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Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition 期刊论文
NATURE, 2020, 577 (7790) : 421-+
作者:  Xue, Jenny Y.;  Zhao, Yulei;  Aronowitz, Jordan;  Mai, Trang T.;  Vides, Alberto;  Qeriqi, Besnik;  Kim, Dongsung;  Li, Chuanchuan;  de Stanchina, Elisa;  Mazutis, Linas;  Risso, Davide;  Lito, Piro
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

KRAS GTPases are activated in one-third of cancers, and KRAS(G12C) is one of the most common activating alterations in lung adenocarcinoma(1,2). KRAS(G12C) inhibitors(3,4) are in phase-I clinical trials and early data show partial responses in nearly half of patients with lung cancer. How cancer cells bypass inhibition to prevent maximal response to therapy is not understood. Because KRAS(G12C) cycles between an active and inactive conformation(4-6), and the inhibitors bind only to the latter, we tested whether isogenic cell populations respond in a non-uniform manner by studying the effect of treatment at a single-cell resolution. Here we report that, shortly after treatment, some cancer cells are sequestered in a quiescent state with low KRAS activity, whereas others bypass this effect to resume proliferation. This rapid divergent response occurs because some quiescent cells produce new KRAS(G12C) in response to suppressed mitogen-activated protein kinase output. New KRAS(G12C) is maintained in its active, drug-insensitive state by epidermal growth factor receptor and aurora kinase signalling. Cells without these adaptive changes-or cells in which these changes are pharmacologically inhibited-remain sensitive to drug treatment, because new KRAS(G12C) is either not available or exists in its inactive, drug-sensitive state. The direct targeting of KRAS oncoproteins has been a longstanding objective in precision oncology. Our study uncovers a flexible non-uniform fitness mechanism that enables groups of cells within a population to rapidly bypass the effect of treatment. This adaptive process must be overcome if we are to achieve complete and durable responses in the clinic.


  
Mapping the twist-angle disorder and Landau levels in magic-angle graphene 期刊论文
NATURE, 2020, 581 (7806) : 47-+
作者:  Luck, Katja;  39;Amata, Cassandra
收藏  |  浏览/下载:18/0  |  提交时间:2020/07/03

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG)(1,2) crucially depend on the interlayer twist angle, theta. Although control of the global theta with a precision of about 0.1 degrees has been demonstrated(1-7), little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip)(8) to obtain tomographic images of the Landau levels in the quantum Hall state(9) and to map the local theta variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moire periods. We find a correlation between the degree of theta disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in theta of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of theta generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of theta disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.


SQUID-on-tip tomographic imaging of Landau levels in magic-angle graphene provides nanoscale maps of local twist-angle disorder and shows that its properties are fundamentally different from common types of disorder.


  
Exploring dynamical phase transitions with cold atoms in an optical cavity 期刊论文
NATURE, 2020, 580 (7805) : 602-+
作者:  Halbach, Rebecca;  Miesen, Pascal;  Joosten, Joep;  Taskopru, Ezgi;  Rondeel, Inge;  Pennings, Bas;  Vogels, Chantal B. F.;  Merkling, Sarah H.;  Koenraadt, Constantianus J.;  Lambrechts, Louis;  van Rij, Ronald P.
收藏  |  浏览/下载:22/0  |  提交时间:2020/07/03

Interactions between light and an ensemble of strontium atoms in an optical cavity can serve as a testbed for studying dynamical phase transitions, which are currently not well understood.


Interactions between atoms and light in optical cavities provide a means of investigating collective (many-body) quantum physics in controlled environments. Such ensembles of atoms in cavities have been proposed for studying collective quantum spin models, where the atomic internal levels mimic a spin degree of freedom and interact through long-range interactions tunable by changing the cavity parameters(1-4). Non-classical steady-state phases arising from the interplay between atom-light interactions and dissipation of light from the cavity have previously been investigated(5-11). These systems also offer the opportunity to study dynamical phases of matter that are precluded from existence at equilibrium but can be stabilized by driving a system out of equilibrium(12-16), as demonstrated by recent experiments(17-22). These phases can also display universal behaviours akin to standard equilibrium phase transitions(8,23,24). Here, we use an ensemble of about a million strontium-88 atoms in an optical cavity to simulate a collective Lipkin-Meshkov-Glick model(25,26), an iconic model in quantum magnetism, and report the observation of distinct dynamical phases of matter in this system. Our system allows us to probe the dependence of dynamical phase transitions on system size, initial state and other parameters. These observations can be linked to similar dynamical phases in related systems, including the Josephson effect in superfluid helium(27), or coupled atomic(28) and solid-state polariton(29) condensates. The system itself offers potential for generation of metrologically useful entangled states in optical transitions, which could permit quantum enhancement in state-of-the-art atomic clocks(30,31).


  
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:30/0  |  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 mechanism of ferritin crystallization revealed by cryo-STEM tomography 期刊论文
NATURE, 2020, 579 (7800) : 540-+
作者:  van Gastel, Nick;  Stegen, Steve;  Eelen, Guy;  Schoors, Sandra;  Carlier, Aurelie;  Daniels, Veerle W.;  Baryawno, Ninib;  Przybylski, Dariusz;  Depypere, Maarten;  Stiers, Pieter-Jan;  Lambrechts, Dennis;  Van Looveren, Riet;  Torrekens, Sophie
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Protein crystallization is important in structural biology, disease research and pharmaceuticals. It has recently been recognized that nonclassical crystallization involving initial formation of an amorphous precursor phase-occurs often in protein, organic and inorganic crystallization processes(1-5). A two-step nucleation theory has thus been proposed, in which initial low-density, solvated amorphous aggregates subsequently densify, leading to nucleation(4,6,7). This view differs from classical nucleation theory, which implies that crystalline nuclei forming in solution have the same density and structure as does the final crystalline state(1). A protein crystallization mechanism involving this classical pathway has recently been observed directly(8). However, a molecular mechanism of nonclassical protein crystallization(9-15) has not been established(9,11,14). To determine the nature of the amorphous precursors and whether crystallization takes place within them (and if so, how order develops at the molecular level), three-dimensional (3D) molecular-level imaging of a crystallization process is required. Here we report cryogenic scanning transmission microscopy tomography of ferritin aggregates at various stages of crystallization, followed by 3D reconstruction using simultaneous iterative reconstruction techniques to provide a 3D picture of crystallization with molecular resolution. As crystalline order gradually increased in the studied aggregates, they exhibited an increase in both order and density from their surface towards their interior. We observed no highly ordered small structures typical of a classical nucleation process, and occasionally we observed several ordered domains emerging within one amorphous aggregate, a phenomenon not predicted by either classical or two-step nucleation theories. Our molecular-level analysis hints at desolvation as the driver of the continuous order-evolution mechanism, a view that goes beyond current nucleation models, yet is consistent with a broad spectrum of protein crystallization mechanisms.


  
Observations of grain-boundary phase transformations in an elemental metal 期刊论文
NATURE, 2020, 579 (7799) : 375-+
作者:  Valente, Luis;  Phillimore, Albert B.;  Melo, Martim;  Warren, Ben H.;  Clegg, Sonya M.;  Havenstein, Katja;  Tiedemann, Ralph;  Illera, Juan Carlos;  Thebaud, Christophe;  Aschenbach, Tina;  Etienne, Rampal S.
收藏  |  浏览/下载:30/0  |  提交时间:2020/07/03

Atomic-resolution observations combined with simulations show that grain boundaries within elemental copper undergo temperature-induced solid-state phase transformation to different structures  grain boundary phases can also coexist and are kinetically trapped structures.


The theory of grain boundary (the interface between crystallites, GB) structure has a long history(1) and the concept of GBs undergoing phase transformations was proposed 50 years ago(2,3). The underlying assumption was that multiple stable and metastable states exist for different GB orientations(4-6). The terminology '  complexion'  was recently proposed to distinguish between interfacial states that differ in any equilibrium thermodynamic property(7). Different types of complexion and transitions between complexions have been characterized, mostly in binary or multicomponent systems(8-19). Simulations have provided insight into the phase behaviour of interfaces and shown that GB transitions can occur in many material systems(20-24). However, the direct experimental observation and transformation kinetics of GBs in an elemental metal have remained elusive. Here we demonstrate atomic-scale GB phase coexistence and transformations at symmetric and asymmetric [111 over bar ] tilt GBs in elemental copper. Atomic-resolution imaging reveals the coexistence of two different structures at sigma 19b GBs (where sigma 19 is the density of coincident sites and b is a GB variant), in agreement with evolutionary GB structure search and clustering analysis(21,25,26). We also use finite-temperature molecular dynamics simulations to explore the coexistence and transformation kinetics of these GB phases. Our results demonstrate how GB phases can be kinetically trapped, enabling atomic-scale room-temperature observations. Our work paves the way for atomic-scale in situ studies of metallic GB phase transformations, which were previously detected only indirectly(9,15,27-29), through their influence on abnormal grain growth, non-Arrhenius-type diffusion or liquid metal embrittlement.


  
Spontaneous gyrotropic electronic order in a transition-metal dichalcogenide 期刊论文
NATURE, 2020, 578 (7796) : 545-+
作者:  Kum, Hyun S.;  Lee, Hyungwoo;  Kim, Sungkyu;  Lindemann, Shane;  Kong, Wei;  Qiao, Kuan;  Chen, Peng;  Irwin, Julian;  Lee, June Hyuk;  Xie, Saien;  Subramanian, Shruti;  Shim, Jaewoo;  Bae, Sang-Hoon;  Choi, Chanyeol;  Ranno, Luigi;  Seo, Seungju;  Lee, Sangho;  Bauer, Jackson;  Li, Huashan;  Lee, Kyusang;  Robinson, Joshua A.;  Ross, Caroline A.;  Schlom, Darrell G.;  Rzchowski, Mark S.;  Eom, Chang-Beom;  Kim, Jeehwan
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Chirality is ubiquitous in nature, and populations of opposite chiralities are surprisingly asymmetric at fundamental levels(1,2). Examples range from parity violation in the subatomic weak force to homochirality in biomolecules. The ability to achieve chirality-selective synthesis (chiral induction) is of great importance in stereochemistry, molecular biology and pharmacology(2). In condensed matter physics, a crystalline electronic system is geometrically chiral when it lacks mirror planes, space-inversion centres or rotoinversion axes(1). Typically, geometrical chirality is predefined by the chiral lattice structure of a material, which is fixed on formation of the crystal. By contrast, in materials with gyrotropic order(3-6), electrons spontaneously organize themselves to exhibit macroscopic chirality in an originally achiral lattice. Although such order-which has been proposed as the quantum analogue of cholesteric liquid crystals-has attracted considerable interest(3-15), no clear observation or manipulation of gyrotropic order has been achieved so far. Here we report the realization of optical chiral induction and the observation of a gyrotropically ordered phase in the transition-metal dichalcogenide semimetal 1T-TiSe2. We show that shining mid-infrared circularly polarized light on 1T-TiSe2 while cooling it below the critical temperature leads to the preferential formation of one chiral domain. The chirality of this state is confirmed by the measurement of an out-of-plane circular photogalvanic current, the direction of which depends on the optical induction. Although the role of domain walls requires further investigation with local probes, the methodology demonstrated here can be applied to realize and control chiral electronic phases in other quantum materials(4,16).


Optical chiral induction and spontaneous gyrotropic electronic order are realized in the transition-metal chalcogenide 1T-TiSe2 by using illumination with mid-infrared circularly polarized light and simultaneous cooling below the critical temperature.


  
Spin current from sub-terahertz-generated antiferromagnetic magnons 期刊论文
NATURE, 2020, 578 (7793) : 70-+
作者:  Zemp, M.;  Huss, M.;  Thibert, E.;  Eckert, N.;  McNabb, R.;  Huber, J.;  Barandun, M.;  Machguth, H.;  Nussbaumer, S. U.;  Gartner-Roer, I.;  Thomson, L.;  Paul, F.;  Maussion, F.;  Kutuzov, S.;  Cogley, J. G.
收藏  |  浏览/下载:54/0  |  提交时间:2020/07/03

Pure spin currents are simultaneously generated and detected electrically through sub-terahertz magnons in the antiferromagnetic insulator Cr2O3, demonstrating the potential of magnon excitations in antiferromagnets for high-frequency spintronic devices.


Spin dynamics in antiferromagnets has much shorter timescales than in ferromagnets, offering attractive properties for potential applications in ultrafast devices(1-3). However, spin-current generation via antiferromagnetic resonance and simultaneous electrical detection by the inverse spin Hall effect in heavy metals have not yet been explicitly demonstrated(4-6). Here we report sub-terahertz spin pumping in heterostructures of a uniaxial antiferromagnetic Cr2O3 crystal and a heavy metal (Pt or Ta in its beta phase). At 0.240 terahertz, the antiferromagnetic resonance in Cr2O3 occurs at about 2.7 tesla, which excites only right-handed magnons. In the spin-canting state, another resonance occurs at 10.5 tesla from the precession of induced magnetic moments. Both resonances generate pure spin currents in the heterostructures, which are detected by the heavy metal as peaks or dips in the open-circuit voltage. The pure-spin-current nature of the electrically detected signals is unambiguously confirmed by the reversal of the voltage polarity observed under two conditions: when switching the detector metal from Pt to Ta, reversing the sign of the spin Hall angle(7-9), and when flipping the magnetic-field direction, reversing the magnon chirality(4,5). The temperature dependence of the electrical signals at both resonances suggests that the spin current contains both coherent and incoherent magnon contributions, which is further confirmed by measurements of the spin Seebeck effect and is well described by a phenomenological theory. These findings reveal the unique characteristics of magnon excitations in antiferromagnets and their distinctive roles in spin-charge conversion in the high-frequency regime.


  
Synchrotron infrared spectroscopic evidence of the probable transition to metal hydrogen 期刊论文
NATURE, 2020, 577 (7792) : 631-+
作者:  Zhuang, Zhe;  Yu, Jin-Quan
收藏  |  浏览/下载:33/0  |  提交时间:2020/07/03

Hydrogen has been an essential element in the development of atomic, molecular and condensed matter physics(1). It is predicted that hydrogen should have a metal state(2)  however, understanding the properties of dense hydrogen has been more complex than originally thought, because under extreme conditions the electrons and protons are strongly coupled to each other and ultimately must both be treated as quantum particles(3,4). Therefore, how and when molecular solid hydrogen may transform into a metal is an open question. Although the quest for metal hydrogen has pushed major developments in modern experimental high-pressure physics, the various claims of its observation remain unconfirmed(5-7). Here a discontinuous change of the direct bandgap of hydrogen, from 0.6 electronvolts to below 0.1 electronvolts, is observed near 425 gigapascals. This result is most probably associated with the formation of the metallic state because the nucleus zero-point energy is larger than this lowest bandgap value. Pressures above 400 gigapascals are achieved with the recently developed toroidal diamond anvil cell(8), and the structural changes and electronic properties of dense solid hydrogen at 80 kelvin are probed using synchrotron infrared absorption spectroscopy. The continuous downward shifts of the vibron wavenumber and the direct bandgap with increased pressure point to the stability of phase-III hydrogen up to 425 gigapascals. The present data suggest that metallization of hydrogen proceeds within the molecular solid, in good agreement with previous calculations that capture many-body electronic correlations(9).


  
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:68/0  |  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.