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Although endocrine therapies targeting estrogen receptor α (ERα) are effective in managing ER positive (+) breast cancer, many patients have primary resistance or develop resistance to endocrine therapies. In addition, ER+ breast cancer with PIK3CA activating mutations and 11q13-14 amplification have poor survival with unclear mechanism. We uncovered that higher expression of deubiquitinase USP35, located in 11q14.1, was associated with ER+ breast cancer and poor survival. Estrogen enhanced USP35 protein levels by downregulating USP35-targeting miRNA-140-3p and miRNA-26a-5p. USP35 promoted the growth of ER+ breast cancer in vitro and in vivo, and reduced the sensitivity of ER+ breast cancer cells to endocrine therapies such as tamoxifen and fulvestrant. Mechanistically, USP35 enhanced ERα stability by interacting and deubiquitinating ERα, and transcriptional activity of ERα by interacting with ERα in DNA regions containing estrogen response element. In addition, AKT, a key effector of PI3K, phosphorylated USP35 at Serine613, which promoted USP35 nuclear translocation, ERα transcriptional activity, and the growth of ER+ breast cancer cells. Our data indicate that USP35 and ERα form a positive feedback loop in promoting the growth of ER+ breast cancer. USP35 may be a treatment target for ER+ breast cancer with endocrine resistance or with PIK3CA mutations or hyperactivation of the PI3K pathway.

Recent angle-resolved $c$-axis resistivity measurements of the stripe-ordered La$_{2-x}$Ba$_x$CuO$_4$ (LBCO) with $x=1/8$ revealed an unexpected dependence on the direction of the in-plane magnetic field. We argue that these and other available data for the $c$-axis transport point to the existence of superconducting pairs of two different types in the $x=1/8$ LBCO below the stripe ordering temperature. The pairs of one type carry finite momentum and are confined to the Cu-O planes; the pairs of other type (probably the conventional $d$-wave with zero momentum) propagate along narrow conducting channels traversing the sample in the $c$-axis direction. The evidence for this comes from the observed exponential temperature dependence of the $c$-axis resistivity $\rho_c(T)$ which we attribute to the thermally excited slips of the superconducting phase and flux flows. We present a simple theory to fit the observed $\pi/2$-periodic dependence of $\rho_c$ on the direction of the in-plane magnetic field and the other data., Comment: 13 pages, 12 figures

Mucin 1 (MUC1) has been regarded as an ideal target for cancer treatment, since it is overexpressed in a variety of different cancers including the majority of breast cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1. In this study, we generated a humanized MUC1 (HzMUC1) antibody from our previously developed MUC1 mouse monoclonal antibody that only recognizes MUC1 on the surface of tumor cells. Furthermore, an antibody-drug conjugate (ADC) was generated by conjugating HzMUC1 with monomethyl auristatin (MMAE), and the efficacy of HzMUC1-MMAE on the MUC1-positive HER2+ breast cancer in vitro and in 'Xenograft' model was tested. Results from western blot analysis and immunoprecipitation revealed that the HzMUC1 antibody did not recognize cell-free MUC1-N in sera from breast cancer patients. Confocal microscopy analysis showed that HzMUC1 antibody bound to MUC1 on the surface of breast cancer cells. Results from mapping experiments suggested that HzMUC1 may recognize an epitope present in the interaction region between MUC1-N and MUC1-C. Results from colony formation assay and flow cytometry demonstrated that HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in trastuzumab-resistant HER2-positive breast cancer cells. Meanwhile, HzMUC1-MMAE significantly reduced the growth of HCC1954 xenograft tumors by inhibiting cell proliferation and enhancing cell death. In conclusion, our results indicate that HzMUC1-ADC is a novel therapeutic drug that can overcome trastuzumab resistance of breast cancer. HzMUC1-ADC should also be an effective therapeutic drug for the treatment of different MUC1-positive cancers in clinic.

In this letter, a cascade-based de-embedding method with thru-halfthru-short structures is presented for millimeter-wave on-wafer device characterization. Distributed effects of interconnect, discontinuity between pad and interconnect, and transistor-access-via-holes are all well considered using only three dummy structures, and forward coupling is also investigated. By providing both extracted junction capacitors and S-parameter results of 0.5- $\mu \text{m}$ InP DHBT transistor using proposed and existing de-embedding methods up to 220 GHz, better high frequency performance and particularly 21° improvement in phase accuracy for ${\text {S}}_{11}$ as well as 12° for ${\text {S}}_{21}$ at 220 GHz are obtained compared with the state-of-the-art cascade-based method.

Electro-optic phase modulators are critical components in modern communication, microwave photonic, and quantum photonic systems. Important for these applications is to achieve modulators with low half-wave voltage at high frequencies. Here we demonstrate an integrated phase modulator, based on a thin-film lithium niobate platform, that simultaneously features small on-chip loss (~ 1 dB) and low half-wave voltage over a large spectral range (3.5 - 4.5 V at 5 - 40 GHz). By driving the modulator with a strong 30-GHz microwave signal corresponding to around four half-wave voltages, we generate an optical frequency comb consisting of over 40 sidebands spanning 10 nm in the telecom L-band. The high electro-optic performance combined with the high RF power-handling ability (3.1 W) of our integrated phase modulator are crucial for future photonics and microwave systems., 5 pages, 4 figures

In this paper, we present a newly designed parameter extraction method of the Schottky barrier diode (SBD) with the purpose of measuring and studying its parasitic properties. This method includes three kinds of auxiliary configurations and is named as three-configuration parameter extraction method (TPEM). TPEM has such features as simplicity of operation, self-consistence, and accuracy. With TPEM, the accurate parasitic parameters of the diode can be easily obtained. Taking a GaAs SBD as an example, the pad-to-pad capacitance is 7 fF, the air-bridge finger self-inductance 11 pH, the air-bridge finger self-resistance 0.6 Ω, and the finger-to-pad capacitance 2.1 fF. A more accurate approach to finding the value of the series resistant of the SBD is also proposed, and then a complete SBD model is built. The evaluation of the modeling technology, as well as TPEM, is implemented by comparing the simulated and measured I-V curves and the S-parameters. And good agreements are observed. By using TPEM, the influence of the variation of the geometric parameters is studied, and several ways to reduce the parasitic effect are presented. The results show that the width of the air-bridge finger and the length of the channel are the two largest influencing parameters, with the normalized impact factors 0.56 and 0.29, respectively. By using TPEM and the modeling technology presented in this paper, a design process of the SBD is proposed. As an example, a type of SBD suitable for 500–600 GHz zero-biased detection is designed, and the agreement between the simulated and measured results has been improved. SBDs for other applications could be designed in a similar way.

This article introduces the design process of a 220 GHz subharmonic mixer with low conversion loss, which is comprised of a pair of anti-parallel Schottky diodes (SBD). For terahertz circuits, the wavelength of the electromagnetic (EM) wave is very close to the size of devices, which results in complicated parasitic effects. This will leads to a very limited optimization space for circuits design when matching the impedance. To solve this problem, we developed the precise 3D EM planar SBD model and the field-circuit co-simulation method to design this terahertz mixer. The diodes are mounted on the quartz-based suspended microstrip line. The measured results show that the single side band conversion loss is less than 12 dB during radio frequency (RF) range from 211 to 226 GHz and the minimum loss is about 5.9 dB. With the intermediate frequency fixed at 1 GHz, the conversion loss varies from 8 dB to 11.2 dB over the RF bandwidth of 211 to 221 GHz. The mixer can be applied in heterodyne receivers of terahertz systems. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:2311–2316, 2016

In this article, a 220 GHz frequency tripler using three-dimensional (3D) electromagnetic simulation is designed. Due to the characteristics of extremely short working wavelength and ultra-small circuit size of terahertz frequency multipliers, complicated parasitic effect cannot be ignored, which leads to a limited optimization space for circuit matching in the design of terahertz components. In this article, a precise 3D electromagnetic (EM) model of the planar Schottky barrier diode (SBD) is established and the field-circuit co-simulation method is proposed for the design of the 220 GHz tripler. Compared with the varistor diode, the frequency multiplier based on the varactor diode will produce higher output power due to its lossless mechanism. The measured results show that the output power is higher than 5 mW in the frequency range 220∼228 GHz, with the maximum output power of 6.34 mW. Typical conversion loss is 15 dB in the frequency range 216∼232 GHz. The frequency tripler has the characteristics of compact size, low loss, and high output power. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:1647–1651, 2016

The present work is aimed at studying the properties of α-FeOOH adsorption for removing Cr(VI) from aqueous solution. Batch adsorption experiments were carried out to measure the influences of various parameters (contact time, pH of the medium and adsorbent dosage) for Cr(VI) adsorption taking place on the α-FeOOH nanoparticles surface. Results showed that the process of Cr(VI) adsorption was strongly dependent on the pH, displaying that the adsorption efficiency of Cr(VI) reached the maximum in the pH 3 at an initial Cr(VI) load of 15 mg/L. The thermodynamic parameters such as enthalpy change (ΔH0), entropy change (ΔS0), Gibbs free energy (ΔG0) and Isosteric heat of adsorption were also estimated. The negative value of ΔG0 and positive value of ΔH0 indicated a spontaneous and an endothermic thermodynamically adsorption process, respectively. The values of ΔHx demonstrated that the interaction between α-FeOOH nanoparticles and Cr(VI) was primarily physical adsorption. The adsorption process of Cr(VI) could be simulated by the pseudo-second-order kinetic equation. Intra-particle diffusion model showed that the overall adsorption rate of α-FeOOH for Cr(VI) was dominated by the film diffusion process with some degree of intra-particle diffusion.

We developed a comprehensive semiclassical theory of solitons in one dimensional systems at BCS-BEC crossover to provide a semiclassical explanation of their excitation spectra. Our semiclassical results agree well with the exact solutions on both the deep BCS and deep BEC side and explain qualitatively the smooth crossover between them. Especially, we showed that the minimum energy of the $S=1/2$ excitation is achieved exactly at the Fermi momentum $k_F=\pi n/2$, where $nm_F$ ($m_F$ is the mass of the fermionic atom) is the total mass density of the system. This momentum remains unchanged along the whole crossover, whether the mass is contained in the bosonic molecules as on the deep BEC side or in the fermionic atoms as on the deep BCS side. This phenomenon comes about as a result of a special feature of one dimensional systems that the conventional quasiparticle is not stable with respect to soliton formation. It is valid not only in exactly solvable models but also on the level of semiclassical theory. Besides, we also resolved the inconsistency of existing semiclassical theory with the exact solution of soliton-like $S=0$ excitations on the deep BCS side by a new proposal of soliton configuration., Comment: 15 pages, 12 figures

Physical systems with discrete energy levels are ubiquitous in nature and are fundamental building blocks of quantum technology. Realizing controllable artifcial atom- and molecule-like systems for light would allow for coherent and dynamic control of the frequency, amplitude and phase of photons. In this work, we demonstrate a photonic molecule with two distinct energy-levels and control it by external microwave excitation. We show signature two-level dynamics including microwave induced photonic Autler-Townes splitting, Stark shift, Rabi oscillation and Ramsey interference. Leveraging the coherent control of optical energy, we show on-demand photon storage and retrieval in optical microresonators by reconfguring the photonic molecule into a bright-dark mode pair. These results of dynamic control of light in a programmable and scalable electro-optic platform open doors to applications in microwave photonic signal processing, quantum photonics in the frequency domain, optical computing concepts and simulations of complex physical systems., Comment: 12 pages, 9 figures

A waveguide 10 dB directional coupler operating from 325 GHz to 400 GHz is designed based on the short-slot Riblet-type coupling configuration and fabricated using the deep reactive ion etching (DRIE) silicon micromachining technique. The skin depth and the conductivity of the gold film with the roughness of 0.2 μm are investigated at 300~1000 GHz frequency band for the higher accuracy. In order to measure the small-size four-port coupler using the two-port VNA with big-size flanges, three testing topologies are designed, in which the terahertz (THz) wedged-type absorbing material terminals are adopted as the waveguide matching loads. The measured average insertion loss is 0.5 dB after deducting the intrinsic loss and the measured average isolation is better than 25 dB, which are in good agreement with simulations. The analysis and the design are verified to be accurate and valuable for the high-performance sub-millimeter-wave waveguide components.

In this paper, we discuss the key technologies of solid state devices on terahertz, including the modeling technology of the semiconductor devices, design of the key components and the fabrication technology.

In this paper, we present a concept called the terahertz C-V characteristic of the Schottky barrier diode, which is different from the conventional C-V characteristics. We have also presented a new equation to precisely describe it. The terahertz C-V characteristic has been carefully examined, first by using the measured capacitances at low frequencies and then by using a 225 GHz tripler. The results show this new concept is rational and necessary in terahertz regions. The agreement between the simulated and measured results of the 225 GHz tripler is improved by using the terahertz C-V characteristic.

Adsorption by carbon materials is one of the relatively fast methods in present research, which is widely used in emergency events. Activated carbon fiber (ACF) modified by nitric acid (N-ACF) was studied in this research to determine the adsorption performance for 2,4-dichlorophenoxyacetic acid (2,4-D). Subsequently, influence factors, adsorption isotherm models, kinetics and thermodynamic were investigated in a batch system to realize this adsorption. Experimental results showed that ACF modified by 0.1M nitric acid had a better removal ability than 2,4-D. Removal rate of 2,4-D by N-ACF was greatly influenced by pH with the optimum pH at 2. The superiority of the Langmuir isotherm model in describing the adsorption equilibrium was revealed by correlation coefficients R2 (R2 ≥ 0.997). Furthermore, adsorption kinetics was well described by pseudo-second-order model. The results of thermodynamic showed that adsorption was a spontaneous, endothermic process with randomness increasing. Additionally, ...

We investigate the possible existence of the bound state in the system of three bosons interacting with each other via zero-radius potentials in two dimensions (it can be atoms confined in two dimensions or tri-exciton states in heterostructures or dihalogenated materials). The bosons are classified in two species (a,b) such that a-a and b-b pairs repel each other and a-b attract each other, forming the two-particle bound state with binding energy $\epsilon_b^{(2)}$ (such as bi-exciton). We developed an efficient routine based on the proper choice of basis for analytic and numerical calculations. For zero-angular momentum we found the energies of the three-particle bound states $\epsilon^{(3)}_b$ for wide ranges of the scattering lengths, and found a universal curve of $\epsilon^{(3)}_b/\epsilon^{(2)}_b$ which depends only on the scattering lengths but not the microscopic details of the interactions, this is in contrast to the three-dimensional Efimov effect, where a non-universal three-body parameter is needed., Comment: 14 pages, 7 figures, references added

A Schottky barrier diode with low-barrier is presented, based on which a terahertz waveguide detector working at 500–600 GHz is designed and fabricated. By using the InGaAs/InP material system, the feature of the low barrier is obtained which greatly improves the performance of the detector. The measured typical voltage responsivity is about 900 V/W at 500–560 GHz and is about 400 V/W at 560–600 GHz. The proposed broadband waveguide detector has the characteristics of simple structure, compact size, low cost and high performance, and can be used in a variety of applications such as imaging, molecular spectroscopy and atmospheric remote sensing.

A 330–500 GHz zero-biased broadband monolithic integrated tripler is reported. The measured results show that the maximum efficiency and the maximum output power are 2% and 194 μW at 348 GHz. The saturation characteristic test shows that the output 1 dB compression point is about −8.5 dBm at 334 GHz and the maximum efficiency is obtained at the point, which is slightly below the 1 dB compression point. Compared with the conventional hybrid integrated circuit, a major advantage of the monolithic integrated circuit is the significant improvement of reliability and consistency. In this work, a terahertz monolithic frequency multiplier at this band is designed and fabricated.

Charge order is commonly believed to compete with superconducting order. An intertwined form of superconducting wave function, known as pair-density-wave (PDW) order, has been proposed; however, there has been no direct evidence, theoretical or experimental, that it forms the ground state of any cuprate superconductor. As a test case, we consider \lbco\ with $x=1/8$, where charge and spin stripe orders within the CuO$_2$ planes compete with three-dimensional superconducting order. We report measurements of the superconducting critical current perpendicular to the planes in the presence of an in-plane magnetic field. The variation of the critical current with orientation of the field is inconsistent with a theoretical prediction specific to the PDW model. It appears, instead, that the orientation dependence of the critical-current density might be determined by a minority phase of $d$-wave superconductivity that is present as a consequence of doped-charge inhomogeneity., 6 pages, 2 figures, Major changes from previous version