A finite population model of mlecular evolution: theory and computation

This article is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.

Length-scale dependent mechanical properties of Al-Cu eutectic alloy: Molecular dynamics based model and its experimental verification

This paper attempts to gain an understanding of the effect of lamellar length scale on the mechanical properties of two-phase metal-intermetallic eutectic structure. We first develop a molecular dynamics model for the in-situ grown eutectic interface followed by a model of deformation of Al-Al2Cu lamellar eutectic. Leveraging the insights obtained from the simulation on the behaviour of dislocations at different length scales of the eutectic, we present and explain the experimental results on Al-Al2Cu eutectic with various different lamellar spacing. The physics behind the mechanism is further quantified with help of atomic level energy model for different length scale as well as different strain. An atomic level energy partitioning of the lamellae and the interface regions reveals that the energy of the lamellae core are accumulated more due to dislocations irrespective of the length-scale. Whereas the energy of the interface is accumulated more due to dislocations when the length-scale is smaller, but the trend is reversed when the length-scale is large beyond a critical size of about 80 nm. (C) 2014 Author(s).

Crossover from Ising to mean-field critical behavior in an aqueous electrolyte solution

The near-critical behavior of the susceptibility deduced from light-scattering measurements in a ternary liquid mixture of 3-methylpyridine, water, and sodium bromide has been determined. The measurements have been performed in the one-phase region near the lower consolute points of samples with different concentrations of sodium bromide. A crossover from Ising asymptotic behavior to mean-field behavior has been observed. As the concentration of sodium bromide increases, the crossover becomes more pronounced, and the crossover temperature shifts closer to the critical temperature. The data are well described by a model that contains two independent crossover parameters. The crossover of the susceptibility critical exponent γ from its Ising value γ=1.24 to the mean-field value γ=1 is sharp and nonmonotonic. We conclude that there exists an additional length scale in the system due to the presence of the electrolyte which competes with the correlation length of the concentration fluctuations. An analogy with crossover phenomena in polymer solutions and a possible connection with multicritical phenomena is discussed.

State Dependent Attempt Rate Modeling of Single Cell IEEE 802.11 WLANs with Homogeneous Nodes and Poisson Arrivals

Analytical models of IEEE 802.11-based WLANs are invariably based on approximations, such as the well-known mean-field approximations proposed by Bianchi for saturated nodes. In this paper, we provide a new approach for modeling the situation when the nodes are not saturated. We study a State Dependent Attempt Rate (SDAR) approximation to model M queues (one queue per node) served by the CSMA/CA protocol as standardized in the IEEE 802.11 DCF. The approximation is that, when n of the M queues are non-empty, the attempt probability of the n non-empty nodes is given by the long-term attempt probability of n saturated nodes as provided by Bianchi's model. This yields a coupled queue system. When packets arrive to the M queues according to independent Poisson processes, we provide an exact model for the coupled queue system with SDAR service. The main contribution of this paper is to provide an analysis of the coupled queue process by studying a lower dimensional process and by introducing a certain conditional independence approximation. We show that the numerical results obtained from our finite buffer analysis are in excellent agreement with the corresponding results obtained from ns-2 simulations. We replace the CSMA/CA protocol as implemented in the ns-2 simulator with the SDAR service model to show that the SDAR approximation provides an accurate model for the CSMA/CA protocol. We also report the simulation speed-ups thus obtained by our model-based simulation.

Description of accretion induced outflows from ultra-luminous sources to under-luminous AGNs

We study the energetics of the accretion-induced outflow and then plausible jet around black holes/compact objects using a newly developed disc-outflow coupled model. Inter-connecting dynamics of outflow and accretion essentially upholds the conservation laws. The energetics depend strongly on the viscosity parameter α and the cooling factor f which exhibit several interesting features. The bolometric luminosities of ultra-luminous X-ray binaries (e.g. SS433) and family of highly luminous AGNs and quasars can be reproduced by the model under the super-Eddington accretion flows. Under appropriate conditions, low-luminous AGNs (e.g. Sagittarius A*) also fit reasonably well with the luminosity corresponding to a sub-Eddington accretion flow with f→1.

Nonspecifically bound proteins spin while diffusing along DNA

It is known that DNA-binding proteins can slide along the DNA helix while searching for specific binding sites, but their path of motion remains obscure. Do these proteins undergo simple one-dimensional (1D) translational diffusion, or do they rotate to maintain a specific orientation with respect to the DNA helix? We measured 1D diffusion constants as a function of protein size while maintaining the DNA-protein interface. Using bootstrap analysis of single-molecule diffusion data, we compared the results to theoretical predictions for pure translational motion and rotation-coupled sliding along the DNA. The data indicate that DNA-binding proteins undergo rotation-coupled sliding along the DNA helix and can be described by a model of diffusion along the DNA helix on a rugged free-energy landscape. A similar analysis including the 1D diffusion constants of eight proteins of varying size shows that rotation-coupled sliding is a general phenomenon. The average free-energy barrier for sliding along the DNA was 1.1 +/- 0.2 k(B)T. Such small barriers facilitate rapid search for binding sites.

Solubilities of Hexadecanoic and Octadecanoic Acids in Supercritical CO2 With and Without Cosolvents

The solubilities of hexadecanoic acid (palmitic acid) and octadecanoic acid (stearic acid) in supercritical carbon dioxide without cosolvents and with two cosolvents, namely, ethanol and 3-methyl-1-butanol, were determined at (308 and 318) K at pressures varying from (12.8 to 22.6) MPa. The solubility data, in both the absence and presence of cosolvents, were correlated by a model proposed by Mendez-Santiago and Teja.

Organometallic chemistry of diphosphazanes. Part 26. Ruthenium hydride complexes of chiral and achiral diphosphazane ligands and asymmetric transfer hydrogenation reactions

The half-sandwhich ruthenium chloro complexes bearing chelated diphosphazane ligands, [(eta(5)-Cp)RuCl{kappa(2)-P,P-(RO)(2)PN(Me)P(OR)(2)}] [R = C6H3Me2-2,6] (1) and [(eta(5)-Cp*)RuCl{kappa(2)-P, P-X2PN(R)PYY'}] [R = Me, X = Y = Y' = OC6H5 (2); R = CHMe2, X-2 = C20H12O2, Y = Y' = OC6H5 (3) or OC6H4'Bu-4 (4)] have been prepared by the reaction of CpRu(PPh3)(2)Cl with (RO)(2)PN(Me)P(OR)(2) [R = C6H3Me2-2,6 (L-1)] or by the reaction of [Cp*RuCl2](n) with X2PN(R)PYY' in the presence of zinc dust. Among the four diastereomers (two enantiomeric pairs) possible for the "chiral at metal" complexes 3 and 4, only two diastereomers (one enantiomeric pair) are formed in these reactions. The complexes 1, 2, 4 and [(eta(5)-Cp)RuCl {kappa(2)-P,P-Ph2PN((S)-*CHMePh)PPhY)] [Y = Ph (5) or N2C3HMe2-3,5 (SCSPRRu)-(6)] react with NaOMe to give the corresponding hydride complexes [(eta(5) -Cp)RuH {kappa(2)-P,P-(RO)(2)PN(Me)P(OR)(2)}] (7), [(eta(5)-Cp*)RuH {kappa(2)-P,P'-X2PN(R)PY2)] [R = Me, X = Y = OC6H5 (8); R = CHMe2, X-2 = C20H12O2, Y = OC6H4'Bu-4 (9)] and [(eta(5) -Cp)RuH(kappa(2)-P, P-Ph2PN((S)-*CHMePh)PPhY)][Y =Ph (10) or N2C3HMe2-3,5 (SCSPRRu)(11a) and (SCSPSRu)-(11b)]. Only one enantiomeric pair of the hydride 9 is obtained from the chloro precursor 4 that bears sterically bulky substituents at the phosphorus centers. On the other hand, the optically pure trichiral complex 6 that bears sterically less bulky substituents at the phosphorus gives a mixture of two diastereomers (11a and 11b). Protonation of complex 7 using different acids (HX) gives a mixture of [(eta(5)- Cp)Ru(eta(2)-H-2){kappa(2)-P, P-(RO)(2)PN(Me)P(OR)(2))]X (12a) and [(eta(5)-Cp)Ru(H)(2){kappa(2)-P, P-(RO)(2)PN(Me)P(OR)(2)}]X (12b) of which 12a is the major product independent of the acid used; the dihydrogen nature of 12a is established by T, measurements and also by synthesizing the deuteride analogue 7-D followed by protonation to obtain the D-H isotopomer. Preliminary investigations on asymmetric transfer hydrogenation of 2-acetonaphthone in the presence of a series of chiral diphosphazane ligands show that diphosphazanes in which the phosphorus centers are strong pi-acceptor in character and bear sterically bulky substituents impart moderate levels of enantioselectivity. Attempts to identify the hydride intermediate involved in the asymmetric transfer hydrogenation by a model reaction suggests that a complex of the type, [Ru(H)(Cl){kappa(2)-P,P-X2PN(R)PY2)(solvent)(2)] could be the active species in this transformation. (c) 2007 Elsevier B.V. All rights reserved.

Microarchitecture sensitive empirical models for compiler optimizations.

This paper proposes the use of empirical modeling techniques for building microarchitecture sensitive models for compiler optimizations. The models we build relate program performance to settings of compiler optimization flags, associated heuristics and key microarchitectural parameters. Unlike traditional analytical modeling methods, this relationship is learned entirely from data obtained by measuring performance at a small number of carefully selected compiler/microarchitecture configurations. We evaluate three different learning techniques in this context viz. linear regression, adaptive regression splines and radial basis function networks. We use the generated models to a) predict program performance at arbitrary compiler/microarchitecture configurations, b) quantify the significance of complex interactions between optimizations and the microarchitecture, and c) efficiently search for'optimal' settings of optimization flags and heuristics for any given microarchitectural configuration. Our evaluation using benchmarks from the SPEC CPU2000 suits suggests that accurate models (< 5% average error in prediction) can be generated using a reasonable number of simulations. We also find that using compiler settings prescribed by a model-based search can improve program performance by as much as 19% (with an average of 9.5%) over highly optimized binaries.

Construction and use of linear regression models for processor performance analysis

Processor architects have a challenging task of evaluating a large design space consisting of several interacting parameters and optimizations. In order to assist architects in making crucial design decisions, we build linear regression models that relate Processor performance to micro-architecture parameters, using simulation based experiments. We obtain good approximate models using an iterative process in which Akaike's information criteria is used to extract a good linear model from a small set of simulations, and limited further simulation is guided by the model using D-optimal experimental designs. The iterative process is repeated until desired error bounds are achieved. We used this procedure to establish the relationship of the CPI performance response to 26 key micro-architectural parameters using a detailed cycle-by-cycle superscalar processor simulator The resulting models provide a significance ordering on all micro-architectural parameters and their interactions, and explain the performance variations of micro-architectural techniques.

Voluntary Control of Multisaccade Gaze Shifts During Movement Preparation and Execution

Ramakrishnan A, Chokhandre S, Murthy A. Voluntary control of multisaccade gaze shifts during movement preparation and execution. J Neurophysiol 103: 2400-2416, 2010. First published February 17, 2010; doi: 10.1152/jn.00843.2009. Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency similar to 215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.

An excitonic mechanism for high-temperature. Superconductivity in YBa2Cu3O7

We propose an excitonic mechanism for high temperature superconductivity in YBa2Cu3O7. We feel that in this material, nature has provided a very elegant system, closely simulated by the model proposed by Allender, Bray and Bardeen1 using Ginzburg's ideas.2 In this system the excitonic layer and the conduction electron layers are indeed atomic planes making contacts on atomic level, an ideal version of the situation envisaged by Allender et al. Further, since these layers are physically separated, the question of screening of charges is avoided.

Elasto-Electrostatic Analysis of Circular Microplates Used in Capacitive Micromachined Ultrasonic Transducers

The active structural component of a capacitive micromachined ultrasonic transducer (CMUT) is the top plate which vibrates under the influence of a time-varying electrostatic force thereby producing ultrasound waves of the desired frequency in the surrounding medium. Analysis of MEMS devices which rely on electrostatic actuation is complicated due to the fact that the structural deformations alter the electrostatic forces, which redistribute and modify the applied loads. Hence, it becomes imperative to consider the electrostatics-structure coupling aspect in the design of these devices. This paper presents an approximate analytical solution for the static deflection of a thin, clamped circular plate caused by electrostatic forces which are inherently nonlinear. Traditionally, finite element simulations using some commercial software such as ANSYS are employed to determine the structural deflections caused by electrostatic forces. Since the structural deformation alters the electrostatic field, a coupled-field simulation is required wherein the electrostatic mesh is continuously updated to coincide with the deflection of the structure. Such simulations are extremely time consuming, in addition to being nontransparent and somewhat hard to implement. We employ the classical thin-plate theory which is adequate when the ratio of the diameter to thickness of the plate is very large, a situation commonly prevalent in many MEMS devices, especially the CMUTs. We solve the thin-plate electrostatic-elastic equation using the Galerkin-weighted residual technique, under the assumption that the deflections are small in comparison to the thickness of the plate. The evaluation of the electrostatic force between the two plates is simplified due to the fact that the electrostatic gap is much smaller than the lateral dimensions of the device. The results obtained are compared to those found from ANSYS simulations and an excellent agreement is observed between the two. The pull-in voltage predicted by our model is close to the value predicted by ANSYS simulations.

Effect of stacking fault energy on the dynamic recrystallization during hot working of FCC metals: A study using processing maps

The influence of stacking fault energy (SFE) on the mechanism of dynamic recrystallization (DRX) during hot deformation of FCC metals is examined in the light of results from the power dissipation maps. The DRX domain for high SFE metals like Al and Ni occurred at homologous temperature below 0·7 and strain rates of 0·001 s−1 while for low SFE metals like Cu and Pb the corresponding values are higher than 0·8 and 100 s−1. The peak efficiencies of power dissipation are 50% and below 40% respectively. A simple model which considers the rate of interface formation (nucleation) involving dislocation generation and simultaneous recovery and the rate of interface migration (growth) occurring with the reduction in interface energy as the driving force, has been proposed to account for the effect of SFE on DRX. The calculations reveal that in high SFE metals, interface migration controls DRX while the interface formation is the controlling factor in low SFE metals. In the latter case, the occurrence of flow softening and oscillations could be accounted for by this model.

Study Of Fluid-Flow And Residence-Time Distribution In A Continuous Slab Casting Mold

The fluid-flow pattern and residence-time distribution (r.t.d.) of the fluid in a continuous casting mould have been studied using a water model. The two recirculating zones below the discharge ports have been found to be asymmetric. The effect of casting speed, discharge port diameter, shroud well depth and the immersion depth on r.t.d. have been investigated. The r.t.d. curve has been well represented by a model of two backmix cells of equal volume in series. The exist of the fluid has been found to be non-uniform across the cross-section of the mould. The fluid-flow pattern has been observed to change with time in a random fashion. Dead volume of upto 31.8% has been found with smaller discharge ports.