Boost-HiC: computational enhancement of long-range contacts in chromosomal contact maps

International audienceGenome-wide chromosomal contact maps are widely used to uncover the 3D organisation of genomes. They rely on the collection of millions of contacting pairs of genomic loci. Contact frequencies at short range are usually well measured in experiments, while there is a lot of missing information about long-range contacts. We propose to use the sparse information contained in raw contact maps to determine high-confidence contact frequency between all pairs of loci. Our algorithmic procedure, Boost-HiC, enables the detection of Hi-C patterns such as chromosomal compartments at a resolution that would be otherwise only attainable by sequencing a hundred times deeper the experimental Hi-C library

beta-amyloid modulation of synaptic transmission and plasticity

The sequencing of β amyloid protein (Aβ) in 1984 led to the formulation of the “amyloid hypothesis” of Alzheimer's disease (AD) (Glenner and Wong, 1984). The hypothesis proposed that accumulation of Aβ is responsible for AD-related pathology, including Aβ deposits, neurofibrillary tangles, and eventual neuronal cell death (Tanzi and Bertram, 2005). Within a few years, four groups cloned the amyloid precursor protein (APP) gene from which Aβ is processed (Goldgaber et al., 1987; Kang et al., 1987; Robakis et al., 1987; Tanzi et al., 1987). Linkage analysis mapped the gene to chromosome 21, and mutations in APP were found that led to the inappropriate processing of APP into the Aβ1–42 peptide (Goate et al., 1991; Mullan et al., 1992) (for review, see Tanzi and Bertram, 2005). However, these mutations are responsible for only a small fraction of the early-onset familial AD, and the search began for other genes that might also influence the processing of Aβ. Several novel mutations were identified in the presenilins (Levy-Lahad et al., 1995; Rogaev et al., 1995; Sherrington et al., 1995), and apolipoprotein E4 was identified as a major risk factor for the most frequent form of AD (Strittmatter et al., 1993; Mahley et al., 2006)

Renormalization Group Approach to Causal Viscous Cosmological Models

The renormalization group method is applied to the study of homogeneous and flat Friedmann-Robertson-Walker type Universes, filled with a causal bulk viscous cosmological fluid. The starting point of the study is the consideration of the scaling properties of the gravitational field equations, of the causal evolution equation of the bulk viscous pressure and of the equations of state. The requirement of scale invariance imposes strong constraints on the temporal evolution of the bulk viscosity coefficient, temperature and relaxation time, thus leading to the possibility of obtaining the bulk viscosity coefficient-energy density dependence. For a cosmological model with bulk viscosity coefficient proportional to the Hubble parameter, we perform the analysis of the renormalization group flow around the scale invariant fixed point, therefore obtaining the long time behavior of the scale factor.Comment: 19 pages. RevTeX4. Revised version. Accepted in Classical and Quantum Gravit

On the Second Law of thermodynamics and the piston problem

The piston problem is investigated in the case where the length of the cylinder is infinite (on both sides) and the ratio $m/M$ is a very small parameter, where $m$ is the mass of one particle of the gaz and $M$ is the mass of the piston. Introducing initial conditions such that the stochastic motion of the piston remains in the average at the origin (no drift), it is shown that the time evolution of the fluids, analytically derived from Liouville equation, agrees with the Second Law of thermodynamics. We thus have a non equilibrium microscopical model whose evolution can be explicitly shown to obey the two laws of thermodynamics.Comment: 29 pages, 9 figures submitted to Journal of Statistical Physics (2003

Chromatin: a tunable spring at work inside chromosomes

This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give for the first time the complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the ``extensible worm-like rope'', allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance in the initiation and regulation of transcription.Comment: 38 pages 15 figure

Suppression of the critical thickness threshold for conductivity at the LaAlO3/SrTiO3 interface

Perovskite materials engineered in epitaxial heterostructures have been intensely investigated during the last decade. The interface formed by an LaAlO3 thin film grown on top of a TiO2-terminated SrTiO3 substrate hosts a two-dimensional electronic system and has become the prototypical example of this field. Although controversy exists regarding some of its physical properties and their precise origin, it is universally found that conductivity only appears beyond an LaAlO3 thickness threshold of four unit cells. Here, we experimentally demonstrate that this critical thickness can be reduced to just one unit cell when a metallic film of cobalt is deposited on top of LaAlO3. First-principles calculations indicate that Co modifies the electrostatic boundary conditions and induces a charge transfer towards the Ti 3d bands, supporting the electrostatic origin of the electronic system at the LaAlO3/SrTiO3 interface. Our results expand the interest of this low-dimensional oxide system from in-plane to perpendicular transport and to the exploration of elastic and inelastic tunnel-type transport of (spin-polarized) carriers

Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS

The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg+ phase to avirulent Bvg- or intermediate Bvgi phases, in which no virulence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using transcriptomic approaches. Recombinant BP-BvgΔ65, which is in the Bvgi phase by default and can be up-modulated to the Bvg+ phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg+-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-BvgΔ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvgi and Bvg+-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions

Search for W' boson production in the W'->tb decay channel

We present a search for the production of a new heavy gauge boson W' that decays to a top quark and a bottom quark. We have analyzed 230 pb^{-1} of data collected with the Dzero detector at the Fermilab Tevatron collider at a center-of-mass energy of 1.96 TeV. No significant excess of events above the standard model expectation is found in any region of the final state invariant mass distribution. We set upper limits on the production cross section of W' bosons times branching ratio to top quarks at the 95% confidence level for several different W' boson masses. We exclude masses between 200 GeV and 610 GeV for a W' boson with standard-model-like couplings, between 200 GeV and 630 GeV for a W' boson with right-handed couplings that is allowed to decay to both leptons and quarks, and between 200 GeV and 670 GeV for a W' boson with right-handed couplings that is only allowed to decay to quarks.Comment: 9 pages, 6 figures, accepted by Phys. Lett.

Search for R-parity violating supersymmetry via the LLE couplings lambda_{121}, lambda_{122} or lambda_{133} in ppbar collisions at sqrt(s)=1.96 TeV

A search for gaugino pair production with a trilepton signature in the framework of R-parity violating supersymmetry via the couplings lambda_121, lambda_122, or lambda_133 is presented. The data, corresponding to an integrated luminosity of L~360/pb, were collected from April 2002 to August 2004 with the D0 detector at the Fermilab Tevatron Collider, at a center-of-mass energy of sqrt(s)=1.96 TeV. This analysis considers final states with three charged leptons with the flavor combinations eel, mumul, and eetau (l=e or mu). No evidence for supersymmetry is found and limits at the 95% confidence level are set on the gaugino pair production cross section and lower bounds on the masses of the lightest neutralino and chargino are derived in two supersymmetric models.Comment: 9 pages, 4 figures (fig2 includes 3 subfigures

Multivariate searches for single top quark production with the D0 detector

We present a search for electroweak production of single top quarks in the s-channel (p-pbar -> t bbar + X) and t-channel (p-pbar -> tq bbar + X) modes. We have analyzed 230 pb^(-1) of data collected with the D0 detector at the Fermilab Tevatron collider at a center-of-mass energy of sqrt(s) = 1.96 TeV. Two separate analysis methods are used: neural networks and a cut-based analysis. No evidence for a single top quark signal is found. We set 95% confidence level upper limits on the production cross sections using Bayesian statistics, based on event counts and binned likelihoods formed from the neural network output. The limits from the neural network (cut-based) analysis are 6.4 pb (10.6 pb) in the s-channel and 5.0 pb (11.3 pb) in the t-channel.Comment: submitted to Phys. Rev. D, Fermilab preprint Fermilab-Pub-06/069-