Sensitivity of peptide conformational dynamics on clustering of a classical molecular dynamics trajectory

We investigate the sensitivity of a Markov model with states and transition probabilities obtained from clustering a molecular dynamics trajectory. We have examined a 500 ns molecular dynamics trajectory of the peptide valine-proline-alanine-leucine in explicit water. The sensitivity is quantified by varying the boundaries of the clusters and investigating the resulting variation in transition probabilities and the average transition time between states. In this way, we represent the effect of clustering using different clustering algorithms. It is found that in terms of the investigated quantities, the peptide dynamics described by the Markov model is sensitive to the clustering; in particular, the average transition times are found to vary up to 46%. Moreover, inclusion of nonphysical sparsely populated clusters can lead to serious errors of up to 814%. In the investigation, the time step used in the transition matrix is determined by the minimum time scale on which the system behaves approximately Markovian. This time step is found to be about 100 ps. It is concluded that the description of peptide dynamics with transition matrices should be performed with care, and that using standard clustering algorithms to obtain states and transition probabilities may not always produce reliable results.

Kineto-elastodynamic analysis of high-speed four-bar mechanism

This thesis addresses the kineto-elastodynamic analysis of a four-bar mechanism running at high-speed where all links are assumed to be flexible. First, the mechanism, at static configurations, is considered as structure. Two methods are used to model the system, namely the finite element method (FEM) and the dynamic stiffness method. The natural frequencies and mode shapes at different positions from both methods are calculated and compared. The FEM is used to model the mechanism running at high-speed. The governing equations of motion are derived using Hamilton's principle. The equations obtained are a set of stiff ordinary differential equations with periodic coefficients. A model is developed whereby the FEM and the dynamic stiffness method are used conjointly to provide high-precision results with only one element per link. The principal concern of the mechanism designer is the behaviour of the mechanism at steady-state. Few algorithms have been developed to deliver the steady-state solution without resorting to costly time marching simulation. In this study two algorithms are developed to overcome the limitations of the existing algorithms. The superiority of the new algorithms is demonstrated. The notion of critical speeds is clarified and a distinction is drawn between "critical speeds", where stresses are at a local maximum, and "unstable bands" where the mechanism deflections will grow boundlessly. Floquet theory is used to assess the stability of the system. A simple method to locate the critical speeds is derived. It is shown that the critical speeds of the mechanism coincide with the local maxima of the eigenvalues of the transition matrix with respect to the rotational speed of the mechanism.

Random walk with restart over dynamic graphs

Random Walk with Restart (RWR) is an appealing measure of proximity between nodes based on graph structures. Since real graphs are often large and subject to minor changes, it is prohibitively expensive to recompute proximities from scratch. Previous methods use LU decomposition and degree reordering heuristics, entailing O(|V|^3) time and O(|V|^2) memory to compute all (|V|^2) pairs of node proximities in a static graph. In this paper, a dynamic scheme to assess RWR proximities is proposed: (1) For unit update, we characterize the changes to all-pairs proximities as the outer product of two vectors. We notice that the multiplication of an RWR matrix and its transition matrix, unlike traditional matrix multiplications, is commutative. This can greatly reduce the computation of all-pairs proximities from O(|V|^3) to O(|delta|) time for each update without loss of accuracy, where |delta| (<<|V|^2) is the number of affected proximities. (2) To avoid O(|V|^2) memory for all pairs of outputs, we also devise efficient partitioning techniques for our dynamic model, which can compute all pairs of proximities segment-wisely within O(l|V|) memory and O(|V|/l) I/O costs, where 1<=l<=|V| is a user-controlled trade-off between memory and I/O costs. (3) For bulk updates, we also devise aggregation and hashing methods, which can discard many unnecessary updates further and handle chunks of unit updates simultaneously. Our experimental results on various datasets demonstrate that our methods can be 1–2 orders of magnitude faster than other competitors while securing scalability and exactness.

Modeling equity market integration using smooth transition analysis:a study of Eastern European stock markets

This paper assesses the extent to which the equity markets of Hungary, Poland the Czech Republic and Russia have become less segmented. Using a variety of tests it is shown there has been a consistent increase in the co-movement of some Eastern European markets and developed markets. Using the variance decompositions from a vector autoregressive representation of returns it is shown that for Poland and Hungary global factors are having an increasing influence on equity returns, suggestive of increased equity market integration. In this paper we model a system of bivariate equity market correlations as a smooth transition logistic trend model in order to establish how rapidly the countries of Eastern Europe are moving away from market segmentation. We find that Hungary is the country which is becoming integrated the most quickly. © 2005 ELsevier Ltd. All rights reserved.

Fast response static var generator for improving the power system performance of an electric arc furnace (EAF)

Cascaded multilevel inverters-based Static Var Generators (SVGs) are FACTS equipment introduced for active and reactive power flow control. They eliminate the need for zigzag transformers and give a fast response. However, with regard to their application for flicker reduction in using Electric Arc Furnace (EAF), the existing multilevel inverter-based SVGs suffer from the following disadvantages. (1) To control the reactive power, an off-line calculation of Modulation Index (MI) is required to adjust the SVG output voltage. This slows down the transient response to the changes of reactive power; and (2) Random active power exchange may cause unbalance to the voltage of the d.c. link (HBI) capacitor when the reactive power control is done by adjusting the power angle d alone. To resolve these problems, a mathematical model of 11-level cascaded SVG, was developed. A new control strategy involving both MI (modulation index) and power angle (d) is proposed. A selected harmonics elimination method (SHEM) is taken for switching pattern calculations. To shorten the response time and simplify the controls system, feed forward neural networks are used for on-line computation of the switching patterns instead of using look-up tables. The proposed controller updates the MI and switching patterns once each line-cycle according to the sampled reactive power Qs. Meanwhile, the remainder reactive power (compensated by the MI) and the reactive power variations during the line-cycle will be continuously compensated by adjusting the power angles, d. The scheme senses both variables MI and d, and takes action through the inverter switching angle, qi. As a result, the proposed SVG is expected to give a faster and more accurate response than present designs allow. In support of the proposal there is a mathematical model for reactive powered distribution and a sensitivity matrix for voltage regulation assessment, MATLAB simulation results are provided to validate the proposed schemes. The performance with non-linear time varying loads is analysed and refers to a general review of flicker, of methods for measuring flickers due to arc furnace and means for mitigation.

Transition from time-continuous systems to discrete mappings

Detailed transport studies in plasmas require the solution of the time evolution of many different initial positions of test particles in the phase space of the systems to be investigated. To reduce this amount of numerical work, one would like to replace the integration of the time-continues system with a mapping.

Formulation and characterisation of lyophilised rapid disintegrating tablets using amino acids as matrix forming agents

Despite recent advances in the formulation of lyophilised rapid disintegrating tablets (RDTs), the inclusion of matrix supporting/disintegration enhancing agents has been limited to the use of saccharides and polyols. In this study, the feasibility of using amino acids as matrix forming agents in lyophilised RDTs was investigated. Twelve amino acids were chosen (alanine, arginine, threonine, glycine, cysteine, serine, histidine, lysine, valine, asparagine, glutamine and proline), and the suitability for freeze drying, mechanical properties and disintegration time after inclusion of the amino acids at varied concentration were studied. In addition, the porosity of the RDTs and wettability profile of the amino acids were investigated to understand the mechanisms of disintegration. The results suggest the suitability of these amino acids for the lyophilisation regime, as they displayed satisfactory safety margin between the glass transition and shelf temperature (-40 degrees C), except proline-based formulations. Moreover, the crystallisation behavior of alanine, glycine, cysteine and serine at high concentration increased the stability of the formulation. The characterisation of the RDTs suggests that high concentration of the amino acids is required to enhance the mechanical properties, whereas only optimum concentrations promote the disintegration. Moreover, wetting time of the amino acid and porosity of the tablet are the two factors that control the disintegration of RDTs.

The end of transition?:The role of informal economies in the post-Soviet space

This book challenges the accepted notion that the transition from the command economy to market based systems is complete across the post-Soviet space. While it is noted that different political economies have developed in such states, such as Russia’s ‘managed democracy’, events such as Ukraine gaining ‘market economy status’ by the European Union and acceding to the World Trade Organisation in 2008 are taken as evidence that the reform period is over. Such thinking is based on numerous assumptions; specifically that economic transition has defined start and end points, that the formal economy now has primacy over other forms of economic practices and that national economic growth leads to the ‘trickle down’ of wealth to those marginalised by the transition process. Based on extensive ethnographic and quantitative research, conducted in Ukraine and Russia between 2004 - 2007, this book questions these assumptions by stating that the economies that operate across post-Soviet spaces are far from the textbook idea of a market economy. Through this the whole notion of ‘transition’ is problematised and the importance of informal economies to everyday life is demonstrated. Using case studies of various sectors, such as entrepreneurial behaviour and the higher education system, it is also shown how corruption has invaded almost all sectors of the post-Soviet every day.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

Modelling of induction motors for system faults and transient stability studies

The research carried out in this thesis was mainly concerned with the effects of large induction motors and their transient performance in power systems. Computer packages using the three phase co-ordinate frame of reference were developed to simulate the induction motor transient performance. A technique using matrix algebra was developed to allow extension of the three phase co-ordinate method to analyse asymmetrical and symmetrical faults on both sides of the three phase delta-star transformer which is usually required when connecting large induction motors to the supply system. System simulation, applying these two techniques, was used to study the transient stability of a power system. The response of a typical system, loaded with a group of large induction motors, two three-phase delta-star transformers, a synchronous generator and an infinite system was analysed. The computer software developed to study this system has the advantage that different types of fault at different locations can be studied by simple changes in input data. The research also involved investigating the possibility of using different integrating routines such as Runge-Kutta-Gill, RungeKutta-Fehlberg and the Predictor-Corrector methods. The investigation enables the reduction of computation time, which is necessary when solving the induction motor equations expressed in terms of the three phase variables. The outcome of this investigation was utilised in analysing an introductory model (containing only minimal control action) of an isolated system having a significant induction motor load compared to the size of the generator energising the system.

A novel plasma etching and emission monitoring system (PEEMS) to assess protein and lipid spoilation for hydrogel contact lenses

The work presents a new method that combines plasma etching with extrinsic techniques to simultaneously measure matrix and surface protein and lipid deposits. The acronym for this technique is PEEMS - Plasma Etching and Emission Monitoring System. Previous work has identified the presence of proteinaceous and lipoidal deposition on the surface of contact lenses and highlighted the probability that penetration of these spoilants will occur. This technique developed here allows unambiguous identification of the depth of penetration of spoilants to be made for various material types. It is for this reason that the technique has been employed in this thesis. The technique is applied as a 'molecular' scalpel, removing known amounts of material from the target. In this case from both the anterior .and posterior surfaces of a 'soft' contact lens. The residual material is then characterised by other analytical techniques such as UV/visible .and fluorescence spectroscopy. Several studies have be.en carried out for both in vivo and in vitro spoilt materials. The analysis and identification of absorbed protein and lipid of the substrate revealed the importance of many factors in the absorption and adsorption process. The effect of the material structure, protein nature (in terms of size, shape and charge) and environment conditions were examined in order to determine the relative uptake of tear proteins. The studies were extended to real cases in order to study the. patient dependent factors and lipoidal penetration.

Transition metal ion coordination in hydrophilic polymer membranes

The research described within this thesis is concerned with the investigation of transition metal ion complexation within hydrophilic copolymer membranes. The membranes are copolymers of 4-methyl-4'-vinyl-2,2'-bipyridine, the 2-hydroxyethyl ester of 4,4'- dicarboxy-2,2'-bipyridine & bis-(5-vinylsalicylidene)ethylenediamine with 2-hydroxyethyl methacrylate. The effect of the polymer matrix on the formation and properties of transition metal iron complexes has been studied, specifically Cr(III) & Fe(II) salts for the bipyridyl- based copolymer membranes and Co(II), Ni(II) & Cu(II) salts for the salenH2- based copolymer membranes. The concomitant effect of complex formation on the properties of the polymer matrix have also been studied, e.g. on mechanical strength. A detailed body of work into the kinetics and thermodynamics for the formation of Cu(II) complexes in the salenH2- based copolymer membranes has been performed. The rate of complex formation is found to be very slow while the value of K for the equilibrium of complex formation is found to be unexpectedly small and shows a slight anion dependence. These phenomena are explained in terms of the effects of the heterogeneous phase provided by the polymer matrix. The transport of Cr(III) ions across uncomplexed and Cr(III)-pre-complexed bipyridyl-based membranes has been studied. In both cases, no Cr(III) coordination occurs within the time-scale of an experiment. Pre-complexation of the membrane does not lead to a change in the rate of permeation of Cr(III) ions. The transport of Co(II), Ni(II) & Cu(II) ions across salenH2- based membranes shows that there is no detectable lag-time in transport of the ions, despite independent evidence that complex formation within the membranes does occur. Finally, the synthesis of a number of functionalised ligands is described. Although they were found to be non-polymerisable by the methods employed in this research, they remain interesting ligands which provide a startmg pomt for further functionalisation.

System identification of linear vibrating structures

Methods of dynamic modelling and analysis of structures, for example the finite element method, are well developed. However, it is generally agreed that accurate modelling of complex structures is difficult and for critical applications it is necessary to validate or update the theoretical models using data measured from actual structures. The techniques of identifying the parameters of linear dynamic models using Vibration test data have attracted considerable interest recently. However, no method has received a general acceptance due to a number of difficulties. These difficulties are mainly due to (i) Incomplete number of Vibration modes that can be excited and measured, (ii) Incomplete number of coordinates that can be measured, (iii) Inaccuracy in the experimental data (iv) Inaccuracy in the model structure. This thesis reports on a new approach to update the parameters of a finite element model as well as a lumped parameter model with a diagonal mass matrix. The structure and its theoretical model are equally perturbed by adding mass or stiffness and the incomplete number of eigen-data is measured. The parameters are then identified by an iterative updating of the initial estimates, by sensitivity analysis, using eigenvalues or both eigenvalues and eigenvectors of the structure before and after perturbation. It is shown that with a suitable choice of the perturbing coordinates exact parameters can be identified if the data and the model structure are exact. The theoretical basis of the technique is presented. To cope with measurement errors and possible inaccuracies in the model structure, a well known Bayesian approach is used to minimize the least squares difference between the updated and the initial parameters. The eigen-data of the structure with added mass or stiffness is also determined using the frequency response data of the unmodified structure by a structural modification technique. Thus, mass or stiffness do not have to be added physically. The mass-stiffness addition technique is demonstrated by simulation examples and Laboratory experiments on beams and an H-frame.

Deformation microstructures and recrystallization in heavily worked copper

Deformation microstructures in two batches of commercially pure copper (A and B) of allnost similar composition have been studied after rolling reductions from 5% to 95%. X- ray diffraction, optical metallography, scanning electron microscopy in the back-scattered mode, transmission and scanning electron microscopy have been used to examine the deformation microstructure. At low strains (~10 %) the deformation is accommodated by uniform octahedral slip. Microbands that occur as sheet like features usually on the {111} slip planes are formed after 10% reduction. The misorientations between rnicrobonds ond the matrix are usually small (1 - 2° ) and the dislocations within the bands suggest that a single slip system has been operative. The number of microbands increases with strain, they start to cluster and rotate after 60% reduction and, after 90 %, they become almost perfectly aligned with the rolling direction. There were no detectable differences in deformation microstructure between the two materials up to a deformation level of 60% but subsequently, copper B started to develop shear bands which became very profuse by 90% reduction. By contrast, copper A at this stage of deformation developed a smooth laminated structure. This difference in the deformation microstructures has been attributed to traces of unknown impurity in D which inhibit recovery of work hardening. The preferred orientations of both were typical of deformed copper although the presence of shear bands was associated wth a slightly weaker texture. The effects of rolling temperature and grain size on deformation microstructure were also investigated. It was concluded that lowering the rolling temperature or increasing the initial grain size encourages the material to develop shear bands after heavy deformation. Recovery and recrystallization have been studied in both materials during annealing. During recrystallization the growth of new grains showed quite different characteristics in the two cases. Where shear bands were present these acted as nucleation sites and produced a wide spread of recrystallized grain orientations. The resulting annealing textures were very weak. In the absence of shear bands, nucleation occurs by a remarkably long range bulging process which creates the cube orientation and an intensely sharp annealing texture. Cube oriented regions occur in long bands of highly elongated and well recovered cells which contain long range cumulative micorientations. They are transition bands with structural characteristics ideally suited for nucleation of recrystallization. Shear banding inhibits the cube texture both by creating alternative nuclei and by destroying the microstructural features necessary for cube nucleation.

Polycaprolactone fibres as a potential delivery system for collagen to support bone regeneration

Poly(e-caprolactone) (PCL) is biocompatible, non-immunogenic and non-toxic, and slowly degrades, allowing sufficient time for tissue regeneration. PCL has the potential for application in bone and cartilage repair as it may provide the essential structure required for bone regeneration, however, an ideal scaffold system is still undeveloped. PCL fibres were prepared using the gravity spinning technique, in which collagen was either incorporated into or coated onto the 'as-spun' fibres, in order to develop novel biodegradable polymer fibres which will effectively deliver collagen and support the attachment and proliferation of human osteoblast (HOB) cells for bone regeneration. The physical and mechanical characteristics and cell fibre interactions were analysed. The PCL fibres were found to be highly flexible and inclusion of collagen did not alter the mechanical properties of PCL fibres. Overall, HOB cells were shown to effectively adhere and proliferate on all fibre platforms tested, although proliferation rates were enhanced by surface coating PCL fibres with collagen compared to PCL fibres incorporating collagen and PCL-only fibres. These findings highlight the potential of using gravity spun PCL fibres as a delivery platform for extracellular matrix proteins, such as collagen, in order to enhance cell adherence and proliferation for tissue repair.