Structural dynamics of calmodulin and troponin C

We present the results of computational simulation studies of the structures of calmodulin (CAM) and troponin C (TNC). Possible differences between the structures of these molecules in the crystal and in solution were suggested by results from some recent experimental studies, which implied that their conformations in solution may be more compacted than the characteristic dumbbell shape observed in the crystal. The molecular dynamics simulations were carried out with the CHARMM system of programs, and the environment was modeled with a distance-dependent dielectric permittivity and discrete water molecules surrounding the proteins at starting positions identified in the crystals of CAM and TNC. Methods of macromolecular structure analysis, including linear distance plots, distance matrices and a matrix representation of hydrogen bonding, were used to analyze the nature, the extent and the source of structural differences between the computed structures of the molecules and their conformations in the crystal. Following the longest simulation, in which intradomain structure was conserved, the crystallographically observed dumbbell structure of the molecule changed due to a kinking or bending in the region of the central tether helix connecting the two Ca2+-binding domains which moved into close proximity. The resulting structure correlates with experimental observations of complexes between CAM and peptides such as melittin and mastoparan. Analysis of the corresponding pair distance distribution functions in comparison to experimental results suggests the dynamic existence of a non-negligible fraction of the compacted structure in aqueous solutions of CAM. In this more nearly globular shape, CAM reveals to the environment two interior pockets that contain a number of hydrophobic residues, in agreement with NMR data suggesting involvement of such residues in the binding of inhibitors and proteins to CA

Path-Fault-Tolerant Approximate Shortest-Path Trees

Let $G=(V,E)$ be an $n$-nodes non-negatively real-weighted undirected graph. In this paper we show how to enrich a {\em single-source shortest-path tree} (SPT) of $G$ with a \emph{sparse} set of \emph{auxiliary} edges selected from $E$, in order to create a structure which tolerates effectively a \emph{path failure} in the SPT. This consists of a simultaneous fault of a set $F$ of at most $f$ adjacent edges along a shortest path emanating from the source, and it is recognized as one of the most frequent disruption in an SPT. We show that, for any integer parameter $k \geq 1$, it is possible to provide a very sparse (i.e., of size $O(kn\cdot f^{1+1/k})$) auxiliary structure that carefully approximates (i.e., within a stretch factor of $(2k-1)(2|F|+1)$) the true shortest paths from the source during the lifetime of the failure. Moreover, we show that our construction can be further refined to get a stretch factor of $3$ and a size of $O(n \log n)$ for the special case $f=2$, and that it can be converted into a very efficient \emph{approximate-distance sensitivity oracle}, that allows to quickly (even in optimal time, if $k=1$) reconstruct the shortest paths (w.r.t. our structure) from the source after a path failure, thus permitting to perform promptly the needed rerouting operations. Our structure compares favorably with previous known solutions, as we discuss in the paper, and moreover it is also very effective in practice, as we assess through a large set of experiments.Comment: 21 pages, 3 figures, SIROCCO 201

Effective representation of RT-LOTOS terms by finite time petri nets

The paper describes a transformational approach for the specification and formal verification of concurrent and real-time systems. At upper level, one system is specified using the timed process algebra RT-LOTOS. The output of the proposed transformation is a Time Petri net (TPN). The paper particularly shows how a TPN can be automatically constructed from an RT-LOTOS specification using a compositionally defined mapping. The proof of the translation consistency is sketched in the paper and developed in [1]. The RT-LOTOS to TPN translation patterns formalized in the paper are being implemented. in a prototype tool. This enables reusing TPNs verification techniques and tools for the profit of RT-LOTOS

Population Inference with Mortality and Attrition in Longitudinal Studies on Aging: A Two-Stage Multiple Imputation Method

First paragraph: Although there are numerous challenges for the investigation of aging-related changes in older adults, statistical analysis with incomplete data and the conceptualization of population processes related to mortality is one of the most difficult. Selective attrition and mortality selection within longitudinal studies on aging are intrinsically related to many aging-related changes and must be carefully considered in the analysis and interpretation of results (e.g., Baltes, 1968; Hofer & Sliwinski, 2006; Schaie, Labouvie, & Barrett, 1973). A key distinction is made between attrition (i.e., selective dropout) and mortality selection (i.e., selective survival) in that attrition affects characteristics of the particular sample under investigation, whereas mortality selection affects both the definition of the population as well as the sample under study (Baltes, 1968). Including time-to-death as a predictor in models for estimating change in outcomes of interest permits conditional inferences to defined populations based on age and survival (and their interaction) and is easily performed when complete data are available for both chronological age and age of death. In most studies, however, complete data for all individuals are not currently available and may not be available for a substantial period of time. The purpose of the current work is to present a two-stage multiple-imputation approach for treating mortality and attrition as distinct processes leading to incomplete data and which permit the use of time-to-death in the predictive models when follow-up is incomplete

Critical behavior at Mott-Anderson transition: a TMT-DMFT perspective

We present a detailed analysis of the critical behavior close to the Mott-Anderson transition. Our findings are based on a combination of numerical and analytical results obtained within the framework of Typical-Medium Theory (TMT-DMFT) - the simplest extension of dynamical mean field theory (DMFT) capable of incorporating Anderson localization effects. By making use of previous scaling studies of Anderson impurity models close to the metal-insulator transition, we solve this problem analytically and reveal the dependence of the critical behavior on the particle-hole symmetry. Our main result is that, for sufficiently strong disorder, the Mott-Anderson transition is characterized by a precisely defined two-fluid behavior, in which only a fraction of the electrons undergo a "site selective" Mott localization; the rest become Anderson-localized quasiparticles.Comment: 4+ pages, 4 figures, v2: minor changes, accepted for publication in Phys. Rev. Let

Proton exchange membrane fuel cell operation and degradation in short-circuit.

International audienceThis paper presents an experimental study dealing with operation and degradation during an electrical short circuit of a proton exchange membrane fuel cell stack. The physical quantities in the fuel cell (electrical voltage and current, gas stoichiometry, pressures, temperatures and gas humidity) are studied before, during and after the failure. After a short circuit occurs, a high peak of current appears but decreases to stabilize in a much lower value. The voltage drops in all the cells and even some cells presents reversal potentials. The degradation is quantified by using electrochemical impedance spectroscopy

Synthesizing SystemC Code from Delay Hybrid CSP

Delay is omnipresent in modern control systems, which can prompt oscillations and may cause deterioration of control performance, invalidate both stability and safety properties. This implies that safety or stability certificates obtained on idealized, delay-free models of systems prone to delayed coupling may be erratic, and further the incorrectness of the executable code generated from these models. However, automated methods for system verification and code generation that ought to address models of system dynamics reflecting delays have not been paid enough attention yet in the computer science community. In our previous work, on one hand, we investigated the verification of delay dynamical and hybrid systems; on the other hand, we also addressed how to synthesize SystemC code from a verified hybrid system modelled by Hybrid CSP (HCSP) without delay. In this paper, we give a first attempt to synthesize SystemC code from a verified delay hybrid system modelled by Delay HCSP (dHCSP), which is an extension of HCSP by replacing ordinary differential equations (ODEs) with delay differential equations (DDEs). We implement a tool to support the automatic translation from dHCSP to SystemC

A survey of agent-oriented methodologies

This article introduces the current agent-oriented methodologies. It discusses what approaches have been followed (mainly extending existing object oriented and knowledge engineering methodologies), the suitability of these approaches for agent modelling, and some conclusions drawn from the survey

Completeness for Flat Modal Fixpoint Logics

This paper exhibits a general and uniform method to prove completeness for certain modal fixpoint logics. Given a set \Gamma of modal formulas of the form \gamma(x, p1, . . ., pn), where x occurs only positively in \gamma, the language L\sharp (\Gamma) is obtained by adding to the language of polymodal logic a connective \sharp\_\gamma for each \gamma \epsilon. The term \sharp\_\gamma (\varphi1, . . ., \varphin) is meant to be interpreted as the least fixed point of the functional interpretation of the term \gamma(x, \varphi 1, . . ., \varphi n). We consider the following problem: given \Gamma, construct an axiom system which is sound and complete with respect to the concrete interpretation of the language L\sharp (\Gamma) on Kripke frames. We prove two results that solve this problem. First, let K\sharp (\Gamma) be the logic obtained from the basic polymodal K by adding a Kozen-Park style fixpoint axiom and a least fixpoint rule, for each fixpoint connective \sharp\_\gamma. Provided that each indexing formula \gamma satisfies the syntactic criterion of being untied in x, we prove this axiom system to be complete. Second, addressing the general case, we prove the soundness and completeness of an extension K+ (\Gamma) of K\_\sharp (\Gamma). This extension is obtained via an effective procedure that, given an indexing formula \gamma as input, returns a finite set of axioms and derivation rules for \sharp\_\gamma, of size bounded by the length of \gamma. Thus the axiom system K+ (\Gamma) is finite whenever \Gamma is finite