The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity.

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.

Layered Ferromagnetic Structure Caused by the Proximity Effect and Interlayer Charge Transfer for LaNiO3/LaMnO3 Superlattices.

Magnetic proximity-induced magnetism in paramagnetic LaNiO3 (LNO) has spurred intensive investigations in the past decade. However, no consensus has been reached so far regarding the magnetic order in LNO layers in relevant heterostructures. This paper reports a layered ferromagnetic structure for the (111)-oriented LNO/LaMnO3 (LMO) superlattices. It is found that each period of the superlattice consisted of an insulating LNO-interfacial phase (five unit cells in thickness, ∼1.1 nm), a metallic LNO-inner phase, a poorly conductive LMO-interfacial phase (three unit cells in thickness, ∼0.7 nm), and an insulating LMO-inner phase. All four of these phases are ferromagnetic, showing different magnetizations. The Mn-to-Ni interlayer charge transfer is responsible for the emergence of a layered magnetic structure, which may cause magnetic interaction across the LNO/LMO interface and double exchange within the LMO-interfacial layer. This work indicates that the proximity effect is an effective means of manipulating the magnetic state and associated properties of complex oxides.

Direct Observation of Magnetic Skyrmions and Their Current-Induced Dynamics in Epitaxial Single-Crystal Oxide Films.

Magnetic skyrmions are scarcely investigated for single-crystal quality films, for which skyrmions may have a remarkable performance. Even in the limited studies in this aspect, the skyrmions are usually probed by the topological Hall effect, missing important information on dynamic properties. Here, we present a comprehensive investigation on the generation/manipulation of magnetic skyrmions in La0.67Ba0.33MnO3 single-crystal films. Using the technique of magnetic force microscopy, the current-driven skyrmion dynamics are directly observed. Unlike isolated skyrmions produced by magnetic field alone, closely packed skyrmions can be generated by electric pulses in a magnetic background, with a high density (∼60/µm2) and a small size (dozens of nanometers). The threshold current moving skyrmions is ∼2.3 × 104 A/cm2, 2-3 orders of magnitude lower than that required by metallic multilayers or van der Waals ferromagnetic heterostructures. Our work demonstrates the great potential of single-crystal oxide films in developing skyrmion-based devices.

Enhancing Interfacial Ferromagnetism and Magnetic Anisotropy of CaRuO3 /SrTiO3 Superlattices via Substrate Orientation.

Artificial oxide heterostructures have provided promising platforms for the exploration of emergent quantum phases with extraordinary properties. One of the most interesting phenomena is the interfacial magnetism formed between two non-magnetic compounds. Here, a robust ferromagnetic phase emerged at the (111)-oriented heterointerface between paramagnetic CaRuO3 and diamagnetic SrTiO3 is reported. The Curie temperature is as high as ≈155 K and the saturation magnetization is as large as ≈1.3 µB per formula unit for the (111)-CaRuO3 /SrTiO3 superlattices, which are obviously superior to those of the (001)-oriented counterparts and are comparable to the typical itinerant ferromagnet SrRuO3 . A strong in-plane magnetic anisotropy with six-fold symmetry is further revealed by the anisotropic magnetoresistance measurements, presenting a large in-plane anisotropic field of 3.0-3.6 T. More importantly, the magnetic easy axis of the (111)-oriented superlattices can be effectively tuned from 〈 11 2 ¯ $11\overline{2}$ 1〉 to 〈 1 1 ¯ 0 $1 \bar{1}0$ 〉 directions by increasing the layer thickness of SrTiO3 . The findings demonstrate a feasible approach to enhance the interface coupling effect by varying the stacking orientation of oxide heterostructures. The tunable magnetic anisotropy also shows potential applications in low-power-consumption or exchange spring devices.

Spin-charge interconversion of two-dimensional electron gases at oxide interfaces.

Oxide two-dimensional electron gas (2DEG) is a low-dimensional carrier system formed at the interface of oxide heterojunctions with strong and tunable Rashba spin-orbit coupling which makes oxide 2DEG an ideal platform for converting spin current and charge current. This review provides a summary of the recent advances on the 2DEGs at oxide interfaces for spin-charge interconversion. On one hand, we analyze properties and the efficiency of the spin-to-charge conversion through different ways of spin current injection. On the other hand, the conversion of charge current to spin current under different experimental methods has been summarized. These research achievements provide perspectives and methods for understanding and regulating the spin-charge interconversion of the 2DEG at the oxide interface.

Circular Photogalvanic Effect in Oxide Two-Dimensional Electron Gases.

Two-dimensional electron gases (2DEGs) at the LaAlO_{3}/SrTiO_{3} interface have attracted wide interest, and some exotic phenomena are observed, including 2D superconductivity, 2D magnetism, and diverse effects associated with Rashba spin-orbit coupling. Despite the intensive investigations, however, there are still hidden aspects that remain unexplored. For the first time, here we report on the circular photogalvanic effect (CPGE) for the oxide 2DEG. Spin polarized electrons are selectively excited by circular polarized light from the in-gap states of SrTiO_{3} to 2DEG and are converted into electric current via the mechanism of spin-momentum locking arising from Rashba spin-orbit coupling. Moreover, the CPGE can be effectively modified by the density and distribution of oxygen vacancies. This Letter presents an effective approach to generate and manipulate the spin polarized current, paving the way toward oxide spintronics.

A Distinct Spin Structure and Giant Baromagnetic Effect in MnNiGe Compounds with Fe-Doping.

Spin structure of a magnetic system results from the competition of various exchange couplings. Pressure-driven spin structure evolution, through altering interatomic distance, and hence, electronic structure produces baromagnetic effect (BME), which has potential applications in sensor/actuator field. Here, we report a new spin structure(CyS-AFMb) with antiferromagnetic(AFM) nature in Fe-doped Mn0.87Fe0.13NiGe. Neutron powder diffraction (NPD) under in situ hydrostatic pressure and magnetic field was conducted to reveal the spin configuration and its instabilities. We discovered that a pressure higher than 4 kbar can induce abnormal change of Mn(Fe)-Mn(Fe) distances and transform the CyS-AFMb into a conical spiral ferromagnetic(FM) configuration(45°-CoS-FMa) with easily magnetized but shortened magnetic moment by as much as 22%. The observed BME far exceeds previous reports. Our first-principles calculations provide theoretical supports for the enhanced BME. The compressed lattice by pressure favors the 45°-CoS-FMa and significantly broadened 3d bandwidth of Mn(Fe) atoms, which leads to the shortened magnetic moment and evolution of spin structure.

Two-Dimensional Superconductivity at the LaAlO_{3}/KTaO_{3}(110) Heterointerface.

We report on the observation of a T_{c}∼0.9 K superconductivity at the interface between LaAlO_{3} film and the 5d transition metal oxide KTaO_{3}(110) single crystal. The interface shows a large anisotropy of the upper critical field, and its superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition. Both facts suggest that the superconductivity is two-dimensional (2D) in nature. The carrier density measured at 5 K is ∼7×10^{13} cm^{-2}. The superconducting layer thickness and coherence length are estimated to be ∼8 and ∼30 nm, respectively. Our result provides a new platform for the study of 2D superconductivity at oxide interfaces.

Thermal Spin Injection and Inverse Edelstein Effect of the Two-Dimensional Electron Gas at EuO-KTaO3 Interfaces.

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.

Two Kinds of Metastable Structures in an Epitaxial Lanthanum Cobalt Oxide Thin Film.

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.

High-Mobility Spin-Polarized Two-Dimensional Electron Gases at EuO/KTaO_{3} Interfaces.

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.

High mobility 2-dimensional electron gas at LaAlO3/SrTiO3 interface prepared by spin coating chemical methods.

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.

Structure versus properties in α-Fe2O3 nanowires and nanoblades.

We report structure/property relationships in bicrystalline α-Fe2O3 nanowires (NWs) and nanoblades (NBs), synthesized by thermal oxidation of iron foils with different surface roughness. The electrical properties of individual nanostructures were studied by in situ transmission electron microscopy. Current-voltage (I-V) measurements using gold electrodes showed that a Schottky contact forms between α-Fe2O3 NWs whereas an ohmic contact forms between α-Fe2O3 NBs. The difference in transport properties is attributed to the existence of oxygen vacancies in the coincidence-site-lattice boundary region of α-Fe2O3 NBs. Magnetic measurements indicate that the temperature-dependent zero-field-cooled magnetization rises more rapidly near the Morin transition temperature for α-Fe2O3 NBs than that for NWs. The distinct magnetic properties of the NBs are ascribed to the enhanced magnetic order induced by the structural order in the two-dimensional NBs. These α-Fe2O3 NBs are promising building blocks for electronic and magnetic devices since their 2D geometries facilitate integration into devices with realistic pathways to manufacturing. In addition, our study shows that boundary engineering is an effective approach for tailoring the physical properties of nanomaterials.

Giant negative thermal expansion in bonded MnCoGe-based compounds with Ni2In-type hexagonal structure.

MnCoGe-based compounds undergo a giant negative thermal expansion (NTE) during the martensitic structural transition from Ni2In-type hexagonal to TiNiSi-type orthorhombic structure. High-resolution neutron diffraction experiments revealed that the expansion of unit cell volume can be as large as ΔV/V ∼ 3.9%. The optimized compositions with concurrent magnetic and structural transitions have been studied for magnetocaloric effect. However, these materials have not been considered as NTE materials partially due to the limited temperature window of phase transition. The as-prepared MnCoGe-based compounds are quite brittle and naturally collapse into powders. By using a few percents (3-4%) of epoxy to bond the powders, we introduced residual stress in the bonded samples and thus realized the broadening of structural transition by utilizing the specific characteristics of lattice softening enforced by the stress. As a result, giant NTE (not only the linear NTE coefficient α but also the operation-temperature window) has been achieved. For example, the average α̅ as much as -51.5 × 10(-6)/K with an operating temperature window as wide as 210 K from 122 to 332 K has been observed in a bonded MnCo0.98Cr0.02Ge compound. Moreover, in the region between 250 and 305 K near room temperature, the α value (-119 × 10(-6)/K) remains nearly independent of temperature. Such an excellent performance exceeds that of most other materials reported previously, suggesting it can potentially be used as a NTE material, particularly for compensating the materials with large positive thermal expansions.

Antagonism of Ang-Tie2 and Dll4-Notch signaling has opposing effects on tumor endothelial cell proliferation, evidenced by a new flow cytometry method.

Sustained angiogenesis is essential for tumor growth as it provides the tumor with a network of blood vessels that supply both oxygen and essential nutrients. Limiting tumor-associated angiogenesis is a proven strategy for the treatment of human cancer. To date, the rapid detection and quantitation of tumor-associated endothelial cell (TAEC) proliferation has been challenging, largely due to the low frequency of endothelial cells (ECs) within the tumor microenvironment. In this report, we address this problem using a new multiparametric flow cytometry method capable of rapid and precise quantitation of proliferation by measuring bromodeoxyuridine (BrdUrd) uptake in mouse TAECs from established human tumor xenografts. We determined the basal proliferation labeling index of TAECs in two human tumor xenografts representing two distinct histologies, COLO 205 (colorectal cancer) and U-87 (glioblastoma). We then investigated the effects of two large-molecule antiangiogenic agents targeting different biochemical pathways. Blocking angiopoietin-Tie2 signaling with the peptide-Fc fusion protein, trebananib (AMG 386), inhibited proliferation of TAECs, whereas blocking Dll4-Notch signaling with an anti-Dll4-specific antibody induced hyperproliferation of TAECs. These pharmacodynamic studies highlight the sensitivity and utility of this flow cytometry-based method and demonstrate the value of this assay to rapidly assess the in vivo proliferative effects of angiogenesis-targeted agents on both the tumor and the associated vasculature.

Charge-Transfer-Induced Interfacial Ferromagnetism in Ferromagnet-Free Oxide Heterostructures.

Due to the strong interlayer coupling between multiple degrees of freedom, oxide heterostructures have demonstrated exotic properties that are not shown by their bulk counterparts. One of the most interesting properties is ferromagnetism at the interface formed between "nonferromagnetic" compounds. Here we report on the interfacial ferromagnetic phase induced in the superlattices consisting of the two paramagnetic oxides CaRuO3 (CRO) and LaNiO3 (LNO). By varying the sublayer thickness in the superlattice period, we demonstrate that the ferromagnetic order has been established in both CaRuO3 and LaNiO3 sublayers, exhibiting an identical Curie temperature of ∼75 K. The X-ray absorption spectra suggest a strong charge transfer from Ru to Ni at the interface, triggering superexchange interactions between Ru/Ni ions and giving rise to the emergent ferromagnetic phase. Moreover, the X-ray linear dichroism spectra reveal the preferential occupancy of the d3z2-r2 orbital for the Ru ions and the dx2-y2 orbital for the Ni ions in the heterostructure. This leads to different magnetic anisotropy of the superlattices when they are dominated by CRO or LNO sublayers. This work clearly demonstrates a charge-transfer-induced interfacial ferromagnetic phase in the whole ferromagnet-free oxide heterostructures, offering a feasible way to tailor oxide materials for desired functionalities.

Giant Tunability of Rashba Splitting at Cation-Exchanged Polar Oxide Interfaces by Selective Orbital Hybridization.

The 2D electron gas (2DEG) at oxide interfaces exhibits extraordinary properties, such as 2D superconductivity and ferromagnetism, coupled to strongly correlated electrons in narrow d-bands. In particular, 2DEGs in KTaO3 (KTO) with 5d t2g orbitals exhibit larger atomic spin-orbit coupling and crystal-facet-dependent superconductivity absent for 3d 2DEGs in SrTiO3 (STO). Herein, by tracing the interfacial chemistry, weak anti-localization magneto-transport behavior, and electronic structures of (001), (110), and (111) KTO 2DEGs, unambiguously cation exchange across KTO interfaces is discovered. Therefore, the origin of the 2DEGs at KTO-based interfaces is dramatically different from the electronic reconstruction observed at STO interfaces. More importantly, as the interface polarization grows with the higher order planes in the KTO case, the Rashba spin splitting becomes maximal for the superconducting (111) interfaces approximately twice that of the (001) interface. The larger Rashba spin splitting couples strongly to the asymmetric chiral texture of the orbital angular moment, and results mainly from the enhanced inter-orbital hopping of the t2g bands and more localized wave functions. This finding has profound implications for the search for topological superconductors, as well as the realization of efficient spin-charge interconversion for low-power spin-orbitronics based on (110) and (111) KTO interfaces.

Low pressure reversibly driving colossal barocaloric effect in two-dimensional vdW alkylammonium halides.

Plastic crystals as barocaloric materials exhibit the large entropy change rivalling freon, however, the limited pressure-sensitivity and large hysteresis of phase transition hinder the colossal barocaloric effect accomplished reversibly at low pressure. Here we report reversible colossal barocaloric effect at low pressure in two-dimensional van-der-Waals alkylammonium halides. Via introducing long carbon chains in ammonium halide plastic crystals, two-dimensional structure forms in (CH3-(CH2)n-1)2NH2X (X: halogen element) with weak interlayer van-der-Waals force, which dictates interlayer expansion as large as 13% and consequently volume change as much as 12% during phase transition. Such anisotropic expansion provides sufficient space for carbon chains to undergo dramatic conformation disordering, which induces colossal entropy change with large pressure-sensitivity and small hysteresis. The record reversible colossal barocaloric effect with entropy change ΔSr ~ 400 J kg-1 K-1 at 0.08 GPa and adiabatic temperature change ΔTr ~ 11 K at 0.1 GPa highlights the design of novel barocaloric materials by engineering the dimensionality of plastic crystals.

Classification and Prediction of Skyrmion Material Based on Machine Learning.

The discovery and study of skyrmion materials play an important role in basic frontier physics research and future information technology. The database of 196 materials, including 64 skyrmions, was established and predicted based on machine learning. A variety of intrinsic features are classified to optimize the model, and more than a dozen methods had been used to estimate the existence of skyrmion in magnetic materials, such as support vector machines, k-nearest neighbor, and ensembles of trees. It is found that magnetic materials can be more accurately divided into skyrmion and non-skyrmion classes by using the classification of electronic layer. Note that the rare earths are the key elements affecting the production of skyrmion. The accuracy and reliability of random undersampling bagged trees were 87.5% and 0.89, respectively, which have the potential to build a reliable machine learning model from small data. The existence of skyrmions in LaBaMnO is predicted by the trained model and verified by micromagnetic theory and experiments.

Large Anomalous Nernst Effects at Room Temperature in Fe3 Pt Thin Films.

Heat current in ferromagnets can generate a transverse electric voltage perpendicular to magnetization, known as anomalous Nernst effect (ANE). ANE originates intrinsically from the combination of large Berry curvature and density of states near the Fermi energy. It shows technical advantages over the conventional longitudinal Seebeck effect in converting waste heat to electricity due to its unique transverse geometry. However, materials showing giant ANE remain to be explored. Herein,  a large ANE thermopower of Syx ≈ 2 µV K-1 at room temperature in ferromagnetic Fe3 Pt epitaxial films is reported, which also show a giant transverse thermoelectric conductivity of αyx ≈ 4 A K-1  m-1 and a remarkable coercive field of 1300 Oe. The theoretical analysis reveals that the strong spin-orbit interaction in addition to the hybridization between Pt 5d and Fe 3d electrons leads to a series of distinct energy gaps and large Berry curvature in the Brillouin zone, which is the key for the large ANE. These results highlight the important roles of both Berry curvature and spin-orbit coupling in achieving large ANE at zero magnetic field, providing pathways to explore materials with giant transverse thermoelectric effect without an external magnetic field.