Beyond position weight matrices: nucleotide correlations in transcription factor binding sites and their description

The identification of transcription factor binding sites (TFBSs) on genomic DNA is of crucial importance for understanding and predicting regulatory elements in gene networks. TFBS motifs are commonly described by Position Weight Matrices (PWMs), in which each DNA base pair independently contributes to the transcription factor (TF) binding, despite mounting evidence of interdependence between base pairs positions. The recent availability of genome-wide data on TF-bound DNA regions offers the possibility to revisit this question in detail for TF binding {\em in vivo}. Here, we use available fly and mouse ChIPseq data, and show that the independent model generally does not reproduce the observed statistics of TFBS, generalizing previous observations. We further show that TFBS description and predictability can be systematically improved by taking into account pairwise correlations in the TFBS via the principle of maximum entropy. The resulting pairwise interaction model is formally equivalent to the disordered Potts models of statistical mechanics and it generalizes previous approaches to interdependent positions. Its structure allows for co-variation of two or more base pairs, as well as secondary motifs. Although models consisting of mixtures of PWMs also have this last feature, we show that pairwise interaction models outperform them. The significant pairwise interactions are found to be sparse and found dominantly between consecutive base pairs. Finally, the use of a pairwise interaction model for the identification of TFBSs is shown to give significantly different predictions than a model based on independent positions

Fast global oscillations in networks of integrate-and-fire neurons with low firing rates

We study analytically the dynamics of a network of sparsely connected inhibitory integrate-and-fire neurons in a regime where individual neurons emit spikes irregularly and at a low rate. In the limit when the number of neurons N tends to infinity,the network exhibits a sharp transition between a stationary and an oscillatory global activity regime where neurons are weakly synchronized. The activity becomes oscillatory when the inhibitory feedback is strong enough. The period of the global oscillation is found to be mainly controlled by synaptic times, but depends also on the characteristics of the external input. In large but finite networks, the analysis shows that global oscillations of finite coherence time generically exist both above and below the critical inhibition threshold. Their characteristics are determined as functions of systems parameters, in these two different regimes. The results are found to be in good agreement with numerical simulations.Comment: 45 pages, 11 figures, to be published in Neural Computatio

Metamorphoses of the flow past an obstacle of a resonantly-driven bistable polariton fluid

Motivated by recent experiments, we theoretically analyze the flow past an obstacle of a one-dimensional "quantum fluid of light" which is resonantly driven, and exhibits bistability. The flow is found to abruptly change several times when the fluid velocity or the obstacle potential strength are increased. In contrast to the cases of usual fluids and superfluids, the transitions take place between stationary states. They involve the fluid bistability in an essential way. Remarkably, at the transitions points, the fluid in the obstacle wake lies in the unstable intermediate density state

Direct Interactions in Relativistic Statistical Mechanics

Directly interacting particles are considered in the multitime formalism of predictive relativistic mechanics. When the equations of motion leave a phase-space volume invariant, it turns out that the phase average of any first integral, covariantly defined as a flux across a $7n$-dimensional surface, is conserved. The Hamiltonian case is discussed, a class of simple models is exhibited, and a tentative definition of equilibrium is proposed.Comment: Plain Tex file, 26 page

Six Homeoproteins and a Iinc-RNA at the Fast MYH Locus Lock Fast Myofiber Terminal Phenotype

International audienceThousands of long intergenic non-coding RNAs (lincRNAs) are encoded by the mammalian genome. However, the function of most of these lincRNAs has not been identified in vivo. Here, we demonstrate a role for a novel lincRNA, linc-MYH, in adult fast-type myofiber specialization. Fast myosin heavy chain (MYH) genes and linc-MYH share a common enhancer, located in the fast MYH gene locus and regulated by Six1 homeoproteins. linc-MYH in nuclei of fast-type myofibers prevents slow-type and enhances fast-type gene expression. Functional fast-sarcomeric unit formation is achieved by the coordinate expression of fast MYHs and linc-MYH, under the control of a common Six-bound enhancer

A core genetic module : the Mixed Feedback Loop

The so-called Mixed Feedback Loop (MFL) is a small two-gene network where protein A regulates the transcription of protein B and the two proteins form a heterodimer. It has been found to be statistically over-represented in statistical analyses of gene and protein interaction databases and to lie at the core of several computer-generated genetic networks. Here, we propose and mathematically study a model of the MFL and show that, by itself, it can serve both as a bistable switch and as a clock (an oscillator) depending on kinetic parameters. The MFL phase diagram as well as a detailed description of the nonlinear oscillation regime are presented and some biological examples are discussed. The results emphasize the role of protein interactions in the function of genetic modules and the usefulness of modelling RNA dynamics explicitly.Comment: To be published in Physical Review

Laws of crack motion and phase-field models of fracture

Recently proposed phase-field models offer self-consistent descriptions of brittle fracture. Here, we analyze these theories in the quasistatic regime of crack propagation. We show how to derive the laws of crack motion either by using solvability conditions in a perturbative treatment for slight departure from the Griffith threshold, or by generalizing the Eshelby tensor to phase-field models. The analysis provides a simple physical interpretation of the second component of the classic Eshelby integral in the limit of vanishing crack propagation velocity: it gives the elastic torque on the crack tip that is needed to balance the Herring torque arising from the anisotropic interface energy. This force balance condition reduces in this limit to the principle of local symmetry in isotropic media and to the principle of maximum energy release rate for smooth curvilinear cracks in anisotropic media. It can also be interpreted physically in this limit based on energetic considerations in the traditional framework of continuum fracture mechanics, in support of its general validity for real systems beyond the scope of phase-field models. Analytical predictions of crack paths in anisotropic media are validated by numerical simulations. Simulations also show that these predictions hold even if the phase-field dynamics is modified to make the failure process irreversible. In addition, the role of dissipative forces on the process zone scale as well as the extension of the results to motion of planar cracks under pure antiplane shear are discussed

DAMPAK SERTIFIKASI GURU TERHADAP PERILAKU SOSIAL DAN EKONOMI GURU DI KABUPATEN NGAWI

Penelitian ini dilakukan di Kabupaten Ngawi, dengan tujuan untuk mengidentifikasi, dan menjelaskan beberapa dampak sertifikasi guru terhadap perilaku sosial dan ekonomi guru di Kabupaten Ngawi,  baik dampak  positif maupun dampak negative. Jenis penelitian ini bersifat deskriptif kualitatif. Teknik pengambilan sampel dilakukan dengan snowball sampling. Metode pengumpulan data yang digunakan adalah wawancara mendalam, pengamatan langsung dan mencatat dokumen. Validitas data menggunakan triangulasi sumber. Teknik analisis data menggunakan reduksi data, display data dan verifikasi.” Hasil penelitian menunjukkan bahwa pemberian tunjangan atau insentif yang didapat dari sertifikasi guru di beberapa sekolah menimbulkan perubahan perilaku sosial antara guru yang mendapat insentif dengan guru yang tidak mendapat insentif. Sertifikasi guru juga berpengaruh terhadap perilaku ekonomi pada profesi guru baik di sekolah Negeri maupun Swasta, yang tampak dengan meningkatnya kesejahteraan hidup mereka