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Direct estimates of biomass burning NOx emissions and lifetimes using daily observations from TROPOMI 期刊论文
Atmospheric Chemistry and Physics, 2021
作者:  Xiaomeng Jin, Qindan Zhu, and Ronald C. Cohen
收藏  |  浏览/下载:14/0  |  提交时间:2021/11/15
Inverse modelling of carbonyl sulfide: implementation, evaluation and implications for the global budget 期刊论文
Atmospheric Chemistry and Physics, 2020
作者:  Jin Ma, Linda M. J. Kooijmans, Ara Cho, Stephen A. Montzka, Norbert Glatthor, John R. Worden, Le Kuai, Elliot L. Atlas, and Maarten C. Krol
收藏  |  浏览/下载:21/0  |  提交时间:2020/07/14
Distinct aerosol effects on cloud-to-ground lightning in the plateau and basin regions of Sichuan, Southwest China 期刊论文
Atmospheric Chemistry and Physics, 2020
作者:  Pengguo Zhao, Zhanqing Li, Hui Xiao, Fang Wu, Youtong Zheng, Maureen C. Cribb, Xiaoai Jin, and Yunjun Zhou
收藏  |  浏览/下载:6/0  |  提交时间:2020/06/22
Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease 期刊论文
NATURE, 2020, 577 (7788) : 103-+
作者:  Lalaoui, Najoua;  Boyden, Steven E.;  Oda, Hirotsugu;  Wood, Geryl M.;  Stone, Deborah L.;  Chau, Diep;  Liu, Lin;  Stoffels, Monique;  Kratina, Tobias;  Lawlor, Kate E.;  Zaal, Kristien J. M.;  Hoffmann, Patrycja M.;  Etemadi, Nima;  Shield-Artin, Kristy;  Biben, Christine;  Tsai, Wanxia Li;  Blake, Mary D.;  Kuehn, Hye Sun;  Yang, Dan;  Anderton, Holly;  Silke, Natasha;  Wachsmuth, Laurens;  Zheng, Lixin;  Moura, Natalia Sampaio;  Beck, David B.;  Gutierrez-Cruz, Gustavo;  Ombrello, Amanda K.;  Pinto-Patarroyo, Gineth P.;  Kueh, Andrew J.;  Herold, Marco J.;  Hall, Cathrine;  Wang, Hongying;  Chae, Jae Jin;  Dmitrieva, Natalia I.;  McKenzie, Mark;  Light, Amanda;  Barham, Beverly K.;  Jones, Anne;  Romeo, Tina M.;  Zhou, Qing;  Aksentijevich, Ivona;  Mullikin, James C.;  Gross, Andrew J.;  Shum, Anthony K.;  Hawkins, Edwin D.;  Masters, Seth L.;  Lenardo, Michael J.;  Boehm, Manfred;  Rosenzweig, Sergio D.;  Pasparakis, Manolis;  Voss, Anne K.;  Gadina, Massimo;  Kastner, Daniel L.;  Silke, John
收藏  |  浏览/下载:23/0  |  提交时间:2020/07/03

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term '  cleavage-resistant RIPK1-induced autoinflammatory syndrome'  . To define the mechanism for this disease, we generated a cleavage-resistant Ripk1(D325A) mutant mouse strain. Whereas Ripk1(-/-) mice died postnatally from systemic inflammation, Ripk1(D325A/D325A) mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1(D325A/D325A) embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1(D325A/D325A) and Ripk1(D325A/+) cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1(D325A/+) mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.


  
A lower X-gate in TASK channels traps inhibitors within the vestibule 期刊论文
NATURE, 2020
作者:  Chen, Tao;  Nomura, Kinya;  Wang, Xiaolin;  Sohrabi, Reza;  Xu, Jin;  Yao, Lingya;  Paasch, Bradley C.;  Ma, Li;  Kremer, James;  Cheng, Yuti;  Zhang, Li;  Wang, Nian;  Wang, Ertao;  Xin, Xiu-Fang;  He, Sheng Yang
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

TWIK-related acid-sensitive potassium (TASK) channels-members of the two pore domain potassium (K-2P) channel family-are found in neurons(1), cardiomyocytes(2-4) and vascular smooth muscle cells(5), where they are involved in the regulation of heart rate(6), pulmonary artery tone(5,7), sleep/wake cycles(8) and responses to volatile anaesthetics(8-11). K-2P channels regulate the resting membrane potential, providing background K+ currents controlled by numerous physiological stimuli(12-15). Unlike other K-2P channels, TASK channels are able to bind inhibitors with high affinity, exceptional selectivity and very slow compound washout rates. As such, these channels are attractive drug targets, and TASK-1 inhibitors are currently in clinical trials for obstructive sleep apnoea and atrial fibrillation(16). In general, potassium channels have an intramembrane vestibule with a selectivity filter situated above and a gate with four parallel helices located below  however, the K-2P channels studied so far all lack a lower gate. Here we present the X-ray crystal structure of TASK-1, and show that it contains a lower gate-which we designate as an '  X-gate'  -created by interaction of the two crossed C-terminal M4 transmembrane helices at the vestibule entrance. This structure is formed by six residues ((VLRFMT248)-V-243) that are essential for responses to volatile anaesthetics(10), neurotransmitters(13) and G-protein-coupled receptors(13). Mutations within the X-gate and the surrounding regions markedly affect both the channel-open probability and the activation of the channel by anaesthetics. Structures of TASK-1 bound to two high-affinity inhibitors show that both compounds bind below the selectivity filter and are trapped in the vestibule by the X-gate, which explains their exceptionally low washout rates. The presence of the X-gate in TASK channels explains many aspects of their physiological and pharmacological behaviour, which will be beneficial for the future development and optimization of TASK modulators for the treatment of heart, lung and sleep disorders.


The X-ray crystal structure of the potassium channel TASK-1 reveals the presence of an X-gate, which traps small-molecule inhibitors in the intramembrane vestibule and explains their low washout rates from the channel.


  
Pharmacologic fibroblast reprogramming into photoreceptors restores vision 期刊论文
NATURE, 2020, 581 (7806) : 83-+
作者:  Jiang, Mingkai;  Medlyn, Belinda E.;  Drake, John E.;  Duursma, Remko A.;  Anderson, Ian C.;  Barton, Craig V. M.;  Boer, Matthias M.;  Carrillo, Yolima;  Castaneda-Gomez, Laura;  Collins, Luke;  Crous, Kristine Y.;  De Kauwe, Martin G.;  dos Santos, Bruna M.;  Emmerson, Kathryn M.;  Facey, Sarah L.;  Gherlenda, Andrew N.;  Gimeno, Teresa E.;  Hasegawa, Shun;  Johnson, Scott N.;  Kannaste, Astrid;  Macdonald, Catriona A.;  Mahmud, Kashif;  Moore, Ben D.;  Nazaries, Loic;  Neilson, Elizabeth H. J.;  Nielsen, Uffe N.;  Niinemets, Ulo;  Noh, Nam Jin;  Ochoa-Hueso, Raul;  Pathare, Varsha S.;  Pendall, Elise;  Pihlblad, Johanna;  Pineiro, Juan;  Powell, Jeff R.;  Power, Sally A.;  Reich, Peter B.;  Renchon, Alexandre A.;  Riegler, Markus;  Rinnan, Riikka;  Rymer, Paul D.;  Salomon, Roberto L.;  Singh, Brajesh K.;  Smith, Benjamin;  Tjoelker, Mark G.;  Walker, Jennifer K. M.;  Wujeska-Klause, Agnieszka;  Yang, Jinyan;  Zaehle, Soenke;  Ellsworth, David S.
收藏  |  浏览/下载:45/0  |  提交时间:2020/07/03

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision(1,2). Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss  however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-kappa B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.


A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.


  
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.


  
Electrical manipulation of a topological antiferromagnetic state 期刊论文
NATURE, 2020, 580 (7805) : 608-+
作者:  Chabon, Jacob J.;  Hamilton, Emily G.;  Kurtz, David M.;  Esfahani, Mohammad S.;  Moding, Everett J.;  Stehr, Henning;  Schroers-Martin, Joseph;  Nabet, Barzin Y.;  Chen, Binbin;  Chaudhuri, Aadel A.;  Liu, Chih Long;  Hui, Angela B.;  Jin, Michael C.;  Azad, Tej D.;  Almanza, Diego;  Jeon, Young-Jun;  Nesselbush, Monica C.;  Keh, Lyron Co Ting;  Bonilla, Rene F.;  Yoo, Christopher H.;  Ko, Ryan B.;  Chen, Emily L.;  Merriott, David J.;  Massion, Pierre P.;  Mansfield, Aaron S.;  Jen, Jin;  Ren, Hong Z.;  Lin, Steven H.;  Costantino, Christina L.;  Burr, Risa;  Tibshirani, Robert;  Gambhir, Sanjiv S.;  Berry, Gerald J.;  Jensen, Kristin C.;  West, Robert B.;  Neal, Joel W.;  Wakelee, Heather A.;  Loo, Billy W., Jr.;  Kunder, Christian A.;  Leung, Ann N.;  Lui, Natalie S.;  Berry, Mark F.;  Shrager, Joseph B.;  Nair, Viswam S.;  Haber, Daniel A.;  Sequist, Lecia V.;  Alizadeh, Ash A.;  Diehn, Maximilian
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

Room-temperature electrical switching of a topological antiferromagnetic state in polycrystalline Mn3Sn thin films is demonstrated using the same protocol as that used for conventional ferromagnetic metals.


Electrical manipulation of phenomena generated by nontrivial band topology is essential for the development of next-generation technology using topological protection. A Weyl semimetal is a three-dimensional gapless system that hosts Weyl fermions as low-energy quasiparticles(1-4). It has various exotic properties, such as a large anomalous Hall effect (AHE) and chiral anomaly, which are robust owing to the topologically protected Weyl nodes(1-16). To manipulate such phenomena, a magnetic version of Weyl semimetals would be useful for controlling the locations of Weyl nodes in the Brillouin zone. Moreover, electrical manipulation of antiferromagnetic Weyl metals would facilitate the use of antiferromagnetic spintronics to realize high-density devices with ultrafast operation(17,18). However, electrical control of a Weyl metal has not yet been reported. Here we demonstrate the electrical switching of a topological antiferromagnetic state and its detection by the AHE at room temperature in a polycrystalline thin film(19) of the antiferromagnetic Weyl metal Mn3Sn9,10,12,20, which exhibits zero-field AHE. Using bilayer devices composed of Mn3Sn and nonmagnetic metals, we find that an electrical current density of about 10(10) to 10(11) amperes per square metre induces magnetic switching in the nonmagnetic metals, with a large change in Hall voltage. In addition, the current polarity along the bias field and the sign of the spin Hall angle of the nonmagnetic metals-positive for Pt (ref. (21)), close to 0 for Cu and negative for W (ref. (22))-determines the sign of the Hall voltage. Notably, the electrical switching in the antiferromagnet is achieved with the same protocol as that used for ferromagnetic metals(23,24). Our results may lead to further scientific and technological advances in topological magnetism and antiferromagnetic spintronics.


  
Simulation of Hubbard model physics in WSe2/WS2 moire superlattices 期刊论文
NATURE, 2020, 579 (7799) : 353-+
作者:  Stein, Reed M.;  Kang, Hye Jin;  McCorvy, John D.;  Glatfelter, Grant C.;  Jones, Anthony J.;  Che, Tao;  Slocum, Samuel;  Huang, Xi-Ping;  Savych, Olena;  Moroz, Yurii S.;  Stauch, Benjamin;  Johansson, Linda C.;  Cherezov, Vadim;  Kenakin, Terry;  Irwin, John J.;  Shoichet, Brian K.;  Roth, Bryan L.;  Dubocovich, Margarita L.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/03

Study of WSe2/WS2 moire superlattices reveals the phase diagram of the triangular-lattice Hubbard model, including a Mott insulating state at half-filling and a possible magnetic quantum phase transition near 0.6 filling.


The Hubbard model, formulated by physicist John Hubbard in the 1960s(1), is a simple theoretical model of interacting quantum particles in a lattice. The model is thought to capture the essential physics of high-temperature superconductors, magnetic insulators and other complex quantum many-body ground states(2,3). Although the Hubbard model provides a greatly simplified representation of most real materials, it is nevertheless difficult to solve accurately except in the one-dimensional case(2,3). Therefore, the physical realization of the Hubbard model in two or three dimensions, which can act as an analogue quantum simulator (that is, it can mimic the model and simulate its phase diagram and dynamics(4,5)), has a vital role in solving the strong-correlation puzzle, namely, revealing the physics of a large number of strongly interacting quantum particles. Here we obtain the phase diagram of the two-dimensional triangular-lattice Hubbard model by studying angle-aligned WSe2/WS2 bilayers, which form moire superlattices(6) because of the difference between the lattice constants of the two materials. We probe the charge and magnetic properties of the system by measuring the dependence of its optical response on an out-of-plane magnetic field and on the gate-tuned carrier density. At half-filling of the first hole moire superlattice band, we observe a Mott insulating state with antiferromagnetic Curie-Weiss behaviour, as expected for a Hubbard model in the strong-interaction regime(2,3,7-9). Above half-filling, our experiment suggests a possible quantum phase transition from an antiferromagnetic to a weak ferromagnetic state at filling factors near 0.6. Our results establish a new solid-state platform based on moire superlattices that can be used to simulate problems in strong-correlation physics that are described by triangular-lattice Hubbard models.


  
A distributional code for value in dopamine-based reinforcement learning 期刊论文
NATURE, 2020, 577 (7792) : 671-+
作者:  House, Robert A.;  Maitra, Urmimala;  Perez-Osorio, Miguel A.;  Lozano, Juan G.;  Jin, Liyu;  Somerville, James W.;  Duda, Laurent C.;  Nag, Abhishek;  Walters, Andrew;  Zhou, Ke-Jin;  Roberts, Matthew R.;  Bruce, Peter G.
收藏  |  浏览/下载:61/0  |  提交时间:2020/07/03

Since its introduction, the reward prediction error theory of dopamine has explained a wealth of empirical phenomena, providing a unifying framework for understanding the representation of reward and value in the brain(1-3). According to the now canonical theory, reward predictions are represented as a single scalar quantity, which supports learning about the expectation, or mean, of stochastic outcomes. Here we propose an account of dopamine-based reinforcement learning inspired by recent artificial intelligence research on distributional reinforcement learning(4-6). We hypothesized that the brain represents possible future rewards not as a single mean, but instead as a probability distribution, effectively representing multiple future outcomes simultaneously and in parallel. This idea implies a set of empirical predictions, which we tested using single-unit recordings from mouse ventral tegmental area. Our findings provide strong evidence for a neural realization of distributional reinforcement learning.


Analyses of single-cell recordings from mouse ventral tegmental area are consistent with a model of reinforcement learning in which the brain represents possible future rewards not as a single mean of stochastic outcomes, as in the canonical model, but instead as a probability distribution.