54 research outputs found

    Bayesian inference of accurate population sizes and FRET efficiencies from single diffusing biomolecules.

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    It is of significant biophysical interest to obtain accurate intramolecular distance information and population sizes from single-molecule Förster resonance energy transfer (smFRET) data obtained from biomolecules in solution. Experimental methods of increasing cost and complexity are being developed to improve the accuracy and precision of data collection. However, the analysis of smFRET data sets currently relies on simplistic, and often arbitrary methods, for the selection and denoising of fluorescent bursts. Although these methods are satisfactory for the analysis of simple, low-noise systems with intermediate FRET efficiencies, they display systematic inaccuracies when applied to more complex systems. We have developed an inference method for the analysis of smFRET data from solution studies based on rigorous model-based Bayesian techniques. We implement a Monte Carlo Markov chain (MCMC) based algorithm that simultaneously estimates population sizes and intramolecular distance information directly from a raw smFRET data set, with no intermediate event selection and denoising steps. Here, we present both our parametric model of the smFRET process and the algorithm developed for data analysis. We test the algorithm using a combination of simulated data sets and data from dual-labeled DNA molecules. We demonstrate that our model-based method systematically outperforms threshold-based techniques in accurately inferring both population sizes and intramolecular distances.This is the final published version. It's also available from ACS in Analytical Chemistry: http://pubs.acs.org/doi/pdf/10.1021/ac501188r

    Noninvasive Assessment of Antenatal Hydronephrosis in Mice Reveals a Critical Role for Robo2 in Maintaining Anti-Reflux Mechanism

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    Antenatal hydronephrosis and vesicoureteral reflux (VUR) are common renal tract birth defects. We recently showed that disruption of the Robo2 gene is associated with VUR in humans and antenatal hydronephrosis in knockout mice. However, the natural history, causal relationship and developmental origins of these clinical conditions remain largely unclear. Although the hydronephrosis phenotype in Robo2 knockout mice has been attributed to the coexistence of ureteral reflux and obstruction in the same mice, this hypothesis has not been tested experimentally. Here we used noninvasive high-resolution micro-ultrasonography and pathological analysis to follow the progression of antenatal hydronephrosis in individual Robo2-deficient mice from embryo to adulthood. We found that hydronephrosis progressed continuously after birth with no spontaneous resolution. With the use of a microbubble ultrasound contrast agent and ultrasound-guided percutaneous aspiration, we demonstrated that antenatal hydronephrosis in Robo2-deficient mice is caused by high-grade VUR resulting from a dilated and incompetent ureterovesical junction rather than ureteral obstruction. We further documented Robo2 expression around the developing ureterovesical junction and identified early dilatation of ureteral orifice structures as a potential fetal origin of antenatal hydronephrosis and VUR. Our results thus demonstrate that Robo2 is crucial for the formation of a normal ureteral orifice and for the maintenance of an effective anti-reflux mechanism. This study also establishes a reproducible genetic mouse model of progressive antenatal hydronephrosis and primary high-grade VUR

    Fox-1 family of RNA-binding proteins

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    The Fox-1 family of RNA-binding proteins are evolutionarily conserved regulators of tissue-specific alternative splicing in metazoans. The Fox-1 family specifically recognizes the (U)GCAUG stretch in regulated exons or in flanking introns, and either promotes or represses target exons. Recent unbiased bioinformatics analyses of alternatively spliced exons and comparison of various vertebrate genomes identified the (U)GCAUG stretch as a highly conserved and widely distributed element enriched in intronic regions surrounding exons with altered inclusion in muscle, heart, and brain, consistent with specific expression of Fox-1 and Fox-2 in these tissues. Global identification of Fox-2 target RNAs in living cells revealed that many of the Fox-2 target genes themselves encode splicing regulators. Further systematic elucidation of target genes of the Fox-1 family and other splicing regulators in various tissues will lead to a comprehensive understanding of splicing regulatory networks

    Data compression and harmonic analysis

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    In this article we review some recent interactions between harmonic analysis and data compression. The story goes back of course to Shannon’s R(D) theory in the case of Gaussian stationary processes, which says that transforming into a Fourier basis followed by block coding gives an optimal lossy compression technique; practical developments like transformbased image compression (JPEG) have been inspired by this result. In this article we also discuss connections perhaps less familiar to the Information Theory community, growing out of the field of harmonic analysis. Recent harmonic analysis constructions, such as wavelet transforms and Gabor transforms, are essentially optimal transforms for transform coding in certain settings. Some of these transforms are under consideration for future compression standards, like JPEG-2000. We discuss some of the lessons of harmonic analysis in this century. Typically, the problems and achievements of this field have involved goals that were not obviously related to practical data compression, and have used a language not immediately accessible to outsiders. Nevertheless, through a extensive generalization of what Shannon called the ‘sampling theorem’, harmonic analysis has succeeded in developing new forms of functional representation which turn out to have significant data compression interpretations. We explain why harmonic analysis has interacted with data compression, and we describe some interesting recent ideas in the field that may affect data compression in the future

    Spatially Separated Electron and Proton Beams in a Simulated Solar Coronal Jet

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    Magnetic reconnection is widely accepted to be a major contributor to nonthermal particle acceleration in the solar atmosphere. In this paper we investigate particle acceleration during the impulsive phase of a coronal jet, which involves bursty reconnection at a magnetic null point. A test-particle approach is employed, using electromagnetic fields from a magnetohydrodynamic simulation of such a jet. Protons and electrons are found to be accelerated nonthermally both downwards toward the domain's lower boundary and the solar photosphere, and outwards along the axis of the coronal jet and into the heliosphere. A key finding is that a circular ribbon of particle deposition on the photosphere is predicted, with the protons and electrons concentrated in different parts of the ribbon. Furthermore, the outgoing protons and electrons form two spatially separated beams parallel to the axis of the jet, signatures that may be observable in in-situ observations of the heliosphere

    The Dynamic Formation of Pseudostreamers

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    Streamers and pseudostreamers structure the corona at the largest scales, as seen in both eclipse and coronagraph white-light images. Their inverted-goblet appearance encloses broad coronal loops at the Sun and tapers to a narrow radial stalk away from the star. The streamer associated with the global solar dipole magnetic field is long-lived, predominantly contains a single arcade of nested loops within it, and separates opposite-polarity interplanetary magnetic fields with the heliospheric current sheet (HCS) anchored at its apex. Pseudostreamers, on the other hand, are transient, enclose double arcades of nested loops, and separate like-polarity fields with a dense plasma sheet. We use numerical magnetohydrodynamic simulations to calculate, for the first time, the formation of pseudostreamers in response to photospheric magnetic-field evolution. Convective transport of a minority-polarity flux concentration, initially positioned under one side of a streamer, through the streamer boundary into the adjacent preexisting coronal hole forms the pseudostreamer. Interchange magnetic reconnection at the overlying coronal null point(s) governs the development of the pseudostreamer above—and of a new satellite coronal hole behind—the moving minority polarity. The reconnection dynamics liberate coronal-loop plasma that can escape into the heliosphere along so-called separatrix-web ("S-Web") arcs, which reach far from the HCS and the solar equatorial plane, and can explain the origin of high-latitude slow solar wind. We describe the implications of our results for in situ and remote-sensing observations of the corona and heliosphere as obtained, most recently, by Parker Solar Probe and Solar Orbiter
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