Breaking the paradigm: Dr Insight empowers signature-free, enhanced drug repurposing

Motivation: Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures. Results: The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the superior performance of Dr Insight over several popular drug-repurposing methods to detect known cancer drugs and drug–target interactions. A proof-of-concept trial using the TCGA breast cancer dataset demonstrates the application of Dr Insight for a comprehensive analysis, from redirection of drug therapies, to a systematic construction of disease-specific drug-target networks

A Simultaneous Dual-Frequency Scintillation Arc Survey of Six Bright Canonical Pulsars Using the Upgraded Giant Metrewave Radio Telescope

We use the Upgraded Giant Metrewave Radio Telescope to measure scintillation arc properties in six bright canonical pulsars with simultaneous dual frequency coverage. These observations at frequencies from 300 to 750 MHz allowed for detailed analysis of arc evolution across frequency and epoch. We perform more robust determinations of arc curvature, scattering delay, and scintillation timescale frequency-dependence, and comparison between arc curvature and pseudo-curvature than allowed by single-frequency-band-per-epoch measurements, which we find to agree with theory and previous literature. We find a strong correlation between arc asymmetry and arc curvature, which we have replicated using simulations, and attribute to a bias in the Hough transform approach to scintillation arc analysis. Possible evidence for an approximately week long timescale over which a given scattering screen dominates signal propagation was found by tracking visible scintillation arcs in each epoch in PSR J1136+1551. The inclusion of a 155 minute observation allowed us to resolve the scale of scintillation variations on short timescales, which we find to be directly tied to the amount of ISM sampled over the observation. Some of our pulsars showed either consistent or emerging asymmetries in arc curvature, indicating instances of refraction across their lines of sight. Significant features in various pulsars, such as multiple scintillation arcs in PSR J1136+1551 and flat arclets in PSR J1509+5531, that have been found in previous works, were also detected. The multiple band capability of the upgraded GMRT shows excellent promise for future pulsar scintillation work

A Silicon-Based Monolithic Optical Frequency Comb Source

Recently developed techniques for generating precisely equidistant optical frequencies over broad wavelength ranges are revolutionizing precision physical measurement [1-3]. These frequency "combs" are produced primarily using relatively large, ultrafast laser systems. However, recent research has shown that broad-bandwidth combs can be produced using highly-nonlinear interactions in microresonator optical parametric oscillators [4-11]. Such devices not only offer the potential for developing extremely compact optical atomic clocks but are also promising for astronomical spectroscopy [12-14], ultrashort pulse shaping [15], and ultrahigh-speed communications systems. Here we demonstrate the generation of broad-bandwidth optical frequency combs from a CMOS-compatible integrated microresonator [16,17], which is a fully-monolithic and sealed chip-scale device making it insensitive to the surrounding environment. We characterize the comb quality using a novel self-referencing method and verify that the comb line frequencies are equidistant over a bandwidth that is nearly an order of magnitude larger than previous measurements. In addition, we investigate the ultrafast temporal properties of the comb and demonstrate its potential to serve as a chip-scale source of ultrafast (sub-ps) pulses

Second-Harmonic Generation in Silicon Nitride Ring Resonators

The emerging field of silicon photonics seeks to unify the high bandwidth of optical communications with CMOS microelectronic circuits. Many components have been demonstrated for on-chip optical communications, including those that utilize the nonlinear optical properties of silicon[1, 2], silicon dioxide[3, 4] and silicon nitride[5, 6]. Processes such as second harmonic generation, which are enabled by the second-order susceptibility, have not been developed since the bulk $\chi^{(2)}$ vanishes in these centrosymmetric CMOS materials. Generating the lowest-order nonlinearity would open the window to a new array of CMOS-compatible optical devices capable of nonlinear functionalities not achievable with the?$\chi^{(3)}$ response such as electro-optic modulation, sum frequency up-conversion, and difference frequency generation. Here we demonstrate second harmonic (SH) generation in CMOS compatible integrated silicon nitride (Si3N4) waveguides. The $\chi^{(2)}$ response is induced in the centrosymmetric material by using the nanoscale structure to break the bulk symmetry. We use a high quality factor Q ring resonator cavity to enhance the efficiency of the nonlinear optical process and detect SH output with milliwatt input powers.Comment: 4 pages, 3 figure

Surface ozone variability and the jet position: Implications for projecting future air quality

Changes in the variability of surface ozone can affect the incidence of ozone pollution events. Analysis of multi-century simulations from a chemistry climate model shows that present-day summertime variability of surface ozone depends strongly on the jet stream position over eastern North America. This relationship holds on decadal time scales under projected climate change scenarios, in which surface ozone variability follows the robust poleward shift of the jet. The correlation between ozone and co-located temperature over eastern North America is also closely tied to the jet position, implying that local ozone-temperature relationships may change as the circulation changes. Jet position can thus serve as a dynamical predictor of future surface ozone variability over eastern North America and may also modulate ozone variability in other northern midlatitude regions

Investigating potential planetary nebula/cluster pairs

Fundamental parameters characterizing the end-state of intermediate-mass stars may be constrained by discovering planetary nebulae (PNe) in open clusters (OCs). Cluster membership may be exploited to establish the distance, luminosity, age, and physical size for PNe, and the intrinsic luminosity and mass of its central star. Four potential PN-OC associations were investigated, to assess the cluster membership for the PNe. Radial velocities were measured from intermediate-resolution optical spectra, complemented with previous estimates in the literature. When the radial velocity study supported the PN/OC association, we analyzed if other parameters (e.g., age, distance, reddening, central star brightness) were consistent with this conclusion. Our measurements imply that the PNe VBe3 and HeFa1 are not members of the OCs NGC5999 and NGC6067, respectively, and likely belong to the background bulge population. Conversely, consistent radial velocities indicate that NGC2452/NGC2453 could be associated, but our results are not conclusive and additional observations are warranted. Finally, we demonstrate that all the available information point to He2-86 being a young, highly internally obscured PN member of NGC4463. New near-infrared photometry acquired via the Vista Variables in the Via Lactea ESO public survey was used in tandem with existing UBV photometry to measure the distance, reddening, and age of NGC4463, finding d=1.55+-0.10 kpc, E(B-V)=0.41+-0.02, and tau=65+-10 Myr, respectively. The same values should be adopted for the PN if the proposed cluster membership will be confirmed.Comment: Accepted for publication in A&

Radial Star Formation Histories in 32 Nearby Galaxies

The spatially resolved star formation histories are studied for 32 normal star-forming galaxies drawn from the the Spitzer Extended Disk Galaxy Exploration Science survey. At surface brightness sensitivities fainter than 28 mag arcsec$^{-2}$, the new optical photometry is deep enough to complement archival ultraviolet and infrared imaging and to explore the properties of the emission well beyond the traditional optical extents of these nearby galaxies. Fits to the spectral energy distributions using a delayed star formation history model indicate a subtle but interesting average radial trend for the spiral galaxies: the inner stellar systems decrease in age with increasing radius, consistent with inside-out disk formation, but the trend reverses in the outermost regions with the stellar age nearly as old as the innermost stars. These results suggest an old stellar outer disk population formed through radial migration and/or the cumulative history of minor mergers and accretions of satellite dwarf galaxies. The subset of S0 galaxies studied here show the opposite trend compared to what is inferred for spirals: characteristic stellar ages that are increasingly older with radius for the inner portions of the galaxies, and increasingly younger stellar ages for the outer portions. This result suggests that either S0 galaxies are not well modeled by a delayed-$\tau$ model, and/or that S0 galaxies have a more complicated formation history than spiral galaxies.Comment: Accepted for publication in the Astronomical Journal. arXiv admin note: text overlap with arXiv:1511.0328

Interferometric Constraints on Gravity Darkening with Application to the Modeling of Spica A & B

In 2005 we obtained very precise interferometric measurements of the pole-on rapid rotator Vega (A0 V) with the longest baselines of the Center for High Angular Angular Resolution (CHARA) Array and the Fiber Linked Unit for Optical Recombination (FLUOR). For the analysis of these data, we developed a code for mapping sophisticated PHOENIX model atmospheres on to the surface of rotationally distorted stars described by a Roche-von Zeipel formalism. Given a set of input parameters for a star or binary pair, this code predicts the interferometric visibility, spectral energy distribution and high-resolution line spectrum expected for the system. For the gravity-darkened Vega, our model provides a very good match to the K-band interferometric data, a good match to the spectral energy distribution - except below 160 nm - and a rather poor match to weak lines in the high dispersion spectrum where the model appears overly gravity darkened. In 2006, we used the CHARA Array and FLUOR to obtain high precision measurements of the massive, non-eclipsing, double-line spectroscopic binary Spica, a 4-day period system where both components are gravity darkened rapid rotators. These data supplement recent data obtained with the Sydney University Stellar Interferometer (SUSI). Our study follows the classic 1971 study by Herbison-Evans et al. who resolved Spica as a binary with the Narrabri Stellar Intensity Interferometer (NSII). We will report on our progress modeling the new interferometric and archival spectroscopic data, with the goal towards better constraining the apsidal constan

Ferromagnetic resonances in single-crystal yttrium iron garnet nanofilms fabricated by metal-organic decomposition

Tunable microwave and millimeter wave oscillators and bandpass filters with ultra-low phase noise play a critical role in electronic devices, including wireless communication, microelectronics, and quantum computing. Magnetic materials, such as yttrium iron garnet (YIG), possess ultra-low phase noise and a ferromagnetic resonance tunable up to tens of gigahertz. Here, we report structural and magnetic properties of single-crystal 60 and 130 nm-thick YIG films prepared by metal-organic decomposition epitaxy. These films, consisting of multiple homoepitaxially grown monolayers, are atomically flat and possess magnetic properties similar to those grown with liquid-phase epitaxy, pulsed laser deposition, and sputtering. Our approach does not involve expensive high-vacuum deposition systems and is a true low-cost alternative to current commercial techniques that have the potential to transform the industry