Topologically invariant reaction coordinates for simulating multistate chemical reactions.

Evaluating free energy profiles of chemical reactions in complex environments such as solvents and enzymes requires extensive sampling, which is usually performed by potential of mean force (PMF) techniques. The reliability of the sampling depends not only on the applied PMF method but also the reaction coordinate space within the dynamics is biased. In contrast to simple geometrical collective variables that depend only on the positions of the atomic coordinates of the reactants, the E(gap) reaction coordinate (the energy difference obtained by evaluating a suitable force field using reactant and product state topologies) has the unique property that it is able to take environmental effects into account leading to better convergence, a more faithful description of the transition state ensemble and therefore more accurate free energy profiles. However, E(gap) requires predefined topologies and is therefore inapplicable for multistate reactions, in which the barrier between the chemically equivalent topologies is comparable to the reaction activation barrier, because undesired "side reactions" occur. In this article, we introduce a new energy-based collective variable by generalizing the E(gap) reaction coordinate such that it becomes invariant to equivalent topologies and show that it yields more well behaved free energy profiles than simpler geometrical reaction coordinates.

The stochastic implicit Euler method - A stable coupling scheme for Monte Carlo burnup calculations

Existing Monte Carlo burnup codes use various schemes to solve the coupled criticality and burnup equations. Previous studies have shown that the coupling schemes of the existing Monte Carlo burnup codes can be numerically unstable. Here we develop the Stochastic Implicit Euler method - a stable and efficient new coupling scheme. The implicit solution is obtained by the stochastic approximation at each time step. Our test calculations demonstrate that the Stochastic Implicit Euler method can provide an accurate solution to problems where the methods in the existing Monte Carlo burnup codes fail. © 2013 Elsevier Ltd. All rights reserved.

Differential geometry and design coupling in MDO

The notion of coupling within a design, particularly within the context of Multidisciplinary Design Optimization (MDO), is much used but ill-defined. There are many different ways of measuring design coupling, but these measures vary in both their conceptions of what design coupling is and how such coupling may be calculated. Within the differential geometry framework which we have previously developed for MDO systems, we put forth our own design coupling metric for consideration. Our metric is not commensurate with similar types of coupling metrics, but we show that it both provides a helpful geo- metric interpretation of coupling (and uncoupledness in particular) and exhibits greater generality and potential for analysis than those similar metrics. Furthermore, we discuss how the metric might be profitably extended to time-varying problems and show how the metric's measure of coupling can be applied to multi-objective optimization problems (in unconstrained optimization and in MDO). © 2013 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

Tests of an adaptive QM/MM calculation on free energy profiles of chemical reactions in solution.

We present reaction free energy calculations using the adaptive buffered force mixing quantum mechanics/molecular mechanics (bf-QM/MM) method. The bf-QM/MM method combines nonadaptive electrostatic embedding QM/MM calculations with extended and reduced QM regions to calculate accurate forces on all atoms, which can be used in free energy calculation methods that require only the forces and not the energy. We calculate the free energy profiles of two reactions in aqueous solution: the nucleophilic substitution reaction of methyl chloride with a chloride anion and the deprotonation reaction of the tyrosine side chain. We validate the bf-QM/MM method against a full QM simulation, and show that it correctly reproduces both geometrical properties and free energy profiles of the QM model, while the electrostatic embedding QM/MM method using a static QM region comprising only the solute is unable to do so. The bf-QM/MM method is not explicitly dependent on the details of the QM and MM methods, so long as it is possible to compute QM forces in a small region and MM forces in the rest of the system, as in a conventional QM/MM calculation. It is simple, with only a few parameters needed to control the QM calculation sizes, and allows (but does not require) a varying and adapting QM region which is necessary for simulating solutions.

Numerically stable Monte Carlo-burnup-thermal hydraulic coupling schemes

This paper presents stochastic implicit coupling method intended for use in Monte-Carlo (MC) based reactor analysis systems that include burnup and thermal hydraulic (TH) feedbacks. Both feedbacks are essential for accurate modeling of advanced reactor designs and analyses of associated fuel cycles. In particular, we investigate the effect of different burnup-TH coupling schemes on the numerical stability and accuracy of coupled MC calculations. First, we present the beginning of time step method which is the most commonly used. The accuracy of this method depends on the time step length and it is only conditionally stable. This work demonstrates that even for relatively short time steps, this method can be numerically unstable. Namely, the spatial distribution of neutronic and thermal hydraulic parameters, such as nuclide densities and temperatures, exhibit oscillatory behavior. To address the numerical stability issue, new implicit stochastic methods are proposed. The methods solve the depletion and TH problems simultaneously and use under-relaxation to speed up convergence. These methods are numerically stable and accurate even for relatively large time steps and require less computation time than the existing methods. © 2013 Elsevier Ltd. All rights reserved.

Coupling model uncertainty for coupled rainfall/runoff and surface water quality models in river problems

Coupled hydrology and water quality models are an important tool today, used in the understanding and management of surface water and watershed areas. Such problems are generally subject to substantial uncertainty in parameters, process understanding, and data. Component models, drawing on different data, concepts, and structures, are affected differently by each of these uncertain elements. This paper proposes a framework wherein the response of component models to their respective uncertain elements can be quantified and assessed, using a hydrological model and water quality model as two exemplars. The resulting assessments can be used to identify model coupling strategies that permit more appropriate use and calibration of individual models, and a better overall coupled model response. One key finding was that an approximate balance of water quality and hydrological model responses can be obtained using both the QUAL2E and Mike11 water quality models. The balance point, however, does not support a particularly narrow surface response (or stringent calibration criteria) with respect to the water quality calibration data, at least in the case examined here. Additionally, it is clear from the results presented that the structural source of uncertainty is at least as significant as parameter-based uncertainties in areal models. © 2012 John Wiley & Sons, Ltd.

Single event molecular signalling for estimation and control

Cell biology is characterised by low molecule numbers and coupled stochastic chemical reactions with intrinsic noise permeating and dominating the interactions between molecules. Recent work [9] has shown that in such environments there are hard limits on the accuracy with which molecular populations can be controlled and estimated. These limits are predicated on a continuous diffusion approximation of the target molecule (although the remainder of the system is non-linear and discrete). The principal result of [9] assumes that the birth rate of the signalling species is linearly dependent on the target molecule population size. In this paper, we investigate the situation when the entire system is kept discrete, and arbitrary non-linear coupling is allowed between the target molecule and downstream signalling molecules. In this case it is possible, by relying solely on the event triggered nature of control and signalling reactions, to define non-linear reaction rate modulation schemes that achieve improved performance in certain parameter regimes. These schemes would not appear to be biologically relevant, raising the question of what are an appropriate set of assumptions for obtaining biologically meaningful results. © 2013 EUCA.

Linear multimodal actuation through discrete coupling

Due to technological limitations, robot actuators are often designed for specific tasks with narrow performance goals, whereas a wide range of behaviors is necessary for autonomous robots in uncertain complex environments. In an effort to increase the versatility of actuators, we introduce a new concept of multimodal actuation (MMA) that employs dynamic coupling in the form of clutches and brakes to change its mode of operation. The dynamic coupling allows motors and passive elements such as springs to be engaged and disengaged within a single actuator. We apply the concept to a linear series elastic actuator which uses friction brakes controlled online for the dynamic coupling. With this prototype, we are able to demonstrate several modes of operation including stiff position control, series elastic actuation as well as the possibility to store and release energy in a controlled manner for explosive tasks such as jumping. In this paper, we model the proposed concept of actuation and show a systematic performance analysis of the physical prototype that we developed in our laboratory. © 1996-2012 IEEE.

Linear multi-modal actuation through discrete coupling

Due to technological limitations robot actuators are often designed for specific tasks with narrow performance goals, whereas a wide range of output and behaviours is necessary for robots to operate autonomously in uncertain complex environments. We present a design framework that employs dynamic couplings in the form of brakes and clutches to increase the performance and diversity of linear actuators. The couplings are used to switch between a diverse range of discrete modes of operation within a single actuator. We also provide a design solution for miniaturized couplings that use dry friction to produce rapid switching and high braking forces. The couplings are designed so that once engaged or disengaged no extra energy is consumed. We apply the design framework and coupling design to a linear series elastic actuator (SEA) and show that this relatively simple implementation increases the performance and adds new behaviours to the standard design. Through a number of performance tests we are able to show rapid switching between a high and a low impedance output mode; that the actuator's spring can be charged to produce short bursts of high output power; and that the actuator has additional passive and rigid modes that consume no power once activated. Robots using actuators from this design framework would see a vast increase in their behavioural diversity and improvements in their performance not yet possible with conventional actuator design. © 2012 IEEE.