Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations

We study the effects of multiple binding sites in the promoter of a genetic oscillator. We evaluate the regulatory function of a promoter with multiple binding sites in the absence of cooperative binding, and consider different hypotheses for how the number of bound repressors affects transcription rate. Effective Hill exponents of the resulting regulatory functions reveal an increase in the nonlinearity of the feedback with the number of binding sites. We identify optimal configurations that maximize the nonlinearity of the feedback. We use a generic model of a biochemical oscillator to show that this increased nonlinearity is reflected in enhanced oscillations, with larger amplitudes over wider oscillatory ranges. Although the study is motivated by genetic oscillations in the zebrafish segmentation clock, our findings may reveal a general principle for gene regulation.Comment: 11 pages, 8 figure

Turing Instability in a Boundary-fed System

The formation of localized structures in the chlorine dioxide-idodine-malonic acid (CDIMA) reaction-diffusion system is investigated numerically using a realistic model of this system. We analyze the one-dimensional patterns formed along the gradients imposed by boundary feeds, and study their linear stability to symmetry-breaking perturbations (Turing instability) in the plane transverse to these gradients. We establish that an often-invoked simple local linear analysis which neglects longitudinal diffusion is inappropriate for predicting the linear stability of these patterns. Using a fully nonuniform analysis, we investigate the structure of the patterns formed along the gradients and their stability to transverse Turing pattern formation as a function of the values of two control parameters: the malonic acid feed concentration and the size of the reactor in the dimension along the gradients. The results from this investigation are compared with existing experiments.Comment: 41 pages, 18 figures, to be published in Physical Review

Pressure-induced change of the pairing symmetry in superconducting CeCu2Si2

Low-temperature (T) heat-capacity measurements under hydrostatic pressure of up to p=2.1 GPa have been performed on single-crystalline CeCu2Si2. A broad superconducting (SC) region exists in the T-p phase diagram. In the low-pressure region antiferromagnetic spin fluctuations and in the high-pressure region valence fluctuations had previously been proposed to mediate Cooper pairing. We could identify these two distinct SC regions. We found different thermodynamic properties of the SC phase in both regions, supporting the proposal that different mechanisms might be implied in the formation of superconductivity.Comment: 4 pages, 5 figure

Response of the Heavy-Fermion Superconductor CeCoIn5_5 to Pressure: Roles of Dimensionality and Proximity to a Quantum-Critical Point

We report measurements of the pressure-dependent superconducting transition temperature $T_c$ and electrical resistivity of the heavy-fermion compound CeCoIn$_5$. Pressure moves CeCoIn$_5$ away from its proximity to a quantum-critical point at atmospheric pressure. Experimental results are qualitatively consistent with theoretical predictions for strong-coupled, d-wave superconductivity in an anisotropic 3D superconductor.Comment: 9 pages, 5 figure

Spin Effects in Two Quark System and Mixed States

Based on the numeric solution of a system of coupled channels for vector mesons ($S$- and $D$-waves mixing) and for tensor mesons ($P$- and $F$-waves mixing) mass spectrum and wave functions of a family of vector mesons $q\bar{q}$ in triplet states are obtained. The calculations are performed using a well known Cornell potential with a mixed Lorentz-structure of the confinement term. The spin-dependent part of the potential is taken from the Breit-Fermi approach. The effect of singular terms of potential is considered in the framework of the perturbation theory and by a configuration interaction approach (CIA), modified for a system of coupled equations. It is shown that even a small contribution of the $D$-wave to be very important at the calculation of certain characteristics of the meson states.Comment: 12 pages, LaTe

Superconductivity and Quantum Criticality in CeCoIn_5

Electrical resistivity measurements on a single crystal of the heavy-fermion superconductor CeCoIn_5 at pressures to 4.2 GPa reveal a strong crossover in transport properties near P^* \approx 1.6 GPa, where T_c is a maximum. The temperature-pressure phase diagram constructed from these data provides a natural connection to cuprate physics, including the possible existence of a pseudogap.Comment: 4 pages, 4 figure

GEOMAGIA50.v3: 1. general structure and modifications to the archeological and volcanic database

Background: GEOMAGIA50.v3 is a comprehensive online database providing access to published paleomagnetic, rock magnetic, and chronological data from a variety of materials that record Earth’s magnetic field over the past 50 ka.Findings: Since its original release in 2006, the structure and function of the database have been updated and a significant number of data have been added. Notable modifications are the following: (1) the inclusion of additional intensity, directional and metadata from archeological and volcanic materials and an improved documentation of radiocarbon dates; (2) a new data model to accommodate paleomagnetic, rock magnetic, and chronological data from lake and marine sediments; (3) a refinement of the geographic constraints in the archeomagnetic/volcanic query allowing selection of particular locations; (4) more flexible methodological and statistical constraints in the archeomagnetic/volcanic query; (5) the calculation of predictions of the Holocene geomagnetic field from a series of time varying global field models; (6) searchable reference lists; and (7) an updated web interface. This paper describes general modifications to the database and specific aspects of the archeomagnetic and volcanic database. The reader is referred to a companion publication for a description of the sediment database.Conclusions: The archeomagnetic and volcanic part of GEOMAGIA50.v3 currently contains 14,645 data (declination, inclination, and paleointensity) from 461 studies published between 1959 and 2014. We review the paleomagnetic methods used to obtain these data and discuss applications of the data within the database. The database continues to expand as legacy data are added and new studies published. The web-based interface can be found at http://geomagia.gfz-potsdam.de webcite

Stripe-hexagon competition in forced pattern forming systems with broken up-down symmetry

We investigate the response of two-dimensional pattern forming systems with a broken up-down symmetry, such as chemical reactions, to spatially resonant forcing and propose related experiments. The nonlinear behavior immediately above threshold is analyzed in terms of amplitude equations suggested for a $1:2$ and $1:1$ ratio between the wavelength of the spatial periodic forcing and the wavelength of the pattern of the respective system. Both sets of coupled amplitude equations are derived by a perturbative method from the Lengyel-Epstein model describing a chemical reaction showing Turing patterns, which gives us the opportunity to relate the generic response scenarios to a specific pattern forming system. The nonlinear competition between stripe patterns and distorted hexagons is explored and their range of existence, stability and coexistence is determined. Whereas without modulations hexagonal patterns are always preferred near onset of pattern formation, single mode solutions (stripes) are favored close to threshold for modulation amplitudes beyond some critical value. Hence distorted hexagons only occur in a finite range of the control parameter and their interval of existence shrinks to zero with increasing values of the modulation amplitude. Furthermore depending on the modulation amplitude the transition between stripes and distorted hexagons is either sub- or supercritical.Comment: 10 pages, 12 figures, submitted to Physical Review

Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

Background: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti- inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 mM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl 2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 mg/kg) significantly lengthened the QT c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT c . Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 mM) decreased the amplitude of rapid (I Kr ) and slow (I Ks ) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I Ca ) was slightly diminished, but the transient outward (I to ) and inward rectifier (I K1 ) potassium currents were not influenced. Conclusions: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve

Scenarios of domain pattern formation in a reaction-diffusion system

We performed an extensive numerical study of a two-dimensional reaction-diffusion system of the activator-inhibitor type in which domain patterns can form. We showed that both multidomain and labyrinthine patterns may form spontaneously as a result of Turing instability. In the stable homogeneous system with the fast inhibitor one can excite both localized and extended patterns by applying a localized stimulus. Depending on the parameters and the excitation level of the system stripes, spots, wriggled stripes, or labyrinthine patterns form. The labyrinthine patterns may be both connected and disconnected. In the the stable homogeneous system with the slow inhibitor one can excite self-replicating spots, breathing patterns, autowaves and turbulence. The parameter regions in which different types of patterns are realized are explained on the basis of the asymptotic theory of instabilities for patterns with sharp interfaces developed by us in Phys. Rev. E. 53, 3101 (1996). The dynamics of the patterns observed in our simulations is very similar to that of the patterns forming in the ferrocyanide-iodate-sulfite reaction.Comment: 15 pages (REVTeX), 15 figures (postscript and gif), submitted to Phys. Rev.