The Josephson heat interferometer

The Josephson effect represents perhaps the prototype of macroscopic phase coherence and is at the basis of the most widespread interferometer, i.e., the superconducting quantum interference device (SQUID). Yet, in analogy to electric interference, Maki and Griffin predicted in 1965 that thermal current flowing through a temperature-biased Josephson tunnel junction is a stationary periodic function of the quantum phase difference between the superconductors. The interplay between quasiparticles and Cooper pairs condensate is at the origin of such phase-dependent heat current, and is unique to Josephson junctions. In this scenario, a temperature-biased SQUID would allow heat currents to interfere thus implementing the thermal version of the electric Josephson interferometer. The dissipative character of heat flux makes this coherent phenomenon not less extraordinary than its electric (non-dissipative) counterpart. Albeit weird, this striking effect has never been demonstrated so far. Here we report the first experimental realization of a heat interferometer. We investigate heat exchange between two normal metal electrodes kept at different temperatures and tunnel-coupled to each other through a thermal `modulator' in the form of a DC-SQUID. Heat transport in the system is found to be phase dependent, in agreement with the original prediction. With our design the Josephson heat interferometer yields magnetic-flux-dependent temperature oscillations of amplitude up to ~21 mK, and provides a flux-to-temperature transfer coefficient exceeding ~ 60mK/Phi_0 at 235 mK [Phi_0 2* 10^(-15) Wb is the flux quantum]. Besides offering remarkable insight into thermal transport in Josephson junctions, our results represent a significant step toward phase-coherent mastering of heat in solid-state nanocircuits, and pave the way to the design of novel-concept coherent caloritronic devices.Comment: 4+ pages, 3 color figure

A hydrostatic pressure-driven passive micropump enhanced with siphon-based autofill function.

Autonomous and self-powered micropumps are in critical demand for versatile cell- and tissue-based applications as well as for low-cost point-of-care testing (POCT) in microfluidics fields. The hydrostatic pressure-driven passive micropumps are simple and widely used, but they cannot maintain steady and continuous flow for long periods of time. Here, we propose a hydrostatic pressure-driven passive micropump enhanced with siphon-based autofill function, which can realize the autonomous and continuous perfusion with well-controlled steady flow over an extended time without electric power consumption. The characterization results reveal that both the cycle number in one refilling loop and the siphon diameter will affect the refilling time. Furthermore, this micropump also enables multiplexed medium delivery under either the same or different flow conditions with high flexibility. The system was validated using an in vitro vasculogenesis model over the course of several days. Most importantly, the device can consistently provide steady medium perfusion for up to 5 days at a predefined hydrostatic pressure drop without the need for supplemental medium changes. We believe that this hydrostatic pressure-driven passive micropump will become a critical module for a broad range of sophisticated microfluidic operations and applications

Photonic waveguide engineering using pulsed lasers - A novel approach for non-clean room fabrication!

Over the last 25 years has seen an unprecedented increase in the growth of phonic components based on semiconductor and solid-state lasers, glass and polymer based optical fibres, and organic LEDs. Emerging technology for component engineering must embed dissimilar materials based devices into an integrated form which is more efficient. In this article, we demonstrate techniques for overcoming the materials related limitations by adopting thin-film deposition techniques based on nano- and femto-second pulsed laser deposition. Three examples of thin-film fabrication for near-IR devices using Er3+-ion doped glass-on-GaAs, Er3+-ion doped glass-polydimethyl silane (PDMS) polymer, and Tm3+-doped nano-silicon thin films and gain medium waveguides are discussed. The modelling tools are used a priori for waveguide engineering for ascertaining the extent to which the structural incompatibility due to mismatch strain can be minimized. The structure and spectroscopic properties of Er3+- ion doped thin films on silica, polymer, and semiconductor GaAs substrates were examined in detail and are reported. We demonstrate the formation of glass-polymer superlattice structures for waveguide fabrication for overcoming the solubility limits of Er3+-ions in PDMS polymers. For inscribing waveguides in superlattice structures and nano silicon structures, the ablation machining using fs-pulsed Ti-sapphire laser was used, and the resulting spectroscopic properties of waveguides are discussed.The authors acknowledge the financial support from RCUK Basic Technology project (EP/D048692/1).This is the accepted manuscript. The final version is available from IEEE at http://ieeexplore.ieee.org/xpls/abs_all.jsp?arnumber=6876466

Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background: The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets. Results: This work developed a novel approach, which is based on a nonlinear mathematical model, to infer genetic regulation from microarray gene expression data. By using the p53 network as a test system, we used the nonlinear model to estimate the activities of transcription factor (TF) p53 from the expression levels of its target genes, and to identify the activation/inhibition status of p53 to its target genes. The predicted top 317 putative p53 target genes were supported by DNA sequence analysis. A comparison between our prediction and the other published predictions of p53 targets suggests that most of putative p53 targets may share a common depleted or enriched sequence signal on their upstream non-coding region. Conclusions: The proposed quantitative model can not only be used to infer the regulatory relationship between TF and its down-stream genes, but also be applied to estimate the protein activities of TF from the expression levels of its target genes

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Female Resistance to Invading Males Increases Infanticide in Langurs

BACKGROUND: Infanticide by adult male occurs in many mammalian species under natural conditions, and it is often assumed to be a goal-directed action and explained predominately by sexual selection. Motivation of this behavior in mammals is limitedly involved. METHODOLOGY AND PRINCIPAL FINDINGS: We used long-term reproductive records and direct observation in captivity and in the field of two snub-nosed langur species on the basis of individual identification to investigate how infanticide happened and to be avoided in nonhuman primates. Our observations suggested that infanticide by invading males might be more accidental than goal-directed. The invading male seemed to monopolize all the females including lactating mothers during takeovers. Multiparous mothers who accepted the invading male shortly after takeovers avoided infanticide in most cases. Our results conjectured primiparous mothers would decrease infanticidal possibility if they sexually accepted the invading male during or immediately after takeovers. In the studied langur species, voluntary abortion or mating with the invading male was evidently adopted by females to limit or avoid infanticide by takeover males. CONCLUSIONS AND SIGNIFICANCE: The objective of the invading male was to monopolize all adult females after his takeover. It appeared that the mother's resistance to accepting the new male as a mating partner was the primary incentive for infanticide. Motivation analysis might be helpful to further understand why infanticide occurs in primate species

A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation

Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50 % with P,0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression

Single-Cell Profiling Reveals the Origin of Phenotypic Variability in Adipogenesis

Phenotypic heterogeneity in a clonal cell population is a well-observed but poorly understood phenomenon. Here, a single-cell approach is employed to investigate non-mutative causes of phenotypic heterogeneity during the differentiation of 3T3-L1 cells into fat cells. Using coherent anti-Stokes Raman scattering microscopy and flow cytometry, adipogenic gene expression, insulin signaling, and glucose import are visualized simultaneously with lipid droplet accumulation in single cells. Expression of adipogenic genes PPARγ, C/EBPα, aP2, LP2 suggests a commitment to fat cell differentiation in all cells. However, the lack of lipid droplet in many differentiating cells suggests adipogenic gene expression is insufficient for lipid droplet formation. Instead, cell-to-cell variability in lipid droplet formation is dependent on the cascade responses of an insulin signaling pathway which includes insulin sensitivity, kinase activity, glucose import, expression of an insulin degradation enzyme, and insulin degradation rate. Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells. Single-cell profiling reveals the kinetics of an insulin signaling cascade as the origin of phenotypic variability in drug-inducible adipogenesis

Precision Orbit of δ Delphini and Prospects for Astrometric Detection of Exoplanets

This is the author accepted manuscript. The final version is available from American Astronomical Society / IOP Publishing via the DOI in this record.Combining visual and spectroscopic orbits of binary stars leads to a determination of the full 3D orbit, individual masses, and distance to the system. We present a full analysis of the evolved binary system δ Delphini using astrometric data from the MIRC and PAVO instruments on the CHARA long-baseline interferometer, 97 new spectra from the Fairborn Observatory, and 87 unpublished spectra from the Lick Observatory. We determine the full set of orbital elements for δ Del, along with masses of 1.78 ± 0.07 M ⊙ and 1.62 ± 0.07 M ⊙ for each component, and a distance of 63.61 ± 0.89 pc. These results are important in two contexts: for testing stellar evolution models and for defining the detection capabilities for future planet searches. We find that the evolutionary state of this system is puzzling, as our measured flux ratios, radii, and masses imply a ~200 Myr age difference between the components, using standard stellar evolution models. Possible explanations for this age discrepancy include mass transfer scenarios with a now-ejected tertiary companion. For individual measurements taken over a span of two years, we achieve 2 M J on orbits >0.75 au around individual components of hot binary stars via differential astrometry.This work is based upon observations obtained with the Georgia State University Center for High Angular Resolution Astronomy Array at Mount Wilson Observatory. The CHARA Array is supported by the National Science Foundation under Grants No. AST-1211929 and AST-1411654. Institutional support has been provided from the GSU College of Arts and Sciences and the GSU Office of the Vice President for Research and Economic Development. This research has made use of the Jean-Marie Mariotti Center SearchCal service2 . JDM and TG wish to gratefully acknowledge support by NASA XRP Grant NNX16AD43G. Astronomy at Tennessee State University is supported by the state of Tennessee through its Centers of Excellence program. SK acknowledges support from an European Research Council Starting Grant (Grant Agreement No. 639889) and STFC Rutherford Fellowship (ST/J004030/1). D.H. acknowledges support by the National Aeronautics and Space Administration under Grant NNX14AB92G issued through the Kepler Participating Scientist Program. TRW acknowledges the support of the Villum Foundation (research grant 10118)

Glass-polymer superlattice for integrated optics

Glass and polymer interstacked superlattice like nanolayers were fabricated by nanosecond-pulsed laser deposition with a 193-nm-ultraviolet laser. The individual layer thickness of this highly transparent thin film could be scaled down to 2 nm, proving a near atomic scale deposition of complex multilayered optical and electronic materials. The layers were selectively doped with Er3\+ and Eu3\+ ions, making it optically active and targeted for integrated sensor application