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

Comparing Infrared Dirac-Born-Infeld Brane Inflation to Observations

We compare the Infrared Dirac-Born-Infeld (IR DBI) brane inflation model to observations using a Bayesian analysis. The current data cannot distinguish it from the \LambdaCDM model, but is able to give interesting constraints on various microscopic parameters including the mass of the brane moduli potential, the fundamental string scale, the charge or warp factor of throats, and the number of the mobile branes. We quantify some distinctive testable predictions with stringy signatures, such as the large non-Gaussianity, and the large, but regional, running of the spectral index. These results illustrate how we may be able to probe aspects of string theory using cosmological observations.Comment: 54 pages, 13 figures. v2: non-Gaussianity constraint has been applied to the model; parameter constraints have tightened significantly, conclusions unchanged. References added; v3, minor revision, PRD versio

Drawing lines in the sand: even skipped et al. and parasegment boundaries.

The pair-rule segmentation gene even skipped (eve) is required to activate engrailed stripes and to organize odd-numbered parasegments (PSs). The protein product Eve has been shown to be an active repressor of transcription, and recent models for Eve function suggest that activation of engrailed is indirect, but these models have not been fully tested. Here we identify the forkhead domain transcription factor Sloppy-paired as the key intermediate in the initial activation of engrailed by Eve in odd-numbered parasegments. We also analyze the roles of the transcription factors Runt and Odd-skipped in this process. Detailed analysis of engrailed and pair-rule gene expression in various mutant combinations shows how eve activates engrailed by repressing these engrailed repressors, and further indicates that mutual repression among pair-rule genes plays an important role in establishing parasegment boundaries. We present a new model of pair-rule gene function that explains the response of these boundaries to the relative levels of Eve and Fushi Tarazu

Laser beam hydrocarbon detector

Portable instrument passes light from helium-neon laser at a wavelength of 3.39 microns through the atmosphere being monitored and measures attenuation of the laser beam. Since beam attenuation is due almost exclusively to absorption of radiation by hydrocarbons, a quantitative measure of their concentration is available

Reciprocity relations between ordinary temperature and the Frieden-Soffer's Fisher-temperature

Frieden and Soffer conjectured some years ago the existence of a ``Fisher temperature" T_F that would play, with regards to Fisher's information measure I, the same role that the ordinary temperature T plays vis-a-vis Shannon's logarithmic measure. Here we exhibit the existence of reciprocity relations between T_F and T and provide an interpretation with reference to the meaning of T_F for the canonical ensemble.Comment: 3 pages, no figure

The Drosophila eve Insulator Homie Promotes eve Expression and Protects the Adjacent Gene from Repression by Polycomb Spreading.

Insulators can block the action of enhancers on promoters and the spreading of repressive chromatin, as well as facilitating specific enhancer-promoter interactions. However, recent studies have called into question whether the activities ascribed to insulators in model transgene assays actually reflect their functions in the genome. The Drosophila even skipped (eve) gene is a Polycomb (Pc) domain with a Pc-group response element (PRE) at one end, flanked by an insulator, an arrangement also seen in other genes. Here, we show that this insulator has three major functions. It blocks the spreading of the eve Pc domain, preventing repression of the adjacent gene, TER94. It prevents activation of TER94 by eve regulatory DNA. It also facilitates normal eve expression. When Homie is deleted in the context of a large transgene that mimics both eve and TER94 regulation, TER94 is repressed. This repression depends on the eve PRE. Ubiquitous TER94 expression is replaced by expression in an eve pattern when Homie is deleted, and this effect is reversed when the PRE is also removed. Repression of TER94 is attributable to spreading of the eve Pc domain into the TER94 locus, accompanied by an increase in histone H3 trimethylation at lysine 27. Other PREs can functionally replace the eve PRE, and other insulators can block PRE-dependent repression in this context. The full activity of the eve promoter is also dependent on Homie, and other insulators can promote normal eve enhancer-promoter communication. Our data suggest that this is not due to preventing promoter competition, but is likely the result of the insulator organizing a chromosomal conformation favorable to normal enhancer-promoter interactions. Thus, insulator activities in a native context include enhancer blocking and enhancer-promoter facilitation, as well as preventing the spread of repressive chromatin

Entanglement sharing in E⊗ϵE\otimes\epsilon Jahn-Teller model in the presence of a magnetic field

We discuss the ground state entanglement of the $E\otimes\epsilon$ Jahn-Teller model in the presence of a strong transverse magnetic field as a function of the vibronic coupling strength. A complete characterization is given of the phenomenon of entanglement sharing in a system composed by a qubit coupled to two bosonic modes. Using the residual $I$-tangle, we find that three-partite entanglement is significantly present in the system in the parameter region near the bifurcation point of the corresponding classical model

Multiphoton Coincidence Spectroscopy

We extend the analysis of photon coincidence spectroscopy beyond bichromatic excitation and two-photon coincidence detection to include multichromatic excitation and multiphoton coincidence detection. Trichromatic excitation and three-photon coincidence spectroscopy are studied in detail, and we identify an observable signature of a triple resonance in an atom-cavity system.Comment: 6 page, REVTeXs, 6 Postscript figures. The abstract appeared in the Proceedings of ACOLS9

MaxEnt and dynamical information

The MaxEnt solutions are shown to display a variety of behaviors (beyond the traditional and customary exponential one) if adequate dynamical information is inserted into the concomitant entropic-variational principle. In particular, we show both theoretically and numerically that power laws and power laws with exponential cut-offs emerge as equilibrium densities in proportional and other dynamics

Entanglement reciprocation between qubits and continuous variables

We investigate how entanglement can be transferred between qubits and continuous variable (CV) systems. We find that one ebit borne in maximally entangled qubits can be fully transferred to two CV systems which are initially prepared in pure separable Gaussian field with high excitation. We show that it is possible, though not straightforward, to retrieve the entanglement back to qubits from the entangled CV systems. The possibility of deposition of multiple ebits from qubits to the initially unentangled CV systems is also pointed out.Comment: 4 pages, 3 figures, RevTeX