Faculty of Engineering and Built Enviroment School of Electrical and Information Engineering 0314356t morayus@engineer.com / A teleworking service allows people to work effectively together from home or other approved locations away from the regular work site, on an established work schedule. This is made possible via the use of Information and Communications Technology (ICT). Presently, there are isolated applications that can assist teleworkers, such as e-mail and video conferencing, which were developed for use over the Internet. But the Internet is a best-effort network with no guarantee of Quality of service (QoS), low security and no standard billing system. The design of this teleworking service involves the integration of many existing services like e-mail, messaging, video conferencing, shared whiteboard and database access. Other requirements are for service providers interworking for service and resource usage, security, and QoS specification. Hence, we explore the emerging open service concept to create this integrated teleworking service that can be made available for subscription by corporate bodies and individuals. Service federation is the interaction between teleworkers across service provider domains. It is achieved via the interworking of providers’ services, and is an essential aspect of teleworking. We have realised a service federation in a secure and seamless manner in the OSA / Parlay environment via the use of the OSA / Parlay framework. We looked at the use of a framework federation for the actual implementation of service federation. This framework federation is an interworking of frameworks based on an agreed-upon federation contract between them. New framework interfaces were introduced to facilitate this proposed solution, as the OSA / Parlay specifications do not yet support this approach. Service composition is the creation of a new service instance by composing one or more other services. We implemented this via the use of framework and trader federation. The trader federation was used to locate services or users in different ASP domains. A high level design of the teleworking service was done with federation explored for actual implementation. The Common Object Request Broker Architecture (CORBA) trading service was used to prove the concept. The RM-ODP methodology is followed in this teleworking service design. The OSA / Parlay terminal capability, generic call control, multiparty and location and Service Capability Features (SCF) were used for implementing in the CORBA Distributed Processing Environment (DPE).

No description available.

Self-interaction error (SIE) is a commonly known problem that most Kohn-Sham density functional theory (KS-DFT) approximate functionals display to varying extents. It originates from the incomplete cancellation of the Coulomb self-repulsion by the approximate exchange functionals. This is one of the major challenges for DFT, and therefore increasing our understanding of it could have great benefits for future use of DFT. Herein we advance techniques to dissect, understand, and textit{avoid} SIE in new ways. Considering that KS-DFT requires solving the self-consistent field (SCF) equations, we first present a robust and economical SCF solver - the ``Quasi-Newton Unitary Optimization with Trust region" (QUOTR) solver.[Slattery, et. al. textit{Phys. Chem. Chem. Phys.}, textbf{2024}, 26, 6557-6573] To be robust, the solver is a direct-minimization solver equipped with a trust region (TR); to be economical, the solver uses an L-BFGS approximate Hessian and a physically-relevant preconditioner. Coupling these two aspects together is a solver for the TR subproblem that exploits the low-rank structure of the L-BFGS Hessian. We demonstrate that QUOTR is useful, not only for obtaining KS-DFT wave functions in difficult cases, but also for solving for Hartree-Fock (HF) orbitals in challenging chemical systems containing Cr or Fm. Although not able to beat the low cost of traditional Roothaan-Hall (RH) solvers with acceleration, QUOTR is robust in its convergence at only a modest increase in computational cost. The many examples of SCF convergence problems when using semi-local KS-DFT functionals are known to be the result of a vanishing HOMO-LUMO gap, which is further the result of SIE. A major motivation for developing QUOTR came from our desire to understand the ``true" (albeit unphysical) ground state solutions in cases where KS-DFT could not be converged by a traditional diagonalization-based SCF solver. We reinvestigate the relationship between the vanishing HOMO-LUMO gap and SCF non-convergence using our QUOTR solver. A set of difficult biological systems that had previously been shown to display convergence problems [Rudberg, et. al. textit{J. Phys.: Condens. Matter}, textbf{2012}, 24, 072202] was selected for deeper analysis. In addition to being able to obtain converged solutions, we analyze the resulting densities matrices in comparison to HF. The source of the vanishing HOMO-LUMO gaps is demonstrated to be incompatible eigenspectrums of spatially distant fragments in the peptides. We show that by using a local solver (QUOTR) with an appropriate initial guess, that a non-Aufbau filled stationary point can be found for vacuum-separated charged fragments. A systematic scan of all 20 natural amino acids for some common DFAs is used to examine the prevalence of predicted non-Aufbau filling. We find that hybrid functionals improve upon GGAs more than meta-generalized gradient approximations (GGAs) do, and range-separated functionals are much better - though not completely solving the problem. Having addressed SIE in biomolecules in terms of where charges comes from and where it goes, we finally analyze SIE on an orbital-by-orbital basis. We define the textit{genuine} exchange energy as the difference between the HF energy and the (self-interaction free) orthogonal Hartree product wave function energy. We propose that the Edmiston-Ruedenberg [Edmiston, et. al. textit{Rev. Mod. Phys.}, textbf{1963}, 35, 457-464] localized HF orbitals are the most appropriate HF frame for this analysis, due to their connection with the Hartree product wave function. Although the use of HF orbitals to quantify the genuine exchange energy is an approximation, we demonstrate that the error of total exchange energy is approximately 10-15% for a set of small molecules. The good performance of two popular GGAs is shown to arise with considerable error cancellation between orbitals (particularly core and valence). We also examine two orbital-dependent DFAs: the Perdew-Zunger self-interaction correction (PZ-SIC), and a generalization of the Hartree-Fock-Gopinathan (HFG) method. / Doctor of Philosophy / Much of theoretical chemistry is built on a formalism where electrons are described by single-particle functions, known as orbitals. Because the orbitals influence each other through a variety of interactions, it is not trivial to determine accurate approximations to the best set of orbitals for any given chemical system. The method for obtaining optimal mathematical forms of the orbitals is called the self-consistent field (SCF) procedure. In essence solving the SCF equations is a nonlinear optimization problem, requiring iterative solution techniques. Both of the major camps in the field of theoretical chemistry, density functional theory (DFT) and wave function methods, almost always start with an SCF calculation. In wave function methods, SCF is typically only the first step, in this case the SCF is done with an approximation called Hartree-Fock (HF), and a further calculation will include many-body effects through other means which are more computationally costly. In Kohn-Sham DFT (the most popular variety), the SCF equations contain approximations to part of the energy known as density functional approximations (DFAs) that in principle account for all many-body effects not included exactly. Thus, for KS-DFT, solving the SCF equations is basically all that needs to be done for a complete description of the system. For this reason DFT is attractive from a cost perspective, but the DFAs are only approximations and this can introduce unphysical errors. In this work, we focus on providing new solutions and perspectives on a major contributor to poor performance of KS-DFT calculations, the self-interaction error (SIE), which is not present in HF. The origin of the SIE in approximate KS-DFT is how the 2-body interactions of electrons are approximated. Classical electrostatics provides a simple formula for the repulsion energy of like-charged particles. When the quantum mechanical electron probability density is treated as a classical charge density then a single electron will unphysically interact with itself. What is missing is the nonclassical ``exchange" interaction, which in the HF method cancels the Coulomb self-repulsion. In KS-DFT this second contribution is approximated, and this causes the cancellation to be inexact. Thus, it is the treatment of these two energy contributions in fundamentally different ways that causes SIE to appear in approximate KS-DFT, but not in wave function methods. Problems with convergence of the SCF equations are more prevalent for approximate KS-DFT than for HF, and this has been attributed to SIE. To address the issue of poor SCF convergence we developed the ``Quasi-Newton Unitary Optimization with Trust region" (QUOTR) SCF solver. [Slattery, et. al. textit{Phys. Chem. Chem. Phys.}, textbf{2024}, 26, 6557-6573] This solver is robust in converging to minima in the energy surface, while also being economical in computational cost. In cref{ch:quotr} we demonstrate the usefulness of QUOTR for solving not only problems where KS-DFT SCF convergence is difficult, but also cases where even HF SCF is not simple. With the QUOTR solver in hand, in cref{ch:sie_pep} we reexamine the SCF non-convergence problem for some approximate KS-DFT functionals when applied to biological systems in vacuum. By comparing the spatial distribution of the electron density of our KS-DFT solutions to that of HF, we are able to pinpoint regions of the biological systems that donate and receive electron density relative to HF. As is already known, how approximate KS-DFT treats charged groups often is generally the source of the error. Therefore, we performed a systematic scan of all 20 naturally occurring amino acids to find combinations that might be problematic. Finally, in cref{ch:orb_anatomy} we investigate the source of SIE in approximate KS-DFT functionals on an orbital-by-orbital basis, and attempt to remove it from the calculation a priori. While the total density is unique, the orbital decomposition within KS-DFT is not. We therefore, first justify our choice of a particular set of orbitals as the most physically reasonable for our analysis. We find that two popular functionals display much error cancellation between orbitals to achieve good overall results. Two generalizations of KS-DFT for orbital-dependent approaches, which attempt to be free of SIE, are examined. Taken as a whole, this work examines SIE in KS-DFT both by improving convergence of the SCF procedure despite the presence of SIE (in order to understand what is really happening), and by dissecting the orbital structure of SIE, including for methods that attempt to be free of SIE.

Student Number :9600874K - MSc research report - School of Electrical Engineering - Faculty of Engineering and the Built Environment / Telecommunication networks have evolved from voice only single service networks to multimedia networks providing bearer services such as voice, data and video transportation. Moreover, these networks, collectively called Next Generation Networks (NGNs), enable rapid creation, deployment and management of advanced services in an efficient manner. However, the initial business model of telcos was to internally develop and provide these advanced services to customers. In this monopolized environment, service development is driven by technological availability rather than customer demands. Furthermore, vendor specific network elements prohibit the development of re-useable service components, which in turn increases the time-to-market of services. Deregulation and advances in Distributed Computing Systems (DCSs) are driving towards open networks and rapid service delivery. Third party Application Service Providers (ASPs) are envisioned to develop and supply the services, with the telco providing bearer services. The use of softswitch architectures such as Open Service Access (OSA) / Parlay (OSA / Parlay) in an open NGN environment abstract services from core network elements through its Application Programming Interface (API). Services are thus decoupled from vendor and protocol specific network equipment and can be provided across a plethora of network architectures. One major advantage of NGN is the ability to provide bearer service in a mobile environment. Location Based Services (LBSs) are envisaged to be an important class of services provided in the NGN environment. For an LBS service to be complete, a geospatial database is necessary to provide location information. This report documents the design and implementation of a Geospatial Data Access Service Capability Feature (GDASCF) as an extension to the OSA / Parlay gateway. The GDASCF encapsulates necessary APIs that offer uniform access to query geospatial databases. One key component of the design is the realization of the Adapter layer which adapts function calls to an appropriate Database Management System (DBMS). The introduction of the GDASCF and Adapter layer provides a solution which results in flexible and rapid service creation.

L'ARN interférence est un mécanisme moléculaire conservé chez les Eucaryotes dont les principaux acteurs sont les protéines ARGONAUTE (AGO). Chez les plantes, AGO1 est une protéine essentielle à la croissance et la défense antivirale. Elle utilise des petits ARNs comme sondes pour reconnaître et réguler des ARN messagers. Les virus ont développé des suppresseurs de l'ARN interférence pour surmonter cette défense. L'un d'entre eux, P0 du virus de la mosaïque jaune du navet, est comme une protéine F-box qui détourne le complexe SCF, une ubiquitine ligase E3, et conduit AGO1 vers la protéolyse ubiquitine-dépendante. Cette dégradation utilise la vacuole au lieu du protéasome 26S, généralement associé à la dégradation ubiquitine-dépendante. Ce mécanisme de protéolyse n'est pas compris et est aussi apparent quand AGO1 est déstabilisé de manière endogène, suggérant que P0 utilise une voie déjà existante. Une protéine F-box d'Arabidopsis, FBW2, a été décrite comme impactant l'homéostasie d'AGO1 indépendamment du protéasome. Mon projet de thèse visait à caractériser l'activité F-box de FBW2 et à comprendre la relation entre AGO1 et FBW2 ainsi que ses conséquences sur l'ARN interférence. Les résultats obtenus dans ce manuscrit montrent que le complexe SCFFBW2 interagit avec AGO1 et déclenche sa dégradation via un processus indépendant de l'autophagie ou du protéasome, tout en n'affectant que faiblement l'ARN interférence. FBW2 ciblerait en fait un sous-ensemble de protéines AGO1 qui semble ne pas contenir de petits ARNs. Cette régulation jouerait un rôle de surveillance pour prévenir une activité délétère d'AGO1 en absence de petits ARNs. / RNA silencing is a conserved molecular mechanism in eukaryotes, of which the main effectors are the ARGONAUTE (AGO) proteins. In plants, AGO1 is a protein that is essential for growth and antiviral defence. It uses small RNAs as probe to recognize and regulate messenger RNAs. Viruses have developed suppressors of RNA silencing to overcome this defence. One of these, P0 from the Turnip Yellows Virus, acts as an F-box protein to hijack the SCF complex, an E3 ubiquitin ligase, and guide AGO1 to the ubiquitin-dependent proteolysis. This degradation uses the vacuole instead of the 26S proteasome, generally associated with ubiquitin-dependant proteolysis. This proteolysis mechanism is not understood and is also apparent when AGO1 is endogenously destabilized, suggesting that P0 uses an already existing pathway. An Arabidopsis F-box protein, FBW2, has been shown to impact AGO1 homeostasis independently from the proteasome. My PhD project aimed at characterizing FBW2 F-box activity and understanding the relationship between AGO1 and FBW2, as well as its consequences on the RNA silencing. The results obtained in this manuscript show that the SCFFBW2 interacts with AGO1 and triggers its degradation through an autophagy- and proteasome- independent process, while only weakly affecting the RNA silencing. FBW2 would actually target a subset of AGO1 proteins, which appears not to contain small RNAs. This regulation would play a surveillance role in order to prevent a deleterious activity of AGO1 in absence of small RNAs.

KIT receptor (CD117) is a receptor tyrosine kinase crucial for homeostasis of mast cells (MCs) in tissues and recruitment to sites of inflammation and tumors in response to its ligand Stem cell factor (SCF). Gain of function mutations in KIT (e.g. D816V) are frequently observed in systemic mastocytosis and other cancer types. Src Homology 2 domain containing phosphatase-2 (SHP2 or PTPN11) is a protein tyrosine phosphatase that promotes cell proliferation, survival and motility in multiple pathways and cell types. To study SHP2 function in MCs, we generated novel MC-specific Shp2 knock-out (KO) mice (MC-shp2 KO). These mice had reduced numbers of MCs in skin and peritoneum, and defective contact hypersensitivity responses compared to control mice, consistent with SHP2 promoting MC homeostasis. Using an inducible SHP2 KO bone marrow-derived MC (BMMC) culture model, we found that SHP2 KO cells were prone to apoptosis and had no MC repopulating activity in vivo. Mechanistically, SHP2 enhanced ERK activation and downregulation of pro-apoptotic protein Bim. SHP2 KO BMMCs also had defects in chemotaxis towards SCF, due to impaired activation of a Lyn/Vav/Rac pathway in SHP2 KO BMMCs. This correlated with defects in cell spreading, and F-actin polymerization in response to SCF. Treatment of BMMCs with a SHP2 inhibitor (II-B08) also led to reduced chemotaxis, consistent with SHP2 phosphatase activity being required for KIT-induced chemotaxis. Lastly, we tested whether SHP2 regulates oncogenic KIT signaling using a P815 mouse mastocytoma model. Stable silencing of SHP2 in P815 cells led to reduced cell growth and survival in vitro, and less aggressive systemic mastocytosis development in syngeneic mice. Overall, these studies identify SHP2 as a key node in SCF/KIT and oncogenic KIT pathways, and as a potential therapeutic target in several human diseases. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2013-06-25 12:03:57.818

In this study we show, to our knowledge, the first description of the role ADAM10 plays on mast cells. ADAM10 is abundantly expressed on mast cells both in vitro and in vivo. Its expression is inhibited by IL-10, a suppressive cytokine. siRNA depletion of ADAM10 on bone marrow-derived mast cells (BMMC) caused decreased IL-6 production following IgE cross-linking and also impaired BMMC stem cell factor (SCF)-induced migration through collagen IV. Mast cells and T helper cells (Th cells) in the peritoneum were reduced in ADAM10 KO mice. In addition, ADAM10 KO BMMC produced significantly less of all cytokines measured following IgE cross-linking, including IL-6, TNF-α, IL-13, and MCP-1, compared to wild type BMMC. Collectively these data show that mast cell ADAM10 can be regulated by a T regulatory cell cytokine, IL-10, and describes key ways in which ADAM10 loss affects prototypical mast cell functions and distribution.

No description available.

This work uses different size of strain gages (Gage Grid Length: 10mm, 1mm, 0.2mm) to measure the stress distributions of metal (Al 6061-T6) and composite (laminates of [0/+45/90/-45]2S and [0/90]4S layers ) with a central circular hole and a crack. Both the SCF (Stress Concentration Factor) and SIF (Stress Intensity Factor) are found to consider the stress scatteredness of experimental data in contrast to micro- mechanics. To understand the strain gage size effect is our main purpose in measuring both types of materials. The size effect of strain gage we find appears obviously in the measuring position with stress changing significantly. We find that the size of strain gage is bigger; the error of stress is higher. Analyzing the stress scattering around a central circular hole, we obtain the experimental result that the stress will first reduce drastically from central circular hole edge and then keep uniform. In analysis of the stress scattering around the crack tip, we observe that first stress rises quickly from the specimen¡¦s free edge to the top of crack tip with a maximum value, and the stress keeps a nominal value in the specimen central part. Comparing the empirical result of SCF and SIF, we find that the data of 0.2mm of strain gage close to the theoretical solution, while those of 1mm and 10mm strain gages appear inexact in measuring and calculating SCF and SIF.

No description available.