Simulation and analysis of in vitro DNA evolution

We study theoretically the in vitro evolution of a DNA sequence by binding to a transcription factor. Using a simple model of protein-DNA binding and available binding constants for the Mnt protein, we perform large-scale, realistic simulations of evolution starting from a single DNA sequence. We identify different parameter regimes characterized by distinct evolutionary behaviors. For each regime we find analytical estimates which agree well with simulation results. For small population sizes, the DNA evolutional path is a random walk on a smooth landscape. While for large population sizes, the evolution dynamics can be well described by a mean-field theory. We also study how the details of the DNA-protein interaction affect the evolution.Comment: 11 pages, 11 figures. Submitted to PNA

Black hole entropy for the general area spectrum

We consider the possibility that the horizon area is expressed by the general area spectrum in loop quantum gravity and calculate the black hole entropy by counting the degrees of freedom in spin-network states related to its area. Although the general area spectrum has a complex expression, we succeeded in obtaining the result that the black hole entropy is proportional to its area as in previous works where the simplified area formula has been used. This gives new values for the Barbero-Immirzi parameter ($\gamma =0.5802... \mathrm{or} 0.7847...$) which are larger than that of previous works.Comment: 5 page

Hyperactivation of NF-κB via the MEK signaling is indispensable for the inhibitory effect of cAMP on DNA damage-induced cell death

With cAMP signaling having a profound inhibitory effect on DNA damage-induced apoptosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, understanding how this signaling pathway affects the survival capacity of the cell has important implications for cancer therapy. We have recently shown that p53 is critical for the inhibitory effect of cAMP on genotoxic agents-mediated apoptosis in BCP-ALLs. Here, we show that elevation of cAMP levels in cells exposed to DNA damage enhances the nuclear translocation and DNA binding of NF-κB by accelerating the phosphorylation of IKKβ and thereby phosphorylation and degradation of IκBα. Furthermore, we show that the ability of cAMP to potentiate the ionizing radiation-induced activation of NF-κB requires the activity of MEK. Importantly, pharmacological or genetic ablation of NF-κB reversed the inhibitory effect of cAMP on DNA damage-induced apoptosis, demonstrating that, in addition to p53, cAMP relies on the activity of NF-κB to provide cells with a survival advantage in the face of DNA damage. Collectively, our results uncover a novel and important interaction between the cAMP and NF-κB pathways that may have implications for the targeted treatment of lymphoid malignancies, such as BCP-ALL, in which aberrant NF-κB activity functions as a driving force for treatment resistance

Generic isolated horizons in loop quantum gravity

Isolated horizons model equilibrium states of classical black holes. A detailed quantization, starting from a classical phase space restricted to spherically symmetric horizons, exists in the literature and has since been extended to axisymmetry. This paper extends the quantum theory to horizons of arbitrary shape. Surprisingly, the Hilbert space obtained by quantizing the full phase space of \textit{all} generic horizons with a fixed area is identical to that originally found in spherical symmetry. The entropy of a large horizon remains one quarter its area, with the Barbero-Immirzi parameter retaining its value from symmetric analyses. These results suggest a reinterpretation of the intrinsic quantum geometry of the horizon surface.Comment: 13 page

Dynamic critical behavior of failure and plastic deformation in the random fiber bundle model

The random fiber bundle (RFB) model, with the strength of the fibers distributed uniformly within a finite interval, is studied under the assumption of global load sharing among all unbroken fibers of the bundle. At any fixed value of the applied stress (load per fiber initially present in the bundle), the fraction of fibers that remain unbroken at successive time steps is shown to follow simple recurrence relations. The model is found to have stable fixed point for applied stress in the range 0 and 1; beyond which total failure of the bundle takes place discontinuously. The dynamic critical behavior near this failure point has been studied for this model analysing the recurrence relations. We also investigated the finite size scaling behavior. At the critical point one finds strict power law decay (with time t) of the fraction of unbroken fibers. The avalanche size distribution for this mean-field dynamics of failure has been studied. The elastic response of the RFB model has also been studied analytically for a specific probability distribution of fiber strengths, where the bundle shows plastic behavior before complete failure, following an initial linear response.Comment: 13 pages, 5 figures, extensively revised and accepted for publication in Phys. Rev.

An Interface View of Directed Sandpile Dynamics

We present a directed unloading sand box type avalanche model, driven by slowly lowering the retaining wall at the bottom of the slope. The avalanche propagation in the two dimensional surface is related to the space-time configurations of one dimensional Kardar-Parisi-Zhang (KPZ) type interface growth dynamics. We express the scaling exponents for the avalanche cluster distributions into that framework. The numerical results agree closely with KPZ scaling, but not perfectly.Comment: 4 pages including 5 figure

Loop quantum gravity without the Hamiltonian constraint

We show that under certain technical assumptions, including the existence of a constant mean curvature (CMC) slice and strict positivity of the scalar field, general relativity conformally coupled to a scalar field can be quantised on a partially reduced phase space, meaning reduced only with respect to the Hamiltonian constraint and a proper gauge fixing. More precisely, we introduce, in close analogy to shape dynamics, the generator of a local conformal transformation acting on both, the metric and the scalar field, which coincides with the CMC gauge condition. A new metric, which is invariant under this transformation, is constructed and used to define connection variables which can be quantised by standard loop quantum gravity methods. While it is hard to address dynamical problems in this framework (due to the complicated 'time' function), it seems, due to good accessibility properties of the CMC gauge, to be well suited for problems such as the computation of black hole entropy, where actual physical states can be counted and the dynamics is only of indirect importance. The corresponding calculation yields the surprising result that the usual prescription of fixing the Barbero-Immirzi parameter beta to a constant value in order to obtain the well-known formula S = a(Phi) A/(4G) does not work for the black holes under consideration, while a recently proposed prescription involving an analytic continuation of beta to the case of a self-dual space-time connection yields the correct result. Also, the interpretation of the geometric operators gets an interesting twist, which exemplifies the deep relationship between observables and the choice of a time function and has consequences for loop quantum cosmology.Comment: 8 pages. v2: Journal version. Black hole state counting based on physical states added. Applications to loop quantum cosmology discussed. Gauge condition used shown to coincide with CMC gauge. Minor clarifications. v3: Erroneous topology dependence of the entropy in journal version corrected, conclusions fixed accordingly. Main results unaffecte

Gravastar Solutions with Continuous Pressures and Equation of State

We study the gravitational vacuum star (gravastar) configuration as proposed by other authors in a model where the interior de Sitter spacetime segment is continuously extended to the exterior Schwarzschild spacetime. The multilayered structure in previous papers is replaced by a continuous stress-energy tensor at the price of introducing anisotropy in the (fluid) model of the gravastar. Either with an ansatz for the equation of state connecting the radial $p_r$ and tangential $p_t$ pressure or with a calculated equation of state with non-homogeneous energy/fluid density, solutions are obtained which in all aspects satisfy the conditions expected for an anisotropic gravastar. Certain energy conditions have been shown to be obeyed and a polytropic equation of state has been derived. Stability of the solution with respect to possible axial perturbation is shown to hold.Comment: 19 pages, 9 figures. Latest version contains new and updated references along with some clarifying remarks in the stability analysi

Shear yielding of amorphous glassy solids: Effect of temperature and strain rate

We study shear yielding and steady state flow of glassy materials with molecular dynamics simulations of two standard models: amorphous polymers and bidisperse Lennard-Jones glasses. For a fixed strain rate, the maximum shear yield stress and the steady state flow stress in simple shear both drop linearly with increasing temperature. The dependence on strain rate can be described by a either a logarithm or a power-law added to a constant. In marked contrast to predictions of traditional thermal activation models, the rate dependence is nearly independent of temperature. The relation to more recent models of plastic deformation and glassy rheology is discussed, and the dynamics of particles and stress in small regions is examined in light of these findings