Effective drug dosage design for treatment of infectious diseases using dynamic inversion

A generic nonlinear mathematical model describing the human immunological dynamics is used to design an effective automatic drug administration scheme. Even though the model describes the effects of various drugs on the dynamic system, this work is confined to the drugs that kill the invading pathogen and heal the affected organ. From a system theoretic point of view, the drug inputs can be interpreted as control inputs, which can be designed based on control theoretic concepts. The controller is designed based on the principle of dynamic inversion and is found to be effective in curing the �nominal model patient� by killing the invading microbes and healing the damaged organ. A major advantage of this technique is that it leads to a closed-form state feedback form of control. It is also proved from a rigorous mathematical analysis that the internal dynamics of the system remains stable when the proposed controller is applied. A robustness study is also carried out for testing the effectiveness of the drug administration scheme for parameter uncertainties. It is observed from simulation studies that the technique has adequate robustness for many �realistic model patients� having off-nominal parameter values as well.

Parallel computing concepts and methods for floquet analysis of helicopter trim and stability

Floquet analysis is widely used for small-order systems (say, order M < 100) to find trim results of control inputs and periodic responses, and stability results of damping levels and frequencies, Presently, however, it is practical neither for design applications nor for comprehensive analysis models that lead to large systems (M > 100); the run time on a sequential computer is simply prohibitive, Accordingly, a massively parallel Floquet analysis is developed with emphasis on large systems, and it is implemented on two SIMD or single-instruction, multiple-data computers with 4096 and 8192 processors, The focus of this development is a parallel shooting method with damped Newton iteration to generate trim results; the Floquet transition matrix (FTM) comes out as a byproduct, The eigenvalues and eigenvectors of the FTM are computed by a parallel QR method, and thereby stability results are generated, For illustration, flap and flap-lag stability of isolated rotors are treated by the parallel analysis and by a corresponding sequential analysis with the conventional shooting and QR methods; linear quasisteady airfoil aerodynamics and a finite-state three-dimensional wake model are used, Computational reliability is quantified by the condition numbers of the Jacobian matrices in Newton iteration, the condition numbers of the eigenvalues and the residual errors of the eigenpairs, and reliability figures are comparable in both the parallel and sequential analyses, Compared to the sequential analysis, the parallel analysis reduces the run time of large systems dramatically, and the reduction increases with increasing system order; this finding offers considerable promise for design and comprehensive-analysis applications.

The determination of spatial pattern in Dictyostelium discoideum

Free-living amoebae of the cellular slime mould Dictyostelium discoideum aggregate when starved and give rise to a long and thin multicellular structure, the slug. The slug resembles a metazoan embryo, and as with other embryos it is possible to specify a fate map. In the case of Dictyostelium discoideum the map is especially simple: cells in the anterior fifth of the slug die and form a stalk while the majority of those in the posterior differentiate into spores. The genesis of this anterior-posterior distinction is the subject of our review. In particular, we ask: what are the relative roles of individual pre-aggregative predispositions and post-aggregative position in determining cell fate? We review the literature on the subject and conclude that both factors are important. Variations in nutritional status, or in cell cycle phase at starvation, can bias the probability that an amoeba differentiates into a stalk cell or a spore. On the other hand, isolates, or slug fragments, consisting of only prestalk cells or only prespore cells can regulate so as to result in a normal range of both cell types. We identify three levels of control, each being responsible for guiding patterning in normal development: (i) 'coin tossing', whereby a cell autonomously exhibits a preference for developing along either the stalk or the spore pathway with relative probabilities that can be influenced by the environment; (ii) 'chemical kinetics', whereby prestalk and prespore cells originate from undifferentiated amoebae on a probabilistic basis but, having originated, interact (e.g. via positive and negative feedbacks), and the interaction influences the possibility of conversion of one cell type into the other, and (iii) 'positional information', in which the spatial distribution of morphogens in the slug influences the pathway of differentiation. In the case of possibilities (i) and (ii), sorting out of like cell types leads to the final spatial pattern. In the case of possibility (iii), the pattern arises in situ.

DNA Free Energy-Based Promoter Prediction and Comparative Analysis of Arabidopsis and Rice Genomes

The cis-regulatory regions on DNA serve as binding sites for proteins such as transcription factors and RNA polymerase. The combinatorial interaction of these proteins plays a crucial role in transcription initiation, which is an important point of control in the regulation of gene expression. We present here an analysis of the performance of an in silico method for predicting cis-regulatory regions in the plant genomes of Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) on the basis of free energy of DNA melting. For protein-coding genes, we achieve recall and precision of 96% and 42% for Arabidopsis and 97% and 31% for rice, respectively. For noncoding RNA genes, the program gives recall and precision of 94% and 75% for Arabidopsis and 95% and 90% for rice, respectively. Moreover, 96% of the false-positive predictions were located in noncoding regions of primary transcripts, out of which 20% were found in the first intron alone, indicating possible regulatory roles. The predictions for orthologous genes from the two genomes showed a good correlation with respect to prediction scores and promoter organization. Comparison of our results with an existing program for promoter prediction in plant genomes indicates that our method shows improved prediction capability.

A chemical approach to understand fragilities of glass-forming liquids

Fragility is viewed as a measure of the loss of rigidity of a glass structure above its glass transition temperature. It is attributed to the weakness of directional bonding and to the presence of a high density of low-energy configurational states. An a priori fragility function of electronegativities and bond distances is proposed which quite remarkably reproduces the entire range of reported fragilities and demonstrates that the fragility of a melt is indeed encrypted in the chemistry of the parent material. It has also been shown that the use of fragility-modified activation barriers in the Arrhenius function account for the whole gamut of viscosity behavior of liquids. It is shown that fragility can be a universal scaling parameter to collapse all viscosity curves on to a master plot.

Temperature profiles of accretion discs around rapidly rotating strange stars in general relativity: A comparison with neutron stars

We compute the temperature profiles of accretion discs around rapidly rotating strange stars, using constant gravitational mass equilibrium sequences of these objects, considering the full effect of general relativity. Beyond a certain critical value of stellar angular momentum (J), we observe the radius ( $r_{\rm orb}$) of the innermost stable circular orbit (ISCO) to increase with J (a property seen neither in rotating black holes nor in rotating neutron stars). The reason for this is traced to the crucial dependence of ${\rm d}r_{\rm orb}/{\rm d}J$ on the rate of change of the radial gradient of the Keplerian angular velocity at $r_{\rm orb}$ with respect to J. The structure parameters and temperature profiles obtained are compared with those of neutron stars, as an attempt to provide signatures for distinguishing between the two. We show that when the full gamut of strange star equation of state models, with varying degrees of stiffness are considered, there exists a substantial overlap in properties of both neutron stars and strange stars. However, applying accretion disc model constraints to rule out stiff strange star equation of state models, we notice that neutron stars and strange stars exclusively occupy certain parameter spaces. This result implies the possibility of distinguishing these objects from each other by sensitive observations through future X-ray detectors.

Sliding mode control-based algorithms for consensus in connected swarms

In this article, finite-time consensus algorithms for a swarm of self-propelling agents based on sliding mode control and graph algebraic theories are presented. Algorithms are developed for swarms that can be described by balanced graphs and that are comprised of agents with dynamics of the same order. Agents with first and higher order dynamics are considered. For consensus, the agents' inputs are chosen to enforce sliding mode on surfaces dependent on the graph Laplacian matrix. The algorithms allow for the tuning of the time taken by the swarm to reach a consensus as well as the consensus value. As an example, the case when a swarm of first-order agents is in cyclic pursuit is considered.

Redox modification of Akt mediated by the dopaminergic neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt

Impairment of Akt phosphorylation, a critical survival signal, has been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. However, the mechanism underlying pAkt loss is unclear. In the current study, we demonstrate pAkt loss in ventral midbrain of mice treated with dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), when compared to ventral midbrain of control mice treated with vehicle alone. Thiol residues of the critical cysteines in Akt are oxidized to a greater degree in mice treated with MPTP, which is reflected as a 40% loss of reduced Akt. Association of oxidatively modified Akt with the phosphatase PP2A, which can lead to enhanced dephosphorylation of pAkt, was significantly stronger after MPTP treatment. Maintaining the protein thiol homeostasis by thiol antioxidants prevented loss of reduced Akt, decreased association with PP2A, and maintained pAkt levels. Overexpression of glutaredoxin, a protein disulfide oxidoreductase, in human primary neurons helped sustain reduced state of Akt and abolished MPP+-mediated pAkt loss. We demonstrate for the first time the selective loss of Akt activity, in vivo, due to oxidative modification of Akt and provide mechanistic insight into oxidative stress-induced down-regulation of cell survival pathway in mouse midbrain following exposure to MPTP.-Durgadoss, L., Nidadavolu, P., Khader Valli, R., Saeed, U., Mishra, M., Seth, P., Ravindranath, R. Redox modification of Akt mediated by the dopaminergic neurotoxin MPTP, in mouse midbrain, leads to down-regulation of pAkt. FASEB J. 26, 1473-1483 (2012). www.fasebj.org

Estimating the Hausdorff-Besicovitch dimension of boundary of basin of attraction in helicopter trim

Helicopter trim involves solution of nonlinear force equilibrium equations. As in many nonlinear dynamic systems, helicopter trim problem can show chaotic behavior. This chaotic behavior is found in the basin of attraction of the nonlinear trim equations which have to be solved to determine the main rotor control inputs given by the pilot. This study focuses on the boundary of the basin of attraction obtained for a set of control inputs. We analyze the boundary by considering it at different magnification levels. The magnified views reveal intricate geometries. It is also found that the basin boundary exhibits the characteristic of statistical self-similarity, which is an essential property of fractal geometries. These results led the authors to investigate the fractal dimension of the basin boundary. It is found that this dimension is indeed greater than the topological dimension. From all the observations, it is evident that the boundary of the basin of attraction for helicopter trim problem is fractal in nature. (C) 2012 Elsevier Inc. All rights reserved.

DNA Binding and Oxidative Cleavage Activity of Ternary (alpha-Lipoic Acid) Copper(II) Complex of Heterocyclic Base

Ternary copper(II) complex Cu(a-lipo)(phen)(Cl)](NO3) where a-lipo = a-lipoic acid, phen is N, N-donor heterocyclic base, 1,10-phenanthroline was synthesized, characterized, and its DNA binding and cleavage activity were studied. Binding interactions of the complex with calf thymus (CT) DNA has been investigated by emission, viscosity, and DNA melting studies. The complex shows efficient oxidative cleavage of SC-DNA in the presence of 3-mercaptopropionic acid involving hydroxyl radical species, and results of control experiments exhibit the inhibition of DNA cleavage in the presence of hydroxyl radical scavengers, viz. DMSO and KI.

DSA image registration using non-uniform MRF model and pivotal control points

In order to reduce the motion artifacts in DSA, non-rigid image registration is commonly used before subtracting the mask from the contrast image. Since DSA registration requires a set of spatially non-uniform control points, a conventional MRF model is not very efficient. In this paper, we introduce the concept of pivotal and non-pivotal control points to address this, and propose a non-uniform MRF for DSA registration. We use quad-trees in a novel way to generate the non-uniform grid of control points. Our MRF formulation produces a smooth displacement field and therefore results in better artifact reduction than that of registering the control points independently. We achieve improved computational performance using pivotal control points without compromising on the artifact reduction. We have tested our approach using several clinical data sets, and have presented the results of quantitative analysis, clinical assessment and performance improvement on a GPU. (C) 2013 Elsevier Ltd. All rights reserved.

Formation flying of small satellites using suboptimal MPSP guidance

Using the recently developed model predictive static programming (MPSP), a suboptimal guidance logic is presented in this paper for formation flying of small satellites. Due to the inherent nature of the problem formulation, MPSP does not require the system dynamics to be linearized. The proposed guidance scheme is valid both for high eccentricity chief satellite orbits as well as large separation distance between chief and deputy satellites. Moreover, since MPSP poses the desired conditions as a set of `hard constraints', the final accuracy level achieved is very high. The proposed guidance scheme has been tested successfully for a variety of initial conditions and for a variety of formation commands as well. Comparison with standard Linear Quadratic Regulator (LQR) solution (which serves as a guess solution for MPSP) and another nonlinear controller, State Dependent Riccati Equation (SDRE) reveals that MPSP guidance achieves the objective with higher accuracy and with lesser amount of control usage as well.

Effects of elastase and collagenase on the nonlinearity and anisotropy of porcine aorta

We use enzymatic manipulation methods to investigate the individual and combined roles of elastin and collagen on arterial mechanics. Porcine aortic tissues were treated for differing amounts of time using enzymes elastase and collagenase to cause degradation in substrate proteins elastin and collagen and obtain variable tissue architecture. We use equibiaxial mechanical tests to quantify the material properties of control and enzyme treated tissues and histological methods to visualize the underlying tissue microstructure in arterial tissues. Our results show that collagenase treated tissues were more compliant in the longitudinal direction as compared to control tissues. Collagenase treatment also caused a decrease in the tissue nonlinearity as compared to the control samples in the study. A one hour collagenase treatment was sufficient to cause fragmentation and degradation of the adventitial collagen. In contrast, elastase treatment leads to significantly stiffer tissue response associated with fragmented and incomplete elastin networks in the tissue. Thus, elastin in arterial walls distributes tensile stresses whereas collagen serves to reinforce the vessel wall in the circumferential direction and also contributes to tissue anisotropy. A microstructurally motivated strain energy function based on circumferentially oriented medial fibers and helically oriented collagen fibers in the adventitia is useful in describing these experimental results.

Optical properties of an inhomogeneously broadened Lambda V-system with multiple excited states

We present a theoretical model using a density matrix approach to show the influence of multiple excited states on the optical properties of an inhomogeneously broadened Lambda V-system of the Rb-87 D2 line. These closely spaced multiple excited states cause asymmetry in absorption and dispersion profiles. We observe the reduced absorption profiles, due to dressed state interactions of the applied electromagnetic fields, which results the Mollow sideband-like transparency windows. In a room temperature vapor, we obtain a narrow enhanced absorption and steep positive dispersion at the line center when the strengths of control and pump fields are equal. Here, we show how the probe transmittance varies when it passes through the atomic medium. We also discuss the transient behavior of our system which agrees well with the corresponding absorption and dispersion profiles. This study has potential applications in controllability of group velocity, and for optical and quantum information processing.

Experimental assessment of concrete damage due to exposure to high temperature and efficacy of the repair system

The present study experimentally evaluates the performance of control (standard cylinder specimen), damaged (mechanical loading after thermal exposure) and repaired / retrofitted normal plain concrete cylinders using different repair schemes such as on use of FRP wraps, Geo-polymers, etc., to restore the capacity of damaged structural concrete elements. The control-companion specimen in the series provides the reference frame against which both, specimen damage levels were quantified and the benefits of a specimen repaired subsequent to damage were assessed.