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Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton’s Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Importantly, this reversible covalent strategy is generalizable to improve other PROTACs, opening a path to enhance PROTAC efficacy., PROTACs have emerged as promising therapeutic agents but their cellular uptake is often inefficient. Here, the authors show that reversible covalent warhead chemistry improves PROTAC intracellular accumulation and target engagement, and develop a dual inhibitor/degrader of Bruton’s tyrosine kinase

The nanoscale adhesive wear of graphene was studied by molecular dynamics simulation of a diamond tip sliding over a few-layer graphene sheet. We obtained the typical adhesive wear tracks with initial rupture cavity induced by adhesive interaction between the tip and graphene. The coupled interaction, between the formation of interfacial bonds and the breakage of in-plane C-C bonds, leads to the usually observed severe damage of graphene after an adhesive wear process. Moreover, the critical contact pressure for onset of adhesive wear of graphene (∼42 GPa) is much lower than that for abrasive wear (∼94 GPa), which also cannot be correctly approximated by the onset condition for initial rupture of graphene during a loading process (∼76 GPa).

Due to structural disorder effects, variable range hopping (VRH) transport via band-tail states has been widely observed in the transition-metal dichalcogenide field-effect transistor (TMD FET). However, this significant mechanism has not been incorporated into existing compact models. In this letter, a continuous physics-based compact model considering VRH in TMD FET is developed. Key parameters are extracted by calibration to experimental molybdenum disulfide FET. The voltage dependent carrier density and temperature dependent current characteristics are physically predicted by utilizing the general percolation theory and generalized Einstein relation. Our model is validated by the good agreement between the simulation and experimental results. Furthermore, the relationship between the disorder effects and circuit-level performances are presented. This letter is significant for material engineering and device optimization of TMD FET.

Previously, we have reported the crystal structures of Fab fragment of Infliximab in complex with TNFα. The structurally identified epitope on TNFα revealed the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface and the possibility to optimize the binding affinity. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the infliximab epitope. To develop novel anti-TNFα antibodies, structural analysis, the phage display antibody isolation, step by step antibody optimization, CDR residues random mutagenesis, and binding affinity characterization were performed. One of the novel antibodies generated on the backbone of infliximab, Inf3D6, has the superior binding affinity to TNFα, thus, demonstrating the potential for structure guided optimization for improvement of existing antibody-based therapeutics.

The interfacial enhanced ferromagnetism in maganite/ruthenate system is regarded as a promising path to broaden the potential of oxide-based electronic device applications. Here, we systematically studied the physical properties of La1−x Ca x MnO3/SrRuO3 superlattices and compared them with the La1−x Ca x MnO3 thin films and bulk compounds. The La1−x Ca x MnO3/SrRuO3 superlattices exhibit significant enhancement of Curie temperature (T C) beyond the corresponding thin films and bulks. Based on these results, we constructed an extended phase diagram of La1−x Ca x MnO3 under interfacial engineering. We considered the interfacial charge transfer and structural proximity effects as the origin of the interface-induced high T C. The structural characterizations revealed a pronounced increase of B–O–B bond angle, which could be the main driving force for the high T C in the superlattices. Our work inspires a deeper understanding of the collective effects of interfacial charge transfer and structural proximity on the physical properties of oxide heterostructures.

This paper reports the design of a narrowband mid-infrared absorber using a structure consisting of low-index dielectric pillar arrays on a highly reflective metal plane. Such a hybrid system can support a high-quality lattice resonance with strongly confined electromagnetic fields at the tops of dielectric structures. For mid-infrared wavelengths around 4 µm, the low-index dielectric can be silica by plasma-enhanced chemical vapor deposition, and the metal can be copper. The lattice resonance can lead to perfect absorption with a quality factor around 1000 when considering realistic dissipative losses for the low-index dielectric pillars. According to Kirchhoff’s radiation law, the narrowband absorber can work as a high- Q surface-emitting thermal emitter in the mid-infrared by heating its substrate.

In situ electrical control of the Dzyaloshinskii-Moriya interaction (DMI) is one of the central but challenging goals toward skyrmion-based device applications. An atomic design of defective interfaces in spin-orbit-coupled transition-metal oxides can be an appealing strategy to achieve this goal. In this work, by utilizing the distinct formation energies and diffusion barriers of oxygen vacancies at SrRuO3 /SrTiO3 (001), a sharp interface is constructed between oxygen-deficient and stoichiometric SrRuO3 . This interfacial inversion-symmetry breaking leads to a sizable DMI, which can induce skyrmionic magnetic bubbles and the topological Hall effect in a more than 10 unit-cell-thick SrRuO3 . This topological spin texture can be reversibly manipulated through the migration of oxygen vacancies under electric gating. In particular, the topological Hall signal can be deterministically switched ON and OFF. This result implies that the defect-engineered topological spin textures may offer an alternate perspective for future skyrmion-based memristor and synaptic devices.

Effective control of magnetic anisotropy is important for developing spintronic devices. In this work, we performed a case study of stacking periods (N)-mediated reorientation of lateral magnetic anisotropy in ultrathin La0.67Ca0.33MnO3/SrRuO3 superlattices. As N increases from 1 to 15, the magnetic easy-axis switches from the orthorhombic [010] to [100]-axis. The maximum anisotropy constant of the superlattice (SL) (N = 15) reaches −1.83 × 105 erg/cm3. X-ray absorption spectroscopy and x-ray linear dichroism further suggest that the observed changes in lateral magnetic anisotropy are driven by in-plane orbital polarization. For SLs with small N, anisotropic strain-induced orbital polarization along the b-axis can result in the [010]-oriented magnetic easy axis. For SLs with large N, the dimension crossover from 2-dimension to 3-dimension could enhance the hybridization of Ru t2g and Mn dx2−y2 orbitals, which can compete with the strain effect and switch the magnetic easy axis to [100]. Our results suggest a potential strategy for engineering magnetic anisotropy through the cooperation of strain engineering and interfacial orbital engineering.

With recent trends on miniaturizing oxide-based devices, the need for atomic-scale control of surface/interface structures by pulsed laser deposition (PLD) has increased. In particular, realizing uniform atomic termination at the surface/interface is highly desirable. However, a lack of understanding on the surface formation mechanism in PLD has limited a deliberate control of surface/interface atomic stacking sequences. Here, taking the prototypical SrRuO3/BaTiO3/SrRuO3 (SRO/BTO/SRO) heterostructure as a model system, we investigated the formation of different interfacial termination sequences (BaO-RuO2 or TiO2-SrO) with oxygen partial pressure (PO2) during PLD. We found that a uniform SrO-TiO2 termination sequence at the SRO/BTO interface can be achieved by lowering the PO2 to 5 mTorr, regardless of the total background gas pressure (Ptotal), growth mode, or growth rate. Our results indicate that the thermodynamic stability of the BTO surface at the low-energy kinetics stage of PLD can play an important role in surface/interface termination formation. This work paves the way for realizing termination engineering in functional oxide heterostructures., Comment: 27 pages, 6 figures, Supporting Information

Mobility degradation at high gate bias is often observed in organic thin film transistors. We propose a mechanism for this confusing phenomenon, based on the percolation theory with the presence of disordered energy landscape with an exponential density of states. Within a simple model we show how the surface states at insulator/organic interface trap a portion of channel carriers, and result in decrease of mobility as well as source/drain current with gate voltage. Depending on the competition between the carrier accumulation and surface trapping effect, two different carrier density dependences of mobility are obtained, in excellent agreement with experiment data.

HER2, a ligand-free tyrosine kinase receptor of the HER family, is frequently overexpressed in breast cancer. The anti-HER2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. Despite the effectiveness of trastuzumab, its efficacy remains variable and often modest. Thus, there is an urgent need to improve ErbB2-targeting therapy. Here, we describe a novel anti-HER2 antibody, 7C3, which was developed using hybridoma technique. Structural analysis confirms that the epitope of this antibody is in domain II/III of HER2. Moreover, a structural conformation change was observed in HER2 in complex with 7C3. Interestingly, this novel anti-HER2 antibody exhibits efficacy in blocking HER2/EGFR heterodimerization and signaling. The results highlight the different function role of HER2 domains and the unique potential of 7C3 to inhibit the HER2/EGFR heterodimer, which may complement current anti-HER2 treatments.

// Lingfei Wang 1, 2, * , Xiaojie Yu 2, * , Chao Wang 2, * , Shujun Pan 3, * , Beibei Liang 1 , Yajun Zhang 2 , Xiaodan Chong 2 , Yanchun Meng 4 , Jian Dong 5 , Yirong Zhao 2 , Yang Yang 2 , Huajing Wang 2 , Jie Gao 6 , Huafeng Wei 1, 2 , Jian Zhao 1, 2 , Hao Wang 2 , Chaohua Hu 7 , Wenze Xiao 8 and Bohua Li 1, 2 1 Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China 2 International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, China 3 Hangzhou Sanatorium of People’s Liberation Army, Hangzhou 310007, China 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College of Fudan University, Shanghai 200032, China 5 Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China 6 Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai 200433, China 7 Department of General Surgery, Xiaogan Central Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 432000, China 8 Department of Rheumatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China * These authors contributed equally to this work Correspondence to: Chaohua Hu, email: huchaohua2006@126.com Wenze Xiao, email: wenzexiao@yahoo.com Bohua Li, email: bohuali1020@163.com Keywords: trastuzumab resistance, GDC-0941, anti-ErbB2 antibody, programmed cell death, breast cancer Received: March 07, 2017 Accepted: May 05, 2017 Published: May 16, 2017 ABSTRACT Trastuzumab, an anti-ErbB2 humanized antibody, brings benefit to patients with ErbB2-amplified metastatic breast cancers. However, the resistance to trastuzumab is common. Our previously reported H2-18, an anti-ErbB2 antibody, potently induced programmed cell death in trastuzumab-resistant breast cancer cells. Here, we aim to investigate the antitumor efficacy of H2-18 in combination with the pan-PI3K inhibitor GDC-0941 in trastuzumab-resistant breast cancer cell lines. The results showed that H2-18 and GDC-0941 synergistically inhibited the in vitro proliferation of BT-474, SKBR-3, HCC-1954 and HCC-1419 breast cancer cells. H2-18 plus GDC-0941 showed significantly enhanced programmed cell death-inducing activity compared with each drug used alone. The combination of H2-18 and GDC-0941 did not increase the effect of single agent on ROS production, cell cycle and ErbB2 signaling. Importantly, the in vivo antitumor efficacy of H2-18 plus GDC-0941 was superior to that of single agent. Thus, the enhanced in vivo antitumor efficacy of H2-18 plus GDC-0941 may mainly be attributable to its increased programmed cell death-inducing activity. Collectively, H2-18 plus GDC-0941 could effectively inhibit tumor growth, suggesting the potential to be translated into clinic as an efficient strategy for ErbB2-overexpressing breast cancers.

// Chao Wang 1, * , Lingfei Wang 1, * , Xiaojie Yu 1, * , Yajun Zhang 1, * , Yanchun Meng 2 , Huajing Wang 1 , Yang Yang 1 , Jie Gao 1 , Huafeng Wei 1, 3 , Jian Zhao 1, 3 , Cuihua Lu 4 , Han Chen 5 , Yanping Sun 6 and Bohua Li 1, 3 1 International Joint Cancer Institute and Department of Pharmaceutical Sciences, The Second Military Medical University, Shanghai, People's Republic of China 2 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China 3 Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China 4 Department of Gastroenterology, The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China 5 Department of General Surgery, 411 Hospital of Chinese People's Liberation Army, Shanghai, People’s Republic of China 6 Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China * These authors contributed equally to this work Correspondence to: Bohua Li, email: bohuali1020@163.com Yanping Sun, email: sunyanping2003@163.com Han Chen, email: chenhan0903@163.com Cuihua Lu, email: lch670608@sina.com Keywords: ErbB2, gastric cancer, acquired resistance to trastuzumab, domain I- specific antibody, programmed cell death Received: December 16, 2016 Accepted: April 12, 2017 Published: April 27, 2017 ABSTRACT Trastuzumab resistance is a common problem that impedes the effectiveness of trastuzumab in ErbB2-amplified cancers. About 70% of ErbB2-amplified breast cancers do not respond to trastuzumab (de novo resistance), and the majority of the trastuzumab-responsive cancers progress within 1 year (acquired resistance). Different mechanisms exist between de novo and acquired resistance. Innate resistance mechanisms are mainly independent of ErbB2 receptor activity, and acquired resistance involves with alterations depending on ErbB2 activity. We previously reported H2-18, an ErbB2 domain I-specific antibody, which could circumvent de novo resistance to trastuzumab. Here, we modeled the development of acquired resistance by treating human gastric cancer cell line NCI-N87 with trastuzumab to obtain the trastuzumab-resistant subline, NCI-N87-TraRT. Next, we investigated the antitumor efficacy of H2-18 in NCI-N87-TraRT cell line. H2-18 exhibited a significantly greater antitumor activity in NCI-N87-TraRT tumor-bearing nude mice than pertuzumab and trastuzumab, either alone or in combination. The unique ability of H2-18 to overcome acquired resistance may be attributable to its potent programmed cell death-inducing activity, which was probably mediated by RIP1-ROS-JNK-c-Jun pathway. In conclusion, H2-18 may have the potential as an effective agent to circumvent acquired resistance to trastuzumab in ErbB2-overexpressing cancers.

Reversible data hiding (RDH) in compression domain is an important research issue in the security of digital multimedia. Obtaining a high embedding rate and a low compression rate are the main goals of compression domain RDH. This paper proposes a novel RDH scheme to improve joint neighboring coding (JNC) scheme. In embedding process, the first index SC 1st in current state codebook (SC) and median edge detector (MED) prediction P med are exploited. These two parameters are employed to replace the right-up and left-up neighboring SMVQ indices, which have lower correlation with the current index. As a result, a more concentrated distribution of difference “d” is obtained. Difference “d” is computed by the difference between the current SMVQ index and its left, upper neighboring indices, P med and SC 1st after embedding secret bits. The experimental results show that our work achieves the average compression rate of 0.45/0.51/0.57 bpp and the average embedding efficiency of 0.28/0.36/0.43 after embedding 2/3/4 bits secret data into each SMVQ index. As demonstrated in the comparative results, it can be observed that the proposed scheme outperforms the other previous works.

In this paper, a novel reversible data hiding scheme which utilizes SMVQ prediction indices to embed secret data is proposed. As a result, it improves Yang’s work, which takes advantage of counts of indices in data embedding. Our approach enhances the prediction of SMVQ, resulting in a more concentrated distribution of indices. Based on the distribution of SMVQ-p indices, in the embedding process, three clusters (CL 0, CL 1 and CL 2) are defined. Indices in CL 0 are employed to embed secret data and can support a high embedding capacity. Indices in cluster CL 1 are employed for supporting a lower bit rate. Indices in cluster CL 2 are utilized for lossless reconstruction. Experimental results indicate that lower bit rate and higher embedding efficiency are obtained after encoding and embedding processes by our approach. Furthermore, experimental results demonstrate that the proposed method outperforms other state-of-the-art reversible data hiding schemes as well.

Little attention has been paid to the stability and reactivity of the C–F bond under different conditions. In this study, the stability and reactivity of tri-, di-, and monofluoromethyl/methoxy/methylthio moiety groups on arenes under acidic or basic conditions are carefully investigated.

Immunocytokines (antibody-cytokine fusions) have been proved to be a promising class of therapeutic agents for tumors. Anti-PD-L1 antibodies or IL-2 have been used to treat a variety of cancers. Here, in order to remove T cell inhibition and increasing the IL-2 concentration in the tumor microenvironment, we engineered a novel anti-PD-L1 antibody based immunocytokine by fusing hIL-2 to the C-Term of atezolizumab, denoted as BIPI. Our results revealed that BIPI was effective in stimulating T cell activation in vitro and could selectively localize to the tumor. Furthermore, tumor regression and prolonged survival were also observed in the metastatic colorectal cancer mouse model. The obviously longer survival mice in BIPI treatment group turned out depending on the function of CD8+ T cells. The IFN- secreted from CD8+ T cells in the spleen also contributed to the better tumor inhibition profile in BIPI treatment group than in anti-PD-L1 or IL-2 treatment alone. Taken together, our data evidenced the enhanced antitumor potency of BIPI, suggesting its potential use for cancers with a low response to the anti-PD-L1 or IL-2 treatment.

Climatic, socio-economic, geophysical, and human activity factors, among others, influence land use patterns. However, these driving factors also have different relationships with each other. Combining machine learning methods and statistical models is a good way to simulate the dominant land use types. The Luan River basin is located in a farming-pastoral transitional zone and is an important ecological barrier between Beijing and Tianjin. In this study, we predicted future land use and land cover changes from 2010 to 2020 in the Luan River’s upper and middle reaches under three scenarios—the natural scenario, the ecological scenario, and the sustainable scenario. The results indicate that cultivated land will decrease while the forested areas will increase quantitatively in the future. Built-up areas would increase quickly in the natural scenario, and augmented expansion of forest would be the main features of land use changes in both the ecological scenario and the sustainable scenario. Regarding the spatial pattern, different land use patterns will be aggregated and patches will become larger. Our findings for the scenario analysis of land use changes can provide a reference case for sustainable land use planning and management in the upper and middle Luan River basin.

In quantum matters hosting electron-electron correlation and spin-orbit coupling, spatial inhomogeneities, arising from competing ground states, can be essential for determining and understanding topological properties. A prominent example is Hall anomalies observed in SrRuO3 films, which were interpreted in terms of either magnetic skyrmion-induced topological Hall effect (THE) or inhomogeneous anomalous Hall effect (AHE). To clarify this ambiguity, we systematically investigated the AHE of SrRuO3 ultrathin films with controllable inhomogeneities in film thickness (tSRO). By harnessing the step-flow growth of SrRuO3 films, we induced microscopically-ordered stripes with one-unit-cell differences in tSRO. The resultant spatial distribution of momentum-space Berry curvatures enables a two-channel AHE, which shows hump-like anomalies similar to the THE and can be continuously engineered via sub-unit-cell control of tSRO. In these inhomogeneous SRO films, we microscopically identified a two-step magnetic switching and stripe-like ferromagnetic domains. These features are fingerprints for distinguishing the two-channel AHE from the skyrmion-induced THE., 24 pages, 6 figures, 4 figures in Supplementary Materials

The vegetation in the agro-pastoral transitional zone of northern China (APTZNC) was significantly restored, and both climate change and ecological restoration projects contributed to vegetation activities with varied proportion. Since few decades ago, APTZNC has undergone significant land degradation and climate change, threatening regional sustainable development, and in response to such ecological crises, multiple ecological restoration projects were implemented, which have caused a profound impact on the terrestrial ecosystem. Taking agro-pastural transitional zone of northern China (APTZNC) as the study area, this study used 16-year (2000-2015) net primary productivity (NPP) as an important indicator of the arid and semi-arid ecosystem's productivity, combing meteorological data in same period to (1) monitor the vegetation dynamics affected by both climate and ecological restoration projects; (2) detect climate changing trend, including annual precipitation, air temperature, and sunlight hours; (3) explicitly distinguish driving forces of climate change and ecological restoration projects on vegetation dynamics based on correlation analysis. The results demonstrated that (1) the annual NPP indicated overall greening (48.77% significant restoration) and partial degradation (0.39% significant degradation) in APTZNC; (2) the annual precipitation was the main factor that widely influences vegetation growth, and the area with significant influence accounted for 55.53%; however, the area with significant temperature influence only accounted for 1%, and the area affected significantly by sunshine hours accounted for 14.33%; (3) In the area of significant greening with proportion of 48.77%, of 26.93% was related to climate change, of 19.80% was related to ecological conservation programs, and of 2.05% was related to multiple factors. In the significantly degraded area with proportion of 0.39%, of 0.1% is related to climate change and of 0.29% is abnormally degraded. Our study is expected to accelerate the understanding of vegetation dynamics and its driving mechanisms, and provide support for scientifically formulating and adjusting ecological restoration projects in APTZNC.

Land use/land cover changes (LULCC) have been affected by ecological processes as well as socioeconomic and human activities, resulting in several environmental problems. The study of the human&ndash, environment system combined with land use/land cover dynamics has received considerable attention in recent decades. We aimed to provide an integrated model that couples land use, socioeconomic influences, and ecosystem processes to explore the future dynamics of land use under two scenarios in China. Under Scenario A, the yield of grain continues to increase, and under Scenario B, the yield of grain remains constant. This study created a LULCC model by integrating a simple global socioeconomic model, a Terrestrial ecosystem simulator (TESim), and a land use allocation model. The results were analyzed by comparing spatiotemporal differences under predicted land use conditions in the two alternative scenarios. The simulation results showed patterns that varied between the two scenarios. In Scenario A, grassland will expand in the future and a large reduction in cropland will be observed. In Scenario B, the augmented expansion of cropland and a drastic shrinkage of forest area will be the main land use conversion features. Scenario A is more promising because more land is preserved for ecological restoration and urbanization, which is in line with China&rsquo, s Grain for Green Program. Economic development should be based on ecological protection. The results are expected to add insight to sustainable land use development and regional natural resource management in China.

This paper studies an online optimization problem, where the cost function at every time stage is summation of a group of local cost functions assigned to to a single agent/node in a multi-agent network. We propose a distributed algorithm by combining the gradient descent method and consensus design. Then we prove that the regret of our online optimization algorithm as well as the accumulative disagreement for the multi-agent network is sublinear under a properly chosen stepsize.

Interfacial charge transfer and structural proximity effects are the two essential routes to trigger and tune numerous functionalities of perovskite oxide heterostructures. However, the cooperation and competition of these two interfacial effects in one epitaxial system have not been fully understood. Herein, we fabricate a series of La0.67Ca0.33MnO3/CaRuO3 superlattices and introduce various chemical doping in the nonmagnetic CaRuO3 interlayers. We found that Ti, Sr, and La doping in the CaRuO3 layer can effectively tune the interfacial charge transfer and octahedral rotation, thus modulating the ferromagnetism of the superlattices. Specifically, the B-site Ti doping depletes the Ru 4d band and suppresses the interfacial charge transfer, leading to a decay of ferromagnetic Curie temperature (TC). In contrast, the A-site Sr doping maintains a sizable charge transfer and meanwhile suppresses the octahedral rotation, which facilitates ferromagnetism and significantly enhances the TC up to 291 K. The La dopi...

Oxide single-crystal substrates with atomically smooth and chemically uniform surfaces are indispensable for constructing high-quality epitaxial heterostructures and sharp heterointerfaces. In this paper, the authors develop a simple and efficient recipe to optimize the surface structure in LaAlO${}_{3}$ (001) single crystal, a widely used substrate for growing perovskite oxide heterostructures. The authors combine thermal annealing and subsequent deionized water leaching processes to treat the LaAlO${}_{3}$ (001) surface. Thanks to the distinct solubility between AlO${}_{2}$ and LaO surface layers, the treated substrate exhibits an atomically flat and uniformly AlO${}_{2}$-terminated surface. This method circumvents the high-temperature instability of LaAlO3 (001) surface due to the intrinsic surface polarity.

ROC (A, C) and Precision-Recall (B, D) curves for all dimension reductions, existing crowd wisdoms (on perfectly binarized data in C, D), the DNN (A, B only) and individual predictions of skin cancer classification (A, B) and DREAM2 challenge (C, D).

Traditional encryption algorithms are inefficient when applied to image encryption because image data have the characteristics of large data sizes and strong correlations between adjacent pixels. The shortcomings of the traditional Data encryption standard (DES) encryption algorithm when applied to image encryption are analyzed, and a new image encryption algorithm based on the traditional DES encryption algorithm model, chaotic systems, DNA computing, and select cipher-text output is proposed. Select cipher-text output selects cipher image with the biggest entropy, and it can increase the randomness of cipher image and reduce the risk of encryption system being broken down. This algorithm overcomes the shortcomings of high computational complexity and inconvenient key management that the traditional text encryption algorithm has when applied to image encryption. The experimental results show that the security of this algorithm is verified by analyzing the information entropy, image correlation of adjacent pixels and other indexes. At the same time, this algorithm passes the noise attack test and the occlusion attack test, so it can resist common attacks.

Reconstruction of causal gene networks can distinguish regulators from targets and reduce false positives by integrating genetic variations. Its recent developments in speed and accuracy have enabled whole-transcriptome causal network inference on a personal computer. Here we demonstrate this technique with program Findr on 3,000 genes from the Geuvadis dataset. Subsequent analysis reveals major hub genes in the reconstructed network.

For the first time, a surface potential- and physics-based compact model for two dimensional (2D) polycrystalline-molybdenum disulfide (MoS 2 ) field effect transistors (FETs) with resistive switching (RS) behavior is developed and verified by experimental data. This model is incorporated with the theories of thermal activation transport, grain boundary (GB) barrier and space charge limited current (SCLC). Based on the GB induced disorders, the grain size, low temperature and high electrical field dependent characteristics are studied. The predicted transfer and output characteristics have excellent quantitative agreement with experimental results. Furthermore, considering the hopping process induced defect- (i.e., sulfur vacancy) redistribution, the GB (e.g., intersecting or bisecting GB) dependent resistive switching behavior is physically investigated. Finally, this model is implemented to simulate the synaptic activity such as short-term/long-term plasticity, which indicates the possibility of using 2D-FETs for neuromorphic computing applications.

Organic thin-film transistor constructs the headstone of flexible electronic world such as conformable sensor arrays and flexible active-matrix displays. With solution-processed methods, it forges ahead toward large-area, low-cost manufacturing goals. As an indispensable complement to traditional silicon-based transistors, organic thin-film field-effect transistors have made great progress in materials, performance, bending capacity, and integrated circuits in recent few years. Flexible transistors and circuitry have extremely promising application prospects and possess irreplaceable status in foldable displays, artificial skins and bendable smart cards. In this review, we will discuss the evolution of flexible organic transistors and integrated circuits in terms of material, fabrication as well as application.

High-quality perovskite monocrystalline films are successfully grown through cavitation-triggered asymmetric crystallization. These films enable a simple cell structure, ITO/CH3 NH3 PbBr3 /Au, with near 100% internal quantum efficiency, promising power conversion efficiencies (PCEs) >5%, and superior stability for prototype cells. Furthermore, the monocrystalline devices using a hole-transporter-free structure yield PCEs ≈6.5%, the highest among other similar-structured CH3 NH3 PbBr3 solar cells to date.

We demonstrate that ultrathin P-type Cu2O thin films fabricated by a facile thermal oxidation method can serve as a promising hole-transporting material in perovskite solar cells. Following a two-step method, inorganic-organic hybrid perovskite solar cells were fabricated and a power conversion efficiency of 11.0% was achieved. We found that the thickness and properties of Cu2O layers must be precisely tuned in order to achieve the optimal solar cell performance. The good performance of such perovskite solar cells can be attributed to the unique properties of ultrathin Cu2O, including high hole mobility, good energy level alignment with CH3NH3PbI3, and longer lifetime of photo-excited carriers. Combining the merits of low cost, facile synthesis, and high device performance, ultrathin Cu2O films fabricated via thermal oxidation hold promise for facilitating the developments of industrial-scale perovskite solar cells.

An improved cut-off frequency model of a modified equivalent circuit of graphene field-effect transistors, which incorporates the additional capacitive effect physically present due to dipole layer between the metal and the graphene, is proposed. The original equivalent circuit is not accurate for a large separation distance dipole layer. Based on the improved equivalent circuit model, a more accurate parameter extraction by two-port analysis is possible, and the cut-off frequency will be more accurate particularly for largely separated dipole layer near the Dirac point. Considering the dipole layer, the equivalent circuit is never investigated before, and the cut-off frequency model shows good agreement with experiments.

In this paper, a surface potential-based gate-leakage current (GLC) model for organic thin-film transistors is proposed. It is found that the Poole–Frenkel emission is the main mechanism of GLC, which can be well described by our model for both accumulation and depletion modes. In addition, the source and drain partitions of the channel leakage current can be well explained based on our model. Furthermore, the dependence of GLC on drain voltage, temperature, and material disorder has been discussed in detail, which yields perfect agreement with the experimental data.

Oxide heterostructures have great potential for spintronics applications due to their well‐defined heterointerfaces and vast functionalities. To integrate such compelling features into practical spintronics devices, effective control of the magnetic switching behavior is key. Here, continuous control of the magnetic coercive field in SrTiO3/SrRuO3 ultrathin heterostructures is achieved by oxygen vacancy (VO) engineering. Pulsed laser deposition of an oxygen‐deficient SrTiO3 capping layer can trigger VO migration into the SrRuO3 layer while avoiding the formation of Ru vacancies. Moreover, by varying the thickness and growth conditions of the SrTiO3 capping layer, the value of the coercive field (HC) in the ferromagnetic SrRuO3 layer can be continuously tuned. The maximum enhancement of HC at 5 K is 3.2 T. Such a wide‐range tunability of HC may originate from a VO‐induced enhancement of perpendicular magnetic anisotropy and domain wall pinning. This study offers effective approaches for controlling physical properties of oxide heterostructures via VO engineering, which may facilitate the development of oxide‐based functional devices.

This article reports refractometric sensing using two optical resonances of different types supported by TiO2 nanopillar arrays on a gold film, which can be exposed to aqueous or organic environmen ...

J.A.Z. and J.M. contributed equally to this work. This work was supported by the Research Center Program of IBS (Institute for Basic Science) in Korea (IBS-R009-D1). STEM measurement was supported by the National Center for Inter-University Research Facilities (NCIRF) at Seoul National University in Korea. J.A.Z., B.W., and L.-Q.C. acknowledge the support by the Computational Materials Sciences Program funded by the US Department of Energy, Office of Science, Basic Energy Sciences, under Award Number DE-SC0020145 (J.A.Z. and L.-Q.C.) and by the US National Science Foundation under Award Number NSF-MRSEC DMR-1420620 (B.W.) and a fellowship from 3M Incorporated. Computations for this research were performed on the Pennsylvania State University’s Institute for CyberScience Advanced CyberInfrastructure, and the Extreme Science and Engineering Discovery Environment (XSEDE) through NSF DMR170006. C.J.R. and J.S.L. acknowledge the support from Science Research Center and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2018R1A2B2005331). The authors from IMRE acknowledge the supports by National Research Foundation Competitive Research Programme of Singapore, NRF-CRP15-2015-04, (IMRE/16-9P1122). M.S., C.W.A., and T.H.K. acknowledge the support from the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. NRF-2019R1A6A1A11053838). The authors acknowledge invaluable suggestions and support from S. M. Yang, Z.-G. Ye, S. H. Chang, and J. H. Ko.

The advent of a large-volume high-pressure apparatus has led to the discovery of many new materials with exceptional properties for widespread applications such as superhard materials (e.g., diamonds). However, for most conventional devices, the pressure and temperature capabilities are often limited to 6 GPa and 2300 K, which severely impedes the study of materials at extended pressures and temperatures. In this work, we present experimental optimizations of the high-pressure cell assembly for cubic press with a focus on the improvement of its temperature capability, leading to a record temperature value of ∼4050 K and largely extended pressure conditions up to ∼10 GPa with a centimeter-sized sample volume. Pressures of the new assembly at high temperatures are investigated by the melting-point method, giving rise to a series of parallel isoforce loading lines associated with thermally induced pressure. For the first time, the high-pressure melting curve of tungsten carbide is determined up to 3800 K and 8 GPa, and single-crystal refractory materials of Mo, Ta, and WC are also grown using the optimized cell.

The metal-insulator transition (MIT) in transition-metal-oxide is fertile ground for exploring intriguing physics and potential device applications. Here, an atomic-scale MIT triggered by surface termination conversion in SrRuO3 ultrathin films is reported. Uniform and effective termination engineering at the SrRuO3 (001) surface can be realized via a self-limiting water-leaching process. As the surface termination converts from SrO to RuO2 , a highly insulating and nonferromagnetic phase emerges within the topmost SrRuO3 monolayer. Such a spatially confined MIT is corroborated by systematic characterizations on electrical transport, magnetism, and scanning tunneling spectroscopy. Density functional theory calculations and X-ray linear dichroism further suggest that the surface termination conversion breaks the local octahedral symmetry of the crystal field. The resultant modulation in 4d orbital occupancy stabilizes a nonferromagnetic insulating surface state. This work introduces a new paradigm to stimulate and tune exotic functionalities of oxide heterostructures with atomic precision.

Significance: The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small-molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development, allowing more selective and quantitative detection of ROS/RNS, especially in live cells. Improvements have been made in sensing reactions, fluorophores, and bioavailability of probe molecules. Critical Issues: In this review, we will not only summarize redox-related small-molecule fluorescent probes but also lay out the challenges of designing probes to help redox biologists independently evaluate the quality of reported small-molecule fluorescent probes, especially in the chemistry literature. We specifically highlight the advantages of reversibility in sensing reactions and its applications in ratiometric probe design for quantitative measurements in living cells. In addition, we compare the advantages and disadvantages of small-molecule probes and protein-based probes. Future Directions: The low physiological relevant concentrations of most ROS/RNS call for new sensing reactions with better selectivity, kinetics, and reversibility; fluorophores with high quantum yield, wide wavelength coverage, and Stokes shifts; and structural design with good aqueous solubility, membrane permeability, low protein interference, and organelle specificity. Antioxid. Redox Signal. 29, 518–540.

MotivationTranscription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data has been widely used to infer the cellular regulatory networks, the methods mainly infer correlations rather than causality. We propose that a causal inference framework successfully used for eQTL data can be extended to infer causal regulatory networks using enhancers as causal anchors and enhancer RNA expression as a readout of enhancer activity.ResultsWe developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM consortium. Predicted causal targets of transcription factors (TFs) in mouse embryonic stem cells, macrophages and erythroblastic leukemia overlapped significantly with experimentally validated targets from ChIP-seq and perturbation data. We further improved the model by taking into account that some TFs might act in a quantitative, dosage-dependent manner, whereas others might act predominantly in a binary on/off fashion. We predicted TF targets from concerted variation of eRNA and TF and target promoter expression levels within a single cell type as well as across multiple cell types. Importantly, TFs with high-confidence predictions were largely different between these two analyses, demonstrating that variability within a cell type is highly relevant for target prediction of cell type specific factors. Finally, we generated a compendium of high-confidence TF targets across diverse human cell and tissue types.AvailabilityMethods have been implemented in the Findr software, available at https://github.com/lingfeiwang/findrContactTom.Michoel@roslin.ed.ac.uk, Anagha.Joshi@roslin.ed.ac.uk

A new image encryption algorithm with low correlation coefficient and high information entropy based on dynamic DNA coding and hyper-chaotic Lorenz system is proposed in this paper. In order to generate the initial values in hyper-chaotic system to construct DNA sequence matrix and dynamic S-box, this algorithm use the SHA-256 algorithm to generate a common key. Then use the SCAN mode and the S-box to scramble the pixel position. In order to scramble the pixel values, this paper uses the DNA sequence matrix to calculate cipher-text. Theoretical analysis and simulation results show that the algorithm improves the sensitivity of key space, and the encryption system can resist statistical attacks and differential attack.

For the first time, a unified surface potential based physical compact model for both unipolar and ambipolar two-dimensional material field effect transistors (2D-FETs) is developed and verified by experimental data. This model is based on the theories of effective transport energy, generalized Einstein relation and multiple defect-induced trapping dynamics. The temperature and carrier density dependent transport (e.g. variable range hopping and nearest neighbour hopping) and metal insulator transition behavior (e.g. hopping to bandlike) are physically incorporated. The predicted transfer and output characteristics of black phosphorous-, WS 2 -and MoS 2 -FETs have excellent quantitative agreement with experimental results. Furthermore, the benchmark of temperature dependent characteristics also confirms the validity of this proposed model. These demonstrate its capability for obtaining deeper understanding on device physics, performance and further optimization. Finally, the compact model is implemented in Verilog-A to evaluate the possibility of using 2D-FETs for digital and RF applications.

Epitaxial strain and chemical doping are two different methods that are commonly used to tune the physical properties of epitaxial perovskite oxide films, but their cooperative effects are less addressed. Here we try to tune the phase separation (PS) in ${(\mathrm{L}{\mathrm{a}}_{1\ensuremath{-}x}\mathrm{P}{\mathrm{r}}_{x})}_{2/3}\mathrm{C}{\mathrm{a}}_{1/3}\mathrm{Mn}{\mathrm{O}}_{3}$ $(0\ensuremath{\le}x\ensuremath{\le}0.4$, LPCMO) films via cooperatively controlling the anisotropic epitaxial strain (AES) and the Pr doping. These films are grown simultaneously on $\mathrm{NdGa}{\mathrm{O}}_{3}(110),{(\mathrm{LaAl}{\mathrm{O}}_{3})}_{0.3}{(\mathrm{SrA}{\mathrm{l}}_{0.5}\mathrm{T}{\mathrm{a}}_{0.5}{\mathrm{O}}_{3})}_{0.7}(001)$, and $\mathrm{NdGa}{\mathrm{O}}_{3}(001)$ substrates with progressively increased in-plane AES, and probed by x-ray diffraction, magnetotransport, and magnetic force microscopy (MFM) measurements. Although it is known that for $x=0$ the AES can enhance the orthorhombicity of the films yielding a phase diagram with the antiferromagnetic charge-ordered insulator (AF-COI) state induced, which is quite different from the bulk one, we illustrate that the Pr doping can further drive the films towards a more robust COI state. This cooperative effect is reflected by the increasing magnetic fields needed to melt the COI phase as a function of AES and the doping level. More strikingly, by directly imaging the phase competition morphology of the $\mathrm{LPCMO}/\mathrm{NdGa}{\mathrm{O}}_{3}(001)$ films via MFM, we find that during COI melting the PS domain structure is subject to both AES and the quenched disorder. However, in the reverse process, as the magnetic field is decreased, the COI phase reappears and the AES dominates leaving a crystalline-orientation determined self-organized microstructure. This finding suggests that the PS states and the domain configurations can be selectively controlled by the AES and/or the quenched disorder, which may shed some light on the engineering of PS domains for device fabrications.