Computation of restoration of ligand response in the random kinetics of a prostate cancer cell signaling pathway

Mutation and/or dysfunction of signaling proteins in the mitogen activated protein kinase (MAPK) signal transduction pathway are frequently observed in various kinds of human cancer. Consistent with this fact, in the present study, we experimentally observe that the epidermal growth factor (EGF) induced activation profile of MAP kinase signaling is not straightforward dose-dependent in the PC3 prostate cancer cells. To find out what parameters and reactions in the pathway are involved in this departure from the normal dose-dependency, a model-based pathway analysis is performed. The pathway is mathematically modeled with 28 rate equations yielding those many ordinary differential equations (ODE) with kinetic rate constants that have been reported to take random values in the existing literature. This has led to us treating the ODE model of the pathways kinetics as a random differential equations (RDE) system in which the parameters are random variables. We show that our RDE model captures the uncertainty in the kinetic rate constants as seen in the behavior of the experimental data and more importantly, upon simulation, exhibits the abnormal EGF dose-dependency of the activation profile of MAP kinase signaling in PC3 prostate cancer cells. The most likely set of values of the kinetic rate constants obtained from fitting the RDE model into the experimental data is then used in a direct transcription based dynamic optimization method for computing the changes needed in these kinetic rate constant values for the restoration of the normal EGF dose response. The last computation identifies the parameters, i.e., the kinetic rate constants in the RDE model, that are the most sensitive to the change in the EGF dose response behavior in the PC3 prostate cancer cells. The reactions in which these most sensitive parameters participate emerge as candidate drug targets on the signaling pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Decoupled three-dimensional finite element computation of thermoelastic damping using Zener's approximation

We consider three dimensional finite element computations of thermoelastic damping ratios of arbitrary bodies using Zener's approach. In our small-damping formulation, unlike existing fully coupled formulations, the calculation is split into three smaller parts. Of these, the first sub-calculation involves routine undamped modal analysis using ANSYS. The second sub-calculation takes the mode shape, and solves on the same mesh a periodic heat conduction problem. Finally, the damping coefficient is a volume integral, evaluated elementwise. In the only other decoupled three dimensional computation of thermoelastic damping reported in the literature, the heat conduction problem is solved much less efficiently, using a modal expansion. We provide numerical examples using some beam-like geometries, for which Zener's and similar formulas are valid. Among these we examine tapered beams, including the limiting case of a sharp tip. The latter's higher-mode damping ratios dramatically exceed those of a comparable uniform beam.

On Computation of Minimum Distance of Linear Block Codes Above 1/2 Rate Coding

The minimum distance of linear block codes is one of the important parameter that indicates the error performance of the code. When the code rate is less than 1/2, efficient algorithms are available for finding minimum distance using the concept of information sets. When the code rate is greater than 1/2, only one information set is available and efficiency suffers. In this paper, we investigate and propose a novel algorithm to find the minimum distance of linear block codes with the code rate greater than 1/2. We propose to reverse the roles of information set and parity set to get virtually another information set to improve the efficiency. This method is 67.7 times faster than the minimum distance algorithm implemented in MAGMA Computational Algebra System for a (80, 45) linear block code.

The primary structure of sheep liver cytosolic serine hydroxymethyltransferase and an analysis of the evolutionary relationships among serine hydroxymethyltransferases

The complete amino-acid sequence of sheep liver cytosolic serine hydroxymethyltransferase was determined from an analysis of tryptic, chymotryptic, CNBr and hydroxylamine peptides. Each subunit of sheep liver serine hydroxymethyltransferase consisted of 483 amino-acid residues. A comparison of this sequence with 8 other serine hydroxymethyltransferases revealed that a possible gene duplication event could have occurred after the divergence of animals and fungi. This analysis also showed independent duplication of SHMT genes in Neurospora crassa. At the secondary structural level, all the serine hydroxymethyltransferases belong to the alpha/beta category of proteins. The predicted secondary structure of sheep liver serine hydroxymethyltransferase was similar to that of the observed structure of tryptophan synthase, another pyridoxal 5'-phosphate containing enzyme, suggesting that sheep liver serine hydroxymethyltransferase might have a similar pyridoxal 5'-phosphate binding domain. In addition, a conserved glycine rich region, G L Q G G P, was identified in all the serine hydroxymethyltransferases and could be important in pyridoxal 5'-phosphate binding. A comparison of the cytosolic serine hydroxymethyltransferases from rabbit and sheep liver with other proteins sequenced from both these sources showed that serine hydroxymethyltransferase was a highly conserved protein. It was slightly less conserved than cytochrome c but better conserved than myoglobin, both of which are well known evolutionary markers. C67 and C203 were specifically protected by pyridoxal 5'-phosphate against modification with [C-14]iodoacetic acid, while C247 and C261 were buried in the native serine hydroxymethyltransferase. However, the cysteines are not conserved among the various serine hydroxymethyltransferases. The exact role of the cysteines in the reaction catalyzed by serine hydroxymethyltransferase remains to be elucidated.

Clan-based evolutionary approach for solving control problems

This paper presents a dan-based evolutionary approach for solving control problems. Three selected control problems, viz. linear-quadratic, harvest, and push-cart problems, are solved using the proposed approach. Results are compared with those of the evolutionary programming (EP) approach. In most of the cases, the proposed approach is successful in obtaining (near) optimal solutions for these selected problems.

Distributed computation of fixed points of infinity-nonexpansive maps

The distributed implementation of an algorithm for computing fixed points of an infinity-nonexpansive map is shown to converge to the set of fixed points under very general conditions.

Fast computation of Legendre and Zernike moments

This paper presents recursive algorithms for fast computation of Legendre and Zernike moments of a grey-level image intensity distribution. For a binary image, a contour integration method is developed for the evaluation of Legendre moments using only the boundary information. A method for recursive calculation of Zernike polynomial coefficients is also given. A square-to-circular image transformation scheme is introduced to minimize the computation involved in Zernike moment functions. The recursive formulae can also be used in inverse moment transforms to reconstruct the original image from moments. The mathematical framework of the algorithms is given in detail, and illustrated with binary and grey-level images.

A current error space vector based hysteresis controller with constant switching frequency and simple online boundary computation for VSI fed IM drive

This paper proposes a simple current error space vector based hysteresis controller for two-level inverter fed Induction Motor (IM) drives. This proposed hysteresis controller retains all advantages of conventional current error space vector based hysteresis controllers like fast dynamic response, simple to implement, adjacent voltage vector switching etc. The additional advantage of this proposed hysteresis controller is that it gives a phase voltage frequency spectrum exactly similar to that of a constant switching frequency space vector pulse width modulated (SVPWM) inverter. In this proposed hysteresis controller the boundary is computed online using estimated stator voltages along alpha and beta axes thus completely eliminating look up tables used for obtaining parabolic hysteresis boundary proposed in. The estimation of stator voltage is carried out using current errors along alpha and beta axes and steady state model of induction motor. The proposed scheme is simple and capable of taking inverter upto six step mode operation, if demanded by drive system. The proposed hysteresis controller based inverter fed drive scheme is simulated extensively using SIMULINK toolbox of MATLAB for steady state and transient performance. The experimental verification for steady state performance of the proposed scheme is carried out on a 3.7kW IM.

Application of an evolutionary fuzzy system for the estimation of workforce deployment and cross-training in an assembly environment

Owing to the increased customer demands for make-to-order products and smaller product life-cycles, today assembly lines are designed to ensure a quick switch-over from one product model to another for companies' survival in market place. The complexity associated with the decisions pertaining to the type of training and number of workers and their exposition to the different tasks especially in the current era of customized production is a serious problem that the managers and the HRD gurus are facing in industry. This paper aims to determine the amount of cross-training and dynamic deployment policy caused by workforce flexibility for a make-to-order assembly. The aforementioned issues have been dealt with by adopting the concept of evolutionary fuzzy system because of the linguistic nature of the attributes associated with product variety and task complexity. A fuzzy system-based methodology is proposed to determine the amount of cross-training and dynamic deployment policy. The proposed methodology is tested on 10 sample products of varying complexities and the results obtained are in line with the conclusions drawn by previous researchers.

REDEFINE: Architecture of a SoC Fabric for Runtime Composition of Computation Structures

In this paper we propose the architecture of a SoC fabric onto which applications described in a HLL are synthesized. The fabric is a homogeneous layout of computation, storage and communication resources on silicon. Through a process of composition of resources (as opposed to decomposition of applications), application specific computational structures are defined on the fabric at runtime to realize different modules of the applications in hardware. Applications synthesized on this fabric offers performance comparable to ASICs while retaining the programmability of processing cores. We outline the application synthesis methodology through examples, and compare our results with software implementations on traditional platforms with unbounded resources.