Dissertations / Theses on the topic 'Structures Behaviors Functions Analysis'

A major challenge for Information Technology (IT) programs is that the rapid pace of evolution of computing technology leads to frequent redesign of IT courses. The problem is exacerbated by several factors. Firstly, the changing technology is the subject matter of the discipline and is also frequently used to support instruction; secondly, this discipline has only been formalized as a four-year university program within recent years and there is a lack of established textbooks and curriculum models; finally, updating courses is seldom rewarded in a higher education system that favors research and teaching for promotion and tenure. Thus, continuously updating their courses place a significant burden on the faculty. A case study approach was used to describe and explain the change processes in updating IT courses. Several faculty members at two institutions were interviewed and course changes were identified and analyzed. The analysis revealed a set of recurrent themes in change processes. An instructional design architecture approach also revealed a set of design domains representing the structure of the change processes. The design domains were analyzed in terms of the design decisions they represented, and also in terms of structures, functions and activities, which are related to Structures-Behaviors-Functions (SBF) analysis. The design domains model helped to explain both negative and positive outcomes that were observed in the data. When design efforts impact multiple domains the design is likely to be more difficult. Understanding the design domain architecture will assist future designers in this discipline.

There has been a continuous production of high quality reports focussing on fruitless as the genetic switch for male sexual behaviour in Drosophila melanogaster, and on fruitless’s contributions to creating a male-specific neural circuit within the CNS. However it has become increasingly clear that fruitless is not sufficient in itself to specify the full complement of male-specific behavioural repertoires. One obvious genetic candidate that contributes to the male neural circuit is doublesex. doublesex has long been known to be pivotal to the specification of the sexually dimorphic adult soma but it’s function in specifying sex-specific neural substrates has, up till now, been largely unexplored. While fruitless has so far shown to be found only in insects, doublesex is a more ancient gene and, as member of the Dmrt family of genes, is both structurally and functionally conserved throughout the animal kingdom. Thus the study of doublesex offers great potential for understanding the neuronal, developmental and physiological logic underlying innate and species-specific behaviours, in not one but both sexes, in organisms throughout the animal kingdom. Using the novel dsxGAL4 transgenic tool, generated by ends-in homologous recombination at the doublesex locus, I have been able to perform a systematic temporal and spatial survey of doublesex expression both within, and outwith, the nervous system. Excitingly, as doublesex is endogenously expressed in both males and females, this has uncovered profound dimorphic differences in male and female neural substrates. In the male this circuit is shared with fruitless (whose expression is restricted to adult males) and has allowed myself, and my colleagues in the Goodwin lab, through functional behavioural analyses, to gain greater understanding into how male-specific behavioural outputs may be generated. Further though, functional analyses impinging on the novel doublesex female circuitry has allowed us to gain new insight into the (largely unstudied) role that females play in the courtship ritual. The dsx GAL4 transgenic tool, and the insights gained in this study, are also of import in relation to dissecting out mechanisms involved in the post-mating physiological and behavioural changes the female undergoes after successful copulation with a male. As well as this, as doublesex is known to play a pivotal role in establishing the dimorphic morphology of the fly, this tool has begun to allow us an understanding of how the assembly of these dimorphic neural circuits is coordinated with the development, and maintenance, of a sex-specific anatomy and physiology to produce the complete male or female ‘state’; Integrating both mind (fly brain) and body (fly soma).

Thesis (Ph. D.)--West Virginia University, 2004.
Title from document title page. Document formatted into pages; contains iv, 65 p. : ill. Includes abstract. Includes bibliographical references (p. 37-39).

The Method of Moments (MoM) has been used extensively to solve electromagnetic problems. Its popularity is largely attributed to its adaptability to structures with various shapes and success in predicting the equivalent induced currents accurately. However, due to its dense matrix, especially for large structures, the MoM suffers from long matrix solution time and large storage requirement. In this thesis it is shown that use of wavelet basis functions result in a MoM matrix which is sparser than the one obtained by using traditional basis functions. A new wavelet system, different from the ones found in literature, is proposed. Stabilized Bi-Conjugate Gradient Method which is an iterative matrix solution method is utilized to solve the resulting sparse matrix equation. Both a one-dimensional problem with a microstrip line example and a two-dimensional problem with a rectangular patch antenna example are studied and the results are compared.

The interest in telecommuting stems from the potential benefits in alleviating traffic congestion, decreasing vehicle miles traveled (VMT), and improving air quality by reducing the necessity for travel between home and the workplace. Despite the potential economic, environmental, and social benefits, telecommuting has not been widely adopted, and there is little consensus on the actual impacts of telecommuting. One of the major hurdles is lack of a sound instrument to quantify the impacts of telecommuting on individuals’ travel behavior. As a result, the telecommuting phenomenon has not received proper attention in most transportation planning and investment decisions, if not completely ignored. This dissertation addresses the knowledge gap in telecommuting studies by examining several factors. First, it proposes a comprehensive outline to reveal and represent the complexity in telecommuting patterns. There are various types of telecommuting engagement, with different impacts on travel outcomes. It is necessary to identify and distinguish between those people for whom telecommuting involves a substitution of work travel and those for whom telecommuting is an ancillary activity. Secondly, it enhances the current modeling framework by supplementing the choice/frequency approach with daily telework dimensions, since the traditional approach fails to recognize the randomness of telecommuting engagement in a daily context. A multi-stage modeling structure is developed, which incorporates choice, frequency, engagement, and commute, as the fundamental dimensions of telecommuting activity. One pioneering perspective of this methodology is that it identifies non-regular telecommuters, who represent a significant share of daily telecommuters. Lastly, advanced statistical modeling techniques are employed to measure the actual impacts of each telecommuting arrangement on travelers’ daily activity-travel behavior, focusing on time-use analysis and work trip departure times. This research provides a systematic and sound instrument that advances the understanding of the benefits and potentials of telecommuting and impacts on travel outcomes. It is expected to facilitate policy and decision makers with higher accuracy and contribute to the better design and analysis of transportation investment decisions.

Le domaine du traitement de la géométrie suit un cheminement similaire à celui de l'analyse d'images avec l'explosion des publications consacrées à l'apprentissage profond ces dernières années. Un important effort de recherche est en cours pour reproduire les succès de l'apprentissage profond dans le domaine de la vision par ordinateur dans le contexte de l'analyse de formes 3D. Contrairement aux images, les formes 3D peuvent peuvent être représentées de différentes manières comme des maillages ou des nuages de points souvent dépourvus d'une structure canonique. Les algorithmes d'apprentissage profond traditionnels tels que les réseaux neuronaux convolutifs (CNN) ne sont donc pas faciles à appliquer aux formes 3D. Dans cette thèse, nous proposons trois contributions principales : premièrement, nous introduisons une méthode permettant de comparer des fonctions sur des domaines différents sans correspondances et de les déformer afin de rendre la topologie de leur ensemble de niveaux similaires. Nous appliquons notre méthode au problème classique de la correspondance de formes dans le contexte des applications fonctionnelles (functional maps) afin de produire des correspondances plus lisses et plus précises. Par ailleurs notre méthode reposant sur l'optimisation continue d'une énergie différentiable par rapport aux fonctions comparées elle est applicable à l'apprentissage profond. Nous apportons deux contributions directes à l'apprentissage profond des données 3D. Nous introduisons un nouvel opérateur de convolution sur des maillages triangulaires basés sur des coordonnées polaires locales et l'appliquons à l'apprentissage profond sur les maillages. Contrairement aux travaux précédents, notre opérateur prend en compte tous les choix de coordonnées polaires sans perte d'information directionnelle. Enfin, nous introduisons un nouveau module de convolution invariant par rotation sur les nuages de points et montrons que les CNN basés sur ce dernier peuvent surpasser l'état de l'art pour des tâches standard sur des ensembles de données non alignés même avec augmentation des données
The field of geometry processing is following a similar path as image analysis with the explosion of publications dedicated to deep learning in recent years. An important research effort is being made to reproduce the successes of deep learning 2D computer vision in the context of 3D shape analysis. Unlike images shapes comes in various representations like meshes or point clouds which often lack canonical structure. This makes traditional deep learning algorithms like Convolutional Neural Networks (CNN) non straightforward to apply to 3D data. In this thesis we propose three main contributions:First, we introduce a method to compare functions on different domains without correspondences and to deform them to make the topology of their set of levels more alike. We apply our method to the classical problem of shape matching in the context of functional maps to produce smoother and more accurate correspondences. Furthermore, our method is based on the continuous optimization of a differentiable energy with respect to the compared functions and is applicable to deep learning. We make two direct contributions to deep learning on 3D data. We introduce a new convolution operator over triangles meshes based on local polar coordinates and apply it to deep learning on meshes. Unlike previous works our operator takes all choices of polar coordinates into account without loss of directional information. Lastly we introduce a new rotation invariant convolution layer over point clouds and show that CNNs based on this layer can outperform state of the art methods in standard tasks on un-alligned datasets even with data augmentation

In the first part of the thesis, the 2-D structures in stratified media are analyzed using an efficient MoM technique. The method is used to optimize transmitted or reflected electric fields from the 2-D structures. The genetic algorithm is used in the optimization process. In the second part a 3-D MoM technique is implemented to analyze multilayered structures with periodically implanted material blocks. Using the method, the dispersion and reflection characteristics of the structure are calculated for different configurations. The results are compared with the results found in the literature and it is seen that they are in good agreement. Asymptotic Waveform Evaluation (AWE) technique is utilized to obtain the Pade approximation of the solution in terms of frequency. The high order derivatives that are required by the AWE technique are calculated through Automatic Differentiation technique. Using the AWE method, the dispersion diagram and reflection characteristics of the periodic structures are obtained in a shorter time. The results are compared with the ones obtained through direct calculation and it is seen that they are in perfect agreement. The reflection coefficients that are obtained from the 3-D MoM procedure are used to calculate Green&rsquo
s functions that approximate electric field of an infinitesimal dipole on the periodically implanted substrate. Using the calculated Green&rsquo
s functions and the spectral domain MoM procedure, dispersion characteristics of a microstrip line on the periodically implanted substrate are obtained.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
Neste trabalho, o Método dos Elementos Finitos é aplicado na análise eletromagnética de estruturas coaxiais circularmente simétricas excitadas pelo modo TEM. A representação do campo magnético é feita através da associação de funções base polinomiais de diferentes ordens a grades que possuem elementos triangulares ou retangulares. Este trabalho apresenta um estudo comparativo entre as diversas possibilidades de associações função base e elemento, considerando o tempo de processamento computacional e a precisão exigida na simulação. A técnica é aplicada na análise de dispositivos de acoplamento entre diferentes guias coaxiais usualmente empregados em antenas de banda larga. Para validar os resultados do algoritmo, os resultados obtidos nas diversas etapas são comparados com aqueles obtidos via Método de Casamento de Modos. Além disto, a técnica é empregada para avaliar a possibilidade de utilização de dispositivos de inspeção de tubulação que utiliza uma onda TEM de alta freqüência. A onda TEM é excitada no interior da tubulação de forma que variações em suas paredes, nas condições de contorno dos campos, produzam alterações nas características de propagação, que serão detectadas e associadas às anomalias de suas paredes internas. Estes dispositivos de inspeção são empregados na indústria de petróleo e gás.
In this work, the Method of Finite Element is applied in the electromagnetic analysis of circularly symmetrical coaxial structures excited by TEM mode. The representation of the magnetic field is made through the association of polynomial basis functions of different orders associated in the grids made of triangular or rectangular elements. This work presents a comparative study between different possibilities of association between basis functions and element, considering the computational time and the accuracy yielded by the simulation. The technique is applied in the electromagnetic analysis of coupling devices used to connect different coaxial waveguides operating at microwave frequencies. To validate the algorithm developed in this work, the MEF results are compared with those obtained by employing Method of Mode Matching (MMM). Moreover, the technique is also employed to evaluate the possibility of use of TEM wave highfrequency for inspection of metallic pipelines. The TEM wave is excited inside cylindrical metallic pipes and anomalies in the metallic walls are associated to the changes in the propagation characteristics. These inspection devices are intensively used in the industry of oil and gas.

Previously data from out lab have shown that BTG2 is up-regulated in both in vitro and in vivo ischemic models. We hypothesize that BTG2 may play a neuro-protective role following glutamate-mediated activation of NMDAR, and that this neuro-protection depends on the collaboration of various transcription factors and cis-acting elements that are found on the BTG2 promoter. To determine the function of BTG2 , BTG2 was either over-expressed or reduced in rat cortical neurons, and treated with either NMDA or oxygen glucose deprivation (OGD). Over-expression of BTG2 reduced NMDA-induced cell death, as measured by LDH assay, and reduced activation of Caspase 3. In addition, CyclinDl mRNA level was significantly increased following NMDA treatment in cells with reduced BTG2 expression by siRNA. Thus, BTG2 appeared to have a neuro-protective function, possibly through down-regulation of CyclinDl expression. To better understand the mechanism that regulated BTG2 expression, we studied the BTG2 promoter by cloning various lengths of BTG2 promoter into a luciferase expression vector. The role of two specific cis-acting elements, a putative P53 binding element P53RE (-53/-94) (-53 to -94 relative to ATG) and a GAGA box, were investigated. While the isolated P53RE (-537-94) sequence functioned as a cis-activating and NMDA inducible element, it became repressive in the context of BTG2 promoter. Removal of P53RE (-53A94) and/or GAGA box not only increased the BTG2 promoter activity, but also made the promoter inducible to NMDA. Consistently, reduction of P53 expression with P53 siRNA led to a significant increase in basal BTG2 expression. Immuno-coprecipitation results showed that the P53 and the GAGA box binding protein were associated together. Taken together, our results suggest that P53 may associate with GAGA box binding protein to form a complex to repress BTG2 expression. A hypothetical mode of action is then proposed, showing that binding of P53 to the P53RE (-53/-94) may activate GAGA box caused suppression, which becomes dominant for BTG2 expression. This mode illustrates a possible mechanism that an transactivating factor P53 and its cis-activating binding site can be turned into a suppressor depending on the location of P53 binding site and the transcriptional regulator(s) P53 associated with.
Medicine, Faculty of
Graduate

Optimisation heuristics rely on implicit or explicit assumptions about the structure of the black-box fitness function they optimise. A review of the literature shows that understanding of structure and linkage is helpful to the design and analysis of heuristics. The aim of this thesis is to investigate the role that problem structure plays in heuristic optimisation. Many heuristics use ordinal operators; which are those that are invariant under monotonic transformations of the fitness function. In this thesis we develop a classification of pseudo-Boolean functions based on rank-invariance. This approach classifies functions which are monotonic transformations of one another as equivalent, and so partitions an infinite set of functions into a finite set of classes. Reasoning about heuristics composed of ordinal operators is, by construction, invariant over these classes. We perform a complete analysis of 2-bit and 3-bit pseudo-Boolean functions. We use Walsh analysis to define concepts of necessary, unnecessary, and conditionally necessary interactions, and of Walsh families. This helps to make precise some existing ideas in the literature such as benign interactions. Many algorithms are invariant under the classes we define, which allows us to examine the difficulty of pseudo-Boolean functions in terms of function classes. We analyse a range of ordinal selection operators for an EDA. Using a concept of directed ordinal linkage, we define precedence networks and precedence profiles to represent key algorithmic steps and their interdependency in terms of problem structure. The precedence profiles provide a measure of problem difficulty. This corresponds to problem difficulty and algorithmic steps for optimisation. This work develops insight into the relationship between function structure and problem difficulty for optimisation, which may be used to direct the development of novel algorithms. Concepts of structure are also used to construct easy and hard problems for a hill-climber.

Selon des études comportementales, les comportements complexes sont des processus multi-échelles, souvent composés de sous-éléments (unités fonctionnelles ou primitives). Cette thèse propose des architectures fonctionnelles afin de représenter la structure dynamique des unités fonctionnelles ainsi que celle des comportements multi-échelles résultants. Dans un premier temps, des unités fonctionnelles sont modélisées comme des flux structurés de faible dimension dans l'espace de phase (modes de fonctionnement). Des dynamiques supplémen-taires (signaux opérationnels) opèrent sur ces modes de fonctionnement faisant émerger des comportements complexes et sont classifiés selon la séparation entre leur échelle temporelle et celle des modes. Ensuite, des mesures de complexité, appliquées sur des architectures dis-tinctes composant un mouvement simple, révèlent un compromis entre la complexité des modes de fonctionnement et celle des signaux opérationnels. Celui-ci dépend de la séparation entre leurs échelles temporelles et soutient l'efficacité des architectures utilisant des modes non triviaux. Dans un deuxième temps, une architecture pour le comportement séquentiel (ici l'écriture) est construite via le couplage des modes de fonctionnement (réalisant des lettres) et des signaux opérationnels, ceux-ci beaucoup plus lents ou beaucoup plus rapides. Ainsi, l'importance des interactions entre les échelles temporelles pour l'organisation du comporte-ment est illustrée. Enfin, les contributions des modes et des signaux sur la sortie de l'architec-ture sont déterminées. Ceci semble être uniquement possible grâce à l'analyse du flux de phase (c'est-à-dire, non pas à partir des trajectoires dans l'espace de phase ni des séries temporelles)
Behavioural studies suggest that complex behaviours are multiscale processes, which may be composed of elementary ones (units or primitives). Traditional approaches to cognitive mod-elling generally employ reductionistic (mostly static) representations and computations of simplistic dynamics. The thesis proposes functional architectures to capture the dynamical structure of both functional units and the composite multiscale behaviours. First, a mathe-matical formalism of functional units as low dimensional, structured flows in phase space is introduced (functional modes). Second, additional dynamics (operational signals), which act upon functional modes for complex behaviours to emerge, are classified according to the separation between their characteristic time scale and the one of modes. Then, complexity measures are applied to distinct architectures for a simple composite movement and reveal a trade off between the complexities of functional modes and operational signals, depending on their time scale separation (in support of the control effectiveness of architectures employing non trivial modes). Subsequently, an architecture for serial behaviour (along the example of handwriting) is demonstrated, comprising of functional modes implementing characters, and operational signals much slower (establishing a mode competition and ‘binding’ modes into sequences) or much faster (as meaningful perturbations). All components being coupled, the importance of time scale interactions for behavioural organization is illustrated. Finally, the contributions of modes and signals to the output are recovered, appearing to be possible only through analysis of the output phase flow (i.e., not from trajectories in phase space or time)

This study's purpose was to investigate the importance of mentoring functions and behaviors for lifelong career development as perceived by protégés. The population included individuals in middle to late adulthood (age 40 years and older) who reported they had been a protégé in at least one mentoring association perceived as beneficial to their lifelong career development; and were either employed or had been employed as a middle manager, senior manager, C-level executive, business owner, or member of a profession. The sample was obtained using a chain-sample method; 67 Ambassadors completed an online survey and each invited 10 contacts to complete the survey. The final number of respondents was 503; of these, 456 reported being a protégé. Data were collected using the Perceptions of Workplace Mentoring Behaviors (PWMB) scale, a modification of Noe's (1988) Mentoring Functions Scale. The online survey included the PWMB scale items plus questions designed to engage the respondent's autobiographical memory and questions regarding respondent and mentoring association characteristics. The PWMB scale included seven new items, posited by the expert panel, enhancing the teaching aspect of mentoring. Confirmatory factor analyses were conducted comparing four tenable models for the PWMB scale. The 8-factor model, which was essentially the protégé's view of Kram's (1985) mentoring functions model and included the seven newly developed items, exhibited the best fit of the four possible models. Results indicated that protégés perceived three factors from the Psychosocial category (Role Model, Acceptance-and-Confirmation, and Relationship Fundamentals) as most important to their lifelong career development. Effective Development Opportunities was perceived as the most important factor from the Career category. Professional Issue Counseling from the Psychosocial category was perceived as the least important factor. Significant differences were found for five of six independent variables (protégé gender, mentor gender, dyad, protégé's mentor group, and birth decade) at the item level and for four of six independent variables (protégé gender, dyad, protégé's mentor group, and decade of birth) at the factor level. Implications included designing mentoring programs that provide opportunities for mentors and protégés to develop relationships rather than directly assigning protégés to mentors.

Background: Freno AB in Piteå has expanded rapidly in recent years and wishes to continue the expansion at aneven faster pace. At the same time, the company has noted that there are challenges to maintain high quality, goodeconomy and good marketability. The expansion sets demand on the finances for new premises and equipment aswell as for the development of new product models. The company shall also be able to provide aftermarket servicesand sell to new customers and market segments. In addition, there is requirements to develop skills in the newemployee’s and continuing to develop the existing employees. Furthermore, there are needs to invest in digitalsupport systems for design, production planning, logistics and financial functions as well as customer support andaftermarket.Freno´s goal is to ensure that the conditions for an expansion in each individual part is set before the expansion isstarted. The reason for the positioning is based on the fact, that there have been shortcomings in their businessactivities in most of the areas mentioned above and that many of the challenges lie in unclear communicationstructures. Task: In the thesis have I investigated how the company’s current knowledge and competence is transferred betweendifferent unites. The starting point has been stated in the fact that the employees are the ones who possessesinsight, knowledge and experience about the company's business and the opportunities and challenges that arecurrently in place. The study is based on the current state of Freno with a question about how streamlining communicationsbetween employees and departments can support a continued expansion. Method: The thesis is based on the methodology of Social Network Analysis, where the data regarding network,logic views and culture has been collected from the 12 employees. The interviewed answered via forms and hadthe opportunity to give open answers to some questions and give complementary information where deemed necessary.The required data was transferred to Excel and transformed into diagrams or further exported into Gephito create and understand the network configurations. The results were analyzed and interpreted via the theoreticalframework and cross referenced with other results to validate the conclusions. Results: The evaluation showed that competence and collaboration was not used in an optimal manner for maximizingproductivity. If the presented result is taken into consideration, will the company likely be able to predicthow strategic decisions can affect both existing and lacking communicational structures. A more transparent communicationbetween departments and with functioning support structure (i.e. production planning, updated schematics,goods, order stock with more) will probably affect the efficiency positively. Findings: The analysis showed that a combination between the bow-tie configuration, the imploded group structuresand a missing culture of the socio-technical multifunctional principle, inhibited the transfer and generationof new knowledge within the company. Causing a drift between the company’s knowledge and information needsand their combability view. The irregular network structures in combination with structural holes has made a heavyworkload on the centerpiece in the company. With that discovery was seven holes noted in the company network,which is assumed to have been handled by the centerpiece.Moreover, was a logical clash identified between the current and the previous CEO, changing the base for validatingactions and causing unclarity. Which in combination a chattered humane orientation culture and unclarity abouthow actions were validated via individual or groups acceptance. It was furthermore discovered that the workinstructions for the employed did define the employees influence via tools and technical support that enhanced thenetworks interaction patterns. Recommendations: The presented solutions includes team-building exercises, establishing a formal learningspace. Furthermore, is it recommended to establish up to seven formal meetings places and that knowledge typerequirements shall be identified and defined to secure what validates work related actions. It is also suggested toestablish mentorship protocols, in order to increase the knowledge transfer within the company and reduce therisks of bottleneck and locking effects. Keywords: Small to medium enterprises, iterative processes, Culture, resistance, influence, groupconfigurations, knowledge transfer, process perspective, social network analysis.

Dans le présent document de thèse, une extension de la méthode de calcul de la diffusion multiple stratifiée est développée en y incluant des structures phononiques à base de diffuseurs sphériques poroélastiques saturés immergés dans un fluide, en combinant la théorie de Biot avec le formalisme de diffusion multiple. La méthode est alors appliquée à une étude théorique, bien au-delà de l’approximation à grandes longueurs d’onde d’un milieu effectif, de la réponse acoustique d’un milieu granulaire à double porosité saturé, formé d’un réseau cristallin compact de sphères poreuses rigides ou molles. On montre que la variation de la taille des pores et/ou celle de la porosité dans une gamme allant du millimètre au micromètre pour le diamètre des sphères altère d’une façon significative les spectres de transmission, réflexion, et d’absorption d’une couche plane d’épaisseur finie de ces matériaux. Les spectres présentés sont analysés par référence aux modes acoustiques de sphères poreuses isolées d’une part, puis par rapport aux diagrammes de dispersion des cristaux infinis correspondants. Une interprétation cohérente de la physique sous-jacente est donnée. Ces résultats mettent en évidence l’occurrence de nouveaux modes, localisés dans la sphère, provenant des ondes longitudinales lentes propres aux milieux poroélastiques. Ces modes induisent quelques caractéristiques remarquables dans le comportement acoustique de ces matériaux à double porosité, comme des bandes d’absorption non-dispersive larges ou étroites en fréquence et/ou des bandes d’arrêt directionnel. Les propriétés acoustiques de ces structures phononiques à l’échelle sub-micrométrique, i.e. en régime hypersonique (GHz), peuvent être évaluées expérimentalement par diffusion Brillouin. Dans ce document, une approche théorique élasto-optique rigoureuse, basée sur les fonctions de Green, est proposée afin de décrire la diffusion inélastique de la lumière due aux variations spatiotemporelles de l’indice de réfraction du matériau induites par des phonons. Dans ce cadre des expressions analytiques de l’intensité d’un faisceau de lumière diffusé par une particule sphérique dans le vide sont dérivées, permettant ainsi d’améliorer la précision et rapidité des calculs précédents. Les grandes lignes de ce développement théorique jettent les bases pour une description rigoureuse de cet effet dans le cas de cristaux phononiques composés de particules sphériques colloïdales
In the present thesis, an extension of the layer multiple scattering computational methodology to phononic structures of fluid-saturated poroelastic spherical bodies, combining Biot's theory with multiple scattering techniques, is developed. The method is applied to the theoretical study, beyond the long wavelength effective-medium approximation, of the acoustic response of double-porosity liquid-saturated granular materials consisting of close-packed hard or soft porous spheres. It is shown that variations of the pore size and/or the porosity within the millimeter and submillimeter-sized spherical grains signicantly alters the transmission, reflection, and absorption spectra of finite slabs of these materials. The calculated spectra are analyzed by reference to the acoustic modes of the constituent porous spherical grains as well as to relevant dispersion diagrams of correspondingly infinite crystals, and a consistent interpretation of the underlying physics is presented. Our results provide evidence for the occurrence of novel, unprecedented modes, localized in the sphere, which arise from slow longitudinal waves that are peculiar to poroelastic media. These modes induce some remarkable features in the acoustic behavior of these double-porosity materials under study, such as broad or narrow dispersionless absorption bands and/or directional transmission gaps. The acoustic properties of phononic (sub)micro structures, in the hypersonic (GHz) regime, can be probed, in general, by Brillouin light scattering experiments. In the present thesis we undertake a rigorous full elasto-optic theoretical approach to inelastic light scattering due to phonon induced spatiotemporal variations of the refractive index of a medium, based on Green's functions, and derive analytical expressions for the intensities of the scattered light beams by single spherical particles in vacuum, thus improving the computational efficiency and accuracy of previous calculations. The above framework provides, also, the basis for a rigorous description of the effect for phononic crystals of colloidal spherical particles

This PhD thesis employed high energy synchrotron x-ray radiation to reveal atomic scale structural features occurring in plastically deformed Zr52.5Ti5Cu18Ni14.5Al10 (Vit105) bulk metallic glass (BMG). The study is divided into three parts: Strain evolution during in-situ compression, strain distribution maps in mechanically-imprinted BMG, and residual strain around a single shear band. 1. Strain evolution during in-situ compression The structural rearrangements occurring during compressive deformation of a plastically deformable BMG showed that the elastic and plastic deformation of the BMG is correlated to the structural changes at short- (SRO) and medium range order (MRO). In the elastic regime, the atomic distances at SRO vary linearly with macroscopic stress. Analysis of the area under radial distribution function indicates that a small fraction of bonds in the first shell is broken in the loading direction whereas some new bonds are formed in the transverse direction. Atomic bonds at SRO appeared significantly stiffer than the MRO shells. Compared to the macroscopic values of the elastic strain, Young’s modulus and Poisson's ratio, both SRO and MRO appeared significantly stiffer, implying that the elastic behavior of the BMG is not only ruled by simple compression of the atoms/clusters but also is aided by rearrangement of atoms/clusters. The deviation of MRO atomic strain-stress correlation from linearity at the onset of plastic deformation was attributed to the activation of irreversible shear transformation zones. It was demonstrated by a strong shear strain value at the onset of yielding. This value is in good agreement with the reported value of the critical shear strain needed for activation of an irreversible STZ. The length scale of 12.5 Å indicated the largest shear strain and is probably the most effective length scale in the formation of STZs. The atomic pairs at SRO with smallest shear strain have the least contribution to the STZs. It was also indicated that the typical fracture angle of this BMG can be explained by the orientation of maximum shear strain at the onset of catastrophic shear band formation. 2. Strain distribution map in mechanically-imprinted BMG In mechanical imprinting, the BMG plate is loaded between two tools with a regular array of linear teeth and, as a result, a regular pattern of linear imprints is created on the surface of the plate. Mechanically imprinting results in considerable tensile plasticity of brittle Vit105 BMG plate. The distribution of hardness and Young’s modulus values at the transverse cross section of imprinted plate probed via nanoindentation revealed oscillating soft and hard regions beneath the surface. Spatially-resolved strain maps obtained via high-energy nano-size beam X-ray diffraction exhibited that the plastic deformation during imprinting creates a spatially heterogeneous atomic arrangement, consisting of strong compressive and tensile strain fields as well as significant shear strain fields in the cross section. It was shown that the heat treatment diminishes the heterogeneous structure resulting in brittle behavior in tension. The analysis of strain tensor components based on changes in the first diffraction maximum of the structure function, q1, revealed that Ɛx, the strain perpendicular to the loading direction, changes from the compressive at near to the surface to the tensile mode at the center of the imprinted plate. In contrast, the strain component along the loading direction, Ɛy, changes from tensile near the surface to the compressive at the center. Beneath the surface, Ɛx reaches to values about 1.5% under the imprints where there is a negligible Ɛy. The distribution map of principal strains, Ɛ1 and Ɛ2, indicated that large regions with compressive Ɛ1 and Ɛ2 exist under the imprints which can result in blocking of the propagating shear bands in agreement with microstructural observations of shear banding after uniaxial tension. Moreover, the region beneath the border of the imprinted and un-imprinted parts has the highest residual shear strain. Microstructural observations indicated that such regions can nucleate new shear bands upon tensile loading of imprinted BMG plate. 3. Residual strain around a single shear band In order to probe structural changes in the shear-induced zone around a single shear band, the distribution of residual strains at short- and medium-range order around a single shear band was determined in cold-rolled BMG plate using the nano-focused high energy x-ray diffraction. Plastic deformation results in significant residual normal and shear strains at distances of more than 15 μm around the shear band. The residual normal strains exhibit an asymmetric distribution whereas the residual shear strain is distributed symmetrically around the shear band. The large amount of residual atomic shear strain magnitude at the vicinity of the shear band triggers the nucleation of the new shear bands. The coincidence of the direction of the nucleating secondary shear bands from the main shear band with the orientation of the residual shear strain at the vicinity of the mature shear band highlight the dominant role of the shear strain in determining further plastic deformation at regions near the shear band
Im Rahmen dieser Arbeit wird hochenergetische Synchrotron Röntgenstrahlung zum Aufzeigen der strukturellen Veränderungen in plastisch verformtem Zr52.5Ti5Cu18Ni14.5Al10 metallischen Glas verwendet. Die Arbeit gliedert sich in drei Teile: Dehnungsentwicklung während in-situ Druckversuch, Dehnungsverteilung eines mechanisch geprägten massiven metallischen Glases, und Restdehnungen in der Umgebung eines einzenen Scherbandes. 1. Dehnungsentwicklung während in-situ Druckversuch Die während der Verformung auftretende strukturelle Neuordnung eines plastisch verformbaren metallischen Glases zeigt die Korrelation der elastischen und plastischen Verformung mit den strukturellen Änderungen in den Größenordnungen der Nah- (SRO) und mittelreichweitigen Ordnung (MRO). Im elastischen Bereich verändern sich die Atomabstände in der SRO linear mit der makroskopisch anliegenden Spannung. Die Untersuchung der Fläche unter der Radialen Verteilungsfunktion (RDF) deutet auf ein Aufbrechen eines geringen Anteils der Bindungen der ersten Schale in Druckspannungsrichtung und deren Neubildung quer dazu. Die atomaren Bindungen in der SRO erscheinen wesentlich steifer als in den MRO Schalen. Vergleicht man die Werte von elastischer Dehnung, E-Modul und Querkontraktionszahl mit ihren makroskopischen Gegenstücken erscheinen beide, SRO und MRO, wesentlich steifer. Dies zeigt, dass die elastische Verformung von metallischen Gläsern nicht nur von der einfachen Stauchung der Atome bzw. Atomgruppen bestimmt, sondern auch durch deren Neuanordnung unterstützt wird. Das Abweichen der Dehnungs-Spannungs-Korrelation vom linearen Verhalten in der MRO am Beginn der plastischen Verformung wird der irreversiblen Bildung von Schertransformations-zonen (STZ) zugeschrieben. Dies zeigt sich zudem in den erhöhten Scherdehnungswerten am Beginn der Dehngrenze, welche mit den in der Literatur berichteten Werten für die kritische Scherdehnung zum Bilden einer STZ übereinstimmen. Bei einem Atomabstand von 12,5 Å tritt der höchste Wert der Scherdehnung auf und markiert den effektivsten Längenbereich der STZ Bildung. Andererseits haben die atomaren Paare in der SRO mit der geringsten Scherdehnung den geringsten Beitrag an der STZ. Es zeigt sich außerdem, dass der typische Bruchwinkel dieses metallischen Glases über die Orientierung der maximalen Scherdehnung am Beginn der kritischen Scherbandbildung erklärt werden kann. 2. Dehnungsverteilung eines mechanisch geprägten massiven metallischen Glases Eine Prägung besteht darin, eine Platte metallischen Glases mit zwei Stempel, auf denen eine regelmäßige Anordnung von geradlinigen Kerben angebracht ist, zu belasten. Dadurch wird eine ebenso regelmäßige Anordnung von geradlinigen Kerben auf der Oberfläche des metallischen Glases erzeugt. Die plastische Verformbarkeit der Vit105 Platte im Zugversuch wird durch Prägung im Vergleich zur gegossenen Probe eindeutig verbessert. Die Untersuchung der Härte und des E-Moduls über den Querschnitt der geprägten Probe zeigt die Einbringung von Abwechselnd weichen und harten Regionen an der Oberfläche. Es wurden räumlich aufgelöste Dehnungskarten des geprägten metallischen Glases durch Beugung eines hochenergetischen nanometergroßen Röntgenstrahles erzeugt. Die Ergebnisse offenbaren, dass die durch Prägung eingebrachte plastische Verformung eine räumlich heterogene Atomanordnung erzeugt, welche aus starken Druck- und Zugdehnungsfeldern besteht. Zusätzlich wird eine signifikante Scherdehnung in die Probe eingebracht. Die Wärmebehandlung beseitigt diese heterogene Struktur und führt sie fast auf den Ausgangszustand zurück. Die Analyse der Dehnungstensorkomponenten basierend auf Änderungen im erstem Maximum des Strukturfaktors, q1, zeigt, dass sich Ɛx von der Oberfläche zur Mitte der Platte hin von einer Stauchung in eine Dehnung umwandelt. Im Gegensatz dazu wandelt sich die Komponente Ɛy von der Oberfläche zur Mitte der Platte hin von einer Dehnung in eine Stauchung um. An der Oberfläche unter den Eindrücken, wo Ɛy vernachlässigbar ist, erreicht Ɛx Werte von ca. 1.5 %. Die Verteilungskarten der Hauptdehnungen zeigt, dass beide e1 und e2 unterhalb der Kerben als Stauchungen vorhanden sind. Daraus resultiert das Blockieren und Ablenken der sich ausbreitenden Scherbänder, was an Zugproben im REM beobachtet werden kann. Weiterhin hat der Bereich an der Grenze der geprägten und nicht geprägten Regionen die höchste Restscherdehnung. Mikrostrukturelle Beobachtungen deuten darauf hin, dass solche Bereiche unter Zuglast Keimstellen für neue Scherbänder sind. 3. Restdehnungen in der Umgebung eines einzenen Scherbandes Es wurde ein einzelnes Scherband einer kaltgewalzte Platte mittels Beugung eines hochenergetischen nanometergroßen Röntgenstrahles untersucht. Die strukturellen Unterschiede in der scherinduzierten Zone um ein einzelnes Scherband werden durch die Verteilung der Restdehnungen in SRO und MRO bestimmt. Plastische Verformung führt zu signifikanten Restnormal- und Restscherdehnungen in Entfernungen von mehr als 15 µm um das Scherband. Die Restnormaldehnungen zeigen eine asymmetrische Verteilung, wohingegen die Restscherdehnungen auf beiden Seiten des Scherbandes symmetrisch verteilt sind. Der große Betrag der atomaren Restscherdehnung in der Nähe des Scherbandes führt zur Bildung von neuen Scherbändern. Das Zusammenfallen der Richtung des sich bildenden sekundären Scherbandes und der Orientierung der Restscherdehnung, in der Nähe des primären Scherbandes, demonstriert die dominierende Rolle der Scherdehnung bei weiterer plastischer Verformung in der Nähe des Scherbandes

The measurement of reliable and valid indicators of early child development is necessary for assessing phenomena and is useful in the monitoring of ongoing efforts to eradicate inequalities in the social determinants of health. There is an increasing awareness of the contextual, cultural, and developmental influences on constructs used in early child development (ECD) research. Using a measurement perspective, this dissertation examined the issue of measurement invariance and psychometric validity in early child development research. A construct violates the principle of invariance when two persons from different populations who are theoretically identical on the construct being measured have different scores on it. This dissertation consists of three journal-style manuscripts (published or under review) that were used as examples to address the importance of the issue of measurement invariance and psychometric validity in ECD research using data from two unique areas: autism and executive functioning. The three data sets were collected on pre-school children with parents and or teachers as informants and were chosen to represent different levels of data collection – clinical, community, and population. These data sets allowed for the examination of measurement invariance by type of informant, sex, and age of child. The results from the three studies illustrate the importance of assessing measurement invariance in ECD and whether or not the instruments examined can be used to assess sub-group differences with confidence. A lack of measurement invariance found for two of the studies, suggests that observed group differences in latent constructs could be attributed, in part, to measurement bias. More importantly, bias in the measurement of the constructs of severity of social impairment symptoms in autism, and executive functioning across groups could have an impact on services such as patient treatment. These biases could also influence public policy development, particularly when there may be an underlying need for a cross-group approach where belief systems may affect the meaning and structure of constructs. In summary, measurement invariance should be a prerequisite for making any meaningful comparisons across groups. A requirement of establishing measurement invariance should be included in the guidelines for comparative research studies as a necessary first step before an instrument is adopted for use.

The aim of this study is to investigate means of efficiently assessing the effects of distributed structural modification on the dynamic properties of a complex structure. The helicopter structure is normally designed to avoid resonance at the main rotor rotational frequency. However, very often military helicopters have to be modified (such as to carry a different weapon system or an additional fuel tank) to fulfill operational requirements. Any modification to a helicopter structure has the potential of changing its resonance frequencies and mode shapes. The dynamic properties of the modified structure can be determined by experimental testing or numerical simulation, both of which are complex, expensive and time-consuming. Assuming that the original dynamic characteristics are already established and that the modification is a relatively simple attachment such as beam or plate modification, the modified dynamic properties may be determined numerically without solving the equations of motion of the full-modified structure. The frequency response functions (FRFs) of the modified structure can be computed by coupling the original FRFs and a delta dynamic stiffness matrix for the modification introduced. The validity of this approach is investigated by applying it to several cases, 1) 1D structure with structural modification but no change in the number of degree of freedom (DOFs). A simply supported beam with double thickness in the middle section is treated as an example for this case; 2) 1D structure with additional DOFs. A cantilever beam to which a smaller beam is attached is treated as an example for this case, 3) 2D structure with a reduction in DOFs. A four-edge-clamped plate with a cut-out in the centre is treated as an example for this case; and 4) 3D structure with additional DOFs. A box frame with a plate attached to it as structural modification with additional DOFs and combination of different structures. The original FRFs were obtained numerically and experimentally except for the first case. The delta dynamic stiffness matrix was determined numerically by modelling the part of the modified structure including the modifying structure and part of the original structure at the same location. The FRFs of the modified structure were then computed. Good agreement is obtained by comparing the results to the FRFs of the modified structure determined experimentally as well as by numerical modelling of the complete modified structure.

Tato práce se zabývá analýzou power-bus struktur využitím metody založené na formulaci problému 2D hraniční integrální rovnicí ve frekvenční oblasti. Uvedená metoda byla implementována v Matlabu. Program umožňuje analyzovat obecné polygonální power-bus struktury s možností nastavení parametrů substrátu a libovolného počtu a umístění budících portů. Výstupem programu je frekvenční závislost rozložení elektrického pole mezi deskami struktury, vztahy mezi porty struktury vyjádřené např. impedanční maticí a vyzařovací diagram. Dále byla implementována možnost převodu výsledné impedanční matice do tzv. Touchstone formátu, pomocí něhož je možné modelovat analyzované struktury jako obecné N-porty (např. v ANSOFT Designeru), což umožňuje analýzu power-bus struktur s dalšími obvodovými prvky. Výsledky byly ověřeny pomocí existujících analytických vztahů pro jednoduché obdélníkové struktury, využitím komerčního simulačního programu a praktickým experimentem.

Die Reichhaltigkeit und breite Anwendbarkeit der Theorie der holomorphen Funktionen in der komplexen Ebene ist stark motivierend eine ähnliche Theorie für höhere Dimensionen zu entwickeln. Viele Forscher waren und sind in diese Aufgaben involviert, insbesondere in der Entwicklung der Quaternionenanalysis. In den letzten Jahren wurde die Quaternionenanalysis bereits erfolgreich auf eine Vielzahl von Problemen der mathematischen Physik angewandt. Das Ziel der Dissertation besteht darin, holomorphe Strukturen in höheren Dimensionen zu studieren. Zunächst wird ein neues Holomorphiekonzept vorgelegt, was auf der Theorie rechtsinvertierbarer Operatoren basiert und nicht auf Verallgemeinerungen des Cauchy-Riemann-Systems wie üblich. Dieser Begriff umfasst die meisten der gut bekannten holomorphen Strukturen in höheren Dimensionen. Unter anderem sind die üblichen Modelle für reelle und komplexe quaternionenwertige Funktionen sowie Clifford-algebra-wertige Funktionen enthalten. Außerdem werden holomorphe Funktionen mittels einer geeignete Formel vom Taylor-Typ durch spezielle Funktionen lokal approximiert. Um globale Approximationen für holomorphe Funktionen zu erhalten, werden im zweiten Teil der Arbeit verschiedene Systeme holomorpher Basisfunktionen in drei und vier Dimensionen mittels geeigneter Fourier-Entwicklungen explizit konstruiert. Das Konzept der Holomorphie ist verbunden mit der Lösung verallgemeinerter Cauchy-Riemann Systeme, deren Funktionswerte reellen Quaternionen bzw. reduzierte Quaternionen sind. In expliziter Form werden orthogonale holomorphe Funktionensysteme konstruiert, die Lösungen des Riesz-Systems bzw. des Moisil-Teodorescu Systems über zylindrischen Gebieten im R3, sowie Lösungen des Riesz-Systems in Kugeln des R4 sind. Um konkrete Anwendungen auf Randwertprobleme realisieren zu können wird eine orthogonale Zerlegung eines Rechts-Quasi-Hilbert-Moduls komplex-quaternionischer Funktionen unter gegebenen Bedingungen studiert. Die Ergebnisse werden auf die Behandlung von Maxwell-Gleichungen mit zeitvariabler elektrischer Dielektrizitätskonstante und magnetischer Permeabilität angewandt
The richness and widely applicability of the theory of holomorphic functions in complex analysis requires to perform a similar theory in higher dimensions. It has been developed by many researchers so far, especially in quaternionic analysis. Over the last years, it has been successfully applied to a vast array of problems in mathematical physics. The aim of this thesis is to study the structure of holomorphy in higher dimensions. First, a new concept of holomorphy is introduced based on the theory of right invertible operators, and not by means of an analogue of the Cauchy-Riemann operator as usual. This notion covers most of the well-known holomorphic structures in higher dimensions including real, complex, quaternionic, Clifford analysis, among others. In addition, from our operators a local approximation of a holomorphic function is attained by the Taylor type formula. In order to obtain the global approximation for holomorphic functions, the second part of the thesis deals with the construction of different systems of basis holomorphic functions in three and four dimensions by means of Fourier analysis. The concept of holomorphy is related to the null-solutions of generalized Cauchy-Riemann systems, which take either values in the reduced quaternions or real quaternions. We obtain several explicit orthogonal holomorphic function systems: solutions to the Riesz and Moisil-Teodorescu systems over cylindrical domains in R3, and solutions to the Riesz system over spherical domains in R4. Having in mind concrete applications to boundary value problems, we investigate an orthogonal decomposition of complex-quaternionic functions over a right quasi-Hilbert module under given conditions. It is then applied to the treatment of Maxwell’s equations with electric permittivity and magnetic permeability depending on the time variable

Cette thèse étudie les problèmes de diagnostic itératif et propose des outilsd’aide au diagnostic interactif. Différents processus de diagnostic où des outils interactifs homme-automate sont utiles, sont présentés. Ces outils permettent de résoudre des difficultés liées à la représentation d’un grand nombre d’éléments d’un système, des difficultés liées à la représentation du comportement et du fonctionnement d’un système et des difficultés liées à l’explicitation de l’expertise. Nos travaux ont conduit à la conception de différents types d’outils interactifs d’aide au diagnostic. Le premier permet d’exploiter des représentations structuro-fonctionnelles pour construire et résoudre progressivement un problème de diagnostic.Le second outil interactif permet d’exploiter des modèles de comportement construit au fur et à mesure de la résolution d’un problème de diagnostic. Enfin, un dernier outil a étéproposé pour montrer qu’il est possible de prendre compte la connaissance implicite d’un expert dans la résolution de problème de diagnostic. Un problème de diagnostic est donc présenté comme un processus itératif avec des interactions homme-automate
This PhD thesis studies the iterative diagnosis problems and provides thecomputer-aided diagnostic tool for interactive diagnosis. Different diagnosis processes wherethe tool to support human-machine interaction are useful, are presented. These tools help totackle difficulties related to the representation of a large number of elements in a system,difficulties related to the representation of the behavior functioning of a system and difficultiesencountered while expliciting the expertise. Our work led to the design of different interactivetools to support the diagnosis process. The first tool allows to exploit the structural-functionalmodeling to build and solve progressively a diagnosis problem. The second interactive toolallows to exploit the behavioral models built step by step in the diagnosis process and tosolve the diagnosis problem. The final tool was proposed to show that it is possible to takeinto account the implicit knowledge of an expert in order to solve the diagnosis problem.A diagnosis problem is therefore presented as an iterative process with human-machineinteractions

La plupart des problèmes d'ingénierie des deux derniers siècles ont été résolus grâce à des modèles structuraux pour poutres, plaques et coques. Les théories classiques, tels que Euler-Bernoulli, Navier et de Saint-Venant pour les poutres, et Kirchhoff-Love et Mindlin-Reissner pour plaques et coques, ont permis de réduire le problème générique 3-D, dans le problème unidimensionnel pour les poutres et deux dimensionnelle pour les coques et les plaques. Théories raffinés d'ordre supérieur ont été proposées au cours du temps, comme les modèles classiques ne consentez pas à d'obtenir une complète domaine des contraintes et des déformations. La Carrera Unified Formulation (UF) a été proposé au cours de la dernière décennie, et permet de développer un grand nombre de théories structurelles avec un nombre variable d'inconnues principales au moyen d'une notation compacte et se référant à des nuclei fondamentales. Cette formulation unifiée permet de dériver carrément des modèles structurels d'ordre supérieur, pour les poutres, plaques et coques. Dans ce cadre, cette thèse vise à étendre la formulation pour l'analyse des structures fonctionnellement gradués (FGM), en introduisant aussi le problème thermo-mécanique, dans le cas des poutres fonctionnellement gradués. Suite à la formulation unifiée, les variables génériques déplacements sont écrits en termes de fonctions de base, qui multiplie les inconnues. Dans la deuxième partie de la thèse, de nouvelles fonctions de bases pour la modélisation des coques, qui représentent une approximation trigonométrique des variables déplacements, sont pris en compte
Most of the engineering problems of the last two centuries have been solved thanks to structural models for both beams, and for plates and shells. Classical theories, such as Euler-Bernoulli, Navier and De Saint-Venant for beams, and Kirchhoff-Love and Mindlin- Reissner for plates and shells, permitted to reduce the generic 3-D problem, in onedimensional one for beams and two-dimensional for shells and plates. Refined higher order theories have been proposed in the course of time, as the classical models do not consent to obtain a complete stress/strain field. Carrera Unified Formulation (UF) has been proposed during the last decade, and allows to develop a large number of structural theories with a variable number of main unknowns by means of a compact notation and referring to few fundamental nuclei. This Unified Formulation allows to derive straightforwardly higher-order structural models, for beams, plates and shells. In this framework, this thesis aims to extend the formulation for the analysis of Functionally Graded structures, introducing also the thermo-mechanical problem, in the case of functionally graded beams. Following the Unified Formulation, the generic displacements variables are written in terms of a base functions, which multiplies the unknowns. In the second part of the thesis, new bases functions for shells modelling, accounting for trigonometric approximation of the displacements variables, are considered

We will create a class of generalized ellipses and explore their ability to define a distance on a space and generate continuous, periodic functions. Connections between these continuous, periodic functions and the generalizations of trigonometric functions known in the literature shall be established along with connections between these generalized ellipses and some spectrahedral projections onto the plane, more specifically the well-known multifocal ellipses. The superellipse, or Lam\'{e} curve, will be a special case of the generalized ellipse. Applications of these generalized ellipses shall be explored with regards to some one-dimensional systems of classical mechanics. We will adopt the Ramberg-Osgood relation for stress and strain ubiquitous in engineering mechanics and define a general internal bending moment for which this expression, and several others, are special cases. We will then apply this general bending moment to some one-dimensional Euler beam-columns along with the continuous, periodic functions we developed with regard to the generalized ellipse. This will allow us to construct new solutions for critical buckling loads of Euler columns and deflections of beam-columns under very general engineering material requirements without some of the usual assumptions associated with the Ramberg-Osgood relation.

L'analyse de données de vols appliquée aux opérations aériennes ou "Flight Data Monitoring" (FDM), est le processus par lequel une compagnie aérienne recueille, analyse et traite de façon régulière les données enregistrées dans les avions, dans le but d'améliorer de façon globale la sécurité.L'objectif de cette thèse est d'élaborer dans le cadre des méthodes à noyau, des techniques pour la détection des vols atypiques qui présentent potentiellement des problèmes qui ne peuvent être trouvés en utilisant les méthodes classiques. Dans la première partie, nous proposons une nouvelle méthode pour la détection d'anomalies.Nous utilisons une nouvelle technique de réduction de dimension appelée analyse en entropie principale par noyau afin de concevoir une méthode qui est à la fois non supervisée et robuste.Dans la deuxième partie, nous résolvons le problème de la structure des données dans le domaine FDM.Tout d'abord, nous étendons la méthode pour prendre en compte les paramètres de différents types tels que continus, discrets ou angulaires.Ensuite, nous explorons des techniques permettant de prendre en compte l'aspect temporel des vols et proposons un nouveau noyau dans la famille des techniques de déformation de temps dynamique, et démontrons qu'il est plus rapide à calculer que les techniques concurrentes et est de plus défini positif.Nous illustrons notre approche avec des résultats prometteurs sur des données réelles des compagnies aériennes TAP et Transavia comprenant plusieurs centaines de vols
Flight Data Monitoring (FDM), is the process by which an airline routinely collects, processes, and analyses the data recorded in aircrafts with the goal of improving the overall safety or operational efficiency.The goal of this thesis is to investigate machine learning methods, and in particular kernel methods, for the detection of atypical flights that may present problems that cannot be found using traditional methods.Atypical flights may present safety of operational issues and thus need to be studied by an FDM expert.In the first part we propose a novel method for anomaly detection that is suited to the constraints of the field of FDM.We rely on a novel dimensionality reduction technique called kernel entropy component analysis to design a method which is both unsupervised and robust.In the second part we solve the most salient issue regarding the field of FDM, which is how the data is structured.Firstly, we extend the method to take into account parameters of diverse types such as continuous, discrete or angular.Secondly, we explore techniques to take into account the temporal aspect of flights and propose a new kernel in the family of dynamic time warping techniques, and demonstrate that it is faster to compute than competing techniques and is positive definite.We illustrate our approach with promising results on real world datasets from airlines TAP and Transavia comprising hundreds of flights

Enforcing security policies to distributed systems is difficult, in particular, when a system contains untrusted components. We designed AspectKE*, a distributed AOP language based on a tuple space, to tackle this issue. In AspectKE*, aspects can enforce access control policies that depend on future behavior of running processes. One of the key language features is the predicates and functions that extract results of static program analysis, which are useful for defining security aspects that have to know about future behavior of a program. AspectKE* also provides a novel variable binding mechanism for pointcuts, so that pointcuts can uniformly specify join points based on both static and dynamic information about the program. Our implementation strategy performs fundamental static analysis at load-time, so as to retain runtime overheads minimal. We implemented a compiler for AspectKE*, and demonstrate usefulness of AspectKE* through a security aspect for a distributed chat system.

To be able to make informed descicions regarding the research of new drug molecules (ligands), it is crucial to have access to information regarding the chemical interaction between the drug and its biological target (protein). Computer-based methods have a given role in drug research today and, by using methods such as molecular docking, it is possible to investigate the way in which ligands and proteins interact. Despite the acceleration in computer power experienced in the last decades many problems persist in modelling these complicated interactions. The main objective of this thesis was to investigate and improve molecular modelling methods aimed to estimate protein-ligand binding. In order to do so, we have utilised chemometric tools, e.g. design of experiments (DoE) and principal component analysis (PCA), in the field of molecular modelling. More specifically, molecular docking was investigated as a tool for reproduction of ligand poses in protein 3D structures and for virtual screening. Adjustable parameters in two docking software were varied using DoE and parameter settings were identified which lead to improved results. In an additional study, we explored the nature of ligand-binding cavities in proteins since they are important factors in protein-ligand interactions, especially in the prediction of the function of newly found proteins. We developed a strategy, comprising a new set of descriptors and PCA, to map proteins based on their cavity physicochemical properties. Finally, we applied our developed strategies to design a set of glycopeptides which were used to study autoimmune arthritis. A combination of docking and statistical molecular design, synthesis and biological evaluation led to new binders for two different class II MHC proteins and recognition by a panel of T-cell hybridomas. New and interesting SAR conclusions could be drawn and the results will serve as a basis for selection of peptides to include in in vivo studies.

La thèse se concentre sur une recherche méthodologique sur l'optimisation structurelle catégorielle au moyen d'un apprentissage multiple. Dans cette thèse, les variables catégorielles non ordinales sont traitées comme des variables discrètes multidimensionnelles. Afin de réduire la dimensionnalité, les nombreuses techniques d'apprentissage sont introduites pour trouver la dimensionnalité intrinsèque et mapper l'espace de conception d'origine sur un espace d'ordre réduit. Les mécanismes des techniques d'apprentissage à la fois linéaires et non linéaires sont d'abord étudiés. Ensuite, des exemples numériques sont testés pour comparer les performances de nombreuses techniques d’apprentissage. Sur la base de la représentation d'ordre réduit obtenue par Isomap, les opérateurs de mutation et de croisement évolutifs basés sur les graphes sont proposés pour traiter des problèmes d'optimisation structurelle catégoriels, notamment la conception du dôme, du cadre rigide de six étages et des structures en forme de dame. Ensuite, la méthode de recherche continue consistant à déplacer des asymptotes est exécutée et fournit une solution compétitive, mais inadmissible, en quelques rares itérations. Ensuite, lors de la deuxième étape, une stratégie de recherche discrète est proposée pour rechercher de meilleures solutions basées sur la recherche de voisins. Afin de traiter le cas dans lequel les instances de conception catégorielles sont réparties sur plusieurs variétés, nous proposons une méthode d'apprentissage des variétés k-variétés basée sur l'analyse en composantes principales pondérées
The thesis concentrates on a methodological research on categorical structural optimizationby means of manifold learning. The main difficulty of handling the categorical optimization problems lies in the description of the categorical variables: they are presented in a category and do not have any orders. Thus the treatment of the design space is a key issue. In this thesis, the non-ordinal categorical variables are treated as multi-dimensional discrete variables, thus the dimensionality of corresponding design space becomes high. In order to reduce the dimensionality, the manifold learning techniques are introduced to find the intrinsic dimensionality and map the original design space to a reduced-order space. The mechanisms of both linear and non-linear manifold learning techniques are firstly studied. Then numerical examples are tested to compare the performance of manifold learning techniques mentioned above. It is found that the PCA and MDS can only deal with linear or globally approximately linear cases. Isomap preserves the geodesic distances for non-linear manifold however, its time consuming is the most. LLE preserves the neighbour weights and can yield good results in a short time. KPCA works like a non-linear classifier and we proves why it cannot preserve distances or angles in some cases. Based on the reduced-order representation obtained by Isomap, the graph-based evolutionary crossover and mutation operators are proposed to deal with categorical structural optimization problems, including the design of dome, six-story rigid frame and dame-like structures. The results show that the proposed graph-based evolutionary approach constructed on the reduced-order space performs more efficiently than traditional methods including simplex approach or evolutionary approach without reduced-order space. In chapter 5, the LLE is applied to reduce the data dimensionality and a polynomial interpolation helps to construct the responding surface from lower dimensional representation to original data. Then the continuous search method of moving asymptotes is executed and yields a competitively good but inadmissible solution within only a few of iteration numbers. Then in the second stage, a discrete search strategy is proposed to find out better solutions based on a neighbour search. The ten-bar truss and dome structural design problems are tested to show the validity of the method. In the end, this method is compared to the Simulated Annealing algorithm and Covariance Matrix Adaptation Evolutionary Strategy, showing its better optimization efficiency. In chapter 6, in order to deal with the case in which the categorical design instances are distributed on several manifolds, we propose a k-manifolds learning method based on the Weighted Principal Component Analysis. And the obtained manifolds are integrated in the lower dimensional design space. Then the method introduced in chapter 4 is applied to solve the ten-bar truss, the dome and the dame-like structural design problems

Software modeling is an integral practice for software engineers especially as the complexity of software solutions increase. There is precedent in industry to model information systems in terms of functions, structures, and behaviors. While constructing these models, abstraction and systems thinking are employed to determine elements essential to the solution and how they are connected. However, both abstraction and systems thinking are difficult to put in practice and difficult to teach due to the, often, ill-structured nature of real-world IT problems. Unified Modeling Language (UML) is the industry standard for software modeling but unfortunately it is often used incorrectly and misunderstood by novices. This has also been observed in educational contexts where students encounter difficulty in employing the appropriate level of abstraction in modeling and programming contexts and not necessarily being able to view or treat software systems as being interconnected.

The researcher detailed a multi-methods approach, through the lens of pragmatism, towards understanding patterns of student proficiency with abstraction and software modeling in terms capturing the functional, structural, and behavioral aspects of an information system, as given by the Structures-Behaviors-Function framework. The quantitative strand involved the development of rubrics to analyze functional, structural, and behavioral models given by UML activity diagrams, class diagrams, and sequence diagrams, respectively. The subjects of this study were students enrolled in a sophomore-level systems analysis and design class. Descriptive analysis revealed patterns of modeling proficiency. Students were generally proficient in modeling the system in terms of functions but there was an overall drop-off in proficiency when modeling the system in terms of structures and behaviors. The results of the clustering analysis revealed underlying profiles of students based on abstract thinking and systems thinking ability. Two distinct clusters – high performing students and moderate performing students – were revealed with statistically significant differences between the groups in terms of abstract thinking and systems thinking ability. Further correlational analysis was performed on each cluster. The results of the correlational analyses pointed to significant positive associations between software modeling proficiency and the constructs of abstract thinking and systems thinking. Logistic regression analysis was then performed, and it could be inferred from the regression model that abstract thinking in terms of behaviors and systems thinking in terms of aligning sequence diagrams with activity diagrams were the most important predictors of high performance.

The qualitative strand of this study involved a case study approach using the think-aloud protocol centered around exploring how students utilized abstract thinking and systems thinking while constructing software models. The participants of this study were students who had completed the sophomore-level systems analysis and design course. Thematic analysis was utilized to identify themes of abstract thinking and systems thinking within the epistemic games of structural, functional, and process analyses. Two different approaches towards modeling information systems were identified and chronological visualizations for each approach were presented. Overall, it could be inferred from the results and findings of the study that the learning design of the sophomore-level course was successful in equipping students with the skills to proficiently model information systems in terms of functions. However, the students were not as proficient in modeling information systems in terms of structures and behaviors. The theoretical contribution of this study was centered around the application of the SBF framework and epistemic forms and games in the context of information systems. The methodological contributions pertain to the rubrics that were developed which can be used to evaluate software modeling proficiency as well as abstract thinking and systems thinking. Abstract thinking and systems thinking were successfully characterized in the context of information systems modeling. The results of this study have implications in computing education. The suggested instructional approaches and scaffolds can be utilized to improve outcomes in terms of structural and behavioral modeling proficiency.

This dissertation investigates the distributed damage effect on Progressive Collapse of structures highlighted by applications on the nonlinear static and dynamic behavior of buildings, and contributes to the theoretical development of the Variability Response Function concept and its applicability extension in two-dimensional elasticity stochastic problems. Part I of this dissertation focuses on the recently emerging research field of Progressive Collapse of structures. The alternate load path method has so far dominated the field of progressive collapse of structures; in order to assess the resilience of structural systems, the concept of the removal of a key element is utilized as a means of damage introduction to the system. Recent studies have indicated that the complete column loss notion is unrealistic and unable to describe a real extreme loading event, e.g. a blast, that will introduce damage to more than one elements in its vicinity. This dissertation presents a new partial distributed damage method (PDDM) for steel moment frames, by utilizing powerful finite element computational tools that are able to capture loss of stability phenomena. Through the application of a damage index δj and the investigation of damage propagation, it is shown that the introduction of partial damage in the system can significantly modify the collapse mechanisms and overall affect the response of the structure. Subsequently, Part I elaborates on the distributed column damage effect on Progressive Collapse vulnerability in steel buildings exposed to an external blast event. Recent terrorist attacks on civil engineering infrastructure around the world have initiated extensive research on progressive collapse analysis of multi-story buildings subjected to blast loading. The widely accepted alternate load path method is a threat-independent method that is able to assess the response of a structure in case of extreme hazard loads, without the consideration of the actual loads occurring. Such simplification offers great advantages but at the same time fails to incorporate the role of a wider damaged area into the collapse modes of structures. To this end, the investigation of damage distribution on adjacent structural members induced by blast loads is considered critical for the evaluation of structural robustness against abnormal loads that may initiate progressive collapse. This dissertation presents detailed 3D nonlinear finite element dynamic analyses of steel frame buildings in order to examine the spatially distributed response and damage to frame members along the building exterior facing an external blast. A methodology to assess the progressive collapse vulnerability is also proposed, which includes four consecutive steps to simulate the loading event sequence. Three case studies of steel buildings with different structural systems serve as examples for the application of the proposed methodology. A high-rise (20-story) building is firstly subjected to a blast load scenario, while the complex 3D system results in the heavily impacted region are compared with individual column responses (SDOF) obtained from a simplified analytical approach consistent with current design recommendations. Parameters affecting the spatially distributed pressure and response quantities are identified, and the sensitivity of the damage results to the spatial variation of these parameters is established for the case of the 20-story building. Subsequently, two typical mid-rise (10-story) office steel buildings with identical floor plan layout but different lateral load resisting systems are examined; one including perimeter moment resisting frames (MRFs) and one including interior reinforced concrete (RC) rigid core. It is shown that MRFs offer a substantial increase in robustness against blast events, and the role of interior gravity columns identified as the `weakest links'\ of the structural framing is discussed. Part II of this dissertation focuses on the development of Variability Response Functions for apparent material properties in 2D elasticity stochastic problems. The material properties of a wide range of structural mechanics problems are often characterized by random spatial fluctuations. Calculation of apparent properties of such randomly heterogeneous materials is an important procedure, yet no general method besides Monte Carlo simulation exists for evaluating the stochastic variability of these apparent properties for structures smaller than the representative volume element (RVE). In this direction, the concept of Variability Response Function (VRF) has been proposed as a means to capture the effect of stochastic spectral characteristics of uncertain system parameters modeled by homogeneous stochastic fields on the uncertain response of structural systems, without the need for computationally expensive Monte Carlo simulations. Recent studies have formally proved the existence of VRF for apparent properties for statically determinate linear beams through elastic strain energy equivalence of the heterogeneous and equivalent homogeneous bodies, while a Monte-Carlo based methodology for the generalization of the VRF concept to statically indeterminate beams has been recently developed. In this dissertation, the VRF methodology of apparent properties is extended to two-dimensional elasticity stochastic problems discretized on a finite element domain, in order to analytically formulate a VRF that is independent of the marginal distribution and spectral density function of the underlying random heterogeneous material property field (it depends only on the boundary conditions and deterministic structural configuration). Representative examples that illustrate the approach include two-dimensional plane stress problems and underline the dependence of the VRFs on scale, shape and aspect ratio of the finite elements.

The availability of completely sequenced genomes for a number of organisms provides an opportunity to understand the molecular basis of physiology, metabolism, regulation and evolution of these organisms. Significant understanding of the complexity of organisms can be obtained from the functional characterization of repertoire of proteins encoded in their genomes. Computational approaches for recognition of function of proteins of unknown function encoded in genomes often rely on ability to detect well characterized homologues. Homology searches based on pair-wise sequence comparisons can reliably detect homologues with sequence identity more than 30%. However, detecting homologues characterized by sequence identity below 30% is difficult using these methods. Distant homology relationship can be established using profiles or position specific scoring matrices, which encapsulate information about structurally and functionally conserved residues. These conserved residues imply high constraints at a particular amino acid residue site due to their involvement in structural stability, enzymatic activity, ligand binding, protein folding or protein–protein interactions. In addition, information on three dimensional structures of proteins also aid in detection of remote homologues, as tertiary structures of proteins are conserved better than the primary structures of proteins. The gross objective of the work reported in this thesis is to employ various sensitive remote homology detection methods to recognize relevant functional information of proteins encoded mainly in pathogenic organisms. Since proteins do not work in isolation in a cell, it has become essential to understand the in vivo context of functions of proteins. For this purpose, it is essential to have an understanding of all molecules that interact with a particular protein. Thus, another major area of bioinformatics has been to integrate protein-protein interaction information to enable better understanding of context of functional events. Protein-protein interaction analysis for host-pathogen can lead to useful insight into mode of pathogenesis and subsequent consequences in host cell. Chapters 2-6 of the thesis discuss the sequence and structural characteristics along with remote evolutionary relationships and functional implications of uncharacterized proteins encoded in genomes of following pathogens: Helicobacter pylori, Plasmodium falciparum and Leishmania donovani. The Chapters 6-8 discuss mainly various sequence, structural and functional aspects of protein kinases encoded in genomes of various prokaryotes and viruses. Chapter 1 discusses background information and literature survey in the areas of homology detection and prediction of protein-protein interactions. The growth of genomic data and need for processing genomic data to infer context of various functional events have been highlighted. Different approaches to recognize functions of proteins (experimental as well as computational) have been discussed. Various experimental and computational approaches to detect/predict protein-protein interactions have been mentioned. Chapter 2 discusses recognition of non-trivial remote homology relationships involving proteins of Helicobacter pylori and their implications for function recognition. H. pylori is microaerophilic, Gram negative bacterial pathogen. It colonizes human gastric mucosa and is a causative agent of gastroduodenal disease. The pathogen infects about 50% of the human population. It can lead to development of Mucosa-associated lymphoid tissue lymphoma. About 10% of the infected population develop gastric or duodenal ulcer and approximately 1% develop gastric cancer. H. pylori has been classified as class I carcinogen by WHO. Pathogen is characterized by type IV secretion system. The complete genomic sequences of three widely studied strains including 26695, J99 and HPAG1 of Helicobacter pylori are available. According to the genome analysis, the number of predicted open reading frames in strain 26695, J99 and HPAG1 are 1590, 1495 and 1536 respectively. Out of predicted H. pylori proteins from 26695, J99 and HPAG1 strains, numbers of proteins with no functional domain assignments in Pfam database (Protein family database) are 453, 357 and 400 respectively. There are proteins in different strains of H. pylori genomes where one part of the protein is associated with at least one protein domain of known function and hence preliminary indication of their functions is available whereas rest of the region is not associated with any function. There are 772, 803 and 790 such segments in proteins from strains 26695, J99 and HPAG1 respectively with at least 45 residues with no functional assignment currently available. Sensitive remote homology detection methods have been employed to establish relationships for 294 amino acid sequences and results have been grouped into 4 categories. Results of homology detection have been further confirmed by studying conservation of amino acid residues which are important for functioning of the proteins concerned. (i) Remote relationship has been established involving protein domain families for which no bonafide member is currently known in H. pylori. For example: DNA binding protein domain (Kor_B) has been assigned to a H. pylori protein at sequence identity of 20%. Study involving secondary structure prediction and conservation of amino acid residues confirms the results of homology detection methods. (ii) Remote relationship has been established involving H. pylori hypothetical proteins and protein domain families, for which paralogous members are present in Helicobacter pylori. For example, Cytochrome_C, an electron transfer protein domain could be associated with a Helicobacter pylori protein sequence which shows a sequence identity of 14% with sequences of bonafide cytochrome C. (iii) “Missing” metabolic proteins of H. pylori have also been recognized. For example, Aspartoacylase (EC 3.5.1.15) catalyzes deacetylation of N-acetylaspartic acid to produce acetate and L-aspartate. This enzyme in aspartate metabolism pathway has not been reported so far from H. pylori. A remote evolutionary relationship between a H. pylori protein and Aspartoacylase domain has been established at sequence identity of 17% thus filling the gap in this metabolic pathway in the pathogen. (iv) New functional assignments for domains in H. pylori sequences with prior assignment of domains for the rest of the sequences have been made. For example, DNA methylase domain has been assigned to C-terminal region of H. pylori protein which already had Helicase domain assigned to the N-terminal region of the protein. All these information should open avenues for further probing by carrying out experiments which will impact the design of inhibitor against this pathogen and will result in better understanding of pathogenesis of this organism in human. Chapter 3 describes prediction of protein–protein interactions between Helicobacter pylori and the human host. A lack of information on protein-protein interactions at the host-pathogen interface is impeding the understanding of the pathogenesis process. A recently developed, homology search-based method to predict protein-protein interactions is applied to the gastric pathogen, Helicobacter pylori to predict the interactions between proteins of H. pylori and human proteins in vitro. Many of the predicted interactions could potentially occur between the pathogen and its human host during pathogenesis as we focused mainly on the H. pylori proteins that have a transmembrane region or are encoded in the pathogenic island and those which are known to be secreted into the human host. By applying the homology search approach to protein-protein interaction databases DIP and iPfam, in vitro interactions for a total of 623 H. pylori proteins with 6559 human proteins could be predicted. The predicted interactions include 549 hypothetical proteins of as yet unknown function encoded in the H. pylori genome and 13 experimentally verified secreted proteins. A total of 833 interactions involving the extracellular domains of transmembrane proteins of H. pylori could be predicted. Structural analysis of some of the examples reveals that the predicted interactions are consistent with the structural compatibility of binding partners. Various probable interactions with discernible biological relevance are discussed in this chapter. For example, interaction between CFTR protein (NP_000483) and multidrug resistance protein (HP1206) has been predicted. The structure of the CFTR intracellular domain is known in the homomeric form and consists of five AAA transport domains in tandem (PDB code 1XMI). Out of the five identical subunits, two subunits (the B chain and the E chain in the PDB structure) have been selected. The structure of multidrug resistance protein of the pathogen based on the B chain (sequence identity 32%) of the template has been modeled. This exercise suggests that interface residues in the model are congenial for interaction. This makes the structural complex feasible in in vitro conditions and suggests that the pathogen protein may compete for occupancy with the host protein. Chapter 4 describes recognition of Plasmodium-specific protein domain families and their roles in Plasmodium falciparum life cycle. Malaria in humans is caused by the parasites of intracellular, eukaryotic protozoan of apicomplexan nature belonging to the genus Plasmodium. Out of five species of Plasmodium, namely, P. falciparum, P. ovale, P. vivax, P. malariae and P. knowlesi which infects human, P. falciparum causes lethal infection. P. falciparum proteins have diverged extensively during the course of evolution. Pathogen genome is rich in A+T composition which larger than the homologous proteins from other organisms due to presence of low complexity regions. Organism specific families are important as they play roles in peculiar life style of an organism. If the organism is a pathogen, then these family members may play roles in pathogenesis. Inhibiting these specific proteins is unlikely to interfere with host system as no homolog may be present in host. In the present work we identify Plasmodium specific protein families and their role in different stages of life cycle of the pathogen. A total of 5086 amino acid sequences (full length sequences/fragments of proteins) show homology only with amino acid sequences from Plasmodium organisms and hence are Plasmodium-specific. These Plasmodium-specific amino acid sequences cluster into 106 Plasmodium-specific families (≥2 members per family). 14 Plasmodium-specific protein domain families with known physico-chemical properties are observed. These Plasmodium-specific protein domain families are involved in various important functions such as rosetting and sequestering of infected erythrocytes, binding to surface of host cell and invasion process in life cycle of pathogen. Also, 89 new Plasmodium-specific protein domain families have been recognized. Analysis of various aspects of members of Plasmodium-specific proteins domain families such as their potential to target apicoplast, protein-protein interaction, expression profile and domain organization has been performed to derive relevant information about function. New Plasmodium specific domain families for which no function can be associated could provide some insight into much diverged Plasmodium species. These proteins may play role in parasite-specific life style. Experimental work on these Plasmodium-specific proteins might fill the gaps of less understood physiology of this parasite. Chapter 5 presents genome-wide compilation of low complexity regions (LCR) in proteins. An indepth analysis of the nature, structure, and functional role of the proteins containing low complexity regions in Plasmodium falciparum, was undertaken given the high prevalence of LCRs in the proteome of this organism. Low complexity regions and repeat patterns have been recognized in proteins encoded in 986 genomes (68 archaea, 896 prokaryotes and 22 eukaryotes). Low complexity regions have been classified into following three categories: a) Composition of LCRs: (i) LCRs can be stretches of homo amino acid residues (ii) LCRs can be stretches of more than one amino acid residue type b) Periodicity of amino acids in LCRs: Certain amino acid residues can be observed at certain specific periodicity in proteins. c) Repeat patterns: Certain motif of amino acid residues are repeated in protein. 850 Plasmodium falciparum proteins are observed to have at least one repeat pattern where the repeating unit is at least 5 amino acid residues long. Statistical analysis on single amino acid residue repeats indicate that occurrence of stretches of homo amino acid residues is not a random event. Studies on recognition of functions, protein protein interactions and organization of tethered domain(s) in proteins containing LCR suggest that these proteins are part of variety of functional events such as signal transduction, enzymatic processes, cell differentiation, pyrimidine biosynthesis, fatty acid biosynthesis and chromosomal replication. Representations of low complexity regions of Plasmodium falciparum in protein data bank suggest that LCRs can take conformation of regular secondary structure (apart from disordered regions) in 3-D structures of proteins. Chapter 6 describes sequence analysis, structural modeling and evolutionary studies of Leishmania donovani hypusine pathway enzymes. Leishmania is an eukaryotic kinetoplastid protozoan parasite which causes leishmaniasis in humans. Hypusine is a non standard polyaminederived amino acid Nε-(4-amino-2-hydroxybutyl) lysine and is named after its two structural components, hydroxyputrescine and lysine. The eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein containing hypusine. Synthesis of hypusine is critical for the function of elF5A and is essential for eukaryotic cell proliferation and survival. Formation of hypusine is the result of a two step post-translational modification process involving enzymes (i) deoxyhypusine synthase (DHS) (ii) deoxyhypusine hydroxylase (DOHH). DHS, the first enzyme involved in hypusine pathway catalyzes the NAD-dependent transfer of the butylamino moiety of spermidine (substrate) to the ε-amino group of a specific lysine residue of eIF5A precursor and generates deoxyhypusine containing intermediate. DOHH, the second enzyme in same pathway catalyzes the hydroxylation of deoxyhypusine-containing intermediate, generating hypusine-containing mature eIF5A. Two putative deoxyhypusine synthase (DHS) sequences DHS34 and DHS20 have been identified in Leishmania donovani, by Professor Madhubala and coworkers (Jawaharlal Nehru University, New Delhi) with whom the work embodied in this chapter was done in collaboration. Detailed comparison of DHS34 sequence from Leishmania with human DHS protein indicated conservation of functionally important residues. 3D structural modeling studies of protein suggested that residues around the active site were absolutely conserved. NAD binding regions are located spatially closer, however, one NAD binding region was observed in a large (225 amino acid residues long) insertion. Based on these observations, DHS34 was predicted to have enzymatic activity. Experimental studies done by our collaborators confirmed preliminary results of computational analysis. Based on sequence and structural analysis of DHS20 and DOHH proteins, DHS20 and DOHH were proposed to be catalytically inactive and active respectively. Experimental studies on these proteins supported results of computational analysis. Deoxyhypusine synthase (DHS) and Deoxyhypusine hydroxylase (DOHH) are key proteins conserved in the hypusine synthesis pathways of eukaryotes. Because they are highly conserved, they could be coevolving. Comparison of the genetic distance matrices of DHS and DOHH proteins reveals that their evolutionary rates are better correlated when compared to the rate of an unrelated protein such as Cytochrome C. This indicates that they are coevolving, further serving as an indicator that, even non-interacting proteins that are functionally coupled, experience correlated evolution. However, this correlation does not extend to their tree topologies. Chapter 7 provides a classification scheme for protein kinases encoded in genomes of prokaryotic organisms. Overwhelming majority of the Ser/Thr protein kinases identified by gleaning archaeal and eubacterial genomes could not be classified into any of the well known Hanks and Hunter subfamilies of protein kinases. This is owing to the development of Hanks and Hunter classification scheme based on eukaryotic protein kinases which are highly divergent from their prokaryotic homologues. A large dataset of prokaryotic Ser/Thr protein kinases prokaryotic Ser/Thr protein kinases. Traditional sequence alignment and phylogenetic approaches have been used to identify and classify prokaryotic kinases which represent 72 subfamilies with at least 4 members in each. Such a clustering enables classification of prokaryotic Ser/Thr kinases and it can be used as a framework to classify newly identified prokaryotic Ser/Thr kinases. After series of searches in a comprehensive sequence databases, it is recognized that 38 subfamilies of prokaryotic protein kinases are associated to a specific taxonomic level. For example 4, 6 and 3 subfamilies have been identified that are currently specific to phylum proteobacteria, cyanobacteria and actinobacteria respectively. Similarly, subfamilies which are specific to an order, sub-order, class, family and genus have also been identified. In addition to these, it was also possible to identify organism-diverse subfamilies. Members of these clusters are from organisms of different taxonomic levels, such as archaea, bacteria, eukaryotes and viruses. Interestingly, occurrence of several taxonomic level specific subfamilies of prokaryotic kinases contrasts with classification of eukaryotic protein kinases in which most of the popular subfamilies of eukaryotic protein kinases occur diversely in several eukaryotes. Many prokaryotic Ser/Thr kinases exhibit a wide variety of modular organization which indicates a degree of complexity in protein-protein interactions and the signaling pathways in these microbes. Chapter 8 focuses on recognition, classification of protein kinases encoded in genomes of viruses and their implications in various functions and diseases. Protein kinases encoded by viral genomes play a major role in infection, replication and survival of viruses. Using traditional sequence homology detection tools, sequence alignment methods and phylogenetic approaches, protein kinases were recognized. 646123 protein sequences from 35799 viral genomes (including strains) have been used in this analysis. Protein kinases are identified using a combination of profile-based search methods such as PSI-BLAST, RPS-BLAST and HMMER approaches. Based upon sequence similarity over the length of catalytic kinase domains, 479 protein kinase domains recognized in 244 viral genomes have been clustered into 46 subfamilies with minimum sequence identity of 35% within a subfamily. Viral protein kinases are encoded in genomes of retro-transcribing viruses or viruses which possess double stranded DNA as genetic material. Based on the available functional information present for one or more members of a subfamily, a putative function has been assigned to other members of the subfamily. Information regarding interaction of viral protein kinases with viral/host protein has also been considered for enhancing understanding of function of kinases in a subfamily. Out of 46 subfamilies, 14 subfamilies are characterized by various functions. Kinases belonging to UL97, US69, UL13 and BGLF subfamilies are virus specific. For 7 subfamilies, nearest neighbors are from well characterized eukaryotic protein kinase groups such as AGC, CAMK and CDK. Out of 25 new uncharacterized subfamilies observed in this analysis, 13 subfamilies are virus specific. Different subfamilies have been characterized by various functions which are crucial for viral infection such as synthesis of structural unit, replication of genetic material, modification of cellular components, alteration in host immune system, competing with cellular protein for efficient usage of host machinery. Also, many viral kinases share very high sequence identity (~97%) with their eukaryotic counterpart and represent disease state. For example, a protein kinase encoded in Avian erythroblastosis virus shares 97% sequence identity with catalytic domain of human epidermal growth factor receptor tyrosine kinase. Leucine at position 861 in human protein is substituted by Gln in cancer conditions; the viral protein kinase sequence possesses Gln at corresponding position and thus represents disease state. Chapter 9 provides study of dependency on the ability of 3-D structural features of comparative models and crystal structures of inactive forms of enzymes to predict enzymes by considering protein kinases as case study. With the advent of structural genomics initiatives, there is a surge in the number of proteins with 3-D structural information even before functional features are understood on many of these proteins. One of the useful annotations of a protein is the demarcation of a protein into an enzyme or non-enzyme solely from the knowledge of 3-D structure. This is facilitated by the identification of active sites and ligand binding sites in a protein. In this work, which was carried out in collaboration with Dr Jim Warwicker of Manchester University, UK, an approach developed by Warwicker and coworkers has been used. In the 3D structure of proteins, the largest clefts are generally considered to be ligand binding sites. This feature along with other sequence alignment independent properties such as residue preferences, fraction of surface residues and secondary structure elements have been considered to differentiate enzymes from non-enzymes. Electrostatic potential at the active site is one of the key properties utilized in this respect. Active sites in enzymes are generally associated with ionizable groups which can take part in catalysis. In addition to the feature of large clefts in enzymes, active site residues are in buried environments and show larger deviation in pKa values than surface residues. The method proposed by Warwicker and co-workers distinguish proteins in to enzymes and non-enzymes considering the electrostatic features at clefts along with the sequence profile of the protein concerned. Conformation of the inactive state of an enzyme is not congenial to the catalytic function. In an ideal situation, a method should be capable of predicting an enzyme irrespective of whether determined structure corresponds to active or inactive state. Peak potential values have been calculated by using Warwicker program for a set of 15 protein kinases for which 3-D structures are present in active as well in inactive conformations. Comparison of peak potential values calculated for active and inactive conformations suggests that algorithm can differentiate between active and inactive conformations as value for active conformations are generally higher than corresponding values for inactive conformations. However, the peak potential values are high enough for even the inactive conformations to be predicted as enzyme. Peak potential values calculated for generated homology models of protein kinases (for which crystal structures are already available) at different sequence identities with template sequences predict protein kinases as enzymes and their peak potential values are comparable to corresponding values for X-ray structures. This suggests that proteins for which there are no crystal or NMR structures yet available and no good template with high sequence identity are present, peak potential values for models generated at low sequence identity can still give insight into probable function of protein as an enzyme. The enzyme/non-enzyme prediction algorithm was also found to be useful in confirming enzyme functionality using 3-D models of putative viral kinases. Initially, putative function of kinase has been assigned to these viral proteins based solely upon their sequence characteristics such as presence of residues/motifs which are important for activity of the protein. The enzyme recognition method which is not directly sensitive to these motifs confirmed that all the analyzed putative viral kinases are enzymes. Chapter 10 presents conclusions of work embodied in the entire thesis. Very briefly, various computational approaches have been used to analyze and understand structural and functional properties of repertoire of proteins of pathogenic organisms. Analysis of uncharacterized protein domain families has helped to understand the functional implications of constituent proteins. Experimental validation of these results can further facilitate unraveling of functional aspects of proteins encoded in various pathogenic organisms. Apart from studies embodied in the thesis, author has been involved in two other studies, which are provided as appendices. Appendix 1 describes comparison of substitution pattern of amino acid residues of protein encoded in P. falciparum genome with substitution pattern of corresponding homologous proteins from non-Plasmodium organisms. Salient differences have been highlighted. Appendix 2 discusses study of bacterial tyrosine kinases with an objective of recognition of all putative protein tyrosine kinases in E. coli. Computational study suggests that protein SopA can be a potential tyrosine kinase and this conclusion is being tested experimentally in collaborator’s laboratory.

This PhD thesis employed high energy synchrotron x-ray radiation to reveal atomic scale structural features occurring in plastically deformed Zr52.5Ti5Cu18Ni14.5Al10 (Vit105) bulk metallic glass (BMG). The study is divided into three parts: Strain evolution during in-situ compression, strain distribution maps in mechanically-imprinted BMG, and residual strain around a single shear band. 1. Strain evolution during in-situ compression The structural rearrangements occurring during compressive deformation of a plastically deformable BMG showed that the elastic and plastic deformation of the BMG is correlated to the structural changes at short- (SRO) and medium range order (MRO). In the elastic regime, the atomic distances at SRO vary linearly with macroscopic stress. Analysis of the area under radial distribution function indicates that a small fraction of bonds in the first shell is broken in the loading direction whereas some new bonds are formed in the transverse direction. Atomic bonds at SRO appeared significantly stiffer than the MRO shells. Compared to the macroscopic values of the elastic strain, Young’s modulus and Poisson's ratio, both SRO and MRO appeared significantly stiffer, implying that the elastic behavior of the BMG is not only ruled by simple compression of the atoms/clusters but also is aided by rearrangement of atoms/clusters. The deviation of MRO atomic strain-stress correlation from linearity at the onset of plastic deformation was attributed to the activation of irreversible shear transformation zones. It was demonstrated by a strong shear strain value at the onset of yielding. This value is in good agreement with the reported value of the critical shear strain needed for activation of an irreversible STZ. The length scale of 12.5 Å indicated the largest shear strain and is probably the most effective length scale in the formation of STZs. The atomic pairs at SRO with smallest shear strain have the least contribution to the STZs. It was also indicated that the typical fracture angle of this BMG can be explained by the orientation of maximum shear strain at the onset of catastrophic shear band formation. 2. Strain distribution map in mechanically-imprinted BMG In mechanical imprinting, the BMG plate is loaded between two tools with a regular array of linear teeth and, as a result, a regular pattern of linear imprints is created on the surface of the plate. Mechanically imprinting results in considerable tensile plasticity of brittle Vit105 BMG plate. The distribution of hardness and Young’s modulus values at the transverse cross section of imprinted plate probed via nanoindentation revealed oscillating soft and hard regions beneath the surface. Spatially-resolved strain maps obtained via high-energy nano-size beam X-ray diffraction exhibited that the plastic deformation during imprinting creates a spatially heterogeneous atomic arrangement, consisting of strong compressive and tensile strain fields as well as significant shear strain fields in the cross section. It was shown that the heat treatment diminishes the heterogeneous structure resulting in brittle behavior in tension. The analysis of strain tensor components based on changes in the first diffraction maximum of the structure function, q1, revealed that Ɛx, the strain perpendicular to the loading direction, changes from the compressive at near to the surface to the tensile mode at the center of the imprinted plate. In contrast, the strain component along the loading direction, Ɛy, changes from tensile near the surface to the compressive at the center. Beneath the surface, Ɛx reaches to values about 1.5% under the imprints where there is a negligible Ɛy. The distribution map of principal strains, Ɛ1 and Ɛ2, indicated that large regions with compressive Ɛ1 and Ɛ2 exist under the imprints which can result in blocking of the propagating shear bands in agreement with microstructural observations of shear banding after uniaxial tension. Moreover, the region beneath the border of the imprinted and un-imprinted parts has the highest residual shear strain. Microstructural observations indicated that such regions can nucleate new shear bands upon tensile loading of imprinted BMG plate. 3. Residual strain around a single shear band In order to probe structural changes in the shear-induced zone around a single shear band, the distribution of residual strains at short- and medium-range order around a single shear band was determined in cold-rolled BMG plate using the nano-focused high energy x-ray diffraction. Plastic deformation results in significant residual normal and shear strains at distances of more than 15 μm around the shear band. The residual normal strains exhibit an asymmetric distribution whereas the residual shear strain is distributed symmetrically around the shear band. The large amount of residual atomic shear strain magnitude at the vicinity of the shear band triggers the nucleation of the new shear bands. The coincidence of the direction of the nucleating secondary shear bands from the main shear band with the orientation of the residual shear strain at the vicinity of the mature shear band highlight the dominant role of the shear strain in determining further plastic deformation at regions near the shear band.
Im Rahmen dieser Arbeit wird hochenergetische Synchrotron Röntgenstrahlung zum Aufzeigen der strukturellen Veränderungen in plastisch verformtem Zr52.5Ti5Cu18Ni14.5Al10 metallischen Glas verwendet. Die Arbeit gliedert sich in drei Teile: Dehnungsentwicklung während in-situ Druckversuch, Dehnungsverteilung eines mechanisch geprägten massiven metallischen Glases, und Restdehnungen in der Umgebung eines einzenen Scherbandes. 1. Dehnungsentwicklung während in-situ Druckversuch Die während der Verformung auftretende strukturelle Neuordnung eines plastisch verformbaren metallischen Glases zeigt die Korrelation der elastischen und plastischen Verformung mit den strukturellen Änderungen in den Größenordnungen der Nah- (SRO) und mittelreichweitigen Ordnung (MRO). Im elastischen Bereich verändern sich die Atomabstände in der SRO linear mit der makroskopisch anliegenden Spannung. Die Untersuchung der Fläche unter der Radialen Verteilungsfunktion (RDF) deutet auf ein Aufbrechen eines geringen Anteils der Bindungen der ersten Schale in Druckspannungsrichtung und deren Neubildung quer dazu. Die atomaren Bindungen in der SRO erscheinen wesentlich steifer als in den MRO Schalen. Vergleicht man die Werte von elastischer Dehnung, E-Modul und Querkontraktionszahl mit ihren makroskopischen Gegenstücken erscheinen beide, SRO und MRO, wesentlich steifer. Dies zeigt, dass die elastische Verformung von metallischen Gläsern nicht nur von der einfachen Stauchung der Atome bzw. Atomgruppen bestimmt, sondern auch durch deren Neuanordnung unterstützt wird. Das Abweichen der Dehnungs-Spannungs-Korrelation vom linearen Verhalten in der MRO am Beginn der plastischen Verformung wird der irreversiblen Bildung von Schertransformations-zonen (STZ) zugeschrieben. Dies zeigt sich zudem in den erhöhten Scherdehnungswerten am Beginn der Dehngrenze, welche mit den in der Literatur berichteten Werten für die kritische Scherdehnung zum Bilden einer STZ übereinstimmen. Bei einem Atomabstand von 12,5 Å tritt der höchste Wert der Scherdehnung auf und markiert den effektivsten Längenbereich der STZ Bildung. Andererseits haben die atomaren Paare in der SRO mit der geringsten Scherdehnung den geringsten Beitrag an der STZ. Es zeigt sich außerdem, dass der typische Bruchwinkel dieses metallischen Glases über die Orientierung der maximalen Scherdehnung am Beginn der kritischen Scherbandbildung erklärt werden kann. 2. Dehnungsverteilung eines mechanisch geprägten massiven metallischen Glases Eine Prägung besteht darin, eine Platte metallischen Glases mit zwei Stempel, auf denen eine regelmäßige Anordnung von geradlinigen Kerben angebracht ist, zu belasten. Dadurch wird eine ebenso regelmäßige Anordnung von geradlinigen Kerben auf der Oberfläche des metallischen Glases erzeugt. Die plastische Verformbarkeit der Vit105 Platte im Zugversuch wird durch Prägung im Vergleich zur gegossenen Probe eindeutig verbessert. Die Untersuchung der Härte und des E-Moduls über den Querschnitt der geprägten Probe zeigt die Einbringung von Abwechselnd weichen und harten Regionen an der Oberfläche. Es wurden räumlich aufgelöste Dehnungskarten des geprägten metallischen Glases durch Beugung eines hochenergetischen nanometergroßen Röntgenstrahles erzeugt. Die Ergebnisse offenbaren, dass die durch Prägung eingebrachte plastische Verformung eine räumlich heterogene Atomanordnung erzeugt, welche aus starken Druck- und Zugdehnungsfeldern besteht. Zusätzlich wird eine signifikante Scherdehnung in die Probe eingebracht. Die Wärmebehandlung beseitigt diese heterogene Struktur und führt sie fast auf den Ausgangszustand zurück. Die Analyse der Dehnungstensorkomponenten basierend auf Änderungen im erstem Maximum des Strukturfaktors, q1, zeigt, dass sich Ɛx von der Oberfläche zur Mitte der Platte hin von einer Stauchung in eine Dehnung umwandelt. Im Gegensatz dazu wandelt sich die Komponente Ɛy von der Oberfläche zur Mitte der Platte hin von einer Dehnung in eine Stauchung um. An der Oberfläche unter den Eindrücken, wo Ɛy vernachlässigbar ist, erreicht Ɛx Werte von ca. 1.5 %. Die Verteilungskarten der Hauptdehnungen zeigt, dass beide e1 und e2 unterhalb der Kerben als Stauchungen vorhanden sind. Daraus resultiert das Blockieren und Ablenken der sich ausbreitenden Scherbänder, was an Zugproben im REM beobachtet werden kann. Weiterhin hat der Bereich an der Grenze der geprägten und nicht geprägten Regionen die höchste Restscherdehnung. Mikrostrukturelle Beobachtungen deuten darauf hin, dass solche Bereiche unter Zuglast Keimstellen für neue Scherbänder sind. 3. Restdehnungen in der Umgebung eines einzenen Scherbandes Es wurde ein einzelnes Scherband einer kaltgewalzte Platte mittels Beugung eines hochenergetischen nanometergroßen Röntgenstrahles untersucht. Die strukturellen Unterschiede in der scherinduzierten Zone um ein einzelnes Scherband werden durch die Verteilung der Restdehnungen in SRO und MRO bestimmt. Plastische Verformung führt zu signifikanten Restnormal- und Restscherdehnungen in Entfernungen von mehr als 15 µm um das Scherband. Die Restnormaldehnungen zeigen eine asymmetrische Verteilung, wohingegen die Restscherdehnungen auf beiden Seiten des Scherbandes symmetrisch verteilt sind. Der große Betrag der atomaren Restscherdehnung in der Nähe des Scherbandes führt zur Bildung von neuen Scherbändern. Das Zusammenfallen der Richtung des sich bildenden sekundären Scherbandes und der Orientierung der Restscherdehnung, in der Nähe des primären Scherbandes, demonstriert die dominierende Rolle der Scherdehnung bei weiterer plastischer Verformung in der Nähe des Scherbandes.

The selection of the forcefield is a crucial issue in any MD related work and there is no clear indication as to which of the many available forcefields is the best for protein analysis. Many recent literature surveys indicate that MD work may be hindered by two limitations, namely conformational sampling and forcefields used (inaccuracies in the potential energy function may bias the simulation toward incorrect conformations). However, the advances in computing infrastructures, theoretical and computing aspects of MD have paved the way to carry out a sampling on a sufficiently longtime scale, putting a need for the accuracies in the forcefield. Because there are established differences in MD results when using forcefields, we have sought to ask how we could assess common mobility segments from a protein by analysis of trajectories using three forcefields in a similar environment. This is important because, disparate fluctuations appear to be more at flexible regions compared to stiff regions; in particular, flexible regions are more relevant to functional activities of the protein molecule. Therefore, we have tried to assess the similarity in the dynamics using three well-known forcefields ENCAD, CHARMM27 and AMBERFF99SB for 61 monomeric proteins and identify the properties of dynamic residues, which may be important for function. The comparison of popular forcefields with different parameterization philosophy may give hints to improve some of the currently existing agnostics in forcefields and characterization of mobile regions based on dynamics of proteins with diverse folds. These may also give some signature on the proteins at the level of dynamics in relation to function, which can be used in protein engineering studies. Nanosecond level MD simulation(30ns) on 61 monomeric proteins were carried out using CHARMM and AMBER forcefields and the trajectories with ENCAD forcefield obtained from Dynameomics database. The trajectories were first analyzed to check whether structural and dynamic properties from the three forcefields similar choosing few parameters in each case. The gross dynamic properties calculated (root mean square deviation (RMSD), TM-score derived RMSD, radius of gyration and accessible surface area) indicated similarity in many proteins. Flexibility index analysis on 17 proteins, which showed a notable difference in the flexibility, indicated that tertiary interactions (fraction of nonnative stable hydrogen bonds and salt bridges) might be responsible for the difference in the flexibility index. The normalized subspace overlap and shape overlap score taken based on the covariance matrices derived from trajectories indicated that majority of the proteins show a range between 0.3-0.5 indicating that the first principal components from these proteins in different combinations may not match well. These results indicate that although dynamic properties in general are similar in many proteins. However, flexibility index and normalized subspace overlap score indicate that subspaces on the first principal component in many proteins may not match completely. The number of proteins showing a better correlation is higher in CHARMM-AMBER combinations than the other two. The structural features from trajectories have been computed in terms of fraction of secondary structure, hydrogen bonds, salt bridges and native contacts. Although secondary structures and native contacts are well preserved during the simulations, the tertiary interactions (hydrogen bonds) are lost in many proteins and may be responsible for the difference in the some of properties among forcefields. Comparison of simulation results to experimental structures in terms of Root mean square fluctuations, Accessible surface area and radius of gyration indicates that the simulations results are on par with the ones derived from experimental structures. We have tried to assess the flexibility in the proteins using normalized Root mean square fluctuations (nRMSF), which for a residue is the ratio of RMSF from simulation to that of crystal structure. We have selected a threshold for this nRMSF to indicate the mobile regions in a protein based on secondary structure analysis. Based on the threshold of nRMSF and conformational properties (deviation in the dihedral angles), we have classified the residue and evaluated the properties of rigid hinge residues and corresponding mobile residues in terms of residue propensity, secondary structure preference and accessible surface area ranges. Since the rigid dynamic residues represent the inherent mobility, they might be important for function. Therefore, we have tried to assess the functional relevance considering the dynamic mobile residues from each protein from each forcefield simulation with the residues important for the function (taken from literature and databases). It is observed that some residues found to be mobile from the simulation are found to match with the experimental ones, although in many cases the number of these mobile residues is higher compared to the experimental ones. In summary, an analysis of protein simulation trajectories using three forcefields on a set of monomeric protein has shown that the gross structural properties and secondary structures from many proteins remain similar, but there are differences as may be seen from flexibility index. However correlation in parameters from CHARMM and AMBER force field is better compared to other two combinations. The differences seen in some of structural properties may arise mainly due to the loss of few tertiary interactions as indicated by the fraction of native hydrogen bonds and salt bridges. Based on the nRMSF, mobile segments obtained from the simulations were identified, and some of the mobile segments are found to match the functionally important residues from the experimental ones. Our work indicates that there are still some differences in the properties from the simulations, which indicates that care must be exercised when choosing a forcefield, especially assessing the functionally relevant residues from the simulations.

Libraries have traditionally facilitated each of the following elements of research: production of new knowledge, its preservation and its organization to make it accessible for use over the generations. In modern times, the library is constantly required to meet the challenges of information explosion. Assimilating resources and restructuring practices to process the large data volumes both in the print and digital form held across the globe, therefore, becomes very important. A recourse by the libraries to application of successive forms of what can be called as Digital Library Technologies (DLT) has been the imperative. The Open Archives Initiative (OAI) is one recent development that is expected to assist the libraries to partner in setting up virtual learning environment and integrating research on a near universal scale. Future extension of this concept is envisaged to be that of Grid Computing. The technologies driving the â Gridâ would let people share computing power, databases, and other on-line tools securely across institutional and geographic boundaries without sacrificing the local autonomy. Ushering an era of the ubiquitous library helping the e-research is thus on the card. This paper reviews the emerging technological changes and charts the future role for the libraries with special reference to India.