Multi-Domain Information Model

The Multi-Domain Information Model for organisation of the information bases is presented.

How Effective Is The Data On Co-Occurrence Of Domains In Multi-Domain Proteins In Prediction Of Protein-Protein Interactions?

We explore the fuse of information on co-occurrence of domains in multi-domain proteins in predicting protein-protein interactions. The basic premise of our work is the assumption that domains co-occurring in a polypeptide chain undergo either structural or functional interactions among themselves. In this study we use a template dataset of domains in multidomain proteins and predict protein-protein interactions in a target organism. We note that maximum number of correct predictions of interacting protein domain families (158) is made in S. cerevisiae when the dataset of closely related organisms is used as the template followed by the more diverse dataset of bacterial proteins (48) and a dataset of randomly chosen proteins (23). We conclude that use of multi-domain information from organisms closely-related to the target can aid prediction of interacting protein families.

Modulation of Catalytic Activity in Multi-Domain Protein Tyrosine Phosphatases

Signaling mechanisms involving protein tyrosine phosphatases govern several cellular and developmental processes. These enzymes are regulated by several mechanisms which include variation in the catalytic turnover rate based on redox stimuli, subcellular localization or protein-protein interactions. In the case of Receptor Protein Tyrosine Phosphatases (RPTPs) containing two PTP domains, phosphatase activity is localized in their membrane-proximal (D1) domains, while the membrane-distal (D2) domain is believed to play a modulatory role. Here we report our analysis of the influence of the D2 domain on the catalytic activity and substrate specificity of the D1 domain using two Drosophila melanogaster RPTPs as a model system. Biochemical studies reveal contrasting roles for the D2 domain of Drosophila Leukocyte antigen Related (DLAR) and Protein Tyrosine Phosphatase on Drosophila chromosome band 99A (PTP99A). While D2 lowers the catalytic activity of the D1 domain in DLAR, the D2 domain of PTP99A leads to an increase in the catalytic activity of its D1 domain. Substrate specificity, on the other hand, is cumulative, whereby the individual specificities of the D1 and D2 domains contribute to the substrate specificity of these two-domain enzymes. Molecular dynamics simulations on structural models of DLAR and PTP99A reveal a conformational rationale for the experimental observations. These studies reveal that concerted structural changes mediate inter-domain communication resulting in either inhibitory or activating effects of the membrane distal PTP domain on the catalytic activity of the membrane proximal PTP domain.

CLAP: A web-server for automatic classification of proteins with special reference to multi-domain proteins

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/.

Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

Domain/Multi-Domain Protection and Provisioning in Optical Networks

L’évolution récente des commutateurs de sélection de longueurs d’onde (WSS -Wavelength Selective Switch) favorise le développement du multiplexeur optique d’insertionextraction reconfigurable (ROADM - Reconfigurable Optical Add/Drop Multiplexers) à plusieurs degrés sans orientation ni coloration, considéré comme un équipement fort prometteur pour les réseaux maillés du futur relativement au multiplexage en longueur d’onde (WDM -Wavelength Division Multiplexing ). Cependant, leur propriété de commutation asymétrique complique la question de l’acheminement et de l’attribution des longueur d’ondes (RWA - Routing andWavelength Assignment). Or la plupart des algorithmes de RWA existants ne tiennent pas compte de cette propriété d’asymétrie. L’interruption des services causée par des défauts d’équipements sur les chemins optiques (résultat provenant de la résolution du problème RWA) a pour conséquence la perte d’une grande quantité de données. Les recherches deviennent ainsi incontournables afin d’assurer la survie fonctionnelle des réseaux optiques, à savoir, le maintien des services, en particulier en cas de pannes d’équipement. La plupart des publications antérieures portaient particulièrement sur l’utilisation d’un système de protection permettant de garantir le reroutage du trafic en cas d’un défaut d’un lien. Cependant, la conception de la protection contre le défaut d’un lien ne s’avère pas toujours suffisante en termes de survie des réseaux WDM à partir de nombreux cas des autres types de pannes devenant courant de nos jours, tels que les bris d’équipements, les pannes de deux ou trois liens, etc. En outre, il y a des défis considérables pour protéger les grands réseaux optiques multidomaines composés de réseaux associés à un domaine simple, interconnectés par des liens interdomaines, où les détails topologiques internes d’un domaine ne sont généralement pas partagés à l’extérieur. La présente thèse a pour objectif de proposer des modèles d’optimisation de grande taille et des solutions aux problèmes mentionnés ci-dessus. Ces modèles-ci permettent de générer des solutions optimales ou quasi-optimales avec des écarts d’optimalité mathématiquement prouvée. Pour ce faire, nous avons recours à la technique de génération de colonnes afin de résoudre les problèmes inhérents à la programmation linéaire de grande envergure. Concernant la question de l’approvisionnement dans les réseaux optiques, nous proposons un nouveau modèle de programmation linéaire en nombres entiers (ILP - Integer Linear Programming) au problème RWA afin de maximiser le nombre de requêtes acceptées (GoS - Grade of Service). Le modèle résultant constitue celui de l’optimisation d’un ILP de grande taille, ce qui permet d’obtenir la solution exacte des instances RWA assez grandes, en supposant que tous les noeuds soient asymétriques et accompagnés d’une matrice de connectivité de commutation donnée. Ensuite, nous modifions le modèle et proposons une solution au problème RWA afin de trouver la meilleure matrice de commutation pour un nombre donné de ports et de connexions de commutation, tout en satisfaisant/maximisant la qualité d’écoulement du trafic GoS. Relativement à la protection des réseaux d’un domaine simple, nous proposons des solutions favorisant la protection contre les pannes multiples. En effet, nous développons la protection d’un réseau d’un domaine simple contre des pannes multiples, en utilisant les p-cycles de protection avec un chemin indépendant des pannes (FIPP - Failure Independent Path Protecting) et de la protection avec un chemin dépendant des pannes (FDPP - Failure Dependent Path-Protecting). Nous proposons ensuite une nouvelle formulation en termes de modèles de flots pour les p-cycles FDPP soumis à des pannes multiples. Le nouveau modèle soulève un problème de taille, qui a un nombre exponentiel de contraintes en raison de certaines contraintes d’élimination de sous-tour. Par conséquent, afin de résoudre efficacement ce problème, on examine : (i) une décomposition hiérarchique du problème auxiliaire dans le modèle de décomposition, (ii) des heuristiques pour gérer efficacement le grand nombre de contraintes. À propos de la protection dans les réseaux multidomaines, nous proposons des systèmes de protection contre les pannes d’un lien. Tout d’abord, un modèle d’optimisation est proposé pour un système de protection centralisée, en supposant que la gestion du réseau soit au courant de tous les détails des topologies physiques des domaines. Nous proposons ensuite un modèle distribué de l’optimisation de la protection dans les réseaux optiques multidomaines, une formulation beaucoup plus réaliste car elle est basée sur l’hypothèse d’une gestion de réseau distribué. Ensuite, nous ajoutons une bande pasiv sante partagée afin de réduire le coût de la protection. Plus précisément, la bande passante de chaque lien intra-domaine est partagée entre les p-cycles FIPP et les p-cycles dans une première étude, puis entre les chemins pour lien/chemin de protection dans une deuxième étude. Enfin, nous recommandons des stratégies parallèles aux solutions de grands réseaux optiques multidomaines. Les résultats de l’étude permettent d’élaborer une conception efficace d’un système de protection pour un très large réseau multidomaine (45 domaines), le plus large examiné dans la littérature, avec un système à la fois centralisé et distribué.

Towards the development of a project decision support framework for adoption of an integrated building information model using a model server

This chapter discusses an action research study towards the development of a decision framework to support a fully integrated multi disciplinary Building Information Model (BIM) using a Model Server. The framework was proposed to facilitate multi disciplinary collaborative BIM adoption through, informed selection of a project specific BIM approach and tools contingent upon project collaborators’ readiness, tool capabilities and workflow dependencies. The aim of the research was to explore the technical concerns in relation to Model Servers to support multi disciplinary model integration and collaboration; however it became clear that there were both technical and non technical issues that needed consideration. The evidence also suggests that there are varying levels of adoption which impacts upon further diffusion of the technologies. Therefore the need for a decision framework was identified based on the findings from an exploratory study conducted to investigate industry expectations. The study revealed that even the market leaders who are early technology adopters in the Australian industry in many cases have varying degrees of practical experiential knowledge of BIM and hence at times low levels of confidence of the future diffusion of BIM technology throughout the industry. The study did not focus on the benefits of BIM implementation as this was not the intention, as the industry partners involved are market leaders and early adopters of the technology and did not need convincing of the benefits. Coupled with this there are various other past studies that have contributed to the ‘benefits’ debate. There were numerous factors affecting BIM adoption which were grouped in to two main areas; technical tool functional requirements and needs, and non technical strategic issues. The need for guidance on where to start, what tools were available and how to work through the legal, procurement and cultural challenges was evidenced in the exploratory study. Therefore a BIM decision framework was initiated, based upon these industry concerns. Eight case studies informed the development of the framework and a summary of the key findings is presented. Primary and secondary case studies from firms that have adopted a structured approach to technology adoption are presented. The Framework consists of four interrelated key elements including a strategic purpose and scoping matrix, work process mapping, technical requirements for BIM tools and Model Servers, and framework implementation guide. The BIM framework was presented in draft format again to key industry stakeholders and considered in comparison with current best practice BIM adoption to further validate the framework. There was no request to change any part of the Framework. However, it is an ongoing process and it will be presented again to industry through the various project partners. The Framework may be refined within the boundaries of the action research process as an ongoing activity as more experiential knowledge can be incorporated.

Landmark Detection for Fusion of Fundus and MRI Towards a Patient-Specific Multi-Modal Eye Model

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise e.g., Fundus photography, Optical Coherence Tomography (OCT), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The presented article’s goal is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI which was not visible before like vessels and the macula. This article’s contributions include automatic detection of the optic disc, the fovea, the optic axis and an automatic segmentation of the vitreous humor of the eye.

Multi Domain-Specific Modeling of the Security Concerns of Service-Oriented Architectures

Service-Oriented Architectures (SOA), and Web Services (WS), the technology generally used to implement them, achieve the integration of heterogeneous technologies, providing interoperability, and yielding the reutilization of pre-existent systems. Model-driven development methodologies provide inherent benefits such as increased productivity, greater reuse, and better maintainability, to name a few. Efforts on achieving model-driven development of SOAs already exist, but there is currently no standard solution that addresses non-functional aspects of these services as well. This paper presents an approach to integrate these non-functional aspects in the development of web services, with an emphasis on security.

Multi-Agent Information Processing and Adaptive Control in Global Telecommunication and Computer Networks

The problems and methods for adaptive control and multi-agent processing of information in global telecommunication and computer networks (TCN) are discussed. Criteria for controllability and communication ability (routing ability) of dataflows are described. Multi-agent model for exchange of divided information resources in global TCN has been suggested. Peculiarities for adaptive and intelligent control of dataflows in uncertain conditions and network collisions are analyzed.

Predicting active material utilisation in LiFePO4 electrodes using a multi-scale mathematical model

A mathematical model is developed to simulate the discharge of a LiFePO4 cathode. This model contains 3 size scales, which match with experimental observations present in the literature on the multi-scale nature of LiFePO4 material. A shrinking-core is used on the smallest scale to represent the phase-transition of LiFePO4 during discharge. The model is then validated against existing experimental data and this validated model is then used to investigate parameters that influence active material utilisation. Specifically the size and composition of agglomerates of LiFePO4 crystals is discussed, and we investigate and quantify the relative effects that the ionic and electronic conductivities within the oxide have on oxide utilisation. We find that agglomerates of crystals can be tolerated under low discharge rates. The role of the electrolyte in limiting (cathodic) discharge is also discussed, and we show that electrolyte transport does limit performance at high discharge rates, confirming the conclusions of recent literature.

The reliability, accuracy and minimal detectable difference of a multi-segment kinematic model of the foot-shoe complex

Kinematic models are commonly used to quantify foot and ankle kinematics, yet no marker sets or models have been proven reliable or accurate when wearing shoes. Further, the minimal detectable difference of a developed model is often not reported. We present a kinematic model that is reliable, accurate and sensitive to describe the kinematics of the foot–shoe complex and lower leg during walking gait. In order to achieve this, a new marker set was established, consisting of 25 markers applied on the shoe and skin surface, which informed a four segment kinematic model of the foot–shoe complex and lower leg. Three independent experiments were conducted to determine the reliability, accuracy and minimal detectable difference of the marker set and model. Inter-rater reliability of marker placement on the shoe was proven to be good to excellent (ICC = 0.75–0.98) indicating that markers could be applied reliably between raters. Intra-rater reliability was better for the experienced rater (ICC = 0.68–0.99) than the inexperienced rater (ICC = 0.38–0.97). The accuracy of marker placement along each axis was <6.7 mm for all markers studied. Minimal detectable difference (MDD90) thresholds were defined for each joint; tibiocalcaneal joint – MDD90 = 2.17–9.36°, tarsometatarsal joint – MDD90 = 1.03–9.29° and the metatarsophalangeal joint – MDD90 = 1.75–9.12°. These thresholds proposed are specific for the description of shod motion, and can be used in future research designed at comparing between different footwear.

The development of a multi-segment kinematic model of footwear

In gait analysis, both shoe mounted and skin mounted markers have been used to quantify the movement of the foot inside the shoe. However, these models have not been demonstrated as reliable or accurate in shod conditions. The purpose of this study was to develop an accurate and reliable marker set to describe foot-shoe complex kinematics during stance phase.

An object oriented road asset information model

Preservation and enhancement of transportation infrastructure is critical to continuous economic development in Australia. Of particular importance are the road assets infrastructure, due to their high costs of setting up and their social and economic impact on the national economy. Continuous availability of road assets, however, is contingent upon their effective design, condition monitoring, maintenance, and renovation and upgrading. However, in order to achieve this data exchange, integration, and interoperability is required across municipal boundaries. On the other hand, there are no agreed reference frameworks that consistently describe road infrastructure assets. As a consequence, specifications and technical solutions being chosen to manage road assets do not provide adequate detail and quality of information to support asset lifecycle management processes and decisions taken are based on perception not reality. This paper presents a road asset information model, which works as reference framework to, link other kinds of information with asset information; integrate different data suppliers; and provide a foundation for service driven integrated information framework for community infrastructure and asset management.