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英学者建议《欧洲气候法》建立独立的专家咨询机制 快报文章
气候变化快报,2020年第18期
作者:  裴惠娟
Microsoft Word(16Kb)  |  收藏  |  浏览/下载:397/0  |  提交时间:2020/09/20
European Climate Law  Independent Expert Advisory Mechanism  Design  
Structure of the human metapneumovirus polymerase phosphoprotein complex 期刊论文
NATURE, 2020, 577 (7789) : 275-+
作者:  Pan, Junhua;  Qian, Xinlei;  Lattmann, Simon;  El Sahili, Abbas;  Yeo, Tiong Han;  Jia, Huan;  Cressey, Tessa;  Ludeke, Barbara;  Noton, Sarah;  Kalocsay, Marian;  Fearns, Rachel;  Lescar, Julien
收藏  |  浏览/下载:38/0  |  提交时间:2020/07/03

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults(1). No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities(2,3). How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 angstrom(2) of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a '  folding-upon-partner-binding'  mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.


  
Can designs inspired by control theory keep deployment policies effective and cost-efficient as technology prices fall? 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2020, 15 (4)
作者:  Nunez-Jimenez, Alejandro;  Knoeri, Christof;  Hoppmann, Joern;  Hoffmann, Volker H.
收藏  |  浏览/下载:41/0  |  提交时间:2020/07/02
policy design  clean energy  deployment policy  agent-based model  feed-in tariff  adjustment mechanism  solar photovoltaics  
Structure of M-pro from SARS-CoV-2 and discovery of its inhibitors 期刊论文
NATURE, 2020, 582 (7811) : 289-+
作者:  Li, Nan;  Jasanoff, Alan
收藏  |  浏览/下载:26/0  |  提交时间:2020/07/03

A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.


A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019-2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)(1-4). Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (M-pro) of SARS-CoV-2: M-pro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-2(5,6). We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of M-pro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds-including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds-as inhibitors of M-pro. Six of these compounds inhibited M-pro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 mu M. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.


  
Dualities and non-Abelian mechanics 期刊论文
NATURE, 2020, 577 (7792) : 636-+
作者:  Song, Xinyang;  Sun, Ximei;  Oh, Sungwhan F.;  Wu, Meng;  Zhang, Yanbo;  Zheng, Wen;  Geva-Zatorsky, Naama;  Jupp, Ray;  Mathis, Diane;  Benoist, Christophe;  Kasper, Dennis L.
收藏  |  浏览/下载:31/0  |  提交时间:2020/07/03

Dualities-mathematical mappings between different systems-can act as hidden symmetries that enable materials design beyond that suggested by crystallographic space groups.


Dualities are mathematical mappings that reveal links between apparently unrelated systems in virtually every branch of physics(1-8). Systems mapped onto themselves by a duality transformation are called self-dual and exhibit remarkable properties, as exemplified by the scale invariance of an Ising magnet at the critical point. Here we show how dualities can enhance the symmetries of a dynamical matrix (or Hamiltonian), enabling the design of metamaterials with emergent properties that escape a standard group theory analysis. As an illustration, we consider twisted kagome lattices(9-15), reconfigurable mechanical structures that change shape by means of a collapse mechanism(9). We observe that pairs of distinct configurations along the mechanism exhibit the same vibrational spectrum and related elastic moduli. We show that these puzzling properties arise from a duality between pairs of configurations on either side of a mechanical critical point. The critical point corresponds to a self-dual structure with isotropic elasticity even in the absence of spatial symmetries and a twofold-degenerate spectrum over the entire Brillouin zone. The spectral degeneracy originates from a version of Kramers'  theorem(16,17) in which fermionic time-reversal invariance is replaced by a hidden symmetry emerging at the self-dual point. The normal modes of the self-dual systems exhibit non-Abelian geometric phases(18,19) that affect the semiclassical propagation of wavepackets(20), leading to non-commuting mechanical responses. Our results hold promise for holonomic computation(21) and mechanical spintronics by allowing on-the-fly manipulation of synthetic spins carried by phonons.


  
Li metal deposition and stripping in a solid-state battery via Coble creep 期刊论文
NATURE, 2020, 578 (7794) : 251-+
作者:  Helmrich, S.;  Arias, A.;  Lochead, G.;  Wintermantel, T. M.;  Buchhold, M.;  Diehl, S.;  Whitlock, S.
收藏  |  浏览/下载:71/0  |  提交时间:2020/07/03

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be(1,2) up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 10(10) MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1x excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.


By containing lithium metal within oriented tubes of a mixed ionic-electronic conductor, a 3D anode for lithium metal batteries is produced that overcomes chemomechanical stability issues at the electrolyte interface.


  
The Bobolink Project: Selling Public Goods From Ecosystem Services Using Provision Point Mechanisms 期刊论文
ECOLOGICAL ECONOMICS, 2018, 143: 236-252
作者:  Swallow, Stephen K.;  Anderson, Christopher M.;  Uchida, Emi
收藏  |  浏览/下载:19/0  |  提交时间:2019/04/09
Cultural  Ecosystem service aggregator  Field experiments  Birds  Grassland habitat  Framing effects  Environmental stewardship  Mechanism design