The current understanding of lactate metabolism in fish is based almost entirely on interpretation of concentration measurements that cannot be used to infer changes in flux. Moreover, the transporters regulating these fluxes have never been characterized in rainbow trout. My goals were: (1) to quantify lactate fluxes in rainbow trout under normoxic resting conditions, during acute hypoxia, and exercise by continuous infusion of [U-14C] lactate; (2) to determine lactate uptake capacity of trout tissues by infusing exogenous lactate in fish rest and during graded exercise, and (3) to clone monocarboxylate transporters (MCTs) and determine the effects of exhausting exercise on their expression. Such information could prove important to understand the mechanisms underlying the classic “lactate retention” seen in trout white muscle after intense exercise. In normoxic resting fish, the rates of appearance (Ra) and disappearance (Rd) of lactate were always matched (~18 to 13 µmol kg-1 min-1), thereby maintaining a low baseline blood lactate concentration (~0.8 mM). In hypoxic fish, Ra lactate increased from baseline to 36.5 µmol kg-1 min-1, and was accompanied by an unexpected 52% increase in Rd reaching 30.3 µmol kg-1 min-1, accounting for a rise in blood lactate to 8.9 mM. In exercising fish, lactate flux was stimulated > 2.4 body lengths per second (BL s-1). As the fish reached critical swimming speed (Ucrit), Ra lactate was more stimulated (+67% to 40.4 μmol kg-1 min-1) than Rd (+41% to 34.7 μmol kg-1 min-1), causing an increase in blood lactate to 5.1mM. Fish infused with exogenous lactate stimulated Rd lactate by 300% (14 to 56 μmol kg-1 min-1) during graded exercise, whereas the Rd in resting fish increased by only 90% (21 to 40 µmol kg-1 min-1). Four MCT isoforms were partially cloned and characterized in rainbow trout: MCT1b was the most abundant in heart, and red muscle, but poorly expressed in gill and brain where MCT1a and MCT2 were prevalent. MCT4 was more expressed in the heart. Transcript levels of MCT2 (+260%; brain), MCT1a (+90%; heart) and MCT1b (+50%; heart) were stimulated by exhausting exercise. This study shows that: (i) the increase in Rd lactate plays a strategic role in reducing the lactate load imposed on the circulation. Without this response, blood lactate accumulation would double; (ii) a high capacity for lactate disposal in rainbow trout tissues is elicited by the increased blood-to-tissue lactate gradient when extra lactate is administered; and (iii) rainbow trout may be unable to release large lactate loads rapidly from white muscle after exhausting exercise (lactate retention) because they poorly express MCT4 in white muscle and fail to upregulate its expression during exercise.

The focus of this research is on the specific relational and particular circumstances that result in an emerging cancer identity expressed through the daily lived- experiences of emerging adults via personal weblogs. Identity, a complex term in its own right, is discussed here under the rubric of social identity as processual, therefore it is expected that an emerging cancer identity will develop as the participants begin to narrativize their daily experiences with cancer on their weblogs. By critically engaging with notions of emerging adulthood theories with theories on the sociology of death and dying and illness narratives, this research seeks to understand the specific psychosocial changes that occur as the participants engage with their illness on their weblogs, which arguably contributes to an emerging cancer identity.

In this dissertation, I examine the constructions, maintenance, and resistance to dominant discourses concerning motherhood and non-motherhood in contemporary Hungary, using the popular Hungarian women’s magazine Nők Lapja as my key illustrative example. I strive to illuminate how gendered discourses, bio-power, history, and geo-politics are implicated not only in the construction of nationhood but also in defining women’s roles in nation-building. I hope to contribute to research that helps to better understand women’s contemporary social roles in Hungary, and the power relations that construct them. I argue that ideas regarding motherhood and non-motherhood in Hungary are often bound up in ideas concerning who should, or should not, have children, and why, and I explore in detail how these ideas have formed through the history of the nation. My analysis reveals different sites of power—focusing on policy and print media—that seek to determine women’s procreative decisions. I argue that, under various regimes, women’s procreative choices have consistently been systemically constrained, and framed as key to the nation’s success—or failure. Concerning Nők Lapja magazine, my research reveals that it both supports and resists traditional gender roles, at times contributing to discourses that naturalize childbearing and motherhood (also defining for readers whose motherhood is deemed desirable), but at other times disputing such ideas and redefining conceptions of womanhood to include women without children. Although ultimately the magazine pathologizes, disbelieves and negates the choice to be childless, Nők Lapja does resist and redefine limited definitions of womanhood and motherhood by carving out a small space for discussions of childlessness, and also by challenging conceptions of singletons as necessarily lonely and mothers as necessarily better if they stay at home.

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Nowell (1976) first proposed that unless cytotoxic cancer therapy eradicates all tumor cells, genetic or heritable variation within heterogeneous tumors will inevitably lead to the evolution of chemotherapeutic resistance through clonal selection. This evolutionary hypothesis was formalized by Goldie and Coldman (1979), who developed one of the earliest mathematical kinetic models of resistance evolution in neoplasms. Their model predicted that the likelihood of response and cure would be increased in combination vs single agent cytotoxic therapies. In a later study, Gardner (2002) developed a computational kinetic model to predict chemotherapeutic combinations, doses, and schedules most likely to result in patient response and prolonged life. This model predicts that combination therapy involving both cytotoxic and cytostatic drugs will be more effective than combination therapy involving only cytotoxic drugs. Thus far, no systematic evaluation of the Goldie and Coldman and Gardner hypotheses have been conducted in the metastatic clinical trial setting. Here I test these hypotheses using the results of over 700 phase II, III and II/III clinical trials. I show that, as predicted by Goldie and Coldman, both overall response rate and overall survival were greater in combination arms. Moreover, median duration of response – the key indicator of the rate of resistance evolution - was also greater in combination vs single agent arms. These results suggest that generally combination chemotherapy is more effective than single agent therapy for advanced solid tumors as predicted by Goldie and Coldman (1979) hypothesis and that, at least in the metastatic setting, the potential disadvantages of combination therapy with respect to accelerated resistance evolution are outweighed by the greater waiting times for resistance mutations to arise. By contrast, although combination cytotoxic and cytostatic therapy is associated with a greater average overall response rate than multi agent cytotoxic therapy, this is not the case for both median duration of response and overall survival. Hence, there is no evidence that, in contrast to the predictions of the Gardner (2002) model, combination cytotoxic and cytostatic therapy decreases the rate of resistance evolution relative to that obtaining under combination cytotoxic therapy.

This thesis introduces normal factor graphs under a new semantics, namely, the exterior function semantics. Initially, this work was motivated by two distinct lines of research. One line is ``holographic algorithms,'' a powerful approach introduced by Valiant for solving various counting problems in computer science; the other is ``normal graphs,'' an elegant framework proposed by Forney for representing codes defined on graphs. The nonrestrictive normality constraint enables the notion of holographic transformations for normal factor graphs. We establish a theorem, called the generalized Holant theorem, which relates a normal factor graph to its holographic transformation. We show that the generalized Holant theorem on one hand underlies the principle of holographic algorithms, and on the other reduces to a general duality theorem for normal factor graphs, a special case of which was first proved by Forney. As an application beyond Forney's duality, we show that the normal factor graphs duality facilitates the approximation of the partition function for the two-dimensional nearest-neighbor Potts model. In the course of our development, we formalize a new semantics for normal factor graphs, which highlights various linear algebraic properties that enables the use of normal factor graphs as a linear algebraic tool. Indeed, we demonstrate the ability of normal factor graphs to encode several concepts from linear algebra and present normal factor graphs as a generalization of ``trace diagrams.'' We illustrate, with examples, the workings of this framework and how several identities from linear algebra may be obtained using a simple graphical manipulation procedure called ``vertex merging/splitting.'' We also discuss translation association schemes with the aid of normal factor graphs, which we believe provides a simple approach to understanding the subject. Further, under the new semantics, normal factor graphs provide a probabilistic model that unifies several graphical models such as factor graphs, convolutional factor graphs, and cumulative distribution networks.

The dissemination of various types of data faces ongoing challenges with the growing need of accessing manifold information. Since the interest in content is what drives data networks, some new technologies and thoughts attempt to cope with these challenges by developing content-based rather than address-based architectures. The Publish/ Subscribe paradigm can be a promising approach toward content-based data dissemination, especially that it provides total decoupling between publishers and subscribers. However, in content-based publish/subscribe systems, subscriptions are expressive and the information is often delivered based on the matched expressive content - which may not deeply alleviate considerable performance challenges. This dissertation explores a hardware solution for disseminating data in content-based publish/subscribe systems. This solution consists of an efficient hardware architecture of an XML/XPath broker that can route information based on content to either other XML/XPath brokers or to ultimate users. A network of such brokers represent an overlay structure for XML content-based publish/subscribe data dissemination systems. Each broker can simultaneously process many XPath subscriptions, efficiently parse XML publications, and subsequently forward notifications that result from high-performance matching processes. In the core of the broker architecture, locates an XML parser that utilizes a novel Skeleton CAM-Based XML Parsing (SCBXP) technique in addition to an XPath processor and a high-performance matching engine. Moreover, the broker employs effective mechanisms for content-based routing, so as subscriptions, publications, and notifications are routed through the network based on content. The inherent reconfigurability feature of the broker’s hardware provides the system architecture with the capability of residing in any FPGA device of moderate logic density. Furthermore, such a system-on-chip architecture is upgradable, if any future hardware add-ons are needed. However, the current architecture is mature and can effectively be implemented on an ASIC device. Finally, this thesis presents and analyzes the experiments conducted on an FPGA prototype implementation of the proposed broker/router. The experiments tackle tests for the SCBXP alone and for two phases of development of the whole broker. The corresponding results indicate the high performance that the involved parsing, storing, matching, and routing processes can achieve.

Several studies were undertaken by various investigators during the last five decades to better understand the engineering behaviour of unsaturated soils. These studies are justified as more than 33% of soils worldwide are found in either arid or semi-arid regions with evaporation losses exceeding water infiltration. Due to this reason, the natural ground water table in these regions is typically at a greater depth and the soil above it is in a state of unsaturated conditions. Foundations of structures such as the housing subdivisions, multi-storey buildings, bridges, retaining walls, silos, and other infrastructure constructed in these regions in sandy soils are usually built within the unsaturated zone (i.e., vadose zone). Limited studies are reported in the literature to understand the influence of capillary stresses (i.e., matric suction) on the bearing capacity, settlement and liquefaction potential of unsaturated sands. The influence of matric suction in the unsaturated zone of the sandy soils is ignored while estimating or evaluating bearing capacity, settlement and liquefaction resistance in conventional engineering practice. The focus of the research presented in the thesis has been directed towards better understanding of these aspects and providing rational and yet simple tools for the design of shallow foundations (i.e., footings) in sands under both static and dynamic loading conditions. Terzaghi (1943) or Meyerhof (1951) equations for bearing capacity and Schmertmann et al. (1978) equation for settlement are routinely used by practicing engineers for sandy soils based on saturated soil properties. The assumption of saturated conditions leads to conservative estimates for bearing capacity; however, neglecting the influence of capillary stresses contributes to unreliable estimates of settlement or differential settlement of footings in unsaturated sands. There are no studies reported in the literature on how capillary stresses influence liquefaction, bearing capacity and settlement behavior in earthquake prone regions under dynamic loading conditions. An extensive experimental program has been undertaken to study these parameters using several specially designed and constructed equipment at the University of Ottawa. The influence of matric suction, confinement and dilation on the bearing capacity of model footings in unsaturated sand was determined using the University of Ottawa Bearing Capacity Equipment (UOBCE-2011). Several series of plate load tests (PLTs) were carried out on a sandy soil both under saturated and unsaturated conditions. Based on these studies, a semi-empirical equation has been proposed for estimating the variation of bearing capacity with respect to matric suction. The saturated shear strength parameters and the soil water characteristic curve (SWCC) are required for using the proposed equation. This equation is consistent with the bearing capacity equation originally proposed by Terzaghi (1943) and later extended by Meyerhof (1951) for saturated soils. Chapter 2 provides the details of these studies. The cone penetration test (CPT) is conventionally used for estimating the bearing capacity of foundations because it is simple and quick, while providing continuous records with depth. In this research program, a cone penetrometer was specially designed to investigate the influence of matric suction on the cone resistance in a controlled laboratory environment. Several series of CPTs were conducted in sand under both saturated and unsaturated conditions. Simple correlations were proposed from CPTs data to relate the bearing capacity of shallow foundations to cone resistance in saturated and unsaturated sands. The details of these studies are presented and summarized in Chapter 3. Standard penetration tests (SPTs) and PLTs were conducted in-situ sand deposit at Carp region in Ottawa under both saturated and unsaturated conditions. The test results from the SPTs and PLTs at Carp were used along with other data from the literature for developing correlations for estimating the bearing capacity of both saturated and unsaturated sands. The proposed SPT-CPT-based technique is simple and reliable for estimation of the bearing capacity of footings in sands. Chapter 4 summarizes the details of these investigations. Empirical relationships were proposed using the CPTs data to estimate the modulus of elasticity of sands for settlement estimation of footings in both saturated and unsaturated sands. This was achieved by modifying the Schmertmann et al. (1978) equation, which is conventionally used for settlement estimations in practice. Comparisons are provided between the three CPT-based methods that are commonly used for settlement estimations in practice and the proposed method for seven large scale footings in sandy soils. The results of the comparisons show that the proposed method provides better estimations for both saturated and unsaturated sands. Chapter 5 summarizes the details of these studies. A Flexible Laminar Shear Box (FLSB of 800-mm3 in size) was specially designed and constructed to simulate and better understand the behaviour of model surface footing under seismic loads taking account of the influence of matric suction in an unsaturated sandy soil. The main purpose of using the FLSB is to simulate realistic in-situ soils behaviour during earthquake ground shaking. The FLSB test setup with model footing was placed on unidirectional 1-g shake table (aluminum platform of 1000-mm2 in size) during testing. The resistance of unsaturated sand to deformations and liquefaction under seismic loads was investigated. The results of the study show that matric suction offers significant resistance to liquefaction and settlement of footings in sand. Details of the equipment setup, test procedure and results of this study are presented in Chapter 6. Simple techniques are provided in this thesis for estimating the bearing capacity and settlement behaviour of sandy soils taking account of the influence of capillary stresses (i.e., matric suction). These techniques are consistent with the methods used in conventional geotechnical engineering practice. The studies show that even low values of capillary stresses (i.e., 0 to 5 kPa) increases the bearing capacity by two to four folds, and the settlement of footings not only decreases significantly but also offers resistance to liquefaction in sands. These studies are promising and encouraging to use ground improvement techniques; such as capillary barrier techniques to maintain capillary stresses within the zone of influence below shallow foundations. Such techniques, not only contribute to the increase of bearing capacity, they reduce settlement and alleviate problems associated with earthquake effects in sandy soils.

In 2005 and 2010, high sea surface temperatures caused widespread coral bleaching on Jamaica’s north coast reefs. Three shallow (9m) reef sites were surveyed during each event to quantify the prevalence and intensity of coral bleaching. In October 2005, 29-57% of the colonies surveyed were bleached. By April 2006, 10% of the corals remained pale/partially bleached. Similarly, in October 2010, 23-51% of corals surveyed at the same sites were bleached. By April 2011, 12% of the colonies remained pale/partially bleached. Follow-up surveys revealed low coral mortality following both events, with an overall mean of 4% partial colony mortality across all species and sites observed in April 2006, and 2% in April 2011. Mixed effects models were used to quantify the relationship between colony size and (a) bleaching intensity, and (b) bleaching related mortality among coral species. The bleaching intensity model explained 51% of the variance in the bleaching response observed during the two events. Of this 51%, fixed effects accounted for ~26% of the variance, 17% of which was attributed to species-specific susceptibility to bleaching , 5% to colony size, <1% colony morphology and 4% to the difference in bleaching intensity between the two events. The random factor (site) accounted for the remaining ~25% of the variance. The mortality model explained 16% of the variance in post bleaching mortality with fixed effects, including colony size, morphology and species explaining ~11% of the variance, and the random effect (site) explaining 5%. On average, there was a twofold difference in bleaching intensity between the smallest and the largest size classes. Modelling the relationship between colony level characteristics and site-specific environmental factors on coral species’ susceptibility to thermal stress can shed light on community level responses to future disturbances.

Many consumer and medical products contain engineered nanomaterials (ENMs) due to their unique properties arising from their small size of <100 nm in at least one dimension. Although ENMs could greatly improve the quality of daily life, concerns for their health and environmental safety emerged in recent years because the same properties that make ENMs beneficial may also render them toxic. The small size allows ENMs’ entrance into the cell where they may attach to biological molecules and membranes, disrupting their function and/or leading to oxidative stress and/or damage. This thesis focused on silver nanoparticles (AgNPs). Several articles demonstrated that during washing AgNPs are released from the AgNP-impregnated fabrics and could pose a risk to aquatic species. Given that the toxicity mechanisms of AgNPs are yet to be clearly understood this thesis investigated the effects of AgNPs from ‘oxidative stress’ and ‘endocrine disruption’ points of view, using both in vivo and in vitro model fish systems. A 4 d exposure of zebrafish (Danio rerio) embryos to AgNPs increased mortality, delayed hatching, and increased oxidative stress. The silver ion (Ag+) was more effective in eliciting these effects at equivalent silver concentrations. Moreover, the Ag-chelator cysteine reduced the toxicity of both Ag-types. Despite these effects AgNPs or Ag+ did not affect the ability of zebrafish larvae or adults (raised to adulthood in Ag-free water) to increase cortisol levels, but there were differential effects on the expression of corticotropin-releasing factor (CRF)-related genes, suggesting that other physiological processes regulated by CRF may be impacted. Furthermore, a 48 h exposure of rainbow trout (Oncorhynchus mykiss) erythrocytes and hepatocytes to AgNPs or Ag+ increased oxidative stress, but Ag+ was more potent. Moreover, AgNPs elevated lipid peroxidation, while Ag+ increased DNA damage, suggesting different modes of action for the two Ag-types. Cysteine treatment reduced the toxicity of Ag+ and AgNPs, while buthionine sulfoximine, which inhibits glutathione synthesis, increased it, suggesting the importance of glutathione in silver toxicity. Finally, AgNPs increased glycogenolysis in trout hepatocytes independently of the beta-adrenoreceptor or the glucocorticoid receptor.