The role of type 4 phosphodiesterases in generating microdomains of cAMP: Large scale stochastic simulations

Cyclic AMP (cAMP) and its main effector Protein Kinase A (PKA) are critical for several aspects of neuronal function including synaptic plasticity. Specificity of synaptic plasticity requires that cAMP activates PKA in a highly localized manner despite the speed with which cAMP diffuses. Two mechanisms have been proposed to produce localized elevations in cAMP, known as microdomains: impeded diffusion, and high phosphodiesterase (PDE) activity. This paper investigates the mechanism of localized cAMP signaling using a computational model of the biochemical network in the HEK293 cell, which is a subset of pathways involved in PKA-dependent synaptic plasticity. This biochemical network includes cAMP production, PKA activation, and cAMP degradation by PDE activity. The model is implemented in NeuroRD: novel, computationally efficient, stochastic reaction-diffusion software, and is constrained by intracellular cAMP dynamics that were determined experimentally by real-time imaging using an Epac-based FRET sensor (H30). The model reproduces the high concentration cAMP microdomain in the submembrane region, distinct from the lower concentration of cAMP in the cytosol. Simulations further demonstrate that generation of the cAMP microdomain requires a pool of PDE4D anchored in the cytosol and also requires PKA-mediated phosphorylation of PDE4D which increases its activity. The microdomain does not require impeded diffusion of cAMP, confirming that barriers are not required for microdomains. The simulations reported here further demonstrate the utility of the new stochastic reaction-diffusion algorithm for exploring signaling pathways in spatially complex structures such as neurons

Operational Classification and Quantification of Multipartite Entangled States

We formalize and extend an operational multipartite entanglement measure introduced by T. R. Oliveira, G. Rigolin, and M. C. de Oliveira, Phys. Rev. A 73, 010305(R) (2006), through the generalization of global entanglement (GE) [D. A. Meyer and N. R. Wallach, J. Math. Phys. 43, 4273 (2002)]. Contrarily to GE the main feature of this measure lies in the fact that we study the mean linear entropy of all possible partitions of a multipartite system. This allows the construction of an operational multipartite entanglement measure which is able to distinguish among different multipartite entangled states that GE failed to discriminate. Furthermore, it is also maximum at the critical point of the Ising chain in a transverse magnetic field, being thus able to detect a quantum phase transition.Comment: 14 pages, RevTex4, published versio

Symmetry breaking effects upon bipartite and multipartite entanglement in the XY model

We analyze the bipartite and multipartite entanglement for the ground state of the one-dimensional XY model in a transverse magnetic field in the thermodynamical limit. We explicitly take into account the spontaneous symmetry breaking in order to explore the relation between entanglement and quantum phase transitions. As a result we show that while both bipartite and multipartite entanglement can be enhanced by spontaneous symmetry breaking deep into the ferromagnetic phase, only the latter is affected by it in the vicinity of the critical point. This result adds to the evidence that multipartite, and not bipartite, entanglement is the fundamental indicator of long range correlations in quantum phase transitions.Comment: 13 pages, 19 figures, comments welcome. V2: small changes, published versio

Simulations of a mortality plateau in the sexual Penna model for biological ageing

The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individuals genomes are represented by bit-strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n, reaches a threshold value, T. Since the number of accumulated diseases increases with age, the probability to die is zero for very young ages (n = T). Here, instead of using a step function to determine the genetic death age, we test several other functions that may or may not slightly increase the death probability at young ages (n < T), but that decreases this probability at old ones. Our purpose is to study the oldest old effect, that is, a plateau in the mortality curves at advanced ages. Imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age-structure of the population and the death probability.Comment: submitted to Phys. Rev.

Density-functionals not based on the electron gas: Local-density approximation for a Luttinger liquid

By shifting the reference system for the local-density approximation (LDA) from the electron gas to other model systems one obtains a new class of density functionals, which by design account for the correlations present in the chosen reference system. This strategy is illustrated by constructing an explicit LDA for the one-dimensional Hubbard model. While the traditional {\it ab initio} LDA is based on a Fermi liquid (the electron gas), this one is based on a Luttinger liquid. First applications to inhomogeneous Hubbard models, including one containing a localized impurity, are reported.Comment: 4 pages, 4 figures (final version, contains additional applications and discussion; accepted by Phys. Rev. Lett.

Exploring microfoundations and multilevel mechanisms of absorptive capacity in an emerging economy: empirical evidence from a leading car manufacturer

Purpose Despite the importance of knowledge processes in building absorptive capacity, we are less clear about the micro-processes of absorptive capacity development and particularly about the role of individuals’ knowledge processes. Design/methodology/approach This study empirically examined, via an in-depth case study, the microfoundations of absorptive capacity and their influence on building absorptive capacity in an automaker across the course of four product innovation projects. Findings Findings suggested that dynamics in a knowledge environment informed individual-level tacit and explicit knowledge processes. In return, knowledge processes at the individual level informed organizational learning processes and the emergence of knowledge processes at organization level for acquisition, assimilation, transformation, and exploitation of new knowledge. Originality This study contributes to the literature by revealing individuals’ knowledge processes from which absorptive capacity emerges. Practically, managers can use the findings of this study to promote certain knowledge processes to develop intended aspects of absorptive capacity at an individual level

A comparison of extremal optimization with flat-histogram dynamics for finding spin-glass ground states

We compare the performance of extremal optimization (EO), flat-histogram and equal-hit algorithms for finding spin-glass ground states. The first-passage-times to a ground state are computed. At optimal parameter of tau=1.15, EO outperforms other methods for small system sizes, but equal-hit algorithm is competitive to EO, particularly for large systems. Flat-histogram and equal-hit algorithms offer additional advantage that they can be used for equilibrium thermodynamic calculations. We also propose a method to turn EO into a useful algorithm for equilibrium calculations. Keywords: extremal optimization. flat-histogram algorithm, equal-hit algorithm, spin-glass model, ground state.Comment: 10 LaTeX pages, 2 figure