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Perovskite solar cells (PSCs) have shown great potential as a next generation photovoltaic candidate due to the low cost and high efficiency of the devices. However, the ionic and polycrystalline natures of perovskite films lead to high defect densities deteriorating device stability and efficiency, which impedes the practical applications of PSCs. Here, we introduce a novel passivation concept which employs a functional amorphous 5-sulfosalicylic acid (5-SSA)/PbI2 layer with COO− and SO3− groups to suppress defects of under-coordinated Pb2+ ions and iodide vacancies at grain boundaries/surfaces of MAPbI3 films. Furthermore, we find that the amorphous phase can lead to the enlargement of grain size, passivation of defects and suppression of ion migration in the as-deposited perovskite films. Consequently, the 5-SSA/PbI2-modified MAPbI3 devices exhibit efficiencies up to 21.47% and 21.02% on rigid and flexible substrates, respectively. Moreover, the shelf life (3000 h in air with low humidity) and thermal stability (500 h at 60 °C in N2) have been significantly improved. This work provides a promising strategy for overcoming the inherent instability of perovskite films in optoelectronic applications.

Electrical contact is an essential issue for all devices. Although the contacts of the emergent two-dimensional materials have been extensively investigated, it is still challenging to produce excellent contacts. The face and edge type contacts have been applied previously, however a comparative study on the site-specific contact performances is lacking. Here we report an in situ transmission electron microscopy study on the contact properties with a series of 2D materials. By manipulating the contact configurations in real time, it is confirmed that, for 2D semiconductors the vdW type face contacts exhibit superior conductivity compared with the non-vdW type contacts. The direct quantum tunneling across the vdW bonded interfaces are virtually more favorable than the Fowler–Nordheim tunneling across chemically bonded interfaces for contacts. Meanwhile, remarkable area, thickness, geometry, and defect site dependences are revealed. Our work sheds light on the significance of contact engineering for 2D materials in future applications., Here, the authors use in situ transmission electron microscopy to measure the interface properties of electrical contacts with MoS2, ReS2, and graphene, and find that direct quantum tunnelling across van-der-Waals-bonded interfaces is more favourable than Fowler–Nordheim tunnelling across chemically bonded interfaces.

Hybrid perovskite single-crystalline thin films are promising for making high-performance perovskite optoelectronic devices due to their superior physical properties. However, it is still challenging to incorporate them into multilayer devices because of their on-substrate growth. Here, a wet transfer method is used in transferring perovskite single-crystalline films perfectly onto various target substrates. More importantly, large millimeter-scaled single-crystalline films can be obtained via a diffusion-facilitated space-confined growth method as thin as a few hundred nanometers, which are capable of sustaining excellent crystalline quality and morphology after the transferring process. The availability of these crystalline films offers us a convenient route to further investigate their intrinsic properties of hybrid perovskites. We also demonstrate that the wet transfer method can be used for scalable fabrication of perovskite single-crystalline film-based photodetectors exhibiting a remarkable photoresponsivity. It is expected that this transferring strategy would promise broad applications of perovskite single-crystalline films for more complex perovskite devices.

Two-dimensional (2D) ferroelectric materials with unique structure and extraordinary optoelectrical properties have attracted intensive research in the field of nanoelectronic and optoelectronic devices, such as optical sensors, transistors, photovoltaics and non-volatile memory devices. However, the transition temperature of the reported ferroelectrics in 2D limit is generally low or slightly above room temperature, hampering their applications in high-temperature electronic devices. Here, we report the robust high-temperature ferroelectricity in 2D α-In2Se3, grown by chemical vapor deposition (CVD), exhibiting an out-of-plane spontaneous polarization reaching above 200 °C. The polarization switching and ferroelectric domains are observed in In2Se3 nanoflakes in a wide temperature range. The coercive field of the CVD grown ferroelectric layers illustrates a room-temperature thickness dependency and increases drastically when the film thickness decreases; whereas there is no large variance in the coercive field at different temperature from the samples with identical thickness. The results show the stable ferroelectricity of In2Se3 nanoflakes maintained at high temperature and open up the opportunities of 2D materials for novel applications in high-temperature nanoelectronic devices.

Tunnel settlement has a significant impact on property security and personal safety. Accurate tunnel-settlement predictions can quickly reveal problems that may be addressed to prevent accidents. However, each acquisition point in the tunnel is only monitored once daily for around two months. This paper presents a new method for predicting tunnel settlement via transfer learning. First, a source model is constructed and trained by deep learning, then parameter transfer is used to transfer the knowledge gained from the source model to the target model, which has a small dataset. Based on this, the training complexity and training time of the target model can be reduced. The proposed method was tested to predict tunnel settlement in the tunnel of Shanghai metro line 13 at Jinshajiang Road and proven to be effective. Artificial neural network and support vector machines were also tested for comparison. The results showed that the transfer-learning method provided the most accurate tunnel-settlement prediction.

Tin (Sn)‐based perovskites with favorable optoelectronic properties and ideal bandgaps have emerged as promising alternatives to toxic lead (Pb)‐based perovskites for photovoltaic applications. However, it is challenging to obtain high‐quality Sn‐based perovskite films by solution process. Here, liquid‐exfoliated 2D transition‐metal dichalcogenides (i.e., MoS2, WS2, and WSe2) with smooth and defect‐free surfaces are applied as growth templates for spin‐coated FASnI3 perovskite films, leading to van der Waals epitaxial growth of perovskite grains with a growth orientation along (100). The authors find that WSe2 has better energy alignment with FASnI3 than MoS2 and WS2 and results in a cascade band structure in resultant perovskite solar cells (PSCs), which can facilitate hole extraction and suppress interfacial charge recombination in the devices. The WSe2‐modified PSCs show a power conversion efficiency up to 10.47%, which is among the highest efficiency of FASnI3‐based PSCs. The appealing solution phase epitaxial growth of FASnI3 perovskite on 2D WSe2 flakes is expected to find broad applications in optoelectronic devices., Liquid‐exfoliated 2D transition‐metal dichalcogenides (MoS2, WS2, and WSe2) are introduced as growth templates for spin‐coated FASnI3 perovskite films, leading to van der Waals epitaxial growth of perovskite grains with a growth orientation along (100). The good energy alignment in the NiOx/WSe2/FASnI3 structure facilitates hole extraction and suppresses interfacial charge recombination, leading to the best PCE of 10.47% for the PSC.

To realize real-time detection of the operating environment of bridge cranes, this paper presents a three-dimensional mapping method using a binocular camera and laser ranging sensor. First, the left and right images are obtained by using the binocular camera, and the block matching is used for stereo correspondence to obtain the disparity image. Then, according to the reprojection matrix and the disparity image, the depth value of each pixel is obtained, and the depth image can be transformed into a three-dimensional point cloud of the current frame. Relying on the camera position data obtained by the laser ranging sensor, the three-dimensional point cloud generated from different positions is registered to obtain the three-dimensional point cloud of the craneʼs global operating environment. Finally, an octree map is used to represent the operating environment. To simulate the construction process of the operating environment of the bridge crane, an experimental platform was built, and experiments were carried out using the method proposed in this paper. The experimental results verified the feasibility of the method proposed in this paper.

In the process of image fusion between visible and infrared images, the infrared image details are seriously lost, the edge is blurred and the visible image contrast is insufficient, etc., so an image fusion method combining the non sub sampled shear wave transform and guided filtering is proposed. Firstly, the visible and infrared images were decomposed by NSST to obtain the low frequency and high frequency sub bands. Secondly, guided filtering weighted sub band coefficients based on local area definition are used to fuse low frequency sub band coefficients, and improved guided filtering fusion is used to fuse high frequency sub band coefficients. Finally, NSST inverse transformation is used to obtain the fused image.Experimental results on different data sets show that this method is superior to other methods in information entropy, standard deviation, mutual information and other evaluation indexes, which verifies the effectiveness and superiority of the method proposed in this paper.

In this paper, we propose a linear optical implementation scheme of the quantum router. A programming unit is designed. The quantum router makes use of devices which are experimentally realized easily. The signal can be routed into a superposition of output modes through the routing operation, and the spatial degree of freedom of each output mode is related to the control parameter. In addition, the strategy of multistage routing is also exploited on the basis of this router model, and it can exponentially expand the number of output ports. The quantum router is deterministic, rather than probabilistic, no matter how many output ports the quantum router has.

Two-dimensional (2D) materials have been emerging as potential candidates for the next-generation materials in various technology fields. The performance of the devices based on these 2D materials depends on their intrinsic band structures as well as the extrinsic (doping) effects such as surrounding chemicals and environmental oxygen/moisture, which strongly determines their Fermi energy level. Herein, we report the UV treatments on the 2D transition-metal dichalcogenides, to controllably dope the samples without damaging the crystal structures or quenching the luminescence properties. More surprisingly, both n-type and p-type doping can be achieved depending on the initial status of the sample and the UV treatment conditions. The doping mechanisms were elaborated on the atomic scale with transmission electron microscopy and ab initio calculations. The facile doping by UV light has potential to be integrated with photolithography processes, aiming for the large-scale integrated device/circuits design and fabrications.

Layered transition-metal dichalcogenides (TMDCs) have received great interest due to their potential applications in many fields including electronics, optoelectronics, electrochemical hydrogen production and so on. Recent research effort on the development of effective hydrogen evolution reaction (HER) is to modulate the active edge sites through controlling surface structure at the atomic scale. Here we firstly demonstrate a facile strategy to synthesize large-area and edge-rich platinum diselenide (PtSe 2 ) via selenization of Pt films by magnetron sputtering physical deposition method. The edge site density of the PtSe 2 can be effectively controlled by tuning the thickness of Pt films. The HER activity of the PtSe 2 can be enhanced significantly as the active edge site density increases. The maximum cathodic current density of 227 mA/cm 2 can be obtained through increasing the edge density, which well agrees with the density functional theory calculations. Our work provides a fundamental insight on the effect of active edge site density towards HER.

Metals have the best dielectric screening capability among all materials; however, it is usually difficult to fabricate continuous and uniform ultrathin (few-atomic-layer thickness) metal films. Conversely, high-quality atomic-thick semiconductor or semimetal materials (so called two-dimensional materials) such as graphene or MoS2 can be readily obtained and robust in ambient conditions; however, their dielectric screening capabilities are greatly reduced by their reduced dimensionality. Particularly, in the vertical direction, the dielectric screening of two-dimensional materials is insufficient; thus, the performances of devices by two-dimensional materials were easily affected by the coulomb-scattering or other kind of sources. Herein, we propose that with a screw dislocation connecting the van der Waals layers in two-dimensional MoS2 spiral structures, excellent dielectric screening in the vertical direction can be achieved. Our Kelvin force microscopy directly demonstrates that the external impurity ...

Despite numerous studies on two-dimensional van der Waals heterostructures, a full understanding of the charge transport and photoinduced current mechanisms in these structures, in particular, associated with charge depletion/inversion layers at the interface remains elusive. Here, we investigate transport properties of a prototype multilayer MoS2/WSe2 heterojunction via a tunable charge inversion/depletion layer. A charge inversion layer was constructed at the surface of WSe2 due to its relatively low doping concentration compared to that of MoS2, which can be tuned by the back-gate bias. The depletion region was limited within a few nanometers in the MoS2 side, while charges are fully depleted on the whole WSe2 side, which are determined by Raman spectroscopy and transport measurements. Charge transport through the heterojunction was influenced by the presence of the inversion layer and involves two regimes of tunneling and recombination. Furthermore, photocurrent measurements clearly revealed recombina...

Purpose The combination of targeting the CDK4/6 and estrogen receptor (ER) signaling pathways with palbociclib and fulvestrant is a proven therapeutic strategy for the treatment of ER-positive breast cancer. However, the poor physicochemical properties of fulvestrant require monthly intramuscular injections to patients, which limit the pharmacokinetic and pharmacodynamic activity of the compound. Therefore, an orally available compound that more rapidly reaches steady state may lead to a better clinical response in patients. Here, we report the identification of G1T48, a novel orally bioavailable, non-steroidal small molecule antagonist of ER. Methods The pharmacological effects and the antineoplastic mechanism of action of G1T48 on tumors was evaluated using human breast cancer cells (in vitro) and xenograft efficacy models (in vivo). Results G1T48 is a potent and efficacious inhibitor of estrogen-mediated transcription and proliferation in ER-positive breast cancer cells, similar to the pure antiestrogen fulvestrant. In addition, G1T48 can effectively suppress ER activity in multiple models of endocrine therapy resistance including those harboring ER mutations and growth factor activation. In vivo, G1T48 has robust antitumor activity in a model of estrogen-dependent breast cancer (MCF7) and significantly inhibited the growth of tamoxifen-resistant (TamR), long-term estrogen-deprived (LTED) and patient-derived xenograft tumors with an increased response being observed with the combination of G1T48 and the CDK4/6 inhibitor lerociclib. Conclusions These data show that G1T48 has the potential to be an efficacious oral antineoplastic agent in ER-positive breast cancer.

The Narrowband-Internet of Things (NB-IoT) is a new form of the internet of things, characterized by low energy consumption, low bandwidth consumption, wide coverage, and multiple-connectivity. Access to 50,000 terminals can be supported by a single NB-IoT base station. However, when network resources cannot meet the demands of a large number of devices at the same time, network congestion may be induced, reducing data transmission efficiency and throughput and increasing delay. The radio link control layer of the NB-IoT uses sliding windows, timers, and status reports to control data transmission and realize automatic repeat-request retransmission. This paper studies and improves the TCP Westwood (TCPW) congestion algorithm in a communication protocol and proposes an adaptive sliding window algorithm, Polling-TCPW, to optimize the status report mechanism in the RLC protocol stack. Simulation results indicate that the proposed algorithm can effectively increase the throughput and reduce the transmission delay of RLC and guarantee system stability.

Deep learning methods have been widely used in the field of intelligent fault diagnosis due to their powerful feature learning and classification capabilities. However, it is easy to overfit depth models because of the large number of parameters brought by the multilayer-structure. As a result, the methods with excellent performance under experimental conditions may severely degrade under noisy environment conditions, which are ubiquitous in practical industrial applications. In this paper, a novel method combining a one-dimensional (1-D) denoising convolutional autoencoder (DCAE) and a 1-D convolutional neural network (CNN) is proposed to address this problem, whereby the former is used for noise reduction of raw vibration signals and the latter for fault diagnosis using the de-noised signals. The DCAE model is trained with noisy input for denoising learning. In the CNN model, a global average pooling layer, instead of fully-connected layers, is applied as a classifier to reduce the number of parameters and the risk of overfitting. In addition, randomly corrupted signals are adopted as training samples to improve the anti-noise diagnosis ability. The proposed method is validated by bearing and gearbox datasets mixed with Gaussian noise. The experimental result shows that the proposed DCAE model is effective in denoising and almost causes no loss of input information, while the using of global average pooling and input-corrupt training improves the anti-noise ability of the CNN model. As a result, the method combined the DCAE model and the CNN model can realize high-accuracy diagnosis even under noisy environment.

Developing metallic co-catalysts is an effective way to enhance the photocatalytic activity of semiconductor by forming the Schottky junction, but it remains challenging to unveil the design principle. Herein, a novel nanocomposite is prepared by coupling ultra-small WP nanoparticles embedded on N-doped carbon (WP NC) with 2D graphitic C3N4 (g-C3N4). The WP NC and g-C3N4 form an intimate interface via PN chemical bonds at atomic level, which facilitates the flow of photoexcited electrons from g-C3N4 to WP NC. Moreover, the Schottky junction formed at the interface can prevent the charge-carrier recombination in the WP NC/g-C3N4 composite and thus significantly enhance the photocatalytic CO production rate from 29 (bare g-C3N4) to 376 μmol g−1 h−1. As the first example of WP applied on the photocatalytic CO2 reduction, this work demonstrates the potential of metallic WP as a co-catalyst in photocatalysis and provides a useful guide on the phosphide-based material designing.

The engineering of polymorphs in two-dimensional layered materials has recently attracted significant interest. Although the semiconducting (2H) and metallic (1T) phases are known to be stable in thin-film MoTe2, semiconducting 2H-MoS2 is locally converted into metallic 1T-MoS2 through chemical lithiation. In this paper, we describe the observation of the 2H, 1T, and 1T' phases coexisting in Li-treated MoS2, which result in unusual transport phenomena. Although multiphase MoS2 shows no transistor-gating response, the channel resistance decreases in proportion to the temperature, similar to the behavior of a typical semiconductor. Transmission electron microscopy images clearly show that the 1T and 1T' phases are randomly distributed and intervened with 2H-MoS2, which is referred to as the 1T and 1T' puddling phenomenon. The resistance curve fits well with 2D-variable range-hopping transport behavior, where electrons hop over 1T domains that are bounded by semiconducting 2H phases. However, near 30 K, electrons hop over charge puddles. The large temperature coefficient of resistance (TCR) of multiphase MoS2, -2.0 × 10(-2) K(-1) at 300 K, allows for efficient IR detection at room temperature by means of the photothermal effect.

Single-crystalline artificial AB-stacked bilayer graphene is formed by aligned transfer of two single-crystalline monolayers on a wafer-scale. The obtained bilayer has a well-defined interface and is electronically equivalent to exfoliated or direct-grown AB-stacked bilayers.

MoS2 spirals grown by the chemical vapor deposition method, driven by a threading dislocation, has a peculiar rhombohedral-like structure. This threading dislocation can carry helical current in the vertical direction and greatly enhances the vertical conductance in the MoS2 multilayer samples.

Layered van der Waals materials have recently attracted attention owing to their exceptional electrical and optical properties in thin layer form. One way to extend their utility is to form a heterostructure which combines various properties of layered materials to reveal intriguing behavior. Conventional heterostructure synthesis methods are difficult to develop and the heterostructure formed can be limited to a small area. Here, we investigate the phase transformation of SnS2 to SnS by removing sulfur atoms at the top surface using Ar plasma. By varying the plasma power and exposure time, we observed that SnS is subsequently formed on top of the mogul-like structure of SnS2. Since SnS is a p-type semiconductor and SnS2 is an n-type semiconductor, we naturally formed a vertical p-n junction. By using graphene at the top and bottom as transparent electrodes, a vertical p-n diode device is constructed. The device demonstrates good rectifying behavior and large photocurrent generation under white light. This method can be applied to large-area heterostructure synthesis using plasma via phase transformation of various metal dichalcogenides to metal monochalcogenides.

Flexible giant crane boom is a statically indeterminate mixed structure equipped in giant boom cranes. It has a soaring complex geometry consisting of a giant combined boom and a flexible luffing structure, and the overall plastic instability is apt to happen under large hoisting, gravity and wind loads. As dually (geometrically and materially) nonlinear buckling analysis for flexible giant crane booms has not been well studied in literature, a detailed investigation is presented in this paper. Prior to carrying out a dually nonlinear buckling analysis, this paper first undertakes a geometric buckling analysis for a better understanding of the buckling behavior. A method of applying temporary constraints is proposed to prevent the non-convergence issue caused by boom tilting. The incremental load method, the incremental displacement method, and the Newton–Raphson method are applied to evaluate the complete load–deflection response and the accurate critical load. Numerical analyses using the proposed method agree well with the conventional Arc-Length method and the survey results of a crane boom collapse accident. Results show that material nonlinearity is a remarkable factor that weakens the overall stability of the structure. The plastic development of the structure happens mainly in chord members of standard sections. The P − ∆ effect of gravity load on the structure determines the first fracture position in the boom. The methodology developed in this paper can be easily extended for the development and applications of other performance-based approaches for enhancing the stability of flexible giant crane booms.

This paper illustrates the product life-cycle management architecture of construction machinery under the background of the rapid development of new technologies such as big data, cloud computing and internet of things. The significance and definition of product life-cycle management is proposed before analyzing the connection among three different stages in detail. Then a more vivid system diagram called product life-cycle management house is proposed and described specifically as the basis of building product life-cycle management system. The operating mechanism is also stated and four specific applications of product life-cycle management are presented. Finally an integrated life-cycle management system of bucket wheel is given to show the effectiveness of this architecture.

With analyzing the environmental status of law enforcement and job demands, the environmental protection mobile enforcement system was developed based on Android platform and SOA architecture. Using this system, the ability of environmental law enforcement supervision and management was improved, and various environmental administrative law enforcement issues were solved under the limited environmental management resource. Taking Shanxi Province as an example, the environmental protection mobile enforcement system was designed and developed in term of data integration, sharing resources, standardize management and function expansion. This system can been connected to the environmental Internet of Things system which was proved practical.

Background Resistance to endocrine therapy in estrogen receptor positive (ER+) breast cancer drives mortality and despite new targeted therapies, resistance is the obstacle to progression-free survival. Fulvestrant (FUL), a selective estrogen receptor degrader (SERD) was approved in 2017 for first-line therapy of metaststic disease in postmenopausal women; however, acquired FUL-resistance in both first-line setting and in combination therapy with CDK4/6 inhibitor, palbociclib, has been observed clinically. The poor pharmacokinetics of FUL may contribute to acquired resistance. Methods Using structure-based design, we optimized: 1) novel SERDs bearing a basic side chain (B-SERDs) as an orally bioavailable and brain penetrant alternative to FUL; 2) novel pyridinone-based bromodomains and extra-terminal motif (BET) inhibitors to be used in combination with B-SERDs or FUL. Biochemical assays and growth inhibition of breast cancer cell lines, resistant to tamoxifen, and/or FUL, both in 2D and 3D cultures were used to optimize and select development candidates. Drug metabolism and pharmacokinetics(DMPK) demonstrated oral bioavailability and dose selection for validation in mouse xenograft models of endocrine resistant breast cancer. Results B-SERDs showed equivalence to FUL in cell culture models, with respect to ERα degradation and antiproliferative activity; and in contrast to FUL, were demonstrated to have good oral and brain bioavailability. A development candidate with improved DMPK characteristics was effective in endocrine-resistant ER+ xenograft models. Novel BET inhibitors, optimized for potency in binding to BRD4-BD1 and selectivity over the larger family of bromodomain containing proteins, inhibited growth of tamoxifen and FUL-resistant breast cancer cells.Optimized compounds showed superior in vitro activity to eight BET inhibitors in clinical trials. The optimized BET inhibitor was validated alone and in combination with B-SERD in endocrine-resistant xenograft models. Conclusions The combination of B-SERD with BET inhibitor provides a multi-targeted suppression of ER signaling that may extend progression-free survival and cdircumvent acquired resistance in metastatic ER+ breast cancer. Legal entity responsible for the study Gregory R J Thatcher. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Approximately 70% of breast cancer patients have estrogen receptor positive (ER+) tumors. Fulvestrant (FUL), a selective estrogen receptor degrader (SERD) able to ablate ER, was first introduced to clinical practice in 2002 as the second and third line treatment for ER+ metastatic breast cancer. In August 2017, FUL was added to first-line therapy in postmenopausal women by demonstrating superiority compared to first-line AI therapy, anastrozole, with improved progression-free-survival (PFS) and a 20% reduction in the risk of disease progression or death. However, acquisition of FUL-resistance in both first-line setting or as combination therapy with CDK4/6 inhibitor has been observed clinically, leaving patients and oncologists with chemotherapy as the only backup therapy. Little is known about resistance mechanisms to FUL alone or in combination with CDK4/6 inhibitors. Here, we showed that targeting epigenetic vulnerabilities in breast cancer using novel bromodomain and extra-terminal (BET) inhibitors can effectively inhibit growth of tamoxifen-, FUL- and CDK4/6- resistant breast cancer cells. We designed and developed a novel series of pyridinone-based BET inhibitors, optimized by growth inhibition in tamoxifen- and FUL- resistant breast cancer cell lines (MCF7:CFR) in both 2D and 3D cultures. Optimized compounds showed superior in vitro activity to BET inhibitors in clinical trials. Selected compounds were further evaluated for pharmacokinetics and shown efficacy in endocrine-resistant xenograft models. Citation Format: Rui Xiong, Yangfeng Li, Jiong Zhao, Debra Tonetti, Gregory Thatcher. Novel bromodomains and extra-terminal motif (BET) inhibitors developed against estrogen receptor positive, fulvestrant- and CDK4/6-resistant breast cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3830.

Prior to the advent of tamoxifen therapy, estradiol (E2) and the ER agonist, diethylstilbestrol, showed efficacy in the clinical in therapeutic treatment of breast cancer. The adverse effects of these therapeutic options led to discontinuation, despite tamoxifen itself sharing the adverse effect of uterine growth. The perceived therapeutic action of tamoxifen in countering the proliferative actions of E2 at the estrogen receptor (ER) in endocrine-sensitive breast tissues is not entirely compatible with the therapeutic actions of E2 itself in breast cancer, and points to a more complex role for ER. Tamoxifen is the standard of care for many patients with ER+ breast cancer; however significantly, 30-50% of women are resistant to tamoxifen therapy. Development of a Selective Estrogen Mimic (SEM) that is effective in breast cancer without uterotrophic and other side effects is a novel treatment option that we hypothesize will be effective in causing regression of tamoxifen-resistant breast cancer. We theorize that a rational approach would be an ER ligand with pharmacological partial agonist actions, thus able to mimic E2 in regressing breast cancer, but with antagonist actions in the face of excessive ER activation. Using the benzothiophene scaffold common to the clinical Selective Estrogen Receptor Modulators (SERMs), raloxifene and arzoxifene, we hypothesized that an ideal SEM could be designed by structural engineering. A library of over 30 compounds was developed and assayed in tamoxifen-resistant cell lines, including MCF-7 and T47D. One SEM was assayed in two mouse xenograft models and shown to cause tumor regression; impressively this SEM did not fuel growth of estrogen-dependent T47D xenografts and did not cause uterine growth. This SEM and several other compounds were observed to act as partial agonists at ERα, with variable actions at ERβ. To understand this phenomenon further, the contributions of apoptotic mechanisms and cell cycle arrest to SEM activity was studied in cell cultures. The results collected to date on SEMs that act as partial agonists at ERα indicate that this is a viable, new approach to breast cancer therapy. Citation Format: Gregory RJ Thatcher, Rui Xiong, Hitisha K Patel, Jiong Zhao, Xiao Liang, Yue-ting Wang, Mary Ellen Molloy, Debra Tonetti. Novel, non-uterotrophic, selective estrogen mimics cause regression of tamoxifen-resistant breast cancer in 2D and 3D cultures and in mouse xenograft models [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-05-23.

There are less topology optimization methods for bars structure than those for continuum structure. Bionic intelligent method is a powerful way to solve the topology optimization problems of bars structure since it is of good global optimization capacity and convenient for numerical calculation. This article presents a SKO topology optimization model for bars structure based on SKO (Soft Kill Option) method derived from adaptive growth rules of trees, bones, etc. The model has been applied to solve the topology optimization problem of a space frame. It uses three optimization strategies, which are constant, decreasing and increasing material removed rate. The impact on the optimization processes and results of different strategies are discussed, and the validity of the proposed model is proved.

The intellectual environmental management can be realized accurately by applying the technology of the Internet of Things (IOT) to sense the environmental monitoring object and to precede the data mining application based on the monitoring. Taking Shanxi Province’s environmental IOT system as an example, this system had been achieved real time monitoring .The monitoring data has been applied to the total pollutant emission reduction verification, pollutant emission charge, administrative penalties, total pollutant emission dynamic management, pollutant emission allowance trade, and environmental mobile law-enforcing system, which provides a solid platform for the environmental management .Applying the technology of the IOT, using the “Whole Circle”environmental management, combining the environmental economic means, the innovation in methods, mechanism and supervision of environmental protection system can be realized.

Nowadays, along with the higher requirement of the customer and the standardization of enterprise management, the finished product of steel bar production must be standardization packaged by root number; management requirements of bar fixed bundle of sticks are more stringent. The artificial count is used into the most of the steel bar production recently. So there are many problems. Such as labor intensity, easy fatigue, less efficient, and error-prone. The image recognition technology for online automatic counting system for a given period of time. It also can improve the speed and make the product more accuracy. This paper mainly talks about the system composition and image processing algorithm.

In HSV color space, the current vector morphological operators have low capability to reduce color noise caused by hue and saturation in color image processing. Because they sort the color pixels according to the hierarchical ordering of V, S, H, which is against the equal principle of the three channels in color image processing. A novel vector ordering based on the combination of H, S and V is proposed in this paper, and the associated vector morphological erosion, dilation and composite filtering operators are defined. Compared with the popular vector morphological operators, experimental results show that the new operators can reduce the color noise effectively without any new color pixels while preserving the image details. And the filtered images have higher peak signal-to-noise ratio (PSNR) and lower mean absolute error (MSE).

Instantaneous electrical breakdown measurements of GaN and Ag nanowires are performed by an in situ transmission electron microscopy method. Our results directly reveal the mechanism that typical thermally heated semiconductor nanowires break at the midpoint, while metallic nanowires breakdown near the two ends due to the stress induced by electromigration. The different breakdown mechanisms for the nanowires are caused by the different thermal and electrical properties of the materials.

Supplemental Digital Content is available in the text, The benefit gained by replacing physicians in the prehospital service is still controversial. The present study compared the difference of achievements of pre-hospital emergency between the physicians from public hospitals and those from the Emergency Medical Center. We included prehospital emergency patients who were sent to the hospital by ambulance after emergency calls from February 1 to May 31, 2016, in Shanghai (24,250,000 inhabitants). Cohort characteristics and diagnoses were described, and the data were analyzed using the Shanghai Emergency Medical Center's database software. We determined whether the physicians from public hospitals were associated with greater success rate of cardiopulmonary resuscitation (CPR) and examined the diseases category and the number of patients with cardiac arrest in prehospital emergency patients. During February 1, 2016, to May 31, 2016, the total turnout of ambulances in the urban area of Shanghai was 107,341 times, among which, first aid was 55,053 times. The number of patients with cardiac arrest was 3012, the 3 principal causes for cardiac arrest were Unknown diagnosis (45.19%), Cardiovascular disease (28.02%) and Respiratory diseases (11.09%), and the successful rate of CPR was 1.56%. The number of critically ill patients, encountered by the physicians from public hospitals, was 10.33% as compared to those from the Emergency Medical Center, which was 11.77% (P .05). Transferring the physicians from public hospitals to work in Emergency Medical Center showed no improvement in the success rates of resuscitation.

Endocrine therapy is the standard of care for breast cancer expressing estrogen receptor (ER), which occurs in 70% of patients. Unfortunately, acquired or de novo resistance to endocrine therapy is observed in up to 50% of patients, leaving a significant portion of patients with insufficient treatment options. Endocrine-resistance, usually defined as resistance to tamoxifen and aromatase inhibitor (AI) therapy, can also include resistance to selective estrogen receptor degraders (SERDs), since these also target ER. Since multiple mechanisms contribute to resistance, development of multiple resistant cell lines is needed for drug discovery and to identify characteristics that may suggest susceptibility to alternative and combination therapies. We have developed 5 stable, endocrine-resistant cell lines from a parent MCF-7 cell line, which all retain ER: one of these cell lines, MCF-7:CFR is resistant to the SERD fulvestrant. Clinical metastatic breast cancers that have gained endocrine resistance are overwhelmingly ER+. In addition to ER, progesterone receptor (PR) and glucocorticoid receptor (GR) status of these lines was assessed, and correlated with the response of these cells in culture to four classes of endocrine therapeutics: SERDs, selective ER modulators (SERMs), and selective human ER partial agonists (ShERPAs). Growth of all 5 cell lines was endocrine independent, indicating resistance to AI therapy. Two of the ER+, PR- cell lines were most resistant to the spectrum of endocrine therapies, but these cell lines both showed sensitivity to ShERPAs, especially in combination with non-endocrine targeted therapies, such as the PI3K inhibitor, alpelisib. Paradoxically, all endocrine-resistant cell lines responded to at least one of the endocrine therapies tested, demonstrating that if ER is not lost in the metastatic state, it remains a vulnerability suitable for therapeutic targeting. Citation Format: Lauren M. Gutgesell, Rui Xiong, Jiong Zhao, Huiping Zhao, Debra A. Tonetti, Gregory R. Thatcher. Multiple endocrine-resistant breast cancer cell lines retain ER and sensitivity to endocrine therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3744.

1 out of every 8 U.S. women will develop invasive breast cancer during her lifetime, making it the second most common form of cancer affecting women. Breast cancer is also a leading cause of cancer related deaths for women in the U.S., second only to lung cancer. Activation of estrogen receptor alpha (ERα) is the primary proliferative mechanism of breast cancer cells, making it a logical target for therapy. ER ligands with antiestrogenic activity, such as the selective estrogen receptor modulator (SERM), tamoxifen, and selective estrogen receptor degrader (SERD), fulvestrant, have proven clinically successful as treatments for breast cancer; however, resistance in up to 50% of patients provides a therapeutic challenge. Once resistant, breast cancer cells become endocrine-independent, because of this, there is an urgent need for both novel therapy and improved models of resistant breast cancer. Our lab has created a panel of various endocrine-independent cell lines to mimic SERM and SERD resistance. Along with traditional 2D cell culturing, 3D spheroids have also been utilized to gain a better understanding of resistance. Importantly, the response to therapeutic agents, of cell lines in 2D versus 3D cultures is not identical. We observe that 3D cultures better replicate observations in mouse xenograft models, demonstrating that elements of the spheroid microenvironment, such as cell-cell interactions and the presence of extracellular matrix (EM), mimic aspects of the tumor microenvironment in vivo. Cells cultured as spheroids are therefore a suitable in vitro model for drug discovery, predictive of response in preclinical animal models, in contrast to 2D monolayer cell cultures. Citation Format: Carlo I. Rosales, Jiong Zhao, Lauren M. Gutgesell, Rui Xiong, Debra A. Tonetti, Gregory R. Thatcher. Three-dimensional treatment-resistant breast cancer spheroids as a predictive model of in vivo response to endocrine therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3738.

Profibus and CAN bus are two kinds of widely used field bus in the industrial control field. However, this two bus protocol conversion devices are not introduced on the market, it can not meet the needs of users. Therefore, the design of a Profibus and CAN protocol translation ngateway is very important. By comparing the OSI reference model, the same points of Profibus and CAN bus can be found, their communication model structure is streamlined by the OSI model, they are only three layers, which makes it possible to interconnect them. This paper designs an embedded protocol conversion gateway, S3C2410 processor is used as main controller, SPC3 and SJA1000 are selected as Profibus and CAN protocol chips. The design has realized Profibus and CAN bus protocol conversion, using this gateway in industrial field can bring certain economic benefits for the enterprise.

The effect of high-energy (200 keV) electron irradiation on ZnO-tetrapod (ZnO-T) nanostructure has been investigated by employing in situ scanning tunneling microscopy (STM) holder inside TEM. The microscopic results have revealed that the product consists of highly single-crystalline ZnO-T structures. The photoluminescence spectra show the increased amount of defects which lead to shift in the emission peak position in ultraviolet (UV) region and enhance the PL performance in visible luminescence (VL) region of ZnO-T nanocrystals. The in situ measurements show asymmetric Schottky contacts at the both ends interfaces under electron irradiation. The current–voltage ( I – V ) characteristics have revealed that the increase in electron density (range of ∼0–25 pA cm −2 ) leads to an increase in the current along with the increase in carrier concentration from 1.1 × 10 17 cm −3 to 3.2 × 10 17 cm −3 . In addition, it has been interestingly found that at high bias voltage, Schottky contacts turn to Ohmic contacts at the both ends with the influence of irradiation–matter interaction. The results strongly suggest that the ZnO-T is considered as a promising candidate for applications in irradiation environments.

Approximately 75% of breast cancer incidences are Estrogen Receptor positive (ER+). Treatment of ER+ breast cancer with antiestrogen endocrine therapy targets the proliferative mechanisms of ER using selective ER modulators (SERMs), such as tamoxifen, and selective ER downregulators (SERDs), such as fulvestrant. The resistance to endocrine therapy, either innate or acquired, is clinically diagnosed in up to 50% of patients within 5 years of treatment. Antiestrogen therapy of ER+ mammary cancer cells in vitro and in xenografts does not cause complete cell death or regression. Through the use of combination therapy to target the remaining sub-population of cells, complete regression can be predicted. Our lab has developed endocrine tamoxifen-resistant models through prolonged exposure to tamoxifen, estrogen deprivation, and overexpression of PKCα, a pro-survival pathway component, in addition to a fulvestrant-resistant model through prolonged exposure to fulvestrant. Investigation of the resistance mechanisms will provide insight into potential, combinatorial targets for overcoming endocrine resistance in ER+ breast cancer. Use of spheroidal 3D cell culture provides a physiologically relevant model with sufficient throughput for drug discovery. Establishing spheroids and subsequent treatment predicts the efficacy of combination treatment on tumor regression. Targeting pathways associated with increased prevalence of resistance, such as CDK 4/6, can be employed for clinical therapy. Using both novel in-house and clinical SERMs and SERDs, we have used these multiple cell lines to discover combinatorial targets using both mechanistic and unbiased screening approaches. The use of combination endocrine therapy in tamoxifen-resistant models has shown antiproliferative synergy, and is able to enhance tumor regression in xenografts. By optimizing combinatorial endocrine treatment against both fulvestrant- and tamoxifen-resistance, novel therapeutic approaches are being developed for ER+ breast cancer. Citation Format: Lauren M. Gutgesell, Rui Xiong, Jiong Zhao, Debra A. Tonetti, Gregory R. Thatcher. Optimizing combination therapy against antiestrogen-resistance in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3603. doi:10.1158/1538-7445.AM2017-3603

e14090 Background: The high prevalence of treatment resistance for estrogen receptor positive (ER+) breast cancer cause more deaths than all other breast cancers, despite the availability of endocrine therapeutics including selective ER downregulators (SERDs). Before tamoxifen, high dose estradiol (E2) delivered clinical efficacy slightly superior to tamoxifen. While recent clinical trials have shown efficacy of low dose E2, unacceptable side effects including vaginal bleeding, endometrial hypertrophy, and the negative perceptions of both patients and physicians limit acceptance. In preclinical models, tamoxifen resistant (TR) breast cancer is sensitive to treatment by E2. TTC-352 is an orally bioavailable selective human ERα partial agonist (ShERPA) designed to mimic E2 in causing tumor regression of TR breast cancer xenografts without uterine proliferation caused by E2 and tamoxifen. Methods: The published preclinical efficacy studies were extended to multiple TR ER+ cell lines in 3D spheroid cell cultures comparing to E2 and the SERD GDC0810. The maximum tolerated dose (MTD) was determined in Sprague-Dawley rats at: 200, 300, 600, 1000 and 2000 mg/kg by oral gavage (N = 3). Animals were observed for 7 days prior to necropsy. A single MTD range finding study was performed in dogs at: 50, 100, and 200 mg/kg TTC-352, administered orally in gelatin capsules. Based on these results, a 7-day repeated dose studies were completed at 30, 100, 300 and 1000 mg/kg/day in rats (3/sex/dose) and 15, 75, and 150 mg/kg (2/sex/dose) in dogs. Results: Growth of three TR ER+ breast cancer cell cultures in 3D was inhibited by TTC-352, which mimicked E2 and was equivalent to GDC0810. In female rats MTD was 1000 mg/kg and TTC-352 was well tolerated following a single oral dose of 200, 300, 600 mg/kg. The oral administration of TTC-352 at doses of 30, 100, and 300 mg/kg/day in rats (both sexes) and 15, 75 or 150 mg/kg/day in dogs (both sexes) for seven days was generally well tolerated. Conclusions: TTC-352 has demonstrated efficacy in preclinical models of TR breast cancer. Completed rat and dog studies indicated favorable tolerability and rapid absorption up to 300 mg/kg/day in rats and 150 mg/kg/day in dogs.

To realize the lightweight design of the combinatorial jib, the design theory of the combinatorial jib was analyzed, and the sectional dimensions and the limb spacing were taken as design variables. Based on the rigidity, strength, and stability of the combinatorial jib, the mathematical model of lightweight design of the combinatorial jib was established. Then, a practical problem was studied. Moreover, the mathematical model was solved, and its lightweight design solution was obtained. The results demonstrated the validity of the solution, and it provided a certain way to realize the lightweight design of the combinatorial jib in engineering.

Defects in bulk crystals can be classified into vacancies, interstitials, grain boundaries, stacking faults, dislocations, and so forth. In particular, the vacancy in semiconductors is a primary defect that governs electrical transport. Concentration of vacancies depends mainly on the growth conditions. Individual vacancies instead of aggregated vacancies are usually energetically more favorable at room temperature because of the entropy contribution. This phenomenon is not guaranteed in van der Waals 2D materials due to the reduced dimensionality (reduced entropy). Here, it is reported that the 1D connected/aggregated vacancies are energetically stable at room temperature. Transmission electron microscopy observations demonstrate the preferential alignment direction of the vacancy chains varies in different 2D crystals: MoS2 and WS2 prefer 〈2¯11〉 direction, while MoTe2 prefers 〈1¯10〉 direction. This difference is mainly caused by the different strain effect near the chalcogen vacancies. Black phosphorous also exhibits directional double-chain vacancies along 〈01〉 direction. Density functional theory calculations predict that the chain vacancies act as extended gap (conductive) states. The observation of the chain vacancies in 2D crystals directly explains the origin of n-type behavior in MoTe2 devices in recent experiments and offers new opportunities for electronic structure engineering with various 2D materials.

Among various transition metal dichalcogenides, MoTe2 has drawn attention due to its capability of robust phase engineering between semiconducting (2H) and semi-metallic distorted octahedral (1T') phase. In particular, 1T'-MoTe2 has been predicted to have intriguing physics such as quantum spin Hall insulator, large magnetoresistance, and superconductivity. Recent progress showed weak antilocalization behavior in 1T'-MoTe2 which is the one of representative characteristics in topological insulator. Here, we grow centimeter-scale monolayer 1T'-MoTe2 on SiO2/Si substrate via chemical vapordeposition and demonstrate dichroism in visible range. Ribbon-like 1T'-MoTe2 flakes were initially nucleated randomly on SiO2 substrate and at a later stage merged to form a continuous monolayer film over the entire substrate. Each flake revealed one dimensional Mo–Mo dimerization feature and anisotropic absorption behavior in visible range (400–600 nm). This allowed us to detect the grain boundary due to stark contrast difference among flakes in different orientations.

Approximately 70% of breast cancer patients are estrogen receptor positive (ER+). Aromatase inhibitors and the selective estrogen receptor modulator (SERM), tamoxifen, are the first line treatments for these patients; however, almost 50% of patients either do not respond or acquire resistance. Multiple mechanisms, including mutations of the ESR1 gene, contribute to resistance via ligand-independent constitutive activation of ER. Selective estrogen down-regulators (SERDs) that block ligand-dependent and independent ER signaling by ablation of ER, offer a therapeutic approach to treatment-resistant, advanced stage and early stage ER+ breast cancer. Therapeutic use of the first generation SERD, fulvestrant (Faslodex), has largely remained 2nd and 3rd line, because of poor physiochemical/pharmacokinetic properties. Novel benzothiophene based SERDs were designed, synthesized, and optimized and assayed in three tamoxifen-resistant (TR), endocrine-independent ER+ MCF-7 and T-47D cell lines. Cell viability, ERE-luciferase response, and ER degradation was measured and compared to parent endocrine-dependent MCF-7 and T-47D cell lines in 2D and/or 3D spheroid cell cultures and compared to SERDs, fulvestrant and GDC-0810. Pharmacokinetic analysis was used to select novel SERDs for xenograft studies. Citation Format: Rui Xiong, Jiong Zhao, Lauren Gutgesell, Debra Tonetti, Gregory Thatcher. Novel selective estrogen receptor downregulators developed using endocrine-independent breast cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3902.

In this letter, effect of Pb-doping on the electrical and optical properties of the as grown ZnO nanowires (NWs) have been investigated. The microstructural investigations show that the Pb-dopant substituted into wurtzite ZnO nanowires without forming any secondary phase. The amount of contents and valence state of Pb ions has been investigated through energy dispersive spectroscopy and X-ray photospectroscopy. The doped nanowires show a remarkable reduction of 15.3 nm (127.4 meV) in the optical band gap, while an increase amount of deep-level defects transition in visible luminescence. Furthermore, the reduction in the band gap and the presence of deep-level defects induces strong effect in the electrical resistivity of doped NWs, which makes their potential for the fabrication of nanodevices. The possible growth mechanism is also briefly discussed.

An interacting multiple model probability data association method for tracking the wake target is presented. When the detections are fed to a tracking system like the Probabilistic Data Association Filter, the estimated track can be misled and sometimes lose the real target because of the wake. This problem becomes even more severe when the target performs maneuvering in the presence of wakes. To prevent this, we propose a probabilistic model of the wakes and deduce the new probability association coefficient, for the target's maneuvering, the Interacting Multiple Model is applied. Simulation result shows, compared with the Interacting Multiple Model Probabilistic Data Association method, the new method could reduce the target loss effectively and retain low target loss ratio with augmenting measurement noise.

Based on the ideas of feature fusion and Kernel Canonical Correlation Analysis (KCCA), a novel framework for fusing global and local features on Automatic Target Recognition (ATR) algorithm is proposed. Firstly, the feature fusion method based on KCCA is established, then pseudo Zernike moments and Scale Invariant Feature Transform (SIFT) are extracted as global features and local features. K-means algorithm is applied to normalize the local features to obtain the same form as global features. After the fusion of two features, one-against-all Support Vector Machine (SVM) is employed as classifier for the Multi-class target recognition. Theoretical analysis and experiments on aircraft images results show that KCCA features fusion representations significantly outperform CCA fusion method and single feature approach. Feature fusion of global features and local features based on target image for recognition are proved to be a promising strategy in object recognition field.

A high estimate accuracy fusion method for multisensor tracking association is presented. Based on the analysis of the state fusion and measurement fusion methods, the estimating effects of the two methods are compared. Considering the measurement covariance's influence on the fusion result, we assign the elements of the measurement covariance matrix to the measurements from different sensors as their weights, and combine the weighted measurements to form the new measurement which is used in the Kalman filter. The simulation shows the new method's estimate accuracy is much higher than the state and measurement fusion methods.

The classification problem of small target is a very significant but challenging task in the field of automatic target recognition. In this paper, an enhanced support vector machine with the wavelet kernel function was proposed. In order to concentrate on the classification, It is assumed that regions containing possible targets are provided. Then the Hu's moment invariants are chosen as the feature vectors used for classifiers. Finally, the classification is performed by a support vector classifier used Db4 wavelet kernel. Compared to the Gaussian kernel classifier, simulation results show that this method leads to a more admissible result in terms of classification accuracy and robustness.

Tamoxifen, an antagonist at estrogen receptor alpha (ERα) in breast tissue, and the prototypical selective estrogen receptor modulator (SERM), is the standard of care for many patients with ER-positive breast cancer. However, continued tamoxifen treatment increases the risk of endometrial cancer and half of ER-positive breast cancer patients do not respond or relapse on treatment with tamoxifen. Tamoxifen-resistant tumors are often ER-positive and endocrine-independent and therefore resistant to aromatase inhibitors. Recent clinical trials have shown the efficacy of estrogen in patients who have undergone exhaustive tamoxifen therapy. Therefore, we propose the development of small molecules that mimic the actions of estradiol in ER-positive breast cancer without the uterotrophic actions of estradiol and tamoxifen: Selective Estrogen Mimics (SEMs). Evidence suggest that a significant subset of ER-positive breast cancer, over-expressing PKCα, and tamoxifen-resistant cancers will respond to SEMs. In order to design and optimize SEMs, tamoxifen-resistant cell lines, MCF-7:5C, T47D: PKCα and T47D: Tam1 were studied. The activation of classical ERα signaling by the estrogen mimics was profiled in MCF-7 cells and cell viability in 2D culture was examined. In an effort to increase throughput and mimic the in vivoenvironment more closely, we assessed the SEMs in a new 3D spheroid model. It was found that in MCF-7:5C cells in 2D and T47D spheroids that SEM induced cell death was mediated by activation of ERα. SEMs caused decreased spheroid viability and growth in all three models of tamoxifen resistance. Extranuclear localization of ER after SEM treatment previously reported in matrigel assays and in vivo xenografts was also observed in spheroids. This emphasizes the capability of the 3D spheroids to replicate in vivo environments, making them a high-throughput translational assay of choice for drug discovery. Three promising SEMs were evaluated in xenograft models of TAM-resistant, PKCα overexpressing breast cancer. While E2 caused regression of these tumors, a significant increase in uterine weight as predicted was observed. More importantly, SEM treated mice had negligible increase in uterine weight underlining the enhanced safety of these molecules. These data suggest that development of SEMs that retain the beneficial properties of estrogen while limiting the side effects is a feasible strategy for the treatment of tamoxifen resistant breast cancer. Citation Format: Hitisha Patel, Rui Xiong, Lauren Gutgesell, Jiong Zhao, Mary Ellen Molloy, Debra Tonetti, Gregory R.J Thatcher. Selective estrogen mimics (SEMs) for the treatment of tamoxifen resistant breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C98.