The genome-wide HaploInsufficieny Profiling (HIPHOP) technique has been validated as a method to quantify the relative abundance of uniquely tagged yeast deletion strains using a microarray readout. The massive throughput of next generation sequencing presents a new technology for assessing HIPHOP profiles. I developed a new method called Barcode analysis by Sequencing (Bar-seq) that applies deep sequencing to genome-scale fitness. I show that Bar-seq outperforms the current benchmark barcode microarray assay in terms of both dynamic range and throughput. When applied to a complex genome-scale fitness assay, Bar-seq quantitatively identifies drug-targets, exceeding the performance of the microarray assay. I also established that Bar-seq is well suited to a multiplex format and provides a dramatic increase in throughput. I used the genome-wide HIPHOP assay and other functional genomics tools to explore the mechanisms underlying drug-drug synergies. Drug combination therapy, and synergistic combinations in particular, have several advantages over monotherapies. Synergistic drug combinations allow the dose of each agent to be reduced, often with the benefit of diminishing side effects while maintaining efficacy and decreasing the chances of drug resistance. I used my yeast model to identify synergistic drug combinations and found that inhibitors of ergosterol biosynthesis are highly synergistic with several agents, including those targeting other points within the same pathway. I also devised a method that enriches for synergistic interactions during screening of compound combinations. This new synergy prediction method can aid in the rapid identification of anti-proliferative combinations and can be readily applied to other organisms for further characterization and/or confirmation. Finally, I examined synergistic combination HIPHOP profiles and identified Gene Ontology enrichments that are combination-specific.

In this exploration, participatory planning workshops are used to implement the Education for Sustainable Development (ESD) initiative in a grade six class in Winnipeg. The approach is an effective student-centered strategy that meets the needs of children with a range of learning abilities. The benefits of participatory planning workshops for students with special needs emerged as a key success of the process. Grounded in the principles of community engagement, this document connects children’s rights to citizenship with the need to engage children in planning for sustainable development. Semi-structured interviews were integral to understanding the unique needs of the participant class. Challenges that emerged during the parental consent and student assent process are examined and strategies for future interdisciplinary collaborations are identified. An extensive literature review explores the emergence of youth participation in planning and a range of best practices for engaging children in participatory student-led processes. This research investigates international strategies for implementing the ESD initiative and considers emergent best practices at student, institutional and government levels. Schools are examined as components of community infrastructure that influence neighbourhood design and shape development. As school infrastructure ages and school facilities are challenged to become more sustainable, engaging with school communities in planning, design, renovation or building will be an important skill for planning professionals. Developing the necessary knowledge, skills and values to engage children in planning processes is illustrated as an integral component of this process. / February 2009

The Bluetooth Scatternet Formation (BSF) problem can be defined as the problem of forming wireless networks of Bluetooth devices in an efficient manner. A number of restrictions imposed by the Bluetooth specifications make the BSF problem challenging and unique. Many interesting solution algorithms have been proposed in the literature to solve this problem. In this thesis, we investigate the BSF problem. We concentrate on problems introduced by the procedures of device discovery of the Bluetooth specifications and on the different solutions used by BSF algorithms to deal with these problems. We study also in this thesis problems introduced by the specifications of link establishment in Bluetooth due to their close interaction with the device discovery specifications. We survey and categorize the different device discovery techniques used by BSF algorithms. This categorization is then used as a basis to identify the different theoretical computational models used to study BSF algorithms. We argue, in this thesis, that the currently available models for Bluetooth wireless networks do not model adequately, in most cases, the complexities of the Bluetooth specifications and we show that these models were oversimplified in many cases. A general computational model will be useful as a starting point to design BSF algorithms and to compare the different and numerous BSF algorithms – especially in term of the execution time efficiency. In this thesis, we provide a set of suggestions that will help in the creation of such model. We survey a number of studies that examined in more depth the specifications of device discovery in Bluetooth. We survey also other studies that attempted to simplify the Bluetooth network model, either by suggesting modifications on the Bluetooth specifications or by the use of communication technologies other than Bluetooth. Finally, we present some experiments accompanied with analyzes to show the complexities of the Bluetooth specifications and their sensitivity to minor changes (whether in the specifications or in their implementation).

The most dominant architecture in the contemporary business domain is Service Oriented Architecture (SOA). The large number of the existing service description and discovery systems available today, including the ones proposed in research proposals, reveals an increasing need for adaptive, semantically enriched and context-aware, wide-area service discovery. This need will become more intense in the years to come as the number of available services increases rapidly. The main reason behind the existence of a plethora of such systems is that before these initiatives, the standard in service discovery was taking into account only the syntactic descriptions of the services, causing conflicts when services, with similar syntactic descriptions, needed to be evaluated. The research solutions available today offer efficient and accurate discovery at the syntactic, functional semantic and non-functional semantic level. However, the problem is that there is no general consensus yet regarding service discovery. Research by its very nature, leads to point solutions rather than complete systems. Based on these observations, we propose an adaptive service description and discovery framework for carrier applications, enabling the model-driven specification of services and client profiles, and also, for allowing the dynamic configuration of the services to meet specific quality requirements defined by the clients. The framework was implemented in the context of Model Driven Development, to ensure platform independence at the level of the specification of services. The framework takes the union of the point solutions offered by research proposals in the area of service description and discovery, creates an abstract model, and can compile that model to platform specific code. More specifically, services for carrier applications can be specified in a platform independent way both in terms of service signatures (syntactic properties) and in terms of the functionality and the QoS service characteristics (semantic properties). A model transformation framework allows for the creation of a platform specific model for the description of services in a specific technology platform (e.g., Web services). The framework is extensible to accommodate future extensions. In addition, as a proof of concept, we designed and developed an Eclipse Rich Client Platform (RCP) prototype tool, implementing our proposal.

Un recueil de toutes les subventions à la découverte du CRSNG détenues à l'université Laurentienne durant 2003-2004. A booklet of all NSERC Discovery grants held at Laurentian University in 2003-2004. / CRSNG et l'université Laurentienne NSERC and Laurentian University

The most dominant architecture in the contemporary business domain is Service Oriented Architecture (SOA). The large number of the existing service description and discovery systems available today, including the ones proposed in research proposals, reveals an increasing need for adaptive, semantically enriched and context-aware, wide-area service discovery. This need will become more intense in the years to come as the number of available services increases rapidly. The main reason behind the existence of a plethora of such systems is that before these initiatives, the standard in service discovery was taking into account only the syntactic descriptions of the services, causing conflicts when services, with similar syntactic descriptions, needed to be evaluated. The research solutions available today offer efficient and accurate discovery at the syntactic, functional semantic and non-functional semantic level. However, the problem is that there is no general consensus yet regarding service discovery. Research by its very nature, leads to point solutions rather than complete systems. Based on these observations, we propose an adaptive service description and discovery framework for carrier applications, enabling the model-driven specification of services and client profiles, and also, for allowing the dynamic configuration of the services to meet specific quality requirements defined by the clients. The framework was implemented in the context of Model Driven Development, to ensure platform independence at the level of the specification of services. The framework takes the union of the point solutions offered by research proposals in the area of service description and discovery, creates an abstract model, and can compile that model to platform specific code. More specifically, services for carrier applications can be specified in a platform independent way both in terms of service signatures (syntactic properties) and in terms of the functionality and the QoS service characteristics (semantic properties). A model transformation framework allows for the creation of a platform specific model for the description of services in a specific technology platform (e.g., Web services). The framework is extensible to accommodate future extensions. In addition, as a proof of concept, we designed and developed an Eclipse Rich Client Platform (RCP) prototype tool, implementing our proposal.

3D ex vivo tumor models are required which better replicate the microenvironment encountered by tumor cells in vivo. In this study, we applied bone tissue engineering culture techniques to develop an ex vivo 3D bone tumor model. Ewing sarcoma cells were cultured on poly(ε-caprolactone) (PCL) microfiber scaffolds, and cellular growth kinetics, morphology, and infiltration were assessed. Cell/scaffold constructs were then exposed to anticancer drugs for up to 16 days and drug response was compared to 2D controls. Ewing sarcoma cells were capable of attachment and proliferation on PCL scaffolds and dense scaffold infiltration up to 200 micrometers. Constructs could be maintained in culture for up to 32 days, and high density 3D cell growth conferred an increased resistance to anticancer drugs over 2D controls. This 3D tumor model shows potential for use in future studies of bone tumor biology, especially as it pertains to the development of new anticancer drugs.

Drug development research on wound repair is challenging and inefficient due to the complex nature of wound healing and scarring processes and the limitations of available in vitro or in vivo models used for preclinical drug testing. Many patients who undergo elective back surgery develop post-surgical complications resulting from excess peridural scarring in and around the site of operation. We tested the effects of two anti-inflammatory compounds, quercetin and L-2-oxothiazolidine-4-carboxylate (OTC), in ameliorating peridural scar formation following spinal laminectomy surgery in laboratory rats. Western blot and immunocytochemical analyses indicated that the peridural scar tissue contained MyoD-positive myoblast cells and expressed prolyl-4-hydroxylase (P4H), a fibroblast marker. Treatment with 1 mM OTC reduced activation of ERK1/2 and p38 mitogen-activated protein kinases (MAPK) at 21 days post-surgery suggesting potential anti-scarring mechanism. However, large animal to animal variation in the expression levels of collagen biosynthesis markers made it difficult to demonstrate any efficacy of quercetin or OTC in reducing peridural scar formation. The shortcomings of this live animal approach led us to develop a novel three-dimensional (3-D) <i>in vitro</i> wound repair model for evaluating quercetin and OTC effects. High-density micromass co-cultures seeded at a 1:3 ratio of FR 3T3 fibroblast cells and L8 myoblast cells formed 3-D microtissues <i>in vitro</i> that expressed MyoD, P4H, and á-smooth muscle actin. The micromass tissue layer remained adherent to the culture plate when inflicted with a single laceration injury, which allowed monitoring of cell migration into the wound site. Wounded cultures were treated with quercetin, OTC and other agents (TGF- â1, mitomycin, p38 inhibitor SB202190, ERK inhibitor PD184352) to determine their effects on collagen accumulation, wound closure rates, MAPK activation, and gene transcript expression. Both OTC and quercetin treatments reduced collagen biosynthesis in dose-dependent manner. In addition, 1.5 mM OTC accelerated wound closure and significantly reduced p38 MAPK activation without affecting ERK1/2. In contrast, 40 µM quercetin delayed wound closure in micromass co-cultures and reduced ERK1/2 activation. Our in vitro findings suggest that OTC might have potential as an anti-scarring agent. Importantly, our novel micromass co-culture system shows promise as an improved 3-D scaffold-free in vitro model for use in preclinical drug development research.

Service-oriented Architecture is now an important issue when it comes to program development. However, there is not yet an efficient and effective way for developer to obtain appropriate component. Current researches mostly focus on either textual meaning or ontology relation of the services. In this research we propose a hybrid approach that integrates both types of information. It starts by defining important attributes and their weights for web service discovery using Multiple Criteria Decision Making. Then a method of similarity calculation based on both textual and ontological information is applied. In the experiment, we collect 103 real-world Web services, and the experimental results show that our approach generally performs better than the existing ones.

An array of ship types was used during the European Age of Expansion (early 15th to early 17th centuries), but one vessel in particular emerges from the historical records as a harbinger of discovery: the caravel. The problem is that little is known about these popular ships of discovery, despite the fair amount of historical evidence that has been uncovered. How big were they? How many men did it take to operate such a vessel? What kind of sailing characteristics did they have? How and by whom were they designed? Where did they originate and how did they develop? These questions cannot be answered by looking at the historical accounts alone. For this reason, scholars must take another approach for learning about caravels by examining additional sources, namely ancient shipbuilding treatises, archaeological evidence, surviving archaic shipbuilding techniques, and iconographic representations from the past. Information gained from the available sources reveals many of the caravel’s characteristics through time. This ship type outclassed its contemporaries during the age of exploration because of its highly adaptive characteristics. These traits were, principally, its shallow draught, speed, maneuverability, and ability to sail close to the wind. This combination of attributes made the caravel the ideal ship for reconnaissance along the rocky African coastline, as well as for making the transatlantic voyages to the New World. It was built in a Mediterranean way during its post-medieval phases, a method that still survives in some parts of the world today. During the Age of Discovery (ca. 1430 to 1530), the caravel sat low in the water, had one sterncastle, and was either lateen-rigged or had a combination of square and lateen sails. This vessel reflects the advanced shipbuilding technology that existed in Europe at this time, and played and important role in the voyages which allowed the Europeans to expand their territories around the world. The results of the studies presented in this thesis provide a history and development of the caravel, which was gradual and often obscure. What has been gained from this work is a body of information that can be applied to other studies about ancient seafaring, and can serve as a starting point for further research.