Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq

© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. Cooperative binding of transcription factors is known to be important in the regulation of gene expression programs conferring cellular identities. However, current methods to measure cooperativity parameters have been laborious and therefore limited to studying only a few sequence variants at a time. We developed Coop-seq (cooperativity by sequencing) that is capable of efficiently and accurately determining the cooperativity parameters for hundreds of different DNA sequences in a single experiment. We apply Coop-seq to 12 dimer pairs from the Sox and POU families of transcription factors using 324 unique sequences with changed half-site orientation, altered spacing and discrete randomization within the binding elements. The study reveals specific dimerization profiles of different Sox factors with Oct4. By contrast, Oct4 and the three neural class III POU factors Brn2, Brn4 and Oct6 assemble with Sox2 in a surprisingly indistinguishable manner. Two novel half-site configurations can support functional Sox/Oct dimerization in addition to known composite motifs. Moreover, Coop-seq uncovers a nucleotide switch within the POU half-site when spacing is altered, which is mirrored in genomic loci bound by Sox2/Oct4 complexes.Link_to_subscribed_fulltex

SO(5) superconductor in a Zeeman magnetic field: Phase diagram and thermodynamic properties

In this paper we present calculations of the SO(5) quantum rotor theory of high-T$_{c}$ superconductivity in Zeeman magnetic field. We use the spherical approach for five-component quantum rotors in three-dimensional lattice to obtain formulas for critical lines, free energy, entropy and specific heat and present temperature dependences of these quantities for different values of magnetic field. Our results are in qualitative agreement with relevant experiments on high-T$_{c}$ cuprates.Comment: 4 pages, 2 figures, to appear in Phys. Rev. B, see http://prb.aps.or

Microwave Background Signals from Tangled Magnetic Fields

An inhomogeneous cosmological magnetic field will create Alfven-wave modes that induce a small rotational velocity perturbation on the last scattering surface of the microwave background radiation. The Alfven-wave mode survives Silk damping on much smaller scales than the compressional modes. This, in combination with its rotational nature, ensures that there will be no sharp cut-off in anisotropy on arc-minute scales. We estimate that a magnetic field which redshifts to a present value of $3\times 10^{-9}$ Gauss produces temperature anisotropies at the 10 micro Kelvin level at and below 10 arc-min scales. A tangled magnetic field, which is large enough to influence the formation of large scale structure is therefore potentially detectable by future observations.Comment: 5 pages, Revtex, no figure

Electroweak Bubble Nucleation, Nonperturbatively

We present a lattice method to compute bubble nucleation rates at radiatively induced first order phase transitions, in high temperature, weakly coupled field theories, nonperturbatively. A generalization of Langer's approach, it makes no recourse to saddle point expansions and includes completely the dynamical prefactor. We test the technique by applying it to the electroweak phase transition in the minimal standard model, at an unphysically small Higgs mass which gives a reasonably strong phase transition (lambda/g^2 =0.036, which corresponds to m(Higgs)/m(W) = 0.54 at tree level but does not correspond to a positive physical Higgs mass when radiative effects of the top quark are included), and compare the results to older perturbative and other estimates. While two loop perturbation theory slightly under-estimates the strength of the transition measured by the latent heat, it over-estimates the amount of supercooling by a factor of 2.Comment: 48 pages, including 16 figures. Minor revisions and typo fixes, nothing substantial, conclusions essentially unchange

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1–2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.National Institute of Allergy and Infectious Diseases (U.S.) (Awards UM1AI100663)National Institute of Allergy and Infectious Diseases (U.S.) (Awards AI110657

Quintessence and Gravitational Waves

We investigate some aspects of quintessence models with a non-minimally coupled scalar field and in particular we show that it can behave as a component of matter with $-3 \lesssim P/\rho \lesssim 0$. We study the properties of gravitational waves in this class of models and discuss their energy spectrum and the cosmic microwave background anisotropies they induce. We also show that gravitational waves are damped by the anisotropic stress of the radiation and that their energy spectrum may help to distinguish between inverse power law potential and supergravity motivated potential. We finish by a discussion on the constraints arising from their density parameter \Omega_\GW.Comment: 21 pages, 18 figures, fianl version, accepted for publication in PR

Dark energy and dark matter from an inhomogeneous dilaton

A cosmological scenario is proposed where the dark matter (DM) and dark energy (DE) of the universe are two simultaneous manifestations of an inhomogenous dilaton. The equation of state of the field is scale-dependent and pressureless at galactic and larger scales and it has negative pressure as a DE at very large scales. The dilaton drives an inflationary phase followed by a kinetic energy-dominated one, as in the "quintessential inflation" model introduced by Peebles & Vilenkin, and soon after the end of inflation particle production seeds the first inhomogeneities that lead to galaxy formation. The dilaton is trapped near the minimum of the potential where it oscillates like a massive field, and the excess of kinetic energy is dissipated via the mechanism of "gravitational cooling" first introduced by Seidel & Suen. The inhomogeneities therefore behave like solitonic oscillations around the minimum of the potential, known as "oscillatons", that we propose account for most DM in galaxies. Those regions where the dilaton does not transform enough kinetic energy into reheating or carry an excess of it from regions that have cooled, evolve to the tail of the potential as DE, driving the acceleration of the universe.Comment: 9 pages, 8 figures, uses revtex, submitted PR

Recent Advances in Modeling Stellar Interiors

Advances in stellar interior modeling are being driven by new data from large-scale surveys and high-precision photometric and spectroscopic observations. Here we focus on single stars in normal evolutionary phases; we will not discuss the many advances in modeling star formation, interacting binaries, supernovae, or neutron stars. We review briefly: 1) updates to input physics of stellar models; 2) progress in two and three-dimensional evolution and hydrodynamic models; 3) insights from oscillation data used to infer stellar interior structure and validate model predictions (asteroseismology). We close by highlighting a few outstanding problems, e.g., the driving mechanisms for hybrid gamma Dor/delta Sct star pulsations, the cause of giant eruptions seen in luminous blue variables such as eta Car and P Cyg, and the solar abundance problem.Comment: Proceedings for invited talk at conference High Energy Density Laboratory Astrophysics 2010, Caltech, March 2010, submitted for special issue of Astrophysics and Space Science; 7 pages; 5 figure

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Structure formation with a self-tuning scalar field

A scalar field with an exponential potential has the particular property that it is attracted into a solution in which its energy scales as the dominant component (radiation or matter) of the Universe, contributing a fixed fraction of the total energy density. We study the growth of perturbations in a CDM dominated $\Omega=1$ universe with this extra field, with an initial flat spectrum of adiabatic fluctuations. The observational constraints from structure formation are satisfied as well, or better, than in other models, with a contribution to the energy density from the scalar field $\Omega_\phi \sim 0.1$ which is small enough to be consistent with entry into the attractor prior to nucleosynthesis.Comment: 4 pages, uses RevTex, 2 figure