Broadband CPW-based impedance-transformed Josephson parametric amplifier

Quantum-limited Josephson parametric amplifiers play a pivotal role in advancing the field of circuit quantum electrodynamics by enabling the fast and high-fidelity measurement of weak microwave signals. Therefore, it is necessary to develop robust parametric amplifiers with low noise, broad bandwidth, and reduced design complexity for microwave detection. However, current broadband parametric amplifiers either have degraded noise performance or rely on complex designs. Here, we present a device based on the broadband impedance-transformed Josephson parametric amplifier (IMPA) that integrates a horn-like coplanar waveguide (CPW) transmission line, which significantly decreases the design and fabrication complexity, while keeping comparable performance. The device shows an instantaneous bandwidth of 700(200) MHz for 15(20) dB gain with an average saturation power of -110 dBm and near quantum-limited added noise. The operating frequency can be tuned over 1.4 GHz using an external flux bias. We further demonstrate the negligible back-action from our device on a transmon qubit. The amplification performance and simplicity of our device promise its wide adaptation in quantum metrology, quantum communication, and quantum information processing.Comment: 11 pages, 8 figure

Freezing Damage Control of Railway Subgrade Miniature Shields in Cold Climatic Regions: Construction Technology Optimization via Numerical Simulation

Microshield structure replacement technology is commonly used to control the freezing damage of railway roadbeds, featuring high efficiency and easy operation. However, improper disposal of measures in the construction process will still cause excessive deformation of the line and endanger the safety of train operations. On the background of a subgrade freezing damage improvement and speed improvement project of the Xige section of Quinghai–Tibet railway, this study performed numerical simulation of the microshield based on the measured data of the field automatic monitoring system to improve the operation safety of the existing lines and optimize the construction technology of the microshield. The effect of the changes in the microshield segment material, construction process, and formation loss on the settlement of the operating railway subgrade was analyzed to control the construction disturbance settlement of the existing operating line. The results obtained show that the overall settlement deformation of the line is small when the steel pipe is used as the shield segment, which meets the safety management requirements of the existing operating line. When PE tube segments are used for construction, construction measures should be strictly controlled to reduce the effect of settlement deformation on the operational lines. When steel pipe segments are used, the settlement generated by the construction process from both sides to the middle is minimal. When PE tube segments are adopted in the construction, the settlement generated by the construction process with unilateral advancement and an interval of two pipe diameters is the least, producing unimodal settlement curve of the line. The latter features a double peak when the shield pipe interval is three pipe diameters or more. When using PE tube pieces for the microshield construction, it is necessary to strictly control the formation loss rate within 10% by optimizing the construction control measures

miR-29a/b enhances cell migration and invasion in nasopharyngeal carcinoma progression by regulating SPARC and COL3A1 gene expression.

Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with a genetic predisposition, Epstein-Barr virus infection and chromosomal abnormalities. Recently, several miRNAs have been shown to target specific mRNAs to regulate NPC development and progression. However, the involvement of miRNAs in processes leading to NPC migration and invasion remains to be elucidated. We predicted that miR-29a/b are associated with dysregulated genes controlling NPC through an integrated interaction network of miRNAs and genes. miR-29a/b over-expression in NPC cell lines had no significant effect on proliferation, whereas miR-29b mildly increased the percentage of cells in the G1 phase with a concomitant decrease in the percentage of cells in S phase. Furthermore, we demonstrated that miR-29a/b might be responsible for increasing S18 cell migration and invasion, and only COL3A1 was identified as a direct target of miR-29b despite the fact that both SPARC and COL3A1 were inhibited by miR-29a/b over-expression. Meanwhile, SPARC proteins were increased in metastatic NPC tissue and are involved in NPC progression. Unexpectedly, we identified that miRNA-29b expression was elevated in the serum of NPC patients with a high risk of metastasis. The 5-year actuarial overall survival rates in NPC patients with high serum miR-29b expression was significantly shorter than those with low serum miR-29b expression; therefore, serum miR-29b expression could be a promising prognostic marker

Integrated microRNA-gene network.

<p>(A) The miRNA-gene network shows the relationships between 9 miRNAs and 51 dysregulated genes. Only genes reported in BioGrid are shown in this network. Interaction among genes and regulation of miRNAs are indicated by arrows. Red nodes represent up-regulated genes in NPC, and blue nodes represent down-regulated genes. miRNAs with more than 2 targets are shown in the figure. (B) The particular network for miR-29a/b and their targets stems from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0120969#pone.0120969.g001" target="_blank">Fig. 1A</a>.</p

miR-29a/b target the SPARC/COL3A1 pathways in NPC cells.

<p>(A, B) S18 cells were transfected with 50 nmol of mimics-NC (control miRNA), mimics-miR-29a/b, anti-scramble (control anti-miRNA) and anti-miR-29a/b. The levels of miR-29a and miR-29b were assessed by qRT-PCR. Cell lysates were prepared for Western blotting with antibodies against SPARC and COL3A1, and GAPDH expression served as a loading control. Western blot figures are representative of at least three independent experiments. The value under each sample indicates the fold change of SPARC and COL3A1 protein levels relative to that of the control. (C) Western blot analysis of the expression level of SPARC and COL3A1 in NPC cells following treatment with vehicle, siRNA-SPARC and siRNA-COL3A1 for 24 h. The value under each sample indicates the fold changes of SPARC and COL3A1 protein levels relative to that of the control. Three independent experiments performed in triplicate. (D) A schematic model shows the function of miR-29a and miR-29b in NPC cell proliferation, migration and cell invasion. In response to miR-29a/b stimuli, the G1/S transition arrest triggers both a classical proliferative inhibition and an adapted metabolic switch. SPARC and COL3A1 protein levels inversely correlate with miR-29a and miR-29b expression in NPC cells, respectively. (i) The indirect effect of miR-29a to increase SPARC expression may be mediated by its unknown targets that affect cell survival, and subsequently SPARC could down-regulate the expression of COL3A1. (ii) COL3A1 is a direct target of miR-29b and affects the expression of the various ECM proteins, resulting in derepression of NPC cell migration and invasion.</p

Effects of miR-29a/b on NPC cell growth and cell cycle.

<p>The results of MTT assays following transfection of pre-miR-29a/b and their inhibitors into S18 cells for the indicated 24 h, 48 h and 72 h post-transfection times. The values are the mean and SD optical density (OD) units. (B) miR-29b increased the proportion of S18 cells at the G1/S transition, whereas miR-29a did not have a similar effect. Cells were treated with pEGFP-miR-29a/b or anti-miR-29a/b transfection and control vector pEGPF-C. Cell cycle distributions were detected 20 h later. A representative result of 3 independent experiments is shown. In all experiments, the negative control was pre-miRNA negative control.</p

High SPARC expression correlates with shorter overall survival in NPC patients.

<p>(A) SPARC protein levels correlate with NPC aggressiveness. Representative tissue is stained with an antibody against NPC. Immunohistochemical stains show absent nuclear staining in normal samples (left, original magnification 100×), moderate and strong nuclear staining in NPC samples with low and high risk of metastasis (center right and right, respectively; original magnification 100×). Weak staining shown is a benign nasopharynx adjacent to NPC (center left, original magnification 100×). (B) Tissue analysis of SPARC expression for each tissue spot. The mean SPARC protein expression for the indicated NPC tissues is summarized using error bars with 95% confidence intervals, demonstrating a significantly lower score in NPC with a high risk of metastasis compared with non-malignant controls (Mann-Whitney test, two-tailed, <i>p</i> < 0.001). (C) The OS of patients with low SPARC expression levels was significantly higher than that of patients with high SPARC expression levels (log rank test, <i>p</i> = 0.04).</p

miR-29b is associated with specific risk groups and NPC patient survival.

<p>(A, B) Comparison of the miR-29a/b abundance in paired NPC tumors (42 NPC patients) and adjacent normal tissues (42 normal controls). The solid squares represent the relative expression level of miR-29a/b. The miR-29a/b abundance for each paired non-tumor and tumor tissues were separately shown in the left and right parts and connected by a dash line. (C, D) The expression levels of miR-29a/b in serum were quantified by real-time PCR in 83 patients with highly metastatic/invasive, 110 patients with low metastatic/non-invasive cancer and 65 healthy donors. (C) There was a small change in miR-29a expression in NPC patients and healthy donors, as well as patients with high risk for metastasis and the low-risk group. The formula used to calculate the relative Ct values was (ΔCt = assay Ct − control Ct). A higher ΔCt value indicates that the miRNA is less abundant in a sample. (D) miR-29b was significantly up-regulated in the NPC patients at high-risk for metastasis compared with the low-risk group. (E) Kaplan–Meier survival curves of NPC patients. No significant differences were observed in OS rates between patients with high and low miR-29a expression. (F) The 5-year overall survival rate of NPC patients with high serum miR-29b expression was significantly lower than that of those with low serum miR-29b expression (<i>p</i> < 0.001).</p