A critical step in mounting an immune response is antigen recognition by T cells. This step proceeds by productive interactions between T cell receptors (TCR) on the surface of T cells and foreign antigen, in the form of peptide-major-histocompatibility-complexes (pMHC), on the surface of antigen-presenting-cells (APC). Antigen recognition is exceedingly difficult to understand because the vast majority of pMHC on APCs are derived from self-proteins. Nevertheless, T cells have been shown to be exquisitely sensitive, responding to as few as 10 antigenic pMHC in an ocean of tens of thousands of self pMHC. In addition, T cells are extremely specific and respond only to a small subset of pMHC by virtue of their specific TCR. To explain the sensitivity of T cells to pMHC it has been proposed that a single pMHC may serially bind multiple TCRs. Integrating present knowledge on the spatial-temporal dynamics of TCR/pMHC in the T cell-APC contact interface, we have constructed mathematical models to investigate the degree of TCR serial engagements by pMHC. In addition to reactions within clusters, the models capture the formation and mobility of TCR clusters. We find that a single pMHC serially binds a substantial number of TCRs in a TCR cluster only if the TCR/pMHC bond is stabilized by coreceptors and/or pMHC dimerization. In a separate study we propose that serial engagements can explain T cell specificity. Using Monte Carlo simulations, we show that the stochastic nature of TCR/pMHC interactions means that multiple binding events are needed for accurate detection of foreign pMHC. Critical to our studies are estimates of TCR/pMHC reaction rates and mobilities. In the second half of the thesis, we show that Fluorescence Recovery After Photobleaching (FRAP) experiments can reveal effective diffusion coefficients. We then show, using asymptotic analysis and model fitting, that FRAP experiments can be used to estimate reaction rates between cell surface proteins, like TCR/pMHC. Lastly, we use FRAP experiments to investigate how the actin cytoskeleton modulates TCR mobility and report effective reaction rates between TCR and the cytoskeleton.

Patterns are used as building blocks for design and construction in many fields such as architecture, music, literature, etc. Researchers and practitioners in the information systems area have been exploring patterns and using them in system analysis and design. Patterns found in the analysis stage, when analysts create conceptual models to abstractly represent domain reality, are call business patterns or analysis patterns. Although various business patterns were proposed in previous studies, we found that business semantics were missing in these patterns. These business patterns failed to show functionalities that is essential to patterns in general. Most of these patterns were also not capable of describing business activities, the dynamic aspect of business. This study is conducted to address these issues. In this thesis, we provide a brief literature review on business patterns, and discuss the major problems we found in these studies. Then we introduce our research approach and the major outcomes. We propose a new definition of business patterns with business semantics, which enables us to recover the missing functionality in business patterns. We suggest the key elements to represent business patterns, and propose a two-level template (functional and operational) to describe these elements. Based on theR²M approach, we propose a modeling method with graphical notations to describe the operational level of patterns, where business activities can be modeled. Examples and a case study are provided in this thesis to demonstrate how to use the modeling method and how to use business patterns in practice.

The municipal solid waste (MSW) management system is consisted of planning, development, execution of capital works, and so on. Too many factors in the system make the decision making process plagued with uncertainties, vagueness and complication. Interval-parameter Linear Programming (ILP) is widely used to deal with uncertainties existed in the MSW system and to assist optimal decision making. However, the existing ILP solution algorithms, i.e., best-worst case algorithm and 2-step algorithm, are found to be ineffective through a validity checking process. Moreover, the results from ILP can not reflect the linkage between decision risks and the system return. In this study, a fuzzy risk explicit interval-parameter linear programming (FREILP) model is developed and applied to the long-term planning of the MSW management system in Halifax Regional Municipality (HRM). This method is specifically designed to deal with extensive uncertainties existed in the MSW management system and to provide decision supports to HRM planners. In the model, ILP is used to reflect uncertainties existed in both objective function and constraints. Based on the basic ILP, a risk function is defined to assist in finding solutions with minimum system cost while minimizing the system risk, under certain aspiration levels. The aspiration level could be conservative, medium or aggressive, and can thus be presented as a fuzzy set to reflect the preference of decision makers. Three sets of solutions are obtained accordingly. Besides, the model was also solved under the aspiration level from 0 to 1, with a step of 0.1, for providing a comprehensive decision support. This approach can effectively reflect dynamic, interactive, uncertain characteristics, as well as the interactions between overall cost and risk level of the MSW management system, thus provide valuable information to support the decision-making process, such as waste allocation pattern, timing and expansion capacities of the municipal solid waste management activities. The result can directly reflect the tradeoff between decision risks and the system return.

Online commerce and service obtain much private data from users. Collection, storage, management, and use of private data are subject to various privacy laws, regulations, and standards. To adhere to legal requirements, many privacy services, such as security, notice, and consent, are required. Inclusion of the required privacy services early in the life cycle of the software development is preferred and advocated. We extend UML use case diagrams with privacy components to represent example privacy services. These components are used to visually model privacy requirements in the analysis phase of the SDLC. We create a prototype by extending Microsoft Visio, a popular UML modeling tool, with our proposed privacy components. In summary, we show how privacy services may be specified in UML use case diagrams rather than adding privacy as an afterthought to software systems and services. The tool is demonstrated with real-world scenarios from the health sector.

The widespread recognition of (ultra)high-pressure ((U)HP) metamorphic rocks in orogens worldwide suggests that subduction and exhumation of crustal rocks from mantle depths are normal processes at convergent plate margins. However, the dynamics of these processes, in particular the comparative roles of erosion and crustal extension, and the driving forces of extension during (U)HP rock exhumation, remain controversial. This thesis presents numerical modeling and field/analytical studies that address the geodynamics of crustal subduction and exhumation in two intensely studied orogens, the Alps and the Caledonides. The 2D numerical models show how different scales and durations of orogeny and plate motions can lead to marked contrasts in the style of orogenic growth, crustal subduction, and (U)HP exhumation. In the Western Alps, rapid exhumation (1-3 cm/a) can be explained by local, syn-orogenic extension driven by the buoyant ascent of deforming (U)HP crust from the subduction channel. Later trans-crustal exhumation probably resulted from the combined effects of syn-convergent thrusting, local extension, and erosion. The low temperatures (500-700°C) of Alpine (U)HP metamorphism are attributable to the small size of the orogen and short duration of subduction/exhumation. Contrary to recent suggestions, neither erosion nor absolute extension is required to explain (U)HP exhumation in the Alps. The Western Gneiss Region (WGR) (Norwegian Caledonides), in contrast, can be explained by subduction to (U)HP conditions followed by plate divergence. Gravitational spreading of a thick, hot orogenic wedge leads to a short period of coeval thrusting and extension. Exhumation of (U)HP crust from the subduction channel is achieved by normal-sense shearing along the top of the (U)HP terrane, with minor associated shortening. Trans-crustal exhumation by vertical thinning of the orogenic wedge results from continued absolute extension and erosion. The comparatively high temperatures (700-800°C) achieved by Caledonian (U)HP rocks reflect the orogen's greater size, slower exhumation rates, and possible stalling of the (U)HP terrane at depth. These contrasting models underscore the variety of possible mechanisms responsible for (U)HP exhumation, and represent new benchmarks in the understanding of Alpine and Caledonian tectonics and (U)HP rock exhumation in general.

This thesis investigates the optimal use of intervention strategies to mitigate the spread of infectious diseases. Three main problems are addressed: (i) The optimal use vaccination and isolation resources under the assumption that these resources are limited. Specifically we address the problem of minimizing the outbreak size and we determine the optimal vaccination-only, isolation-only and mixed vaccination-isolation strategies. (ii) The optimal use of a single antiviral drug to minimize the total outbreak size, under the assumption that treatment causes de novo resistance. (iii) The optimal use of two antiviral drugs to minimize the total infectious burden. Specifically we address the situation where there are two different strains and each strain is effectively treated by only one drug. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2011-01-25 19:59:17.263

No description available.

No description available.

No description available.

No description available.