Identifying the Onset of Phase Separation in Quaternary Lipid Bilayer Systems from Coarse-Grained Simulations

Understanding the (de)mixing behavior of multicomponent lipid bilayers is an important step towards unraveling the nature of spatial composition heterogeneities in cellular membranes and their role in biological function. We use coarse-grained molecular dynamics simulations to study the composition phase diagram of a quaternary mixture of phospholipids and cholesterol. This mixture is known to exhibit both uniform and coexisting phases. We compare and combine different statistical measures of membrane structure to identify the onset of phase coexistence in composition space. An important element in our approach is the dependence of composition heterogeneities on the size of the system. While homogeneous phases can be structured and display long correlation lengths, the hallmark behavior of phase coexistence is the scaling of the apparent correlation length with system size. Because the latter cannot be easily varied in simulations, our method instead uses information obtained from observation windows of different sizes to accurately distinguish phase coexistence from structured homogeneous phases. This approach is built on very general physical principles, and will be beneficial to future studies of the phase behavior of multicomponent lipid bilayers

Free Energy Calculations of Membrane Permeation: Challenges due to Strong Headgroup-Solute Interactions

Understanding how different classes of molecules move across biological membranes is a prerequisite to predicting a solute's permeation rate, which is a critical factor in the fields of drug design and pharmacology. We use biased Molecular Dynamics computer simulations to calculate and compare the free energy profiles of translocation of several small molecules across 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid bilayers as a first step towards determining the most efficient method for free energy calculations. We study the translocation of arginine, a sodium ion, alanine, and a single water molecule using the Metadynamics, Umbrella Sampling, and Replica Exchange Umbrella Sampling techniques. Within the fixed lengths of our simulations, we find that all methods produce similar results for charge-neutral permeants, but not for polar or positively charged molecules. We identify the long relaxation timescale of electrostatic interactions between lipid headgroups and the solute to be the principal cause of this difference, and show that this slow process can lead to an erroneous dependence of computed free energy profiles on the initial system configuration. We demonstrate the use of committor analysis to validate the proper sampling of the presumed transition state, which in our simulations is achieved only in replica exchange calculations. Based on these results we provide some useful guidance to perform and evaluate free energy calculations of membrane permeation

Tasking Framework: Parallelization of Computations in Onboard Control Systems

For the next generation of onboard computer in space application a high demand on processing power exists. Currently used onboard system didn't provide the necessary computing power. The in the paper describe tasking frame work is the core processing model for the OBC-NG (On Board Computer - Next Generation) operating system with an reactive computing model

Actions and Events in Concurrent Systems Design

In this work, having in mind the construction of concurrent systems from components, we discuss the difference between actions and events. For this discussion, we propose an(other) architecture description language in which actions and events are made explicit in the description of a component and a system. Our work builds from the ideas set forth by the categorical approach to the construction of software based systems from components advocated by Goguen and Burstall, in the context of institutions, and by Fiadeiro and Maibaum, in the context of temporal logic. In this context, we formalize a notion of a component as an element of an indexed category and we elicit a notion of a morphism between components as morphisms of this category. Moreover, we elaborate on how this formalization captures, in a convenient manner, the underlying structure of a component and the basic interaction mechanisms for putting components together. Further, we advance some ideas on how certain matters related to the openness and the compositionality of a component/system may be described in terms of classes of morphisms, thus potentially supporting a compositional rely/guarantee reasoning.Comment: In Proceedings LAFM 2013, arXiv:1401.056

Micelle Formation and the Hydrophobic Effect

The tendency of amphiphilic molecules to form micelles in aqueous solution is a consequence of the hydrophobic effect. The fundamental difference between micelle assembly and macroscopic phase separation is the stoichiometric constraint that frustrates the demixing of polar and hydrophobic groups. We present a theory for micelle assembly that combines the account of this constraint with a description of the hydrophobic driving force. The latter arises from the length scale dependence of aqueous solvation. The theoretical predictions for temperature dependence and surfactant chain length dependence of critical micelle concentrations for nonionic surfactants agree favorably with experiment.Comment: Accepted for publication in J. Phys. Chem.

Automated Reasoning over Deontic Action Logics with Finite Vocabularies

In this paper we investigate further the tableaux system for a deontic action logic we presented in previous work. This tableaux system uses atoms (of a given boolean algebra of action terms) as labels of formulae, this allows us to embrace parallel execution of actions and action complement, two action operators that may present difficulties in their treatment. One of the restrictions of this logic is that it uses vocabularies with a finite number of actions. In this article we prove that this restriction does not affect the coherence of the deduction system; in other words, we prove that the system is complete with respect to language extension. We also study the computational complexity of this extended deductive framework and we prove that the complexity of this system is in PSPACE, which is an improvement with respect to related systems.Comment: In Proceedings LAFM 2013, arXiv:1401.056

The epigenetic regulation of C4-photosynthesis genes from Zea mays heterologously expressed in Oryza sativa indica in response to different stimuli

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