The rate of dissociation of a DNA-protein complex is often considered to be a property of that complex, without dependence on other nearby molecules in solution. We study the kinetics of dissociation of the abundant E. coli nucleoid protein Fis from DNA, using a single-molecule mechanics assay. The rate of Fis dissociation from DNA is strongly dependent on the solution concentration of DNA. The off-rate (koff) of Fis from DNA shows an initially linear dependence on solution DNA concentration, characterized by an exchange rate of kex ≈ 9×10−4 s−1 (ng/μl)−1 for 100 mM univalent salt buffer, with a very small off-rate at zero DNA concentration. The off-rate saturates at approximately koff,max ≈ 8×10−3 s−1 for DNA concentrations above ≈ 20 ng/μl. This exchange reaction depends mainly on DNA concentration with little dependence on the length of the DNA molecules in solution or on binding affinity, but does increase with increasing salt concentration. We also show data for the yeast HMGB protein NHP6A showing a similar DNA-concentration-dependent dissociation effect, with faster rates suggesting generally weaker DNA binding by NHP6A relative to Fis. Our results are well-described by a model with an intermediate partially-dissociated state where the protein is susceptible to being captured by a second DNA segment, in the manner of “direct transfer” reactions studied for other DNA-binding proteins. This type of dissociation pathway may be important to protein-DNA binding kinetics in vivo where DNA concentrations are large.
The Beyond Ultra-deep Frontier Fields and Legacy Observations (BUFFALO) is a 101 orbit + 101 parallel Cycle 25 Hubble Space Telescope (HST) Treasury program taking data from 2018 to 2020. BUFFALO will expand existing coverage of the Hubble Frontier Fields (HFF) in Wide Field Camera 3/IR F105W, F125W, and F160W and Advanced Camera for Surveys/WFC F606W and F814W around each of the six HFF clusters and flanking fields. This additional area has not been observed by HST but is already covered by deep multiwavelength data sets, including Spitzer and Chandra. As with the original HFF program, BUFFALO is designed to take advantage of gravitational lensing from massive clusters to simultaneously find high-redshift galaxies that would otherwise lie below HST detection limits and model foreground clusters to study the properties of dark matter and galaxy assembly. The expanded area will provide the first opportunity to study both cosmic variance at high redshift and galaxy assembly in the outskirts of the large HFF clusters. Five additional orbits are reserved for transient followup. BUFFALO data including mosaics, value-added catalogs, and cluster mass distribution models will be released via MAST on a regular basis as the observations and analysis are completed for the six individual clusters.
A core-collapse supernova releases the vast majority of the gravitational binding energy of its compact remnant in the form of neutrinos over an interval of a few tens of seconds. In the event of a core-collapse supernova within our galaxy, multiple current and future neutrino detectors would see a large burst in activity. Neutrinos escape a supernova hours before light does, so any prompt information about the supernova's direction that can be inferred via the neutrino signal will help to enable early electromagnetic observations of the supernova. While there are methods to determine the direction via intrinsic directionality of some neutrino-matter interaction channels, a complementary method which will reach maturity with the next generation of large neutrino detectors is the use of relative neutrino arrival times at different detectors around the globe. To evaluate this triangulation method for realistic detector configurations of the next few decades, we generate random supernova neutrino signals with realistic detector assumptions, and quantify the error in expected time delay between detections. We investigate a practical and robust method of estimating the time differences between burst detections, also correcting for detection efficiency bias. With this method, we determine the pointing precision of supernova neutrino triangulation as a function of supernova distance and location, detectors used, detector background level and neutrino mass ordering assumption. Under favorable conditions, the 1σ supernova search area from triangulation could be reduced to a few percent of the sky. It should be possible to implement this method with low latency under realistic conditions.
One of the primary goals for the upcoming James Webb Space Telescope is to observe the first galaxies. Predictions for planned and proposed surveys have typically focused on average galaxy counts, assuming a random distribution of galaxies across the observed field. The first and most-massive galaxies, however, are expected to be tightly clustered, an effect known as cosmic variance. We show that cosmic variance is likely to be the dominant contribution to uncertainty for high-redshift mass and luminosity functions, and that median high-redshift and high-mass galaxy counts for planned observations lie significantly below average counts. Several different strategies are considered for improving our understanding of the first galaxies, including adding depth, area, and independent pointings. Adding independent pointings is shown to be the most efficient both for discovering the single highest-redshift galaxy and also for constraining mass and luminosity functions.
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