• Sclerostin Response to Exercise: Association with Bone Turnover, Oxidative Stress and Inflammation

      Kouvelioti, Rozalia; Applied Health Sciences Program
      The purpose of this thesis was to compare the response of sclerostin, a bone-specific glycoprotein that downregulates bone formation, to two modes (high impact vs non-impact) of high intensity interval exercise and to examine its relationship to potential exercise-induced changes in bone turnover (Study 1), oxidative stress (Study 2) and inflammation (Study 3). For the three studies included in this thesis, 40 healthy, young (18-25 years old) female and male adults performed two high intensity interval exercise trials in random order. Trials consisted of eight repetitions of 1 min high intensity running or cycling (mean heart rate 90% of maximum), separated by 1 min passive recovery intervals between repetitions. Blood samples were collected pre-exercise, and 5 min, 1h, 24h and 48h post-exercise. Sclerostin, bone turnover markers (cross linked telopeptide of type Ⅰ collagen [CTXI], procollagen type I amino-terminal propeptide [PINP]), oxidative stress markers (thiobarbituric acid reactive substances [TBARS], protein carbonyls [PC]) and inflammatory cytokines (interleukin-1β [IL-1β], -10 [IL-10], -6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) were measured in serum. In the first two studies, sclerostin showed a significant time effect, but no significant exercise mode effect or interaction in both females (study 1) and males (study 2). In study 3, sclerostin showed a significant main effect for sex and a significant sex-by-time interaction. Specifically, sclerostin significantly increased from pre- to 5 min post-exercise and returned to baseline levels within 1h post-exercise with greater increase in males than females (47% vs. 34%, respectively). Furthermore, there were no correlations between sclerostin’s exercise-induced increase and the corresponding changes in bone turnover and oxidative stress markers. In contrast, sclerostin’s increase 5 min post-exercise was significantly correlated with the corresponding increase in the inflammatory cytokines, especially TNF-α, which along with sex, significantly explained 34% of the variance in its post-exercise elevation. In conclusion, in both young females and males, one session of high intensity interval exercise leads to an increase in sclerostin immediately post-exercise, and this increase is of similar magnitude following high impact and no impact exercise. Furthermore, the increase in sclerostin 5 min post-exercise seems to be associated with the exercise-induced inflammation.
    • Self-Care as a Pedagogical Ontology in the Professional Care Practice of Others and with Others: A Hermeneutic Phenomenology of Self-Care in Nursing Education

      Docherty-Skippen, Susan Maureen; Department of Graduate and Undergraduate Studies in Education
      Healthcare practitioners work in reciprocally dynamic roles in which their health and well-being directly impact their professional competence. This interplay is often understated in ways that regulatory colleges influence training and education programs. In Ontario, for example, we see this in nursing. Although the College of Nurses of Ontario stipulates nursing professional competencies, it does not provide explicit performance expectations related to nursing self-care (i.e., the intentional way one takes care of one’s self). Accordingly, not all Ontario nursing education programs teach self-care. Different from research that deliberates nursing as a discipline or body of knowledge, this research examined how self-care is articulated, prioritized, taught, and assessed in nursing education. As such, the scholarly contribution it offers in the context of education is a pedagogy supporting self-care as a professional competency. Eight nursing faculty shared their lived experiences (through one-on-one interviews) surrounding the notion and phenomenon of self-care in nursing. Through a reiterative hermeneutic interchange that focused on whose voice is missing, an art-informed method that paralleled knowledge creation metaphorically according to the depth and breadth of “delving beneath the surface,” transformed participants spoken words into interpretive texts. Study conclusions suggest that self-care in nursing may be understood and taught through emotionally engaged self-reflection, not as a prescribed set of behaviours or individual task-based activities, but instead, as a pedagogical ontology in the professional care practice of others and with others. To foster successful self-care practice in nursing, educators should consider using arts-based methods to help learners enter and navigate spaces for emotionally engaged self-reflection. Given the urgent need for innovative and rigorous curriculum to support successful self-care practices as part of a healthcare practitioner’s professional role, this research is both timely and relevant.
    • Sex differences in the neural control of muscle

      Inglis, J Greig; Applied Health Sciences Program
      Sex-differences in muscle strength have been linked to differences in muscle size, involved limb, and daily activities. Early work has shown that sex-differences are greater in the upper compared to lower limb, making the upper limb an ideal model to investigate the best statistical approaches for sex comparison. Large differences in the upper limb reveals how biomechanical factors may impact neural control. Since males and females are more comparable with respect to strength in the lower limb, it allows for a determination of whether potential sex-differences in neural control exist without large differences in biomechanics. Understanding sex-differences allows for prescription of rehabilitation and training modalities, taking into account potential specificities in sex-related neuromuscular and musculoskeletal factors. The overall purpose was to examine neural and biomechanical differences that would account for sex-differences in neural control of muscle. Manuscript 1 examined normalization versus an ANCOVA to assess sex-differences. Sex-differences were seen in elbow flexor strength and rate of force development (RFD). Normalization by either maximum strength or neural factors couldn’t account for all sex-differences in RFD, resulting in an ambiguous interpretation. In contrast, both variables were able to be incorporated in an ANCOVA to determine their relative contribution. Manuscript 2 examined the effect of task familiarization and the contribution of maximum strength, twitch contraction time, muscle fiber condition velocity, and rate of muscle activation to sex-differences in the RFD during dorsiflexion. There were no significant differences between the sexes in muscle properties, but there were differences in neural control. Additionally, across days females exhibited a neural adaptation leading to an improvement in the RFD. Manuscript 3 directly assessed potential sex-differences in neural control during force gradation by recording motor unit activity during maximal and submaximal contractions. Females had less force steadiness (FS), which may have resulted from neural compensation for a less optimal pennation angle or a tendency towards greater joint laxity. Higher motor unit discharge rates and incidence of doublets may increase twitch force summation leading to a reduction in FS. Thus, biomechanical, not inherent sex-differences in neural drive led to neural compensation strategies manifesting as a difference in FS.
    • Show me, help me, let me : supporting teachers' changing conceptions of reading assessment and reading instruction

      Grierson, Arlene L.; Department of Graduate and Undergraduate Studies in Education (Brock University, 2009-01-28)
      This qualitative inquiry used case study methodology to explore the change processes of 3 primary-grade teachers throughout their participation in 7 -month professional learning initiative focused on reading assessment and instruction. Participants took part in semimonthly inquiry-based professional learning community sessions, as well as concurrent individualized classroom-based literacy coaching. Each participant's experiences were first analyzed as a single case study, followed by cross-case analyses. While their patterns of professional growth differed, findings documented how all participants altered their understandings of the roles and relevancy of individual components of reading instruction (e.g., comprehension, decoding) and instructional approaches to scaffold students' growth (e.g., levelled text, strategy instruction), and experienced some form of conceptual change. Factors identified as affecting their change processes included; motivation, professional knowledge, professional beliefs (self-efficacy and theoretical orientation), resources (e.g., time, support), differentiated professional learning with associated goal-setting, and uncontrollable influences, with the affect of each factor compounded by interaction with the others. Comparison of participants' experiences to the Cognitive-Affective Model of Conceptual Change (CAMCC) and the Interconnected Model of Teacher Professional Growth (IMTPG) demonstrated the applicability of using both conceptual models, with the IMTPG providing macrolevel insights over time and the CAMCC microlevel insights at each change intervaL Recommendations include the provision of differentiated teacher professional learning opportunities, as well as research documenting the effects of teacher mentorship programs and the professional growth of teacher educators. ii
    • Single-Molecule Magnets and Multifunctional Molecular Magnetic Materials Based on Polynuclear Metal Complexes

      Alexandropoulos, Dimitrios; Department of Chemistry
      Our work on single molecule magnets and multifunctional magnetic materials is presented in four projects. In the first project we show for first time that heteroatomic-type pseudohalides, such as OCN-, can be employed as structure-directing ligands and ferromagnetic couplers in higher oxidation state metal cluster chemistry. The initial use of cyanato groups in Mn cluster chemistry has afforded structurally interesting MnII/III14 (1) and MnII/III/IV16 (2) clusters in which the end-on bridging cyanates show a preference in binding through their O-atom. The Mn14 compound shows entirely visible out-of-phase alternating currect signals below 5 K and large hysteresis loops below 2 K. Furthermore, the amalgamation of azido groups with the triethanolamine tripodal ligand in manganese carboxylate cluster chemistry has led to the isolation of a new ferromagnetic, high-nuclearity and mixed-valence MnII/III15Na2 (3) cluster with a large ground-state spin value of S = 14. In the second project we demonstrate a new synthetic route to purely inorganic-bridged, transition metal-azido clusters [CoII7 (4) and NiII7 (5)] and coordination polymers [{FeII/III2}n (6)] which exhibit strong ferromagnetic, SMM and long-range magnetic ordering behaviors. We also show that access to such a unique ferromagnetic class of inorganic, N-rich and O-free materials is feasible through the use of Me3SiN3 as the azido-ligand precursor without requiring the addition of any organic chelating/bridging ligand. In the last projects we have tried to bring together molecular magnetism and optics via the synthesis of multifunctional magnetic materials based on 3d- or 4f-metal ions. We decided to approach such challenge from two different directions: firstly, in our third project, by the deliberate replacement of non-emissive carboxylato ligands in known 3d-SMMs with their fluorescent analogues, without perturbing the metal-core structure and SMM properties (complexes 7, 8, and 9). The second route (last project) involves the use of naphthalene or pyridine-based polyalcohol bridging ligands for the synthesis of new polynuclear LnIII metal clusters (Ln = lanthanide) with novel topologies, SMM behaviors and luminescent properties arising from the increased efficiency of the “antenna” organic group. This approach has led us to the isolation of two new families of LnIII8 (complexes 10-13) and LnIII4 (complexes 14-20) clusters.
    • Sleep and information processing in individuals who have sustained a traumatic brain injury

      Milner, Catherine; Department of Psychology (Brock University, 2011-05-17)
      Individuals who have sustained a traumatic brain injury (TBI) often complain of t roubl e sleeping and daytime fatigue but little is known about the neurophysiological underpinnings of the s e sleep difficulties. The fragile sleep of thos e with a TBI was predicted to be characterized by impairments in gating, hyperarousal and a breakdown in sleep homeostatic mechanisms. To test these hypotheses, 20 individuals with a TBI (18- 64 years old, 10 men) and 20 age-matched controls (18-61 years old, 9 men) took part in a comprehensive investigation of their sleep. While TBI participants were not recruited based on sleep complaint, the fmal sample was comprised of individuals with a variety of sleep complaints, across a range of injury severities. Rigorous screening procedures were used to reduce potential confounds (e.g., medication). Sleep and waking data were recorded with a 20-channel montage on three consecutive nights. Results showed dysregulation in sleep/wake mechanisms. The sleep of individuals with a TBI was less efficient than that of controls, as measured by sleep architecture variables. There was a clear breakdown in both spontaneous and evoked K-complexes in those with a TBI. Greater injury severities were associated with reductions in spindle density, though sleep spindles in slow wave sleep were longer for individuals with TBI than controls. Quantitative EEG revealed an impairment in sleep homeostatic mechanisms during sleep in the TBI group. As well, results showed the presence of hyper arousal based on quantitative EEG during sleep. In wakefulness, quantitative EEG showed a clear dissociation in arousal level between TBls with complaints of insomnia and TBls with daytime fatigue. In addition, ERPs indicated that the experience of hyper arousal in persons with a TBI was supported by neural evidence, particularly in wakefulness and Stage 2 sleep, and especially for those with insomnia symptoms. ERPs during sleep suggested that individuals with a TBI experienced impairments in information processing and sensory gating. Whereas neuropsychological testing and subjective data confirmed predicted deficits in the waking function of those with a TBI, particularly for those with more severe injuries, there were few group differences on laboratory computer-based tasks. Finally, the use of correlation analyses confirmed distinct sleep-wake relationships for each group. In sum, the mechanisms contributing to sleep disruption in TBI are particular to this condition, and unique neurobiological mechanisms predict the experience of insomnia versus daytime fatigue following a TBI. An understanding of how sleep becomes disrupted after a TBI is important to directing future research and neurorehabilitation.
    • Social Anxiety and Psychosocial Functioning: Investigating Relations Across Emerging Adulthood

      Brook, Christina; Department of Psychology
      The social, emotional and academic tasks associated with emerging adulthood are particularly challenging for those with social anxiety, a behavior defined as fear of negative evaluation, distress with social interactions, and/or avoidance of new or all social situations. The goal of this dissertation was to research the longitudinal effects of social anxiety on psychosocial functioning in university students, looking at various behaviors key to this developmental stage of life. In my first study, I examined the relation between social anxiety, social ties, and academic achievement in an autoregressive cross-lagged analysis across three years of university. There were two major findings: the symptoms of social anxiety directly linked to academic achievement, and social ties appeared to play a pivot role through their reciprocal negative and positive relation with social anxiety and academic achievement, respectively. Study two examined social anxiety with respect to alcohol use over three years of university through latent class growth analysis. Five classes were identified, two with social anxiety that differed in levels of alcohol use, and three with low social anxiety and varying levels of alcohol use. The heterogeneity in social anxiety was related to psychosocial functioning. While both social anxiety groups reported similar social anxiety symptomology, only the group linked to higher alcohol use exhibited a greater vulnerability to other at-risk behaviors in year one (e.g., self injury). The third study followed the previously identified five groups through latent growth analysis for a total of seven years, to determine whether there was stability or change in psychosocial functioning over the long term. The results indicated that there was stability within and among groups across time in psychosocial functioning. Notably, the differences detected between the two social anxiety groups in year one continued over the long term, indicating that the at-risk behaviors associated with the social anxiety group reporting higher alcohol use persisted. Overall, this program of research revealed that those with social anxiety in university struggled more than their peers in a variety of domains. From a developmental perspective, the findings of stability in behavior suggested it might be important for intervention and prevention programs to target younger populations with strategies that are continued in a cohesive manner across university, a time when students are exposed to the pressures of achieving in competing developmental tasks.
    • Social neuroendocrinology of competition

      Carré, Justin M.; Department of Psychology (Brock University, 2010-10-26)
      The relationship between testosterone concentrations and aggressive behaviour in studies of people has produced very inconsistent findings. However, one consistent fmding that has emerged is that competitive and aggressive interactions potentiate testosterone release in both human and non-human species. It has been argued that socially-induced alterations in testosterone concentrations may function to influence ongoing and/or future social behaviour. Nonetheless, few studies have empirically tested this hypothesis. The current series of experiments was designed to address the extent to which competitioninduced fluctuations in testosterone concentrations were associated with ongoing and/or subsequent social behaviour. In Study 1, men (n = 38) provided saliva samples prior to, and at the conclusion of, the Point Subtraction Aggression Paradigm (PSAP). Although baseline testosterone concentrations were not related to aggressive behaviour, there was a positive correlation between change in testosterone and aggressive behaviour such that men who were most aggressive on the PSAP demonstrated the largest increase in testosterone concentrations. Furthermore, a rise in testosterone during the PSAP predicted willingness to choose a subsequent competitive task. In Study 2, men and women provided saliva samples prior to and after competing against a same-sex opponent on the Number Tracing Task (NTT). The outcome of the competition was rigged such that half of the individuals won most of the races, while the other half lost most of the races, thus experimentally creating a winner and loser in the laboratory. Following the competitive interaction, men and women played the PSAP with their same-sex partner. Results indicated that men selected the aggressive response (but not reward or protection responses), more frequently than women. For men assigned to the loss condition, an increase in testosterone concentrations in response to the NTT predicted subsequent aggressive behaviour. For men assigned to the win condition, an increase in testosterone concentrations in response to the NTT predicted subsequent aggressive behaviour, but only among those men who scored high on trait dominance. Change in testosterone and trait dominance did not predict aggressive behaviour in women. In Study 3, men provided saliva samples prior to, during, and at the end of the PSAP. They were randomly assigned to one of four experimental conditions that differed in the extent to which they were provoked and whether they received reward for behaving aggressively (i.e., stealing points). Results indicated that baseline testosterone concentrations did not correlate with aggression in any of the experimental conditions. Consistent with Study 1, there was a positive correlation between change in testosterone and aggressive behaviour among men who were provoked, but did not receive reward for aggression (i.e., reactive condition). Men who were provoked but did not receive reward for aggression enjoyed the task the most and were more likely to choose the competitive versus non-competitive task relative to men assigned to the other experimental conditions. Also, individual differences in aggressive behaviour among these men were positively correlated with the extent to which they enjoyed the task. Together, these studies indicate that testosterone dynamics within the context of competition influence subsequent competitive and aggressive behaviours in humans and that testosterone may be a marker of the intrinsically rewarding nature of costly aggressive behaviour.
    • South Asian Immigrant Women Conceptualizing Gender Roles in the Context of Family and Society in Southwestern Ontario

      Ahmed, Ghazala; Department of Graduate and Undergraduate Studies in Education
      Perceptions of gender roles vary in different cultures, influenced by social location and time. Migration to countries that promote liberal values can impact how men and women perceive their gender roles, their interpersonal relationships with family members, and their day to day activities. Informed by a postcolonial-feminist theoretical perspective, this qualitative study aimed to understand South Asian immigrant women’s perceptions about gender roles in the context of family and society, prior to migration, and after immigration to Canada. A unique aspect of this study is that it explored how participants negotiated their gender roles and identity and exercised their agency prior to migration and post immigration. Four major themes emerged in response to the interview questions: 1) immigration and resettlement challenges; 2) gender roles and a patriarchal society in the native country; 3) perceptions of gender role/women’s role in the Canadian society; and 4) negotiating of gender roles, agency and empowerment. The results of the study indicate that immigration experiences were diverse and should be analyzed through many intersecting lenses including gender, class, social status, and education level to highlight unique challenges experienced by women as opposed to a monolithic representation of women from the East. The study contributes to the literature on South Asian immigrant women by using an interpretation that is based on the knowledge produced by the participants, and by acknowledging their voices as a central focus. Women in this study show that they are agents of change and are not weak and voiceless as depicted through Western discourses.
    • Special Educators’ Experiences of Change Through Inclusive Education: The Development of the Inclusion Continuum of Change

      Somma, Monique; Department of Graduate and Undergraduate Studies in Education
      This phenomenological case study explored the change experiences of special education teachers who have transitioned from teaching in self-contained classes to inclusive class settings. Ten educators completed surveys and participated in a focus group. Of the original ten, five chose to participate in individual interviews. Descriptive statistics and focus group themes indicated that all ten of these educators had experienced shifts in their pedagogy and their overall beliefs and teaching methods for students with exceptionalities in inclusive classrooms. Data collected from the five individual interviews was combined using a descriptive phenomenological method, to create a single collective description that illustrated the change experience of special education teachers from segregated education for students with exceptionalities to inclusive education settings. The overall findings indicated that despite their special education training, these educators were challenged by their own beliefs and expectations, the attitudes of others and systematic barriers in the education system. They were equally surprised by the academic and social performance of students with exceptionalities in inclusive classes, as well as, the growth and development of the other students, and the overall pedagogical shifts they recognized in themselves. These findings suggest implications for professional development and training with special education teachers for inclusive practice. As well, opportunities to maximize the skills of these educators in a Professional Learning Community (PLC) and in mentorship opportunities within their schools where they serve as experts working with their colleagues is recommended. Consideration is also given to how these implications affect all educators as schools become more inclusive environments. From examining the literature on inclusion and teacher change and the findings of this research, a graphic representation titled The Inclusive Educators’ Continuum of Change was developed to illustrate the change experience of these special educators. This figure can provide special educators with a framework for which to map their own change experience. Further research to establish whether this graphic representation applies to all educators in inclusive settings is needed.
    • Spin labile conducting metallopolymers : a new architecture for hybrid multifunctional materials

      Djukic, Brandon; Department of Chemistry (Brock University, 2011-03-08)
      The synthesis of 3-ethynylthienyl- (2.07), 3-ethynylterthienyl- (2.19) substituted qsal [qsalH = N-(8-quinolyl)salicylaldimine] and 3,3' -diethynyl-2,2' -bithienyl bridging bisqsal (5.06) ligands are described along with the preparation and characterization of eight cationic iron(III) complexes containing these ligands with a selection of counteranions [(2.07) with: SCN- (2.08), PF6- (2.09), and CI04- (2.10); (2.19) with PF6 - (2.20); (5.06) with: cr (5.07), SeN- (5.08), PF6- (5.09), and CI04- (5.10)]. Spin-crossover is observed in the solid state for (2.08) - (2.10) and (5.07) - (5.10), including a ve ry rare S = 5/2 to 3/2 spin-crossover in complex (2.09). The unusal reduction of complex (2.10) produces a high-spin iron(I1) complex (2.12). Six iron(II) complexes that are derived from thienyl analogues of bispicen [bispicen = bis(2-pyridylmethyl)-diamine] [2,5-thienyl substituents = H- (3.11), Phenyl- (3.12), 2- thienyl (3.13) or N-phenyl-2-pyridinalimine ligands [2,5-phenyl substituents = diphenyl (3.23), di(2-thienyl) (3.24), 4-phenyl substituent = 3-thienyl (3.25)] are reported Complexes (3.11), (3.23) and (3.25) display thermal spin-crossover in the solid state and (3.12) remains high-spin at all temperatures. Complex (3.13) rearranges to form an iron(II) complex (3.14) with temperature dependent magnetic properties be s t described as a one-dimensional ferromagnetic chain, with interchain antiferromagnetic interactions and/or ZFS dominant at low temperatures. Magnetic succeptibility and Mossbauer data for complex (3.24) display a temperature dependent mixture of spin isomers. The preparation and characterization of two cobalt(II) complexes containing 3- ethynylthienyl- (4.04) and 3-ethynylterhienyl- (4.06) substituted bipyridine ligands [(4.05): [Co(dbsqh(4.04)]; (4.07): [Co(dbsq)2(4.06)]] [dbsq = 3,5-dbsq=3,5-di-tert-butylI ,2-semiquinonate] are reported. Complexes (4.05) and (4.07) exhibit thermal valence tautomerism in the solid state and in solution. Self assembly of complex (2.10) into polymeric spheres (6.11) afforded the first spincrossover, polydisperse, micro- to nanoscale material of its kind. . Complexes (2.20), (3.24) and (4.07) also form polymers through electrochemical synthesis to produce hybrid metaUopolymer films (6.12), (6.15) and (6.16), respectively. The films have been characterized by EDX, FT-IR and UV-Vis spectroscopy. Variable-temperature magnetic susceptibility measurements demonstrate that spin lability is operative in the polymers and conductivity measurements confirm the electron transport properties. Polymer (6.15) has a persistent oxidized state that shows a significant decrease in electrical resistance.
    • Stereoselective Synthesis of N-Propargyl Alkynes and Axial Chiral N-Allenes with Epimeric Imidazolone Auxiliaries

      Sechi, Maria Laura; Department of Chemistry
      This thesis describes the synthesis of an N-propargyl pyrroloimidazolone chiral auxiliary/directing group with syn or anti stereochemistry derived from L-proline hydantoin and its diastereoselective lithiation for the synthesis of central chiral alkynes and axial chiral allenamides. Lithiation followed by quench with alkylating electrophiles or aldehydes/ketones gives access to chiral propargyl or allene derivatives respectively, both in high diastereomeric ratio (>95:5 dr). Use of the anti epimer of the aforementioned imidazolone chiral auxiliary results in the reversal of stereochemistry at the propargyl position of the products, again with high diastereoselectivity. This conclusion was confirmed by the synthesis and comparison of the solely central chiral alkynes from both the syn and anti series, obtained via acid-induced elimination of the labile silyloxy protecting group. Therefore, this method allows for the preparation of both enantiomeric propargyl products without the need to prepare additional starting materials from more expensive unnatural D-proline. X-Ray analysis of an allene derivative confirmed that lithiation of the syn pyrroloimidazolone followed by direct quench with prochiral benzaldehydes led to axial chiral allenamides in high selectivity (>95:5 dr) with atypical stereochemistry of the resulting benzylic alcohol. Lithiation followed by transmetalation to a titanium triisopropoxide intermediate before benzaldehyde quench gave epimeric allenamides with opposite stereochemistry at the benzylic alcohol. Density Functional Theory (DFT) computational modelling explained this reversal of stereochemistry at the benzylic position as arising from stereofacial attack in 6,5-bicyclic or 6-membered transition states in the lithium or titanium series, respectively.
    • Stereoselective synthesis of substituted hexahydro-3a,4a-diazacyclopentaphenanthren-4-ones and aminoferrocenes

      Zaifman, Joshua David; Department of Chemistry (Brock University, 2011-05-17)
      This thesis explored the development of several methodologies for the stereoselective construction of ligand frameworks and some of their applications. The first segment concerns the application of an enantioselective lithiation at an Sp3_ hybridized position adjacent to nitrogen by means of the widely used and typically highly effective enantioselective lithiation with ( -)-sparteine. This investigation was intended to develop a method to install chirality into a system that would be converted into a family of diaminoylidenes for use as phosphine mimics in transition metal catalysis or as nucleophilic reagents. Molecular modeling of the system revealed some key interactions between the substrate and (-)-sparteine that provided general insight into the diamine's mode of action and should lend some predictive value to its future applications. The second portion focuses on the development of methods to access 1,2- disubstituted aminoferrocenes, an underexplored class of metallocenes possessing planar chirality. Two routes were examined involving a diastereoselective and an enantioselective pathway, where the latter method made use of the first BF3-mediated lithiation-substitution to install planar chirality. Key derivatives such as 1,2- aminophosphines, made readily accessible by the new route, were evaluated as ligands for Pd(II), Pt(II) and Ir(I). These complexes show activity in a number of transformations with both achiral and prochiral substrates. Optimization experiments were conducted to prepare enantiomerically enriched 2-substituted-I-aminoferrocenes by direct asymmetric lithiation of BF3-coordinated tertiary aminoferrocenes. A predictive computational model describing the transition state of this reaction was developed in collaboration with Professor Travis Dudding's group (Department of Chemistry, Brock University). The predicted stereochemistry of the process was confirmed by single-crystal X-ray analysis of a 2-phosphino-l-dimethylaminoferrocene derivative. Enantiomerically pure samples of the aminophosphine ligands derived from this new process have given promising preliminary results in the enantioselective hydrogenation of prochiral alkenes and warrant further stUdy in metal-mediated catalysis.

      Mansour, Hayam; Department of Biological Sciences (Brock University, 2012-06-04)
      Hepatitis C virus (HCV) is the causative agent of Hepatitis C, a serious global health problem which results in liver cirrhosis and hepatocellular carcinoma. Currently there is no effective treatment or vaccine against the virus. Therefore, development of a therapeutic vaccine is of paramount importance. In this project, three alternative approaches were used to control HCV including a DNA vaccine, a recombinant viral vaccine and RNA interference. The first approach was to test the effect of different promoters on the efficacy of a DNA vaccine against HCV. Plasmids encoding HCV-NS3 and E1 antigens were designed under three different promoters, adenoviral E1A, MLP, and CMV ie. The promoter effect on the antigen expression in 293 cells, as well as on the antibody level in immunized BALB/c mice, was evaluated. The results showed that the antigens were successfully expressed from all vectors. The CMV ie promoter induced the highest antigen expression and the highest antibody level. Second, the efficiency of a recombinant adenovirus vaccine encoding HCV-NS3 was compared to that of a HCV-NS3 plasmid vaccine. The results showed that the recombinant adenovirus vaccine induced higher antibody levels as compared to the plasmid vaccine. The relationship between the immune response and miRNA was also evaluated. The levels of mir-181, mir-155, mir-21 and mir-296 were quantified in the sera of immunized animals. mir-181 and mir-21 were found to be upregulated in animals injected with adenoviral vectors. Third, two recombinant adenoviruses encoding siRNAs targeting both the helicase and protease parts of the NS3 region were tested for their ability to inhibit NS3 expression. The results showed that the siRNA against protease was more effective in silencing the HCV-NS3 gene in a HCV replicon cell line. This result confirmed the efficiency of adenovirus for siRNA delivery. These results confirmed that CMV ie is optimum promoter for immune response induction. Adenovirus was shown to be an effective delivery vector for antigens or siRNAs. In addition, miRNAs were proved to be involved in the regulation of immune response.
    • Stretching the Vitruvian Man: Investigating Affective and Representational Arts-based Methodologies Towards Theorizing a More Humanistic Model of Medicine

      Couse, Candace; Interdisciplinary Humanities Program
      Westernized medicine can be said to illustrate its history and structure, as well as its current understanding of the capacity and appearance of the human through its visual representations of the body. Scientific images, this paper argues, become a site for interrogating the tangle of idealism, truth, objectivity and knowledge in how knowledge is actively used, replicated, paralleled and otherwise functions. First, asking how depictions of the medicalized body inform the epistemological foundations of medicine, and to what end, this work opens up the question of methodology, arguing that the integration of the modes of arts-based practices can bring medicine toward a much more realistic picture of the world. A parallel argument is a similarly concentrated interrogation of the affective quality of arts-based methodology, which is commonly understood to be the nucleus of work on the political dimensions of non-representational theory. I complicate the dominant scholarly preference for an ontologically rooted affect theory, finding it theoretically non-viable for art and humanistic medicine by thinking through subjectivity, autobiographical accounts of illness and epistemological flexibility. I see a path forward using a biologically and evolutionarily rooted affect theory, noting the ethical implications of its differences for a humanistic approach to medicine.
    • Structural, Magnetic and Thermal Studies of Ce1-xEuxCrO3 Nano-Powders

      Taheri, Maryam; Department of Physics
      A new series of nano-sized Ce1-xEuxCrO3 (x = 0.0 to 1.0) with an average particle size of 50 - 80 nm were synthesized using a solution combustion method. Nano-powders Ce1-xEuxCrO3 with the canted antiferromagnetic property exhibited interesting magnetic behaviours including the reversal magnetization and the exchange bias effect. The effect of europium doping as the ion with the smaller radius size and different electron con figuration on structural, magnetic and thermal properties of Ce1-xEuxCrO3 were investigated using various experimental techniques, i.e. DC/AC magnetic susceptibility, heat capacity, thermal expansion, Raman scattering, X-ray photoemission spectroscopy, transmission/scanning electron microscopy, X-ray powder diffraction and neutron scattering. An exchange bias effect, magnetization irreversibility and AC susceptibility dispersion in these samples confirmed the existence of the spin disorder magnetic phase in Ce1-xEuxCrO3 compounds. The exchange bias phenomenon, which is assigned to the exchange coupling between glassy-like shell and canted antiferromagnetic core, showed the opposite sign in CeCrO3 and EuCrO3 at low temperatures, suggesting different exchange interactions at the interfaces in these compounds. The energy level excitation of samples were examined by an inelastic neutron scattering which was in good agreement with the heat capacity data. Neutron scattering analysis of EuCrO3 was challenging due to the large neutron absorption cross-section of europium. All diffraction patterns of Ce1-xEuxCrO3 showed the magnetic peak attributed to the antiferromagnetic Cr3+ spins while none of the diffraction patterns could detect the magnetic ordering of the rare-earth ions in these samples.
    • Structural, Magnetic and Vibrational Studies of Entropy Stabilized Oxides

      Afsharvosoughi, Tahereh; Department of Physics
      The structural, magnetic and vibrational properties of high entropy oxide (HEO) and medium entropy oxides (MEOs) made from mixtures of five and four metal oxides were studied in this work. The HEO and MEOs obtained from solid state reactions in quinary and quaternary equimolar mixtures of oxides including ZnO, CuO, CoO, MgO and NiO which are called 5-HEO, 4-MEO(-Cu), 4-MEO(-Mg), 4-MEO(-Co), 4-MEO(-Ni) and 4-MEO(-Zn) in this thesis. The samples were sintered at high temperatures followed by air quenching. The x-ray diffraction measurements results show the formation of single rocksalt phase in all of them except 4MEO(-Ni). The magnetization measurements in zero field cooled (ZFC) and field cooled (FC) regimes under H=5000 Oe have provided strong evidence for long range magnetic ordering in 5-HEO and 4-MEOs. Two samples including 4-MEO(-Co) and 4-MEO(-Ni) exhibit high frustration factor which is a major component for spin glass phase. The AC susceptibility measurements for 4-MEO(-Co) and 4-MEO(-Ni) with the highest frustration factors have carried out in order to investigate the presence of spin glass. The segregation of Cu from the rocksalt phase in 5-HEO by resintering at intermediate temperature (700oC) was confirmed by x-ray diffraction measurements, SEM-EDS elemental mapping and magnetization measurements. Infrared refectance spectroscopy measurements (100-15000 cm-1) for 5-HEO and 4-MEOs with single rocksalt structures have revealed one strong mode and a weaker mode at lower frequency in the far infrared spectra. The Lorentz model and Kramers-Kronig (KK) analysis were implemented for the samples and the results were used in effective charge calculations which reveal that 4-MEO(-Cu) has the greatest ionic character whereas 4-MEO(-Mg) showed the least ionic character. The Raman spectroscopy which complements the infrared spectroscopy was carried out for 5-HEO and 4-MEOs. The results have indicated first and second order Raman modes in addition to a two-magnon mode at around 1600 cm-1 which was confirmed by studying the temperature dependence. While 4-MEO(-Co) also shows a peak near 1600cm-1 it is likely of different origin. In 4-MEO(-Cu) the two magnon scattering peak was not observed and it rather causes a high background which increases with decreasing temperature.
    • Structural, Magnetic, Dielectric, and Optical Properties of DyCrO3 and GeNi2O4 Materials

      Indovski, Biljana; Department of Physics
      GeNi2O4 is a cubic spinel with two antiferromagnetic transitions at low temperatures, while DyCrO3 has an orthorhombic perovskite structure with an antiferromagnetic transition at a higher temperature. Thin films of these compounds are widely researched for their applications in spintronics. The investigation of the structural, magnetic, dielectric, and optical properties of deposited thin films of these two materials can contribute to a better understanding of their physical characteristics which may lead to possible applications. In this research, DyCrO3 and GeNi2-xMgxO4 (x=0, 0.03) epitaxial thin films were deposited on SrTiO3 substrates using the pulsed laser deposition technique. As the c-lattice parameter of the orthorhombic DyCrO3 and a-lattice parameter of the cubic GeNi2O4 are almost having the same value, this is giving a rise to a small strain in their epitaxial thin films. Therefore, composite thin films of the DyCrO3 and GeNi2-xMgxO4 (x=0, 0.03) materials were also deposited. The structural properties of these thin films were examined using different X-ray techniques such as an X-ray diffraction, X-ray reflectivity, reciprocal space mapping, and in-plane pole figures. The results were analyzed to determine the preferred orientation, the thickness of the thin films, the presence of strain and defects, and the degree of epitaxy. The reciprocal space mapping results reveal a dependence between the thickness of the thin films and the presence of defects in the epitaxial films. The in-plane pole figure results show the presence of domains with different orientation in several thin films, although the results from the high-resolution X-ray diffraction indicate a single orientation in those films. The temperature dependence of magnetization in epitaxial thin films was measured in order to examine the magnetic anisotropy for the magnetic field normal and parallel to the surface of the films. These results indicate the presence of magnetic anisotropy in several thin films. GeNi2O4 is an interesting antiferromagnet as it has two closely spaced antiferromagnetic transitions that are the result of a spin reorientation in two types of {111} planes. Therefore, to better understand the ordering of the spins with respect to the {111} planes, additional measurements and analysis of the results were done on GeNi2O4 single crystals. The temperature dependence of magnetization was measured for the magnetic field applied parallel and perpendicular to the {111} planes. In addition, the temperature dependence of Raman spectra of a GeNi2O4 single crystal was measured and analyzed. These single crystal results of GeNi2O4 provide a better understanding of spin-phonon coupling and spin ordering and reorientation in this spinel compound.
    • A study of biting midge populations and an assessment of Bluetongue virus presence in southern Ontario, with a visual dichotomous key to the North American genera of Ceratopogonidae

      Jewiss-Gaines, Adam; Centre for Biotechnology
      Biting midges (Diptera: Ceratopogonidae) are flying insects that feed on blood in order to produce eggs. Due to their bloodfeeding habits, some species act as vectors for viruses, many of which affect ruminant animals. This establishes ceratopogonids as possible threats to livestock farmers, and therefore it is important to understand their distribution and habits. This study focussed on collecting biting midge specimens from localities across Ontario where livestock farms are present, and determining if they were carrying Bluetongue virus (BTV). Fourteen livestock farms were sampled to assess presence of ceratopogonid vectors. Captured Culicoides specimens were subjected to RT-qPCR analysis to test for BTV. The North American vector for BTV (Culicoides sonorensis) was collected at multiple localities, constituting the first record of this species in Ontario. Identity of C. sonorensis specimens was verified using molecular analysis of three gene regions: CO1, ITS1, and EF1α. Gene sequences for Culicoides variipennis, a species easily confused with C. sonorensis, were also analyzed. Analysis revealed that EF1α introns differed between the species and may be useful as molecular identifiers. Sequences for all three gene regions were submitted to the National Center for Biotechnology Information gene database. The Brock University Rothamsted Trap operated during the summer seasons of 2013 to 2017, collecting insects at ~12m above ground on a daily basis. Collected biting midges were identified to genus, and genus tallies were compared with five climate variables using redundancy analysis (RDA) to determine factors that affect the activity of collected genera. Phenological patterns of Bezzia, Culicoides, and Probezzia were compared in detail to temperature values. A literature search was performed to evaluate progression of BTV and epizootic hemorrhagic disease virus (EHDV) across North America since their initial detections in the 1950s. Records detailing virus outbreaks were analyzed and maps displaying the chronological progression of BTV and EHDV were created, providing a visual representation of their dispersal patterns. Finally, a dichotomous key to the Nearctic biting midge genera was constructed and illustrated with high-definition photography to show key characters. This key aids with taxonomic identification of the 35 recognized genera occurring north of Mexico.
    • A study of lipid recognition and membrane binding by the human oxysterol-binding protein (OSBP).

      Mukherjee, Parthajit; Centre for Biotechnology
      Recent studies have established oxysterol-binding protein (OSBP) and members of the OSBP-related protein (ORP) family as global cellular sterol sensors that participate in non-vesicular anterograde transport of monomeric sterols from the endoplasmic reticulum to other organelles such as the Golgi and the plasma membrane. By exchanging sterols for phosphoinositides, these multi-domain proteins change the bilayer composition at membrane contact sites and thus, regulate various signaling pathways. Despite the wealth of knowledge garnered from the study of fluorescent/radiolabeled ligand-protein interactions and inter-vesicular lipid transfer assays in vitro, the precise nature of the association of ORPs with organellar membranes and the factors modulating such interactions have remained largely enigmatic. The goal of my project was to characterize the behaviour of human OSBP using a label-free analytical technique called dual polarization interferometry (DPI). This technique enables surface-immobilization of phospholipid vesicles to observe and analyze the behaviour of proteins towards adsorbed bilayers. From my investigation, I found that OSBP prefers binding to membranes containing anionic phospholipids, such as phosphatidylinositol-4-phosphate (PI(4)P), over membranes made up of neutral phosphatidylcholine (PC). In the presence of PI(4)P, the wild-type protein clearly demonstrated a rapid bilayer association, followed by PI(4)P extraction and a slower dissociation, in a dosage-dependent fashion. The OSBP-related domain (ORD) mutant, OSBP-HH/AA, due to its impaired ability to extract PI(4)P, failed to dissociate from the membrane while the pleckstrin homology domain (PHD) mutant, OSBP-RR/EE, could not associate with membranes at all. The presence of sterols did not alter OSBP’s affinity for PC membranes despite a two-fold increase in protein adsorption per unit area in the presence of cholesterol in the membrane, compared to 25-hydroxycholesterol. Both cholesterol and 25-hydroxycholesterol competed with 22-NBD-cholesterol for the binding site in the ORD of OSBP, with resulting EC50 values of 15.6 ± 0.7 nM for the former and 5.0 ± 0.5 nM for the latter. OSBP also transferred ORD-bound fluorescent cholesterol to acceptor vesicles, but the rate remained unaltered upon incorporation of PI(4)P in those membranes. These results provide useful insight into the preferential association of OSBP with membranes containing specific recognizable ligands, such as sterols and PI(4)P, and help build a molecular level description of the mechanism of this protein.