39 research outputs found

    Gene Network Reconstruction using Global-Local Shrinkage Priors

    Get PDF
    Reconstructing a gene network from high-throughput molecular data is an important but challenging task, as the number of parameters to estimate easily is much larger than the sample size. A conventional remedy is to regularize or penalize the model likelihood. In network models, this is often done locally\textit{locally} in the neighborhood of each node or gene. However, estimation of the many regularization parameters is often difficult and can result in large statistical uncertainties. In this paper we propose to combine local regularization with global\textit{global} shrinkage of the regularization parameters to borrow strength between genes and improve inference. We employ a simple Bayesian model with nonsparse, conjugate priors to facilitate the use of fast variational approximations to posteriors. We discuss empirical Bayes estimation of hyperparameters of the priors, and propose a novel approach to rank-based posterior thresholding. Using extensive model- and data-based simulations, we demonstrate that the proposed inference strategy outperforms popular (sparse) methods, yields more stable edges, and is more reproducible. The proposed method, termed ShrinkNet\texttt{ShrinkNet}, is then applied to Glioblastoma to investigate the interactions between genes associated with patient survival.This work was supported by the Center for Medical Systems Biology (CMSB), and the European Union Grant EpiRadBio, established by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NGI/NWO), nr. FP7-269553

    A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances

    Get PDF
    This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18–19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10–80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR “core” reveals two different velocities in the scintillation pattern: a primary velocity of ~20–40 ms−1 with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of ~110 ms−1 with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported

    Tracking of an electron beam through the solar corona with LOFAR

    Get PDF
    © ESO 2018. The Sun's activity leads to bursts of radio emission, among other phenomena. An example is type-III radio bursts. They occur frequently and appear as short-lived structures rapidly drifting from high to low frequencies in dynamic radio spectra. They are usually interpreted as signatures of beams of energetic electrons propagating along coronal magnetic field lines. Here we present novel interferometric LOFAR (LOw Frequency ARray) observations of three solar type-III radio bursts and their reverse bursts with high spectral, spatial, and temporal resolution. They are consistent with a propagation of the radio sources along the coronal magnetic field lines with nonuniform speed. Hence, the type-III radio bursts cannot be generated by a monoenergetic electron beam, but by an ensemble of energetic electrons with a spread distribution in velocity and energy. Additionally, the density profile along the propagation path is derived in the corona. It agrees well with three-fold coronal density model by (1961, ApJ, 133, 983)

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

    Get PDF
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    LOFAR 144-MHz follow-up observations of GW170817

    Full text link
    ABSTRACT We present low-radio-frequency follow-up observations of AT 2017gfo, the electromagnetic counterpart of GW170817, which was the first binary neutron star merger to be detected by Advanced LIGO–Virgo. These data, with a central frequency of 144 MHz, were obtained with LOFAR, the Low-Frequency Array. The maximum elevation of the target is just 13.{_{.}^{\circ}}7 when observed with LOFAR, making our observations particularly challenging to calibrate and significantly limiting the achievable sensitivity. On time-scales of 130–138 and 371–374 d after the merger event, we obtain 3σ upper limits for the afterglow component of 6.6 and 19.5 mJy beam−1, respectively. Using our best upper limit and previously published, contemporaneous higher frequency radio data, we place a limit on any potential steepening of the radio spectrum between 610 and 144 MHz: the two-point spectral index α144610\alpha ^{610}_{144} \gtrsim −2.5. We also show that LOFAR can detect the afterglows of future binary neutron star merger events occurring at more favourable elevations.</jats:p
    corecore