Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nature ; 575(7781): 217-223, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31666701

RESUMO

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling protein in tumours1,2. The KRAS(G12C) mutant has a cysteine residue that has been exploited to design covalent inhibitors that have promising preclinical activity3-5. Here we optimized a series of inhibitors, using novel binding interactions to markedly enhance their potency and selectivity. Our efforts have led to the discovery of AMG 510, which is, to our knowledge, the first KRAS(G12C) inhibitor in clinical development. In preclinical analyses, treatment with AMG 510 led to the regression of KRASG12C tumours and improved the anti-tumour efficacy of chemotherapy and targeted agents. In immune-competent mice, treatment with AMG 510 resulted in a pro-inflammatory tumour microenvironment and produced durable cures alone as well as in combination with immune-checkpoint inhibitors. Cured mice rejected the growth of isogenic KRASG12D tumours, which suggests adaptive immunity against shared antigens. Furthermore, in clinical trials, AMG 510 demonstrated anti-tumour activity in the first dosing cohorts and represents a potentially transformative therapy for patients for whom effective treatments are lacking.

2.
Inorg Chem ; 58(19): 13440-13445, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31556288

RESUMO

Thin films have attracted much interest because they often have novel properties different from those of their bulk counterparts. In this work, we tune two metastable states in three kinds of lanthanum cobalt oxide thin films by electron beam irradiation and record their dynamic transition process in situ in a transmission electron microscope. The lanthanum cobalt oxide thin films exhibit a homogeneous microstructure in the initial state and then transfer to a stripelike superstructure with 3a0 periodicity (a0 is the perovskite lattice parameter), further developing into a superstructure with 2a0 periodicity in dark stripes (brownmillerite structure). To explore the inherent energy discrepancy within the two metastable states, we perform first-principles calculations on a LaCoO3-δ (0 ≤ δ ≤ 0.5) thin film system by geometry optimization. The calculation results suggest that the forming energy of the 3a0 periodicity stripelike structure is a little lower than that of the 2a0 periodicity in the LaCoO3-δ thin film. Our work explains why the two stripelike structures coexist in lanthanum cobalt oxide thin films and extends prospective applications related to oxygen vacancies in thin films.

3.
ACS Appl Mater Interfaces ; 11(40): 36800-36806, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31539219

RESUMO

The oxygen vacancy profile in LaCoO3 exhibits rich phases with distinct structures, symmetries, and magnetic properties. Exploration of the lattice degree of freedom of LaCoO3 in the transition between these different structural phases may provide a route to enable new functionality in oxide materials with potential applications. To date, the oxygen vacancy profile transition in LaCoO3 has mainly been induced by transition-metal doping or thermal treatment. Epitaxial strain was proposed to compete with the lattice degree of freedom but has not yet been rationalized. Here, the experimental findings of strain-inhibited structural transition from perovskite to brownmillerite during the electromigration of oxygen vacancies in epitaxial LaCoO3 thin films are demonstrated. The results indicate that the oxygen vacancy ordering phase induced by the electric field is suppressed locally by both epitaxial strain field and external loads shown by in situ aberration-corrected (scanning)/ transmission electron microscopy. The demonstrated complex interplay between the electric and strain fields in the structural transitions of LaCoO3 opens up prospects for manipulating new physical properties by external excitations and/or strain engineering of a substrate.

4.
ACS Appl Mater Interfaces ; 11(21): 19584-19595, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31056893

RESUMO

Manipulation of oxygen vacancies via electric-field-controlled ionic liquid gating has been reported in many model systems within the emergent fields of oxide electronics and iontronics. It is then significant to investigate the oxygen vacancy formation/annihilation and migration across an additional ferroelectric layer with ionic liquid gating. Here, we report that via a combination of ionic liquid and ferroelectric gating, the remote control of oxygen vacancies and magnetic phase transition can be achieved in SrCoO2.5 films capped with an ultrathin ferroelectric BaTiO3 layer at room temperature. The ultrathin BaTiO3 layer acts as an atomic oxygen valve and is semitransparent to oxygen-ion transport due to the competing interaction between vertical electron tunneling and ferroelectric polarization plus surface electrochemical changes in itself, thus resulting in the striking emergence of new mixed-phase SrCoO x. The lateral coexistence of brownmillerite phase SrCoO2.5 and perovskite phase SrCoO3-δ was directly observed by transmission electron microscopy. Besides the fundamental significance of long-range interaction in ionic liquid gating, the ability to control the flow of oxygen ions across the heterointerface by the oxygen valve provides a new approach on the atomic scale for designing multistate memories, sensors, and solid-oxide fuel cells.

5.
Nanoscale ; 11(11): 4999-5004, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30839014

RESUMO

Ni-Mn-In magnetic shape-memory alloys are attractive materials due to their important functional properties relating to the martensitic transition. Understanding the complex martensitic magnetism and the transition process is of crucial importance not only from a fundamental but also from a technological point of view. Here, we demonstrate the dynamic magnetic domains and microstructures during the martensitic transition in the bulk and melt-spun ribbons of Ni50Mn35In15via in situ Lorentz transmission electron microscopy. The significant evolutionary differences in correlation with the temperature dependence of magnetization are identified between the bulk and ribbons. For a bulk alloy with L21 crystal structure at room temperature, the complete martensite with 7 M modulation in the paramagnetic state and the successive stripe magnetic domains in ferromagnetic martensite develop with a further decrease in the temperature. The stripe domains evolve into biskyrmion-like spin configurations when a perpendicular magnetic field is applied. In contrast, the partial austenitic phase always coexists with the martensitic phase in the ribbons even far below the martensitic transition temperatures and the martensitic phase presents a dominant twinning stack morphology with 5 M modulation and various magnetic domains. During the subsequent reheating-cooling cycles, the thermal hysteresis behavior and the transition reversibility in the bulk and ribbons are represented via the microstructural evolution.

6.
Nano Lett ; 19(3): 1605-1612, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30715894

RESUMO

With the help of the two-dimensional electron gas (2DEG) at the LaAlO3-SrTiO3 interface, spin and charge currents can be interconverted. However, the conversion efficiency has been strongly depressed by LaAlO3, which blocks spin transmission. It is therefore highly desired to explore 2DEGs sandwiched between ferromagnetic insulators that are transparent for magnons. By constructing epitaxial heterostructure with ferromagnetic EuO, which is conducting for spin current but insulating for electric current, and KTaO3, we successfully obtained the 2DEGs, which can receive thermally injected spin current directly from EuO and convert the spin current to charge current via inverse Edelstein effect of the interface. Strong dependence of the spin Seebeck coefficient on the layer thickness of EuO is further observed and the propagation length for non-equilibrium magnons in EuO has been determined. The present work demonstrates the great potential of the 2DEGs formed by ferromagnetic oxides for spin caloritronics.

7.
Adv Mater ; 31(10): e1805970, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30637817

RESUMO

The metallic interface between two oxide insulators, such as LaAlO3 /SrTiO3 (LAO/STO), provides new opportunities for electronics and spintronics. However, due to the presence of multiple orbital populations, tailoring the interfacial properties such as the ground state and metal-insulator transitions remains challenging. Here, an unforeseen tunability of the phase diagram of LAO/STO is reported by alloying LAO with a ferromagnetic LaMnO3 insulator without forming lattice disorder and at the same time without changing the polarity of the system. By increasing the Mn-doping level, x, of LaAl1- x Mnx O3 /STO (0 ≤ x ≤ 1), the interface undergoes a Lifshitz transition at x = 0.225 across a critical carrier density of nc = 2.8 × 1013 cm-2 , where a peak TSC ≈255 mK of superconducting transition temperature is observed. Moreover, the LaAl1- x Mnx O3 turns ferromagnetic at x ≥ 0.25. Remarkably, at x = 0.3, where the metallic interface is populated by only dxy electrons and just before it becomes insulating, a same device with both signatures of superconductivity and clear anomalous Hall effect (7.6 × 1012 cm-2 < ns ≤ 1.1 × 1013 cm-2 ) is achieved reproducibly. This provides a unique and effective way to tailor oxide interfaces for designing on-demand electronic and spintronic devices.

8.
ACS Nano ; 13(1): 609-615, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30604953

RESUMO

Controlling electronic processes in low-dimension electron systems is centrally important for both fundamental and applied researches. While most of the previous works focused on SrTiO3-based two-dimensional electron gases (2DEGs), here we report on a comprehensive investigation in this regard for amorphous-LaAlO3/KTaO3 2DEGs with the Fermi energy ranging from ∼13 meV to ∼488 meV. The most important observation is the dramatic variation of the Rashba spin-orbit coupling (SOC) as Fermi energy sweeps through 313 meV: The SOC effective field first jumps and then drops, leading to a cusp of ∼2.6 T. Above 313 meV, an additional species of mobile electrons emerges, with a 50-fold enhanced Hall mobility. A relationship between spin relaxation distance and the degree of band filling has been established in a wide range. It indicates that the maximal spin precession length is ∼70.1 nm and the maximal Rashba spin splitting energy is ∼30 meV. Both values are much larger than the previously reported ones. As evidenced by density functional theory calculation, these unusual phenomena are closely related to the distinct band structure of the 2DEGs composed of 5d electrons. The present work further deepens our understanding of perovskite conducting interfaces, particularly those composed of 5d transition-metal oxides.

9.
Nanoscale ; 11(1): 246-257, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30534792

RESUMO

The tunable, nonvolatile electrical modulation of magnetization at room temperature is firstly demonstrated in a magnetically hard amorphous SmCo film grown on a (011)-cut 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) substrate. Uniaxial in-plane anisotropy with hard and easy axes lying in the [100] and [01-1] directions, respectively, occurs. Bipolar electric field, E, across the thickness direction enhances the remnant magnetization, Mr, along the hard axis, while suppresses the Mr along the easy axis, and the maximal regulation is about -5.8% and +2.2%, respectively. Detailed analysis indicates that the induced effective uniaxial magnetic anisotropy field, which arises from the magnetostrictive properties of the amorphous SmCo thin film and the anisotropic strain from the PMN-PT substrate, is mainly responsible for the anisotropic tunability. The variation of the directional pair ordering of the SmCo film, which is caused by the anisotropic strain due to the electric field, also contributes to the tunability. More importantly, nonvolatile modulation and a stable two-state memory effect are demonstrated for the bipolar case, and in situ X-ray diffraction and X-ray diffraction reciprocal space mapping reveal that these phenomena originate from the electric-field-induced rhombohedral-orthorhombic phase transformation in the PMN-PT substrate. Moreover, by unipolarizing the ferroelectric substrate, a nonvolatile modulation is also observed. The anisotropic nonvolatile control of magnetization in SmCo amorphous films opens a new avenue for developing multifunctional information storage and novel spintronics devices based on hard magnetic materials.

10.
Front Chem ; 6: 438, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30320069

RESUMO

Negative thermal expansion (NTE) behaviors in the materials with giant magnetocaloric effects (MCE) have been reviewed. Attentions are mainly focused on the hexagonal Ni2In-type MM'X compounds. Other MCE materials, such as La(Fe,Si)13, RCo2, and antiperovskite compounds are also simply introduced. The novel MCE and phase-transition-type NTE materials have similar physics origin though the applications are distinct. Spin-lattice coupling plays a key role for the both effect of NTE and giant MCE. Most of the giant MCE materials show abnormal lattice expansion owing to magnetic interactions, which provides a natural platform for exploring NTE materials. We anticipate that the present review can help finding more ways to regulate phase transition and dig novel NTE materials.

11.
ACS Appl Mater Interfaces ; 10(47): 40951-40957, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30338983

RESUMO

Interface engineering is an important approach leading to multifunctional artificial materials. Although most of the previous works focused on the effects of the rotation/tilting of interfacial oxygen octahedron on perovskite multilayers, here, we report on a new kind of lattice distortion characterized by an off-center shift of the Mn ions within the MnO6 oxygen octahedra at the interfaces of La1- xSr xCoO3/La2/3Sr1/3MnO3/La1- xSr xCoO3/LaAlO3 trilayers ( x = 0-1/3), which drives the initially perpendicularly aligned magnetic axis of the La2/3Sr1/3MnO3 (LSMO) film toward the in-plane direction, though the film is in a strongly compressive state. It is further found that the magnetic anisotropy considerably depends on the content of Sr in La1- xSr xCoO3, enhancing as x decreases. The maximal anisotropy constant at 10 K is +2.5 × 106 erg/cm3 for the trilayers with x = 0, whereas it is -1.5 × 105 erg/cm3 for a bare LSMO film on LaAlO3. On the basis of the analysis of X-ray absorption spectroscopy and the results of density functional theory calculations, we found that the off-center displacement of the Mn ions has caused a strong orbital reconstruction at interfaces, resulting in the anomalous spin orientation against magnetoelastic coupling.

12.
Phys Rev Lett ; 121(11): 116803, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30265094

RESUMO

Two-dimensional electron gases (2DEGs) at oxide interfaces, which provide unique playgrounds for emergent phenomena, have attracted increasing attention in recent years. While most of the previous works focused on the 2DEGs at LaAlO_{3}/SrTiO_{3} interfaces, here we report on a new kind of 2DEGs formed between a magnetic insulator EuO and a high-k perovskite KTaO_{3}. The 2DEGs are not only highly conducting, with a maximal Hall mobility of 111.6 cm^{2}/V s at 2 K, but also well spin polarized, showing strongly hysteretic magnetoresistance up to 25 K and well-defined anomalous Hall effect up to 70 K. Moreover, unambiguous correspondences between the hysteretic behaviors of 2DEGs and the EuO layer are captured, suggesting the proximity effect of the latter on the former. This is confirmed by the results of density-functional theory calculations: Through interlayer exchange, EuO drives the neighboring TaO_{2} layer into a ferromagnetic state. The present work opens new avenues for the exploration for high performance spin-polarized 2DEGs at oxide interfaces.

13.
ACS Appl Mater Interfaces ; 10(38): 32597-32606, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30175581

RESUMO

An anomalous polarity-dependent electrostatic field modulation effect, facilitated by spatial confinement, is found in an oxide-based field-effect prototype device with a spatial-confined Pr0.7(Ca0.6Sr0.4)0.3MnO3 channel. It is revealed that the dominant field modulation mode under a small bias field varies from a polarity-independent strain-mediated one to a nonvolatile polarity-dependent one with enhanced modulation sensitivity as the channel width narrows down to several micrometers. Specially, in the structure confined to length scales similar to that of the phase domains, the field modulation exhibits a greatly increased modulation amplitude around the transition temperature and an anomalous bias-polarity dependence that is diametrically opposite to the normal one observed in regular polarization field-effect. Further simulations show that a large in-plane polarization field is unexpectedly induced by a small out-of-plane bias field of 4 kV/cm in the narrow strip (up to 790 kV/cm for the 3 µm strip). Such large in-plane polarization field, facilitated and enhanced by size reduction, drives phase transitions in the narrow channel film, leading to the reconfiguration of percolation channel and nonvolatile modulation of transport properties. Accordingly, the accompanied polarity relationship between the induced in-plane polarization field and the applied vertical bias field well explains the observed anomalous polarity-dependence of the modulation. Our studies reveal a new acting channel in the nanoscale control of lateral configurations of electronic phase separation and macroscopic behaviors by a small vertical electric bias field in spatial-confined field-effect structures. This distinct acting mechanism offers new possibilities for designing low-power all-oxide-based electronic devices and exploiting new types of multifunctionality to other strongly correlated materials where electronic phase competition exists.

15.
Nat Commun ; 9(1): 1923, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29765023

RESUMO

Grouping different transition metal oxides together by interface engineering is an important route toward emergent phenomenon. While most of the previous works focused on the interface effects in perovskite/perovskite heterostructures, here we reported on a symmetry mismatch-driven spin reorientation toward perpendicular magnetic anisotropy in perovskite/brownmillerite heterostructures, which is scarcely seen in tensile perovskite/perovskite heterostructures. We show that alternately stacking perovskite La2/3Sr1/3MnO3 and brownmillerite LaCoO2.5 causes a strong interface reconstruction due to symmetry discontinuity at interface: neighboring MnO6 octahedra and CoO4 tetrahedra at the perovskite/brownmillerite interface cooperatively relax in a manner that is unavailable for perovskite/perovskite interface, leading to distinct orbital reconstructions and thus the perpendicular magnetic anisotropy. Moreover, the perpendicular magnetic anisotropy is robust, with an anisotropy constant two orders of magnitude greater than the in-plane anisotropy of the perovskite/perovskite interface. The present work demonstrates the great potential of symmetry engineering in designing artificial materials on demand.

16.
ACS Appl Mater Interfaces ; 10(1): 1434-1439, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29226677

RESUMO

A chemical redox reaction can lead to a two-dimensional electron gas at the interface between a TiO2-terminated SrTiO3 (STO) substrate and an amorphous LaAlO3 capping layer. When replacing the STO substrate with rutile and anatase TiO2 substrates, considerable differences in the interfacial conduction are observed. On the basis of X-ray photoelectron spectroscopy (XPS) and transport measurements, we conclude that the interfacial conduction comes from redox reactions, and that the differences among the materials systems result mainly from variations in the activation energies for the diffusion of oxygen vacancies at substrate surfaces.

17.
Trials ; 18(1): 606, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29262859

RESUMO

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina. METHODS/DESIGN: This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. DISCUSSION: This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Angina Estável/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Adolescente , Adulto , Idoso , Angina Estável/diagnóstico , Angina Estável/enzimologia , Biomarcadores/sangue , Fármacos Cardiovasculares/efeitos adversos , Espessura Intima-Media Carotídea , China , Protocolos Clínicos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Projetos de Pesquisa , Método Simples-Cego , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
ACS Appl Mater Interfaces ; 9(41): 36456-36461, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28972361

RESUMO

Two-dimensional electron gas (2DEG) at the perovskite oxide interface exhibits a lot of exotic properties, presenting a promising platform for the exploration of emergent phenomena. While most of the previous works focused on SrTiO3-based 2DEG, here we report on the fabrication of high-quality 2DEGs by growing an amorphous LaAlO3 layer on a (001)-orientated KTaO3 substrate, which is a 5d metal oxide with a polar surface, at a high temperature that is usually adopted for crystalline LaAlO3. Metallic 2DEGs with a Hall mobility as high as ∼2150 cm2/(V s) and a sheet carrier density as low as 2 × 1012 cm-2 are obtained. For the first time, the gating effect on the transport process is studied, and its influence on spin relaxation and inelastic and elastic scattering is determined. Remarkably, the spin relaxation time can be strongly tuned by a back gate. It is reduced by a factor of ∼69 while the gate voltage is swept from -25 to +100 V. The mechanism that dominates the spin relaxation is elucidated.

19.
Nanotechnology ; 28(43): 435701, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-28837042

RESUMO

Highly mobile 2-dimensional electron gases (2DEGs) at the (001), (011) and (111)-oriented LaAlO3/SrTiO3 (LAO/STO) interfaces are obtained using spin coating chemical method, which is a gentle technique without plasma bombardment of the pulsed laser deposition. As revealed by x-ray diffraction spectrum and x-ray reflectivity analysis, the LAO over layer is epitaxially grown, and has a uniform thickness of ∼15 nm, ∼20 nm and ∼26 nm for (001), (011) and (111) orientations, respectively. The interfaces are well metallic down to 2 K. The carrier mobilities are ∼28 000 cm2 V-1 s-1, ∼22 000 cm2 V-1 s-1 and ∼8300 cm2 V-1 s-1 at 2 K for the (001), (011) and (111) LAO/STO interfaces, respectively, and ∼8 cm2 V-1 s-1, ∼4 cm2 V-1 s-1 and ∼4 cm2 V-1 s-1 at room temperature. The present work shows that the spin coating chemical method is a feasible approach to get high quality 2DEG at both the polar/non-polar and polar/polar interfaces.

20.
Sci Adv ; 3(3): e1602312, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28345050

RESUMO

The Rashba physics has been intensively studied in the field of spin orbitronics for the purpose of searching novel physical properties and the ferromagnetic (FM) magnetization switching for technological applications. We report our observation of the inverse Edelstein effect up to room temperature in the Rashba-split two-dimensional electron gas (2DEG) between two insulating oxides, SrTiO3 and LaAlO3, with the LaAlO3 layer thickness from 3 to 40 unit cells (UC). We further demonstrate that the spin voltage could be markedly manipulated by electric field effect for the 2DEG between SrTiO3 and 3-UC LaAlO3. These results demonstrate that the Rashba-split 2DEG at the complex oxide interface can be used for efficient charge-and-spin conversion at room temperature for the generation and detection of spin current.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA