We exposed a native endangered species, bonytail chub (Gila elegans), to graded concentrations of secondarily-treated effluent. At the end of each treatment period, we collected water from all raceways and samples were analyzed for the presence of 83 organic wastewater compounds. We extracted blood plasma from control and treatment fish in each raceway and samples were analyzed for hormones, 17β-estradiol and 11-ketotestosterone, and the egg yolk protein, vitellogenin.17β-estradiol concentrations were consistently lower in treatment females than those detected in control females. The 17β-estradiol and vitellogenin concentrations were always higher in treatment males than those found in control males. Concentrations of 11-ketotestosterone were consistently lower in treatment males than those detected in control males.Endocrine disrupting effects occurred in male and female fish exposed to low concentrations of effluent. Changes in hormone levels suggested a feminizing effect in treatment male fish and an androgenizing effect in treatment female fish.

The networking paradigm uses new information vectors consisting of human carried devices is known as disruption-tolerant networks (DTN) or opportunistic networks. We identify the binary assertion issue in DTN. We notice how most DTNs mainly analyze nodes that are in contact. So all nodes that are not in contact are in intercontact. Nevertheless, when two nodes are not in contact, this does not mean that they are topologically far away from one another. We propose a formal definition of vicinities in DTNs and study the new resulting contact/intercontact temporal characterization. Then, we examine the internal organization of vicinities using the Vicinity Motion framework. We highlight movement types such as birth, death, and sequential moves. We analyze a number of their characteristics and extract vicinity usage directions for mobile networks. Based on the vicinity motion outputs and extracted directions, we build the TiGeR that simulates how pairs of nodes interact within their vicinities. Finally, we inquire about the possibilities of vicinity movement prediction in opportunistic networks. We expose a Vicinity Motion-based heuristic for pairwise shortest distance forecasting. We use two Vicinity Motion variants called AVM and SVM to collect vicinity information. We find that both heuristics perform quite well with performances up to 99% for SVM and around 40% for AVM.

Phytosterols are naturally occurring compounds which regulate membrane fluidity and serve as hormone precursors in plants. They also have the potential to cause endocrine disturbances in aquatic animals at concentrations as low as 10 µg/L. Wastewaters from several industries which process plant matter can contain phytosterols at concentrations in excess of the above-stated level. Despite their endocrine disruption potential, very little is known about phytosterol physical properties and their biotransformation potential in biological treatment systems. Aerated stabilization basins (ASBs) are common biological treatment systems in North American pulp and paper mills. ASBs are large open lagoons which use tapered surface aeration to remove COD and prevent sulfate reduction in the water column. Phytosterols are released from wood during the pulping process and a small fraction enters the wastewater stream during washing of the pulp. Therefore, phytosterols may be exposed to aerobic or anaerobic environments depending on their solubility and solid-liquid partitioning behavior. The overall objective of this research was to systematically and quantitatively assess the biotransformation potential of phytosterols in biological treatment systems and to examine conditions leading to reduction of these compounds in wastewater effluent streams. The results of this research showed that phytosterols are sparingly soluble with aqueous solubility below 1 µg/L when present as a mixture. Phytosterols have a strong affinity to adsorb to solids and dissolved organic matter. The affinity for aerobic biomass was greater than for wastewater solids. The stigmasterol desorption rate and extent from wastewater solids increased with an increase in pH from 5 or 7 to 9. Phytosterols were biotransformed under aerobic conditions but not under sulfate-reducing or methanogenic conditions by stock cultures developed in this study. Biotransformation under nitrate-reducing conditions could not be confirmed conclusively. The continuous-flow system was successful in removing 72 to 96% of phytosterols. Biotransformation accounted for 23, 14 and 41 % of campesterol, stigmasterol and β-sitosterol removal, respectively. Phytosterols accumulated in the reactor sediment and accounted for 97 % of the total phytosterols remaining in the system. Phytosterols can be removed from wastewater streams during biological treatment by a combination of biotransformation and solids partitioning and control of system pH, DO and available carbon and energy sources can increase the degree of phytosterols removal. The results of this research can be used to engineer effective biological treatment systems for the removal of phytosterols from pulp mill wastewaters and other phytosterol-bearing wastewater streams.

As part of their reclamation plan, oil sands operators propose to transfer the mature fine tailings, which are a by-product of the oil sands extraction process, to open-pits and cap them with either a layer of surface water or oil sands process-affected waters (OSPW). These oil sands pit lakes are expected to develop habitats with productive capabilities comparable to natural lakes in the region. The studies presented in this thesis evaluate the potential impact of OSPW and its associated constituents [i.e. acid-extractable organics (e.g. naphthenic acids; NAs) and salts] on the reproductive physiology of adult fathead minnow (Pimephales promelas). Through 14-21 day fathead minnow reproduction assays it was demonstrated that aged OSPW can impair spawning, lower plasma sex steroid concentrations, and reduce male secondary sexual characteristics. The acid-extractable organics in OSPW were demonstrated to have an adverse effect on fathead minnow reproductive physiology. Other studies showed that the high salinity which characterizes OSPW also influences toxicity. When fathead minnows were exposed to the OSPW extract and 700 mg/l of NaHCO3, the NaHCO3 reduced the inhibitory effects of the extract on the numbers of reproductive tubercles and plasma testosterone levels by reducing the uptake of NAE to the fish. Embyro and larval bioassays also revealed that NaHCO3 reduces the acute toxic effects of the OSPW extract. An assessment of a wild population of fathead minnows inhabiting an OSPW pond determined that there were differences in the condition factor (CF), gonadosomatic indices (GSIs), liver somatic indices (LSIs), male secondary sexual characteristics, and 11-ketotestosterone concentrations in the fathead minnows from the OSPW pond relative to fish collected at reference sites. The opercula of fathead minnows from the OSPW pond also differed from those of reference fish and an examination of the gills revealed that were a number of proliferative and degenerative alterations relative to reference fish. Collectively, these studies demonstrate that aged OSPW has the potential to negatively affect the reproductive physiology of fathead minnows and suggest that aquatic habitats with high NAs concentrations (>10 mg/l) will have adverse effects on fish. / Canadian Natural Resources Ltd., Canadian Water Network, Canadian Oil Sands Network for Research and Development (CONRAD), Imperial Oil Ltd., NSERC, Shell Canada Energy, Suncor Energy Inc., Syncrude Canada Ltd., and Total E&P Canada

A cancer diagnosis often causes biographical disruption in the lives of young adult (i.e., 18-39; YA) survivors and their close social network members (i.e., familial, plutonic, or romantic relational partners with whom the survivor has a salient relationship; SNM). In order to integrate their illness into their lives, normatively regain balance and equilibrium, and achieve a “new normal” following a cancer diagnosis, YA survivors and their close SNMs must work to reconstruct their biographies by engaging in tangible interpersonal communication processes often used to initiate and maintain relationships. However, YA cancer survivors report facing social struggles due to the biographical disruption of their illness across the trajectory of diagnosis, treatment, and survivorship. To learn more about their unique social experience of cancer, I conducted private, open-ended narrative interviews with 20 YA survivor-close SNM dyads, 1 YA survivor-SNM close triad, and 10 individual YA survivors (N = 51). I used thematic narrative analysis to determine how and why YA cancer survivors and their close SNMs communicate social support messages with romantic partners, family, friends, peers, and one another. By examining the narratives of YA survivors, their close SNMs, and the dyad itself, this dissertation explores the interpersonal communication processes used to initiate and maintain relationships across the illness trajectory by focusing on the barriers and facilitators these individuals experience in the communication of social support. Through their individual narrative accounts, YA survivors explained why and how they perceived various support attempts from others to be positive or negative, and their close SNMs detailed their attempts to navigate the YA’s larger support network and assume the duties inherent in their newly-adopted “top supporter” role. In addition, reports from YAs and their SNMs revealed that they often engaged in mutual pretense, a unique and often unsustainable form of support that occurred between YA survivors and their close SNMs involving topic avoidance and emotional management. Implications for the advancement of interpersonal communication theory and for practical intervention targeting YA patients and survivors, their close SNMs, and medical practitioners are also discussed.

Background: Approximately 40% of low back pain cases are attributed to internal disc disruption. Since mechanical loading directly affects intradiscal pressure and the stresses that the inner annulus fibrosus experiences, the mechanism that leads to disruption of the inner annulus fibrosus may be linked to changes in intradiscal pressure. Hence, there is a need to examine how intradiscal pressure changes over time during a flexion extension cyclic (FEC) loading protocol known to induce internal disc disruption. Purpose: 1) To determine whether a bore-screw pressure sensor system could be used as an alternative sensor for measuring intradiscal pressure, and 2) to characterize changes in intradiscal pressure, moments, and axial deformation using a FEC loading protocol. Study 1 summary: Technical specifications of the bore-screw pressure sensor system were compared to the needle pressure sensor. The error projected at a static compressive load of 1500 N was approximately eight percent and the bore-screw pressure sensor had an excellent dynamic response compared to the needle pressure sensor. Study 2 methods: The bore-screw pressure sensor system was successfully instrumented in 14 porcine specimens. The FEC loading protocol consisted of 3600 cycles of 1 Hz flexion-extension movement while applying a 1500 N compressive load. The four dependent variables collected were intradiscal pressure, moment, axial deformation, and angular displacement. Study 2 results: Intradiscal pressure and specimen height decreased by 45 % and 62 %, respectively, and the peak moment increased by 102 % following the FEC loading protocol. There were strong correlations between average intradiscal pressure and both peak moment and average axial deformation. The angle where maximum pressure occurred demonstrated a significant difference after 2700 cycles. There were no sequential changes in pressure difference after 2100 cycles. Twelve out of 14 specimens showed partial herniation (85.7%); however, the injury type was not correlated to the pressure change. Conclusions: Changes in intradiscal pressure were successfully characterized over time using a new pressure sensor system. Although the change in pressure difference was not predictive of an injury type, its increasing trend over time suggested that the inner annulus fibrosus failure mechanism may be related to fatigue.

Nanoparticles (NPs) are engineered in the nanoscale (<100nm) to have unique physico-chemical properties from their bulk counterparts. Nanosilver (nAg) is the most prevalent nanoparticle in consumer products due to its strong antimicrobial action and can be released to the environment during product manufacture, usage and disposal. The predicted environmental concentrations are within the North American guidelines for the protection of aquatic life and in drinking water. While nAg toxicity at high concentrations has been well described, the sublethal effects at environmentally-relevant concentrations are relatively unknown. Initial screening in our lab showed nAg was a potential endocrine disrupting chemical (EDC). Amphibian metamorphosis is mediated by thyroid hormone (TH), and nAg perturbed TH-dependent transcriptional responses in the tailfin of bullfrog (Rana catesbeiana) tadpoles. The primary objective of this thesis was to further investigate and characterize the effects of low, environmentally relevant concentrations of nAg on TH-dependent metamorphosis in R. catesbeiana and Xenopus laevis. Two chronic, 28 day in vivo exposures at 0.06 and 6µg/L nAg were conducted with premetamorphic R. catesbeiana tadpoles using TH to induce precocious metamorphosis. Ionic silver (iAg) was also examined to control for the complete dissolution of Ag. Analysis of metamorphic stage progression demonstrated nAg-induced acceleration of hindlimb growth and development. After 6 days of nAg exposure, analysis with quantitative real-time polymerase chain reaction (QPCR) demonstrated nAg-induced disruption of TH-responsive transcripts in a tissue-specific manner. Furthermore, the nAg effects could not be fully explained by iAg, indicating NP-specific disruption. Two chronic, 28 day exposures to 0.018-1.8 µg/L nAg were conducted on X. laevis premetamorphic and prometamorphic tadpoles. nAg was found to significantly bioaccumulate in tadpole tissue after 28 days. Furthermore, nAg increased the hindlimb length during early premetamorphosis and in post-metamorphic juvenile tadpoles. Using an in-house MAGEX microarray and QPCR transcriptional analysis, 7 biomarkers of nAg exposure were validated. Five of these targets showed disruption to their TH-response. Furthermore, the increased mRNA abundance of two peroxidases indicated that nAg generated reactive oxygen species (ROS) even at low, environmental concentrations. This thesis demonstrates that nAg has consistent EDC actions across two distinct amphibian species, and the data suggest that regulatory guidelines for silver may need revision. A X. laevis derived fibroblast-like TH-responsive cell line, XTC-2, was used in conjunction with the 7 biomarkers of nAg exposure to gain mechanistic insight into the role of ROS in TH signaling disruption. Monocultures were created and validated to increase the specificity of TH-response. While the monocultures were successfully created, the biomarkers were not responsive to nAg in this cell line. Additional investigations were made into the relationship between genetic sex and responsiveness to TH. Genetic sexing methods were used to investigate transcriptional differences between males and females during natural and TH-induced metamorphosis. The sexing protocol was optimized and validated successfully. The genetic sex was determined for premetamorphic and prometamorphic X. laevis tadpoles exposed to TH for 48 h. QPCR and microarray analysis were used to identify three markers that demonstrated transcriptional sex-bias during early gonadal differentiation stages. / Graduate / 0307 / 0383 / 0487 / amanda_carew14@yahoo.ca

The mitochondrion is an important therapeutic target due to its roles in energy metabolism, reactive oxygen species production, and activation of cell death. The connection of these cellular processes with diabetes, obesity, neurodegenerative disorders, and cancer makes this organelle a potential control point for treatment of these diseases. The advancement of mitochondrial medicine will be accelerated by the development of organelle-specific cellular transporters as well as by strategies to enhance the activity of mitochondrially-active drugs. Here, the discovery and development of a new class of mitochondria-specific agents, mitochondria-penetrating peptides (MPPs), is described. These peptides, exemplified by the sequences (FXY)3 and (FXY)4 where FX=cyclohexylalanine and Y=basic arginine or lysine residues, display hydrophobic and cationic residues critical for access to this organelle, and appear to accumulate within cells and mitochondria through membrane potential-dependent mechanisms. Subcellular localization of the peptides was determined by the interplay of hydrophobicity and positive charge, and necessary lipophilicity “thresholds” for access to the mitochondrion. MPPs can be engineered to have minimal mitochondrial disruptive activity and cytotoxicity through minimization of hydrophobicity and length. Furthermore, MPPs appear to accumulate predominantly in the mitochondrial matrix, a feature which places them within an exclusive class of mitochondria-specific transporters and may enable delivery applications for a number of therapeutically-relevant cargoes. Information gained from MPP studies on the physiochemical parameters that drive mitochondrial localization were applied to improve the activity of the anticancer peptide d-(KLAKLAK)2, an agent that activates apoptosis through mitochondrial disruption. Residue substitutions that increased peptide hydrophobicity, regardless of changes to secondary structure, enhanced mitochondrial localization, activity, and cytotoxicity induced by the peptide. In conclusion, these studies provide important guidelines for how to drive the subcellular localization and activity of peptides, and expand the possibilities for mitochondrially-targeted therapeutics.

Fluoxetine (FLX), the active ingredient of Prozac™, is a member of the selective serotonin reuptake inhibitor (SSRI) class of anti-depressant drugs and is present in aquatic environments worldwide. Previous studies reported that FLX is an endocrine disruptor in fish, bioconcentrating in tissues including the brain. Evidence implicates that serotonin influences the activity of the hypothalamo-pituitary-interrenal (HPI) stress axis, thus exposure to FLX may disrupt the teleost stress response. This study examined in vitro cortisol production in rainbow trout (Oncorhynchus mykiss) head kidney/interrenal cells exposed to FLX and 14C-pregnenolone metabolism in head kidney microsome preparations of FLX-exposed trout. Results indicated that cells exposed in vitro to increasing concentrations of FLX had lower cortisol production and cell viability (versus control) and microsomes isolated from trout exposed to 54 μg/L FLX had higher pregnenolone metabolism versus those of control and low FLX-exposed (0.54 μg/L) trout.

Disturbance has been recognised as a presence in Yeats’s poetry for some time, although its discussion has not been extensive. The purpose of this thesis is to explore a particular type of disturbance in Yeat’s poetry that has not yet been investigated: disruption, and its relation to the Bible. I argue that disruption, in its meanings of interruption, disorder, fracturing, and division, is a distinct presence in a number of Yeat’s poems, and that it manifests in three key categories: disruption relating to Yeatsian poiesis, Yeat’s interest in and use of instances of disruption in the Bible, and disruption of the Bible itself. / I begin by considering “The Second Coming” as a notable instance of disruption and its religious and biblical resonances. I argue that this work, in reference to an instance of disruption in the Bible, undergoes textual disruption close to its centre. I develop an account of the poem as divided into opposing texts, identities, and prophetic currents, all in close relation to the Bible. I then turn to a range of contextual matters raised by the discussion of “The Second Coming”. Starting with a consideration of religion and the Bible in Yeat’s artistic vision, I argue that these two factors are important to Yeat’s envisioning of art and that disruption is deeply involved with both. Following this I investigate the relation between disruption and the Bible itself, demonstrating that disruption is a strong presence in the biblical narrative. I then consider Yeat’s reception of the Bible, focusing on Yeat’s perception of the Authorised Version and on Blake as a precursor. I argue that the Authorised Version was significant for Yeats, and that Blake was influential in demonstrating the poetic possibilities of biblically-related disruption for Yeats. / After discussing these contextual matters I embark upon a wider survey of biblically-related disruption in Yeat’s poetry. First, I consider a group of poems from one of Yeat’s earlier poetic books, The Wind Among the Reeds. I argue that these works, through the figure of the biblical wind, explore the conjunction of disruption and the Bible in each of the three categories of disruption outlined above. I then turn to a second set of poems that I group together due to a shared theme of inspiration. I argue that these works also engage with disruption and the Bible, particularly in relation to the category of disruption relating to the act of poiesis. The last group of poems that I consider are concerned with central events in the life of Christ. I argue that these works demonstrate a dynamic exploration of disruption and the Bible in relation to these events, focusing particularly on the nature of Christ as God and Saviour. I then proceed to a consideration of disruption in Yeats apart from its expression in the poetry. Seeking to gain a deeper insight into disruption as an element of Yeatsian poiesis, I consider some relevant theoretical perspectives before suggesting that disruption in Yeats can be constructively interpreted in terms of potentiality.