Twenty-First Century Glucocorticoid Receptor Molecular Biology

Glucocorticoids are central to homeostasis as a function of the circadian cycle, temporally preceding circulating adrenaline concentration circadian fluctuations. Virtually, all cell types express the glucocorticoid receptor (GR). GR is a transcription factor that activates gene expression by binding to enhancers. Intriguingly, not all cell types respond to GR stimulation in the same fashion at the molecular level. This indicates that GR activity is subject to epigenetic control. We discuss the molecular basis for epigenetic control of GR action at the genomic level, including the concept of topologically associating domains which may restrain the roaming range of distal enhancers. Furthermore, much evidence indicates that GR can repress gene expression programs. We therefore discuss current concepts of the molecular basis of GR-mediated gene expression repression, including non-genomic mechanisms that involve mRNA destabilization

On the Geometry of the Nodal Lines of Eigenfunctions of the Two-Dimensional Torus

The width of a convex curve in the plane is the minimal distance between a pair of parallel supporting lines of the curve. In this paper we study the width of nodal lines of eigenfunctions of the Laplacian on the standard flat torus. We prove a variety of results on the width, some having stronger versions assuming a conjecture of Cilleruelo and Granville asserting a uniform bound for the number of lattice points on the circle lying in short arcs.Comment: 4 figures. Added some comments about total curvature and other detail

Dynamics of Gravity in a Higgs Phase

We investigate the universal low-energy dynamics of the simplest Higgs phase for gravity, `ghost condensation.' We show that the nonlinear dynamics of the `ghostone' field dominate for all interesting gravitational sources. Away from caustic singularities, the dynamics is equivalent to the irrotational flow of a perfect fluid with equation of state p \propto \rho^2, where the fluid particles can have negative mass. We argue that this theory is free from catastrophic instabilities due to growing modes, even though the null energy condition is violated. Numerical simulations show that solutions generally have singularities in which negative energy regions shrink to zero size. We exhibit partial UV completions of the theory in which these singularities are smoothly resolved, so this does not signal any inconsistency in the effective theory. We also consider the bounds on the symmetry breaking scale M in this theory. We argue that the nonlinear dynamics cuts off the Jeans instability of the linear theory, and allows M \lsim 100MeV.Comment: 54 pages, 15 figures; postscript figures downloadable from http://schwinger.harvard.edu/~wiseman/Ghost/ghostepsfigs.tar.gz ; v2: substantial revision to section 5 on bound

Matrix theory of gravitation

A new classical theory of gravitation within the framework of general relativity is presented. It is based on a matrix formulation of four-dimensional Riemann-spaces and uses no artificial fields or adjustable parameters. The geometrical stress-energy tensor is derived from a matrix-trace Lagrangian, which is not equivalent to the curvature scalar R. To enable a direct comparison with the Einstein-theory a tetrad formalism is utilized, which shows similarities to teleparallel gravitation theories, but uses complex tetrads. Matrix theory might solve a 27-year-old, fundamental problem of those theories (sec. 4.1). For the standard test cases (PPN scheme, Schwarzschild-solution) no differences to the Einstein-theory are found. However, the matrix theory exhibits novel, interesting vacuum solutions.Comment: 24 page

Inferring Condition-Specific Targets of Human TF-TF Complexes Using ChIP-seq Data

Background: Transcription factors (TFs) often interact with one another to form TF complexes that bind DNA and regulate gene expression. Many databases are created to describe known TF complexes identified by either mammalian two-hybrid experiments or data mining. Lately, a wealth of ChIP-seq data on human TFs under different experiment conditions are available, making it possible to investigate condition-specific (cell type and/or physiologic state) TF complexes and their target genes. Results: Here, we developed a systematic pipeline to infer Condition-Specific Targets of human TF-TF complexes (called the CST pipeline) by integrating ChIP-seq data and TF motifs. In total, we predicted 2,392 TF complexes and 13,504 high-confidence or 127,994 low-confidence regulatory interactions amongst TF complexes and their target genes. We validated our predictions by (i) comparing predicted TF complexes to external TF complex databases, (ii) validating selected target genes of TF complexes using ChIP-qPCR and RT-PCR experiments, and (iii) analysing target genes of select TF complexes using gene ontology enrichment to demonstrate the accuracy of our work. Finally, the predicted results above were integrated and employed to construct a CST database. Conclusions: We built up a methodology to construct the CST database, which contributes to the analysis of transcriptional regulation and the identification of novel TF-TF complex formation in a certain condition. This database also allows users to visualize condition-specific TF regulatory networks through a user-friendly web interface

Threshold criterion for wetting at the triple point

Grand canonical simulations are used to calculate adsorption isotherms of various classical gases on alkali metal and Mg surfaces. Ab initio adsorption potentials and Lennard-Jones gas-gas interactions are used. Depending on the system, the resulting behavior can be nonwetting for all temperatures studied, complete wetting, or (in the intermediate case) exhibit a wetting transition. An unusual variety of wetting transitions at the triple point is found in the case of a specific adsorption potential of intermediate strength. The general threshold for wetting near the triple point is found to be close to that predicted with a heuristic model of Cheng et al. This same conclusion was drawn in a recent experimental and simulation study of Ar on CO_2 by Mistura et al. These results imply that a dimensionless wetting parameter w is useful for predicting whether wetting behavior is present at and above the triple temperature. The nonwetting/wetting crossover value found here is w circa 3.3.Comment: 15 pages, 8 figure

From nonwetting to prewetting: the asymptotic behavior of 4He drops on alkali substrates

We investigate the spreading of 4He droplets on alkali surfaces at zero temperature, within the frame of Finite Range Density Functional theory. The equilibrium configurations of several 4He_N clusters and their asymptotic trend with increasing particle number N, which can be traced to the wetting behavior of the quantum fluid, are examined for nanoscopic droplets. We discuss the size effects, inferring that the asymptotic properties of large droplets correspond to those of the prewetting film