Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion. Together, our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis.

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Fabrication of sub-micron Josephson junctions is demonstrated using standard processing techniques for high-coherence, superconducting qubits. These junctions are made in two separate lithography steps with normal-angle evaporation. Most significantly, this work demonstrates that it is possible to achieve high coherence with junctions formed on aluminum surfaces cleaned in situ with Ar milling before the junction oxidation. This method eliminates the angle-dependent shadow masks typically used for small junctions. Therefore, this is conducive to the implementation of typical methods for improving margins and yield using conventional CMOS processing. The current method uses electron-beam lithography and an additive process to define the top and bottom electrodes. Extension of this work to optical lithography and subtractive processes is discussed. Superconducting devices implemented as quantum bits (qubits) are among the leading candidates for building quantum computers. Key elements in all types of superconducting qubits are Josephson junctions, which are the non-linear elements in the superconducting circuitry. This non-linearity separates the two lowest energy levels from higher excitations, forming a two-level system as the physical qubit. Coherence times of superconducting qubits have been increased significantly in both 2D and 3D geometries (∼10-100µs) [1][2][3][4][5]. These relatively long coherence times, combined with fast, high-fidelity gate schemes, have enabled the demonstration of quantum error detection with superconducting devices [6][7][8].While the design and fabrication for various other elements that form quantum circuits, i.e., resonators, shunt capacitors, and inductors, have been well studied and brought into line with standard cleanroom techniques, the preparation of the non-linear Josephson junction is still typically conducted separately on a device-by-device basis. In general, low participation ratios from both the Josephson junction and it's immediate surroundings are essential to the success of present-day superconducting qubits [4,9]. This goal is typically achieved by shrinking the junction size. These low-loss junctions have predominantly been fabricated using a multi-angle shadowevaporation (SE) technique, because it naturally yields small structures in a single step process and works well enough for demonstrations of small-scale circuits [10,11]. SE is also convenient in that the oxidation of the base electrode is conducted in-situ on the as-deposited film and, then immediately covered by the top electrode.To satisfy the requirement of scalability of quantum circuits, it is becoming critical to bring the junction fabrication step in line with standard fabrication techniques. This is difficult with the angle-dependence of the SE technique because it limits the wafer size for preparing junctions with tight margins. One possible avenue is to use overlap junctions, as shown in Ref. [12], where the two electrodes of Josephson junctions are prepared in separate steps. The coherence time...

Quantum networks will enable extraordinary capabilities for communicating and processing quantum information. These networks require a reliable means of storage, retrieval, and manipulation of quantum states at the network nodes. A node receives one or more coherent inputs and sends a conditional output to the next cascaded node in the network through a quantum channel. Here, we demonstrate this basic functionality by using the quantum interference mechanism of electromagnetically induced transparency in a transmon qubit coupled to a superconducting resonator. First, we apply a microwave bias, i.e., drive, to the the qubit–cavity system to prepare a Λ-type three-level system of polariton states. Second, we input two interchangeable microwave signals, i.e., a probe tone and a control tone, and observe that transmission of the probe tone is conditional upon the presence of the control tone that switches the state of the device with up to 99.73 % transmission extinction. Importantly, our EIT scheme uses all dipole allowed transitions. We infer high dark state preparation fidelities of > 99.39 % and negative group velocities of up to −0.52 ± 0.09 km/s based on our data.

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The expression of hypoxia-inducible factor 1α (HIF-1α) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1α was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. In vivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1α (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1α, suggesting it may be a potential therapeutic target for melanoma treatment.

The geometric parameters of labyrinth channels play an important role in the hydraulic and anti‐clogging performance of drip emitters. In this study, the flow fields, individual representative sands and sand groups in the labyrinth channel of emitters, with dentation angles of 90°, 60°, 45° and 30°, were firstly simulated using a computational fluid dynamics discrete element method (CFD–DEM) of coupling. Particle tracking velocimetry (PTV) was used to trace individual representative sands. The numerical results were verified with clear water hydraulic performance tests and muddy water anti‐clogging performance tests. The results suggest that the discharge coefficient and flow exponent declined when the dentation angle of the labyrinth channel was reduced. A large number of sand groups were observed to enter the vortex areas and move in a circular manner. The time it took for particles to pass through the labyrinth channel lengthened when the velocity decreased and as a result, the probability of emitter clogging increased. Therefore, by using a recommended angle range of 90° to 60° and a combined higher hydraulic performance level, emitters were less likely to clog. It was a novel approach to adopt a CFD–DEM coupling method to conduct numerical analysis of individual sand particles and sand groups in the investigation of emitter anti‐clogging issues. The findings will increase the design efficiency of flow channels and will save human and material resources. © 2018 John Wiley & Sons, Ltd.

We describe a kinetic inductance traveling-wave (KIT) amplifier suitable for superconducting quantum information measurements and characterize its wideband scattering and noise properties. We use mechanical microwave switches to calibrate the four amplifier scattering parameters up to the device input and output connectors at the dilution refrigerator base temperature and a tunable temperature load to characterize the amplifier noise. Finally, we demonstrate the high fidelity simultaneous dispersive readout of two superconducting transmon qubits. The KIT amplifier provides low-noise amplification of both readout tones with readout fidelities of 83% and 89% and negligible effect on qubit lifetime and coherence.