Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential

Induced p-type semiconductivity in Mg-doped Nd2Zr2O7 pyrochlore system

Heterovalent B-site MgO substitution in the Nd2Zr2O7-system (Nd2Zr2−xMgxO7−x) has been explored. The pyrochlores were synthesized by a polymeric sol-gel method and characterized by X-ray diffraction (XRD), Raman spectroscopy and Scanning Electron Microscopy to determine structure, phase composition and microstructure. Impedance Spectroscopy (IS) was employed to study the electrical behavior of the ceramics over the ranges 200–800 °C and under pure N2 and O2. The XRD showed that the solid solution limit was x > 0.02 and all the materials show a cubic ̅ structure. The Raman results confirm the structural disorder created by the introduction of Mg2+ and the subsequent generation of oxygen vacancies. The IS data shows a dramatical increase of the oxide-ion conductivity when doping and that the conductivity depends strongly on the atmosphere, leading to p-type semiconductivity under pure O2 atmosphere. The present study highlights the use of heterovalent dopants to drastically increase the oxide-ion conductivity of pyrochlore-like materials

Structural and electrical properties of Zr-doped K0.48 Na 0.52 NbO 3 ceramics: “Hard” lead-free piezoelectric

The structural and electrical properties of K0.48Na0.52Nb1−xZrxO3−δ (x = 0–0.04) ceramics prepared by the conventional solid-state reaction method were studied. Pellets with composition x ≤ 0.03 sintered at 1125 °C for 2 h showed single-phase of potassium sodium niobate (KNN) perovskite structure. Based on X-ray diffraction and Raman results, a mixture of orthorhombic and monoclinic phases was observed in intermediate compositions. The addition of Zr improved the sinterability and the “hard” piezoelectric properties of KNN, increasing the Ec and Qm values. The composition with x = 0.03 presented the highest permittivity at room temperature, ɛr′ = 363 and the lowest dielectric losses, tan δ = 0.027. Moreover, it was the sample with the highest Qm and d33 values, with Qm = 1781 and d33 = 82 pC/N. It was therefore the best compositions to obtain a “hard” piezoelectric material based on Zr-doped KNN, which makes it promising candidate for use as “hard” lead-free piezoelectric material for high power applications

Phase preserving amplification near the quantum limit with a Josephson Ring Modulator

Recent progress in solid state quantum information processing has stimulated the search for ultra-low-noise amplifiers and frequency converters in the microwave frequency range, which could attain the ultimate limit imposed by quantum mechanics. In this article, we report the first realization of an intrinsically phase-preserving, non-degenerate superconducting parametric amplifier, a so far missing component. It is based on the Josephson ring modulator, which consists of four junctions in a Wheatstone bridge configuration. The device symmetry greatly enhances the purity of the amplification process and simplifies both its operation and analysis. The measured characteristics of the amplifier in terms of gain and bandwidth are in good agreement with analytical predictions. Using a newly developed noise source, we also show that our device operates within a factor of three of the quantum limit. This development opens new applications in the area of quantum analog signal processing

Josephson junction microwave amplifier in self-organized noise compression mode

The fundamental noise limit of a phase-preserving amplifier at frequency is the standard quantum limit . In the microwave range, the best candidates have been amplifiers based on superconducting quantum interference devices (reaching the noise temperature at 700 MHz), and non-degenerate parametric amplifiers (reaching noise levels close to the quantum limit at 8 GHz). We introduce a new type of an amplifier based on the negative resistance of a selectively damped Josephson junction. Noise performance of our amplifier is limited by mixing of quantum noise from Josephson oscillation regime down to the signal frequency. Measurements yield nearly quantum-limited operation, at 2.8 GHz, owing to self-organization of the working point. Simulations describe the characteristics of our device well and indicate potential for wide bandwidth operation

Experimental violation of a Bell's inequality in time with weak measurement

The violation of J. Bell's inequality with two entangled and spatially separated quantum two- level systems (TLS) is often considered as the most prominent demonstration that nature does not obey ?local realism?. Under different but related assumptions of "macrorealism", plausible for macroscopic systems, Leggett and Garg derived a similar inequality for a single degree of freedom undergoing coherent oscillations and being measured at successive times. Such a "Bell's inequality in time", which should be violated by a quantum TLS, is tested here. In this work, the TLS is a superconducting quantum circuit whose Rabi oscillations are continuously driven while it is continuously and weakly measured. The time correlations present at the detector output agree with quantum-mechanical predictions and violate the inequality by 5 standard deviations.Comment: 26 pages including 10 figures, preprint forma

Noiseless nonreciprocity in a parametric active device

Nonreciprocal devices such as circulators and isolators belong to an important class of microwave components employed in applications like the measurement of mesoscopic circuits at cryogenic temperatures. The measurement protocols usually involve an amplification chain which relies on circulators to separate input and output channels and to suppress backaction from different stages on the sample under test. In these devices the usual reciprocal symmetry of circuits is broken by the phenomenon of Faraday rotation based on magnetic materials and fields. However, magnets are averse to on-chip integration, and magnetic fields are deleterious to delicate superconducting devices. Here we present a new proposal combining two stages of parametric modulation emulating the action of a circulator. It is devoid of magnetic components and suitable for on-chip integration. As the design is free of any dissipative elements and based on reversible operation, the device operates noiselessly, giving it an important advantage over other nonreciprocal active devices for quantum information processing applications.Comment: 17 pages, 4 figures + 12 pages Supplementary Informatio