renewable energy(3-8). Copper has been the predominant electrocatalyst for this reaction when aiming for more valuable multi-carbon products(9-16), and process improvements have been particularly notable when targeting ethylene. However, the energy efficiency and productivity (current density) achieved so far still fall below the values required to produce ethylene at cost-competitive prices. Here we describe Cu-Al electrocatalysts, identified using density functional theory calculations in combination with active machine learning, that efficiently reduce CO2 to ethylene with the highest Faradaic efficiency reported so far. This Faradaic efficiency of over 80 per cent (compared to about 66 per cent for pure Cu) is achieved at a current density of 400 milliamperes per square centimetre (at 1.5 volts versus a reversible hydrogen electrode) and a cathodic-side (half-cell) ethylene power conversion efficiency of 55 +/- 2 per cent at 150 milliamperes per square centimetre. We perform computational studies that suggest that the Cu-Al alloys provide multiple sites and surface orientations with near-optimal CO binding for both efficient and selective CO2 reduction(17). Furthermore, in situ X-ray absorption measurements reveal that Cu and Al enable a favourable Cu coordination environment that enhances C-C dimerization. These findings illustrate the value of computation and machine learning in guiding the experimental exploration of multi-metallic systems that go beyond the limitations of conventional single-metal electrocatalysts.


  
Short-range order and its impact on the CrCoNi medium-entropy alloy 期刊论文
NATURE, 2020, 581 (7808) : 283-+
作者:  Tan, Hwei-Ee;  Sisti, Alexander C.;  Jin, Hao;  Vignovich, Martin;  Villavicencio, Miguel;  Tsang, Katherine S.;  Goffer, Yossef;  Zuker, Charles S.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Traditional metallic alloys are mixtures of elements in which the atoms of minority species tend to be distributed randomly if they are below their solubility limit, or to form secondary phases if they are above it. The concept of multiple-principal-element alloys has recently expanded this view, as these materials are single-phase solid solutions of generally equiatomic mixtures of metallic elements. This group of materials has received much interest owing to their enhanced mechanical properties(1-5). They are usually called medium-entropy alloys in ternary systems and high-entropy alloys in quaternary or quinary systems, alluding to their high degree of configurational entropy. However, the question has remained as to how random these solid solutions actually are, with the influence of short-range order being suggested in computational simulations but not seen experimentally(6,7). Here we report the observation, using energy-filtered transmission electron microscopy, of structural features attributable to short-range order in the CrCoNi medium-entropy alloy. Increasing amounts of such order give rise to both higher stacking-fault energy and hardness. These findings suggest that the degree of local ordering at the nanometre scale can be tailored through thermomechanical processing, providing a new avenue for tuning the mechanical properties of medium- and high-entropy alloys.


Metal alloys consisting of three or more major elemental components show enhanced mechanical properties, which are now shown to be correlated with short-range order observed with electron microscopy.


  
Late-stage oxidative C(sp(3))-H methylation 期刊论文
NATURE, 2020, 580 (7805) : 621-+
作者:  Fessler, Evelyn;  Eckl, Eva-Maria;  Schmitt, Sabine;  Mancilla, Igor Alves;  Meyer-Bender, Matthias F.;  Hanf, Monika;  Philippou-Massier, Julia;  Krebs, Stefan;  Zischka, Hans;  Jae, Lucas T.
收藏  |  浏览/下载:46/0  |  提交时间:2020/07/03

Frequently referred to as the '  magic methyl effect'  , the installation of methyl groups-especially adjacent (alpha) to heteroatoms-has been shown to dramatically increase the potency of biologically active molecules(1-3). However, existing methylation methods show limited scope and have not been demonstrated in complex settings(1). Here we report a regioselective and chemoselective oxidative C(sp(3))-H methylation method that is compatible with late-stage functionalization of drug scaffolds and natural products. This combines a highly site-selective and chemoselective C-H hydroxylation with a mild, functional-group-tolerant methylation. Using a small-molecule manganese catalyst, Mn(CF3PDP), at low loading (at a substrate/catalyst ratio of 200) affords targeted C-H hydroxylation on heterocyclic cores, while preserving electron-neutral and electron-rich aryls. Fluorine- or Lewis-acid-assisted formation of reactive iminium or oxonium intermediates enables the use of a mildly nucleophilic organoaluminium methylating reagent that preserves other electrophilic functionalities on the substrate. We show this late-stage C(sp(3))-H methylation on 41 substrates housing 16 different medicinally important cores that include electron-rich aryls, heterocycles, carbonyls and amines. Eighteen pharmacologically relevant molecules with competing sites-including drugs (for example, tedizolid) and natural products-are methylated site-selectively at the most electron rich, least sterically hindered position. We demonstrate the syntheses of two magic methyl substrates-an inverse agonist for the nuclear receptor RORc and an antagonist of the sphingosine-1-phosphate receptor-1-via late-stage methylation from the drug or its advanced precursor. We also show a remote methylation of the B-ring carbocycle of an abiraterone analogue. The ability to methylate such complex molecules at late stages will reduce synthetic effort and thereby expedite broader exploration of the magic methyl effect in pursuit of new small-molecule therapeutics and chemical probes.


A manganese-catalysed oxidative C(sp(3))-H methylation method allows a methyl group to be selectively installed into medicinally important heterocycles, providing a way to improve pharmaceuticals and better understand the '  magic methyl effect'  .


  
Microbiome analyses of blood and tissues suggest cancer diagnostic approach 期刊论文
NATURE, 2020, 579 (7800) : 567-+
作者:  Shao, Zhengping;  Flynn, Ryan A.;  Crowe, Jennifer L.;  Zhu, Yimeng;  Liang, Jialiang;  Jiang, Wenxia;  Aryan, Fardin;  Aoude, Patrick;  Bertozzi, Carolyn R.;  Estes, Verna M.;  Lee, Brian J.;  Bhagat, Govind;  Zha, Shan;  Calo, Eliezer
收藏  |  浏览/下载:54/0  |  提交时间:2020/07/03

Microbial nucleic acids are detected in samples of tissues and blood from more than 10,000 patients with cancer, and machine learning is used to show that these can be used to discriminate between and among different types of cancer, suggesting a new microbiome-based diagnostic approach.


Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions(1-10), we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas(11) (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma  100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.


  
Imaging magnetic polarons in the doped Fermi-Hubbard model 期刊论文
NATURE, 2019, 572 (7769) : 358-+
作者:  Koepsell, Joannis;  Vijayan, Jayadev;  Sompet, Pimonpan;  Grusdt, Fabian;  Hilker, Timon A.;  Demler, Eugene;  Salomon, Guillaume;  Bloch, Immanuel;  Gross, Christian
收藏  |  浏览/下载:4/0  |  提交时间:2019/11/27
Tripled yield in direct-drive laser fusion through statistical modelling 期刊论文
NATURE, 2019, 565 (7741) : 581-+
作者:  Gopalaswamy, V.;  Betti, R.;  Knauer, J. P.;  Luciani, N.;  Patel, D.;  Woo, K. M.;  Bose, A.;  Igumenshchev, I. V.;  Campbell, E. M.;  Anderson, K. S.;  Bauer, K. A.;  Bonino, M. J.;  Cao, D.;  Christopherson, A. R.;  Collins, G. W.;  Collins, T. J. B.;  Davies, J. R.;  Delettrez, J. A.;  Edgell, D. H.;  Epstein, R.;  Forrest, C. J.;  Froula, D. H.;  Glebov, V. Y.;  Goncharov, V. N.;  Harding, D. R.;  Hu, S. X.;  Jacobs-Perkins, D. W.;  Janezic, R. T.;  Kelly, J. H.;  Mannion, O. M.;  Maximov, A.;  Marshall, F. J.;  Michel, D. T.;  Miller, S.;  Morse, S. F. B.;  Palastro, J.;  Peebles, J.;  Radha, P. B.;  Regan, S. P.;  Sampat, S.;  Sangster, T. C.;  Sefkow, A. B.;  Seka, W.;  Shah, R. C.;  Shmyada, W. T.;  Shvydky, A.;  Stoeckl, C.;  Solodov, A. A.;  Theobald, W.;  Zuegel, J. D.;  Johnson, M. Gatu;  Petrasso, R. D.;  Li, C. K.;  Frenje, J. A.
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
A low-spin Fe(III) complex with 100-ps ligand-to-metal charge transfer photoluminescence 期刊论文
NATURE, 2017, 543 (7647) : 695-+
作者:  Chabera, Pavel;  Liu, Yizhu;  Prakash, Om;  Thyrhaug, Erling;  El Nahhas, Amal;  Honarfar, Alireza;  Essen, Sofia;  Fredin, Lisa A.;  Harlang, Tobias C. B.;  Kjaer, Kasper S.;  Handrup, Karsten;  Ericson, Fredric;  Tatsuno, Hideyuki;  Morgan, Kelsey;  Schnadt, Joachim;  Haggstrom, Lennart;  Ericsson, Tore;  Sobkowiak, Adam;  Lidin, Sven;  Huang, Ping;  Styring, Stenbjorn;  Uhlig, Jens;  Bendix, Jesper;  Lomoth, Reiner;  Sundstrom, Villy;  Persson, Petter;  Warnmark, Kenneth
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09