Crises of In/Humanity: Posthumanism, Afrofuturism, and Science and/as Fiction

This thesis engages black critical thought on the human and its contemporary iterations in posthumanism and transhumanism. It articulates five categories of analysis: displace, interrupt, disrupt, expand, and wither. Each is meant to allude to the generative potential in different iterations of black thought that engages the human. Working through Sylvia Wynter’s theories of the rise of Man-as-human in particular, the project highlights how black thought on the human displaces the uncritical whiteness of posthumanist thought. It argues that Afrofuturism has the potential to interrupt the linear progression from human to posthuman and that Octavia Butler’s Fledgling proffers a narrative of race as a technology that disrupts the presumed post-raciality of posthumanism and transhumanism. It then contends that Katherine McKittrick’s rearticulation of the Promise of Science can be extended to incorporate the promise of science fiction. In so doing, it avers that a more curated conversation between McKittrick and Wynter, one already ongoing, and Octavia Butler, through Mind of My Mind from her Patternist series, expands our notions of the human as a category even at the risk of seeing it wither as a politic or praxis. It ends on a speculative note meant to imagine the possibilities within the promise of science fiction.

Targeting the actin cytoskeleton in HER2+ metastatic cancer cells using a macrolide toxin

Breast and ovarian cancers are among the leading causes of cancer related deaths in women worldwide. In a subset of these cancers, dysregulation of the human epidermal growth factor receptor 2 (HER2) leads to overexpression of the receptor on the cell surface. Previous studies have found that these HER2+ cancers show high rates of progression to metastatic disease. Metastasis is driven by cytoskeletal rearrangements that produce filamentous actin (F-actin) based structures that penetrate and degrade extracellular matrix to facilitate tumour invasion. Advancements in targeted therapy have made F-actin an attractive target for the development of new cancer therapies. In this thesis, we tested the actin-depolymerizing macrolide toxin, Mycalolide B (MycB), as a potential warhead for a novel antibody drug conjugate (ADC) to target highly metastatic HER2+ breast and ovarian cancers. We found that MycB treatment of HER2+ breast (SKBR3, MDA-MB-453) and ovarian (SKOV3) cancer cells led to loss of viability (IC50 values ≤ 64 nM). Sub-lethal doses of MycB treatment caused potent suppression of leading edge protrusions, migration and invasion potential of HER2+ cancer cells (IC50 ≤ 32 nM). In contrast, other F-actin based processes such as receptor endocytosis were less sensitive to MycB treatment. MycB treatment skewed the size of endocytic vesicles, which may reflect defects in F-actin based vesicle motility or maturation. Given that HER2+ cancers have been effectively targeted by Trastuzumab and Trastuzumab-based ADCs, we tested the effects of a combination of Trastuzumab and MycB on cell migration and invasion. We found that MycB/ Trastuzumab combination treatments inhibited motility of SKOV3 cells to a greater degree than either treatment alone. Altogether, our results provide proof-of-principle that actin toxins such as MycB can be used as a novel class of warheads for ADCs to target and combat highly metastatic cancers.

Does estrogen fluctuation throughout the menstrual cycle impact flow-mediated dilation during exercise in healthy premenopausal women?

The endothelium is the inner most layer of cells that lines all arteries. A primary function of endothelial cells is to regulate responses to increased blood flow and the resulting frictional forces or shear stress by producing factors such as nitric oxide that mediate arterial dilation (flow mediated dilation (FMD)). Menstrual cycle variations in estrogen (E2) have been shown to influence brachial artery (BA) FMD in response to transient increases in shear stress brought about by the release of a brief forearm occlusion (reactive hyperemia (RH)). FMD can also be assessed in response to a sustained shear stress stimulus such as that created with handgrip exercise (HGEX), and studies have shown that RH- and HGEX stimulated FMD provide unique information regarding endothelial function. However, the impact of menstrual phase on HGEX-FMD is unknown. Therefore, the purpose of this study was to determine the impact of cyclical changes in E2 levels on HGEX-FMD over two discrete phases of the menstrual cycle. FMD was assessed via ultrasound. 12 subjects (21 ± 2yrs) completed two experimental visits: (1) low estrogen phase (early follicular) and (2) High estrogen phase (late follicular). In each visit both RH- and HGEX-FMD (6 min handgrip exercise) were assessed. Results are mean ± SD. E2 increased from the low to the high estrogen phase of the menstrual cycle (low: 34 ± 8, high: 161 ± 113pg/mL, p = 0.004). There was no change in mean FMD between phases (RH-FMD: 7.7 ± 4.3% vs. 6.4 ± 3.1%, p = 0.139; HGEX-FMD: 4.8 ± 2.8% vs. 4.8 ± 2.3%, p = 0.979). The observation that both RH- and HGEX-FMD did not differ between phases indicates that menstrual cycle fluctuations in estrogen may not universally impact endothelial function in young, healthy premenopausal women. Further research is needed to improve our understanding of the mechanisms that underlie variability in the impact of menstrual phase on both transient and sustained FMD responses.

PHYSICAL ACTIVITY EXPERIENCES OF PERSIAN WOMEN RECENTLY IMMIGRATED TO CANADA

New immigrants to Canada are generally in similar or better physical and mental health than people born in Canada, however, many studies suggest that their health tends to decline quickly after immigration. Lower physical activity levels among new immigrants might be contributing to this phenomenon. There is a paucity of information regarding the physical activity behaviour of the Canadian immigrant population in general and of West Asian women, such as Iranians (Persians), in particular. Given that this group is characterised by an increasing population growth and lower rates of physical activity, it is critical to understand how best to address physical activity promotion in this population. Purpose: To understand the physical activity experiences of Persian women recently immigrated to Toronto, Canada in order to develop recommendations for the design and implementation of tailored physical activity programs. Methods: A qualitative interpretive description approach was chosen to collect and describe ideas, experiences, and perceptions of physical activity within 10 new immigrant women. Using an inductive approach, two fundamental techniques of immersion and crystallization were used throughout the analysis. Thematic analysis was conducted by performing a sequential process of open and axial coding. Emerged themes were further conceptualized through a socio-ecological lens. Results: The facilitators and barriers to physical activity among the women were situated within five overarching categories, 1) Perceptions about physical activity, 2) New physical environment and social structure, 3) Cultural heritage values, 4) Settlement and immigration factors, and 5) Physical activity program features. Discussion: Findings revealed that Persian new immigrant women’s engagement in physical activity after immigration is influenced by factors across the individual, sociocultural, environmental, institutional, and policy levels. Newcomer women’s physical activity was influenced by their transition from their society of origin to the host society and the challenges and successes experienced throughout the settlement and acculturation process. The most noticeable barrier to physical activity in Canada for the women emerged as the lack of communication of physical activity information to newcomers. A set of recommendations is provided for developing efficient physical activity programs for Persian immigrant women, which may also be relevant for other immigrant groups in Canada.

Differential contributions of the mIPS and PMd in the movement planning of reaches investigated through HD-tDCS

To reach for a target, we must formulate a movement plan - a difference vector of the target position with respect to the starting hand position. While it is known that the medial part of the intraparietal sulcus (mIPS) and the dorsal premotor (PMd) activity reflects aspects of a kinematic plan for a reaching movement, it is unclear whether or how the two regions may differ. We investigated the functional roles of the mIPS and PMd in the planning of reaching movements using high definition transcranial direct current stimulation (HD-tDCS) and examined changes in horizontal endpoint error when participants were subjected to anodal and cathodal stimulation. The left mIPS and PMd were functionally localized with fMRI in each participant using an interleaved center-out pointing and saccade task and mapped onto the scalp using Brainsight. We adopted a randomized, single-blind design and applied anodal and cathodal stimulation (2mA for 20 min; 3cm radius 4x1 electrode placement) during 4 separate visits scheduled at least a week apart. Each participant performed 250 baseline, stimulation, and post-stimulation memory-guided reaches starting from one of two initial hand positions (IHPs) to one of 4 briefly flashed targets (20 cm distant, 5 cm apart horizontally) while fixating on a straight-ahead cross located at the target line. Separate 2-way repeated measures ANOVAs of horizontal endpoint error difference after cathodal tDCS at each stimulation site revealed a significant IHP by target position interaction effect at the left mIPS, and significant IHP and target main effects at the left PMd. Behaviorally, these effects corresponded to IHP-dependent contractions after cathodal mIPS tDCS and IHP-independent contractions after cathodal PMd tDCS. These results suggest that the movement vector is not yet formed at the input level of mIPS, but is encoded at the input of PMd. These results also indicate that tDCS is a viable, useful method in investigating movement planning properties through temporary perturbations of the system.

Conjuring Canadas: Historians and the Quest to Define a Canadian Nation and its Past, 1920-1967

This dissertation examines the various ways in which Canadian historical researchers confronted the “Canada question,” namely the challenge of defining the basis of a unified national community. In doing so, it follows the scholarship and activities of a network of historians and intellectuals centred on the Canadian Historical Review, a quarterly publication founded in 1920. This study examines their scholarship with the aim of identifying not only the various solutions they posed to the problem, but also the philosophical undercurrents that informed their reasoning in the process. It also traces the rise of a rival network in the Revue d’histoire de l’Amérique française, a French-language historical publication founded in 1947 that by its very existence posed a significant challenge to the definition of the nation at the core of the Canadian Historical Review. This dissertation argues that the network bound together by the Review was engaged in a hegemonic project, one that sought to present a particular definition of Canada through a historical narrative that rested upon a liberal logic. Yet the greatest sustained challenge they faced in this endeavour emerged from Francophone historical scholars, who, although proposing vastly different Canadas to those imagined at the Canadian Historical Review, came under the sway of a number of liberal currents of thought as well. A detailed summary of the key traits of these liberal Canadas is found in the conclusion.

THE EFFECT OF PREECLAMPSIA ON RENAL FUNCTION: CROSS-SECTIONAL STUDIES OF POSTPARTUM PREECLAMPTICS AND WOMEN WHO WERE DESTINED TO DEVELOP PREECLAMPSIA

Preeclampsia (PE) is a pregnancy complication that is new-onset of hypertension and proteinuria after 20 weeks of gestation. However, subclinical renal dysfunction may be apparent earlier in gestation prior to the clinical presentation of PE. Although the maternal syndrome of PE resolves early postpartum, women with a history of PE are at higher risk of renal dysfunction later in life. Mineral metabolism, such as phosphate balance is heavily dependent on renal function, yet, phosphate handling in women with a history of PE is largely unknown. To investigate whether women with a history of PE would exhibit changes in phosphate metabolism compared to healthy parous women, phosphate loading test was used. Women with or without a history of PE, who were 6 months to 5 years postpartum, were recruited for this study. Blood and urine samples were collected before and after the oral dosing of 500mg phosphate solution. Biochemical markers of phosphate metabolism and renal function were evaluated. In order to assess the difference in renal function alteration between first trimester women who were or were not destined to develop PE, plasma cystatin C concentration was analysed. After phosphate loading, women with a history of PE had significantly elevated serum phosphate at both 1- and 2-hour, while controls had higher urine phosphate:urine creatinine excretion ratio at 1-hour than women with a history of PE. Women with a history of PE had no changes in intact parathyroid hormone (iPTH) concentration throughout the study period, whereas controls had elevated iPTH at 1-hour from baseline. In terms of renal function in the first trimester, there was no difference in plasma cystatin C concentration between women who were or were not destined to develop PE. The elevation of serum phosphate in women with a history of PE could be due to the delay in phosphate excretion. Prolong elevation of serum phosphate can have serious consequences later in life. Thus, oral phosphate challenge may serve as a useful method of early screening for altered phosphate metabolism and renal function.

Education and Self-Cultivation: Foundational Changes for Existential Flourishing

The strained relationship between pedagogy and self-cultivation is often overlooked in favour of more pressing and profitable concerns within educational institutions. However, the end of education is not a well-paying job. It is often thought that education will produce a certain type of learned individual. Students are entered into educational institutions from a very young age and spend most of their youth within them, subsequently forming a part of themselves, their self-identify and agency, through these institutions. A significant amount of trust is placed in the hands of educators not only to impart information about various subject matters but to teach students how to think. This, however, is a difficult task which cannot be completely accomplished; thinking is a skill which an educator can promote but only the individual can cultivate. If self-cultivation is not the end of pedagogical practice and education, there is something deeply contradictory between the theoretical and practical values and aims of educational institutions.This thesis will address the problems caused by the neglect of self-cultivation within the pedagogical practices of contemporary educational institutions. I argue that self-cultivation, existential learning and flourishing should be the focus of these institutions. Educational institutions can make alternative efforts not only to improve the learning environment for these students but to prepare them to cope with existential questions. By acknowledging and focusing on the significance of self-cultivation, educational institutions can and should make efforts not only to teach useful, marketable skills and information but to also nurture the agency and mental well-being of the student him- or herself. My hope is that this thesis will be the first step towards answering a larger concern: How can educational institutions alleviate the struggles of students, particularly the seemingly growing number who are suffering from depression, by appealing to notions of self-cultivation?

RE-MEANING THE SACRED: COLONIAL DAMAGE AND INDIGENOUS COSMOLOGIES

Indigenous ways of knowing are dependent on an inheriting process both amongst humans and between human and non-human being. These multi-relationships cross material and immaterial borders as sites of knowledge production. This manuscript will interrogate how three particular Indigenous cosmological relationships have been purposefully re-meaninged by colonial institutions: 1) How Anishinaabe and Haudenosaunee origin stories have been abstracted into a distinctive epistemological versus ontological site; 2) How Anishnaabe spirit worlds are impacted by colonial relations, and how state institutions benefit from the re-meaning of these worlds; and 3) How Indigenous sovereignty in Canada is imagined from a statist perspective, and how these polices have re-meaninged the sacred relationships within a cosmological understanding of Haudenosaunee governance. The re-meaning of sacredly-held Indigenous relationships is both accelerated by, and contributes to, a practice of reducing upon Indigenous and non-human societies. Throughout expressions of colonialism on Indigenous territories (the academy, the state, Indian policy), Indigenous knowledge is consistently either dismissed or appropriated. This reduction of Indigenous knowledge continues to bolster functions of the state as related to the elimination of the “Indian Problem” via reducing the “Indian” to an adaptive subject.

Radical Ambition: A Portrait of the Toronto New Left, 1958-1985

This thesis examines the rise and decline of the New Left in Toronto from 1958 to 1985. It argues that New Leftism — whose three leading ideals were self-management, national liberation, and community — arose as much from the Old Left as it did from the peace movement. In contrast to earlier readings that interpret the New Left narrowly — essentially, as the combined forces of the white student and peace movements evident mainly on university campuses — this thesis documents the extent to which New Leftism, interpreted as a political formation, provided a framework for a diversity of radical social movements, especially feminism, Black Power, gay liberation, resistance to the capitalist redevelopment of the city, and transnational solidarity. It also questions a declensionist narrative that adopts a “decadal” approach to the radicalism of the sixties, according to which 1970 spelled the end of “60s” radicalism. Quite the contrary, this thesis argues: in Toronto, it would be truer to say that 1970s were “the sixties,” in that only in this later decade did many New Left movements attain their full maturity. New Leftists successfully challenged a host of institutions, sometimes with permanent effects. The educational system was transformed. Cultural institutions and practices were revolutionized. Questions of race and gender, once peripheral to the left, were made central to it. Democratic community institutions became far more powerful. A token of the strength and durability of the New Left in Toronto was the extent to which it remained the bête noir of a series of other radical groups upholding the model of the vanguard communist party — which challenged the New Leftists’ prominence but many members of which often wound up agreeing with their positions. It was only in the early 1980s, with the ascent of a new right, that Toronto’s New Left unmistakably entered a period of decline. Yet, even then, many of its key themes were picked up by fast-growing anarchist and socialist feminist currents. Far from constituting a minor phenomenon, Toronto’s New Left, one of the largest movements for social justice in Canadian history, bequeathed to its progressive successors an imposing legacy of struggle and cultural achievements. It is the purpose of this thesis to evaluate, both critically and sympathetically, the extent to which the New Left attained its radical ambition.

Accommodating Muslim Minorities in Secular Societies: Public Education in England, Scotland, Ontario, and Quebec

Abstract This thesis examines one of the most sensitive challenges facing contemporary democracies: the accommodation of Muslim minorities in public institutions and services. It focuses on the field of education, and on two particular issues: the public funding of Islamic schools and the accommodation of Muslim needs in public secular schools. The analysis is based on an examination of outcomes in four jurisdictions that differ significantly in the level of accommodation that has emerged: England, Scotland, Ontario, and Quebec. I seek to explain why such variation in outcomes exists among these four cases. I draw on four bodies of literature to underpin the theoretical framework: historical institutionalism, political mobilization by civil society, political parties, and ideationalism. My argument can be summarized simply; historic church-state settlements, unique in each case, are the most important factor explaining the variation in outcomes in England, Scotland, Ontario, and Quebec. In some cases, the historic church-state template is incrementally adapted to accommodate Muslim minorities. In other cases, relatively little accommodation occurs and the path-dependent trajectory of church-state relations remains entrenched. While the historic church-state template is a necessary factor in the explanation, it does not fully account for the variation. For a more complete picture, I demonstrate that there are several additional key factors that also shape the outcomes: first, national identity and public attitudes towards immigration and immigrants; second, the extent of mobilization by political agents, such as civil society organizations and historic churches; and third, the response of political parties to demands by Muslims for institutional accommodation. Ultimately, I conclude that Muslims in these jurisdictions are receiving some accommodation, but the process is slow and partial. This thesis makes important theoretical and empirical contributions to the discussion of Muslim integration in liberal democratic states. First, a framework has yet to be developed that considers the theoretical implications of institutional accommodation of Muslims; I address this gap. Second, this research demonstrates the utility of historical institutionalism in explaining the adaptation of church-state templates to accommodate Muslims’ demands. Last, this study makes an original contribution by comparing the cases of England, Scotland, Ontario, and Quebec in the accommodation of Muslims in education. A comparison of Canada with the United Kingdom has not yet been done.  

Identical Origins, Divergent Paths: Filial Responsibility Laws in Canada and the United States

This dissertation examines the origins of filial responsibility laws in Canada and the United States, laws which prescribe that adult children have an obligation of support which is owed to their parents. Filial responsibility laws enable an indigent parent, or an institution providing medical treatment and care to an indigent parent, to seek financial support from that parent’s adult children through the use of litigation. While those who favour these rarely-used laws claim that they bring many benefits to both the family and the state, there is little evidence to suggest that such benefits are actualized. The development and use of the laws in Canada and the United States make it clear that the limitation of the expenditure of government funds was the primary motive for these laws and the support of families a distant secondary motive.

Investigating Multiple Roles of Vocal Confidence in Persuasion

Although persuasion often occurs via oral communication, it remains a comparatively understudied area. This research tested the hypothesis that changes in three properties of voice influence perceptions of speaker confidence, which in turn differentially affects attitudes according to different underlying psychological processes that the Elaboration Likelihood Model (ELM, Petty & Cacioppo, 1984), suggests should emerge under different levels of thought. Experiment 1 was a 2 (Elaboration: high vs. low) x 2 (Vocal speed: increased speed vs. decreased speed) x 2 (Vocal intonation: falling intonation vs. rising intonation) between participants factorial design. Vocal speed and vocal intonation influenced perceptions of speaker confidence as predicted. In line with the ELM, under high elaboration, confidence biased thought favorability, which in turn influenced attitudes. Under low elaboration, confidence did not bias thoughts but rather directly influenced attitudes as a peripheral cue. Experiment 2 used a similar design as Experiment 1 but focused on vocal pitch. Results confirmed pitch influenced perceptions of confidence as predicted. Importantly, we also replicated the bias and cue processes found in Experiment 1. Experiment 3 investigated the process by which a broader spectrum of speech rate influenced persuasion under moderate elaboration. In a 2 (Argument quality: strong vs. weak) x 4 (Vocal speed: extremely slow vs. moderately slow vs. moderately fast vs. extremely fast) between participants factorial design, results confirmed the hypothesized non-linear relationship between speech rate and perceptions of confidence. In line with the ELM, speech rate influenced persuasion based on the amount of processing. Experiment 4 investigated the effects of a broader spectrum of vocal intonation on persuasion under moderate elaboration and used a similar design as Experiment 3. Results indicated a partial success of our vocal intonation manipulation. No evidence was found to support the hypothesized mechanism. These studies show that changes in several different properties of voice can influence the extent to which others perceive them as confident. Importantly, evidence suggests different vocal properties influence persuasion by the same bias and cue processes under high and low thought. Evidence also suggests that under moderate thought, speech rate influences persuasion based on the amount of processing.

Language, Logos, and Social Ontology: Naturalist and Post-Naturalist Narratives of Human Rationality and Social Reality

I distinguish two ways that philosophers have approached and explained the reality and status of human social institutions. I call these approaches “naturalist” and “post-naturalist”. Common to both approaches is an understanding that the status of mind and its relation to the world or “nature” has implications on a conception of the status of institutional reality. Naturalists hold that mind is explicable within a scientific frame that conceives of mind as a fundamentally material process. By proxy, social reality is also materially explicable. Post-naturalists critique this view, holding instead that naturalism is parasitic on contemporary science—it therefore is non-compulsory and distorts how we ought to understand mind and social reality. A comparison of naturalism and post-naturalism will comprise the content of the first chapter. The second chapter turns to tracing out the dimensions of a post-naturalist narrative of mind and social reality. Post-naturalists conceive of mind and its activity of thought as sui generis, and it transpires from this that social institutions are better understood as a rational mind’s mode of the expression in the world. Post-naturalism conceives of social reality as a necessary dimension of thought. Thought requires a second person and thereby a tradition or context of norms that come to both structure its expression and become the products of expression. This is in contrast to the idea that social reality is a production of minds, and thereby derivative. Social reality, self-conscious thought, and thought of the second person are therefore three dimensions of a greater unity.

Reversibly Photo-Crosslinkable Polycarbonate-Based Polymersomes for Drug Encapsulation and Delivery

This thesis describes the preparation of polymersomes from poly(ethylene glycol)-block-polycarbonate (PEG-PC) copolymers functionalized with pendant coumarin groups. Coumarin groups undergo photo-reversible dimerization when irradiated with specific ultraviolet wavelengths, so they can be used to prepare polymers with photo-responsive properties. In this case, the pendant coumarin groups enable stabilization of the polymersome membrane through photo-crosslinking of the hydrophobic block. Initially, several novel cinnamoyl and coumarin functionalized cyclic carbonate monomers were synthesized using ester, ether, or amide linkages. While the homopolymerization of these functionalized monomers proved challenging due to their high melting points, both cinnamoyl and coumarin functionalized monomers were successfully copolymerized with trimethylene carbonate (TMC) at 100 ℃ using a catalyst-free melt polymerization process where the TMC doubled as a solvent for the higher melting point monomer. Using this system, polycarbonate copolymers with up to 33% incorporation of the functionalized monomers were prepared. In addition, an investigation of some anomalous polymerization results identified previously unreported triethylamine-based catalysts for the melt polymerization of carbonate monomers. These studies also demonstrated that the catalyst-free polymerization of TMC occurs faster and at lower temperatures than previously reported. Subsequently, the photo-crosslinking of cinnamoyl and coumarin functionalized polycarbonates was compared and coumarin was identified as the more effective crosslinking agent when using 300-400 nm UV. An investigation of the photo-reversibility of the coumarin dimerization revealed no discernible change in the properties of crosslinked networks, but rapid photo-reversion in dilute solutions. The photo-crosslinking and photo-reversion kinetics of the coumarin functionalized polycarbonates were determined to be second-order in both cases. Finally, the self-assembly of PEG-PC diblock copolymers functionalized with coumarin was examined and both reverse solvent evaporation and solvent displacement were found to induce self-assembly, with hydrophilic mass fractions (f-factors) of 12-28% resulting in the formation of solid microparticles and nanoparticles and f-factors of 33-43% resulting in the formation of polymersomes. The stabilization of these polymersome membranes through photo-initiator-free photo-crosslinking was demonstrated with the crosslinking allowing polymersomes to withstand centrifugation at 12,000 x g. In addition, the encapsulation of calcein, as a model small molecule drug, in the stabilized polymersomes was successfully demonstrated using confocal microscopy.