Using competition assays to quantitatively model cooperative binding by transcription factors and other ligands.

BACKGROUND: The affinities of DNA binding proteins for target sites can be used to model the regulation of gene expression. These proteins can bind to DNA cooperatively, strongly impacting their affinity and specificity. However, current methods for measuring cooperativity do not provide the means to accurately predict binding behavior over a wide range of concentrations. METHODS: We use standard computational and mathematical methods, and develop novel methods as described in Results. RESULTS: We explore some complexities of cooperative binding, and develop an improved method for relating in vitro measurements to in vivo function, based on ternary complex formation. We derive expressions for the equilibria among the various complexes, and explore the limitations of binding experiments that model the system using a single parameter. We describe how to use single-ligand binding and ternary complex formation in tandem to determine parameters that have thermodynamic relevance. We develop an improved method for finding both single-ligand dissociation constants and concentrations simultaneously. We show how the cooperativity factor can be found when only one of the single-ligand dissociation constants can be measured. CONCLUSIONS: The methods that we develop constitute an optimized approach to accurately model cooperative binding. GENERAL SIGNIFICANCE: The expressions and methods we develop for modeling and analyzing DNA binding and cooperativity are applicable to most cases where multiple ligands bind to distinct sites on a common substrate. The parameters determined using these methods can be fed into models of higher-order cooperativity to increase their predictive power

Signatures of multiple stellar populations in unresolved extragalactic globular/ young massive star clusters

We present an investigation of potential signatures of the formation of multiple stellar populations in recently formed extragalactic star clusters. All of the Galactic globular clusters for which good samples of individual stellar abundances are available show evidence for multiple populations. This appears to require that multiple episodes of star formation and light element enrichment are the norm in the history of a globular cluster. We show that there are detectable observational signatures of multiple formation events in the unresolved spectra of massive, young extragalactic star clusters. We present the results of a pilot program to search for one of the cleanest signatures that we identify - the combined presence of emission lines from a very recently formed population and absorption lines from a somewhat older population. A possible example of such a system is identified in the Antennae galaxies. This source's spectrum shows evidence of two stellar populations with ages of 8 Myr and 80 Myr. Further investigation shows that these populations are in fact physically separated, but only by a projected distance of 59 pc. We show that the clusters are consistent with being bound and discuss the possibility that their coalescence could result in a single globular cluster hosting multiple stellar populations. While not the prototypical system proposed by most theories of the formation of multiple populations in clusters, the detection of this system in a small sample is both encouraging and interesting. Our investigation suggests that expanded surveys of massive young star clusters should detect more clusters with such signatures.Comment: 11 pages, 7 figures: accepted for publication in Ap

Continuing the education of autistic pupils while focusing on family wellbeing during the Coronavirus Pandemic

This advice is given in the form of numbered points in no particular order. Some will be very relevant and useful to some autistic children and young people and their families and others will not. It is for the reader to select those that make most sense and seem worth trying. As this document was developed at the start of the pandemic lockdown, transition back in to school /college was not then at the top of the priority list. Supporting learners going back into schools and colleges which may look very different from their pre pandemic presentation is clearly an important consideration now. The first bullet point raises this concern which is unpacked further later in the document

Radio Galaxy Clustering at z~0.3

Radio galaxies are uniquely useful as probes of large-scale structure as their uniform identification with giant elliptical galaxies out to high redshift means that the evolution of their bias factor can be predicted. As the initial stage in a project to study large-scale structure with radio galaxies we have performed a small redshift survey, selecting 29 radio galaxies in the range 0.19<z<0.45 from a contiguous 40 square degree area of sky. We detect significant clustering within this sample. The amplitude of the two-point correlation function we measure is consistent with no evolution from the local (z<0.1) value. This is as expected in a model in which radio galaxy hosts form at high redshift and thereafter obey a continuity equation, although the signal:noise of the detection is too low to rule out other models. Larger surveys out to z~1 should reveal the structures of superclusters at intermediate redshifts and strongly constrain models for the evolution of large-scale structure.Comment: 7 pages, 3 figures, accepted by ApJ Letter

Limits on [OIII] 5007 emission from NGC4472's globular clusters: constraints on planetary nebulae and ultraluminous black hole X-ray binaries in globular clusters

We have searched for [OIII] 5007 emission in high resolution spectroscopic data from Flames/Giraffe VLT observations of 174 massive globular clusters (GCs) in NGC4472. No planetary nebulae (PNe) are observed in these clusters, constraining the number of PNe per bolometric luminosity, \alpha<0.8*10^{-7}PN/L_{\odot}. This is significantly lower than the rate predicted from stellar evolution, if all stars produce PNe. Comparing our results to populations of PNe in galaxies, we find most galaxies have a higher \alpha than these GCs (more PNe per bolometric luminosity - though some massive early-type galaxies do have similarly low \alpha). The low \alpha required in these GCs suggests that the number of PNe per bolometric luminosity does not increase strongly with decreasing mass or metallicity of the stellar population. We find no evidence for correlations between the presence of known GC PNe and either the presence of low mass X-ray binaries (LMXBs) or the stellar interaction rates in the GCs. This, and the low \alpha observed, suggests that the formation of PNe may not be enhanced in tight binary systems. These data do identify one [OIII] emission feature, this is the (previously published) broad [OIII] emission from the cluster RZ 2109. This emission is thought to originate from the LMXB in this cluster, which is accreting at super-Eddington rates. The absence of any similar [OIII] emission from the other clusters favors the hypothesis that this source is a black hole LMXB, rather than a neutron star LMXB with significant geometric beaming of its X-ray emission.Comment: 10 pages, 3 figures, accepted for publication in Ap

Large Surveys in Cosmology: The Changing Sociology

Galaxy redshift surveys and Cosmic Microwave Background experiments are undertaken with larger and larger teams, in a fashion reminiscent of particle physics experiments and the human genome projects. We discuss the role of young researchers, the issue of multiple authorship, and ways to communicate effectively in teams of tens to hundreds of collaborators.Comment: Invited article for "Organizations and Strategies in Astronomy II", ed. A. Heck, Kluwer Acad. Publ., in press (7 pages, no figures

The finite size effect of galaxies on the cosmic virial theorem and the pairwise peculiar velocity dispersions

We discuss the effect of the finite size of galaxies on estimating small-scale relative pairwise peculiar velocity dispersions from the cosmic virial theorem (CVT). Specifically we evaluate the effect by incorporating the finite core radius $r_c$ in the two-point correlation function of mass, i.e. $\xi_\rho(r) \propto (r+r_c)^{-\gamma}$ and the effective gravitational force softening $r_s$ on small scales. We analytically obtain the lowest-order correction term for $\gamma <2$ which is in quantitative agreement with the full numerical evaluation. With a nonzero $r_s$ and/or $r_c$ the cosmic virial theorem is no longer limited to the case of $\gamma<2$. We present accurate fitting formulae for the CVT predicted pairwise velocity dispersion for the case of $\gamma>2$. Compared with the idealistic point-mass approximation ($r_s=r_c=0$), the finite size effect can significantly reduce the small-scale velocity dispersions of galaxies at scales much larger than $r_s$ and $r_c$. Even without considering the finite size of galaxies, nonzero values for $r_c$ are generally expected, for instance, for cold dark matter (CDM) models with a scale-invariant primordial spectrum. For these CDM models, a reasonable force softening r_s\le 100 \hikpc would have rather tiny effect. We present the CVT predictions for the small-scale pairwise velocity dispersion in the CDM models normalized by the COBE observation. The implication of our results for confrontation of observations of galaxy pair-wise velocity dispersions and theoretical predictions of the CVT is also discussed.Comment: 18 pages. LaTeX text and 8 postcript figures. submitted to Ap

Hall Effect and Specific Resistance in Thin Evaporated Film of Fe, Co, Ni, Pd, and Pt

Further investigation of the Hall effect and specific resistance in thin films of iron, cobalt, nickel , palladium, and platinum give the following results: (1) the specific resistances of films deposited on a cool surface range from 4 to 30 times the accepted values for the corresponding bulk metals; (2) the Hall coefficients for the paramagnetic metals palladium and platinum are slightly smaller than bulk values: (3) the Hall coefficients for iron, cobalt, and nickel deposited on a cool surface are respectively 1.8 times, 5 times, and 7 times, the bulk values; (4) heating films of iron, cobalt, and nickel during deposition causes both the Hall coefficients and specific resistances to decrease almost to bulk values; (5) saturation of the Hall effect occurs for iron at a slightly lower magnetic field than for bulk values, for cobalt at 12500 as compared with 13500 for bulk, and for nickel at 2500 as compared with 6000 for bulk; and (6) microscopic investigation of nickel and cobalt shows some evidence of crystal structure

Hierarchy in the Phase Space and Dark Matter Astronomy

We develop a theoretical framework for describing the hierarchical structure of the phase space of cold dark matter haloes, due to gravitationally bound substructures. Because it includes the full hierarchy of the cold dark matter initial conditions and is hence complementary to the halo model, the stable clustering hypothesis is applied for the first time here to the small-scale phase space structure. As an application, we show that the particle dark matter annihilation signal could be up to two orders of magnitude larger than that of the smooth halo within the Galactic virial radius. The local boost is inversely proportional to the smooth halo density, and thus is O(1) within the solar radius, which could translate into interesting signatures for dark matter direct detection experiments: The temporal correlation of dark matter detection can change by a factor of 2 in the span of 10 years, while there will be significant correlations in the velocity space of dark matter particles. This can introduce O(1) uncertainty in the direction of local dark matter wind, which was believed to be a benchmark of directional dark matter searches or the annual modulation signal.Comment: 5 pages, 4 figure