ROLE OF CAVEOLIN-3 IN THE MODULATION OF HERG POTASSIUM CHANNEL

The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr) that is important for cardiac repolarization. Previously, we have discovered that hERG channels rapidly internalize in low extracellular K+ ([K+]o). In cell culture, this process is driven by the endocytic protein, caveolin-1 (Cav1), which is an integral player in the caveolae-dependant endocytosis pathway. However, in the heart, Caveolin-3 (Cav3) is, in fact, the predominant form in the myocyte, and thus may play a direct role in regulating hERG expression in the heart. Thus, I hypothesize that this reduction of hERG conductance in cardiac myocytes derives from the presence of Cav3, which is integral regulator of hERG homeostasis innately in the heart. To investigate the effect of Cav3 on hERG, I overexpressed Cav3 in human embryonic kidney 293 (HEK-293) cells stably expressing hERG channels. Cav3 overexpression significantly and specifically decreased both the hERG current amplitude and the mature channel expression in normal culture conditions. Co-immunoprecipitation analysis and confocal imaging demonstrated an association between hERG and Cav3 in HEK cells as well as rat and rabbit cardiomyocytes. Mechanistically, I discovered that Cav3 possesses a faster turnover rate compared to Cav1, and can enhance hERG degradation through up-regulating mature channel ubiquitination via the ubiquitin ligase, NEDD4-2. Knockdown of Cav3 in neonatal cardiac myocytes also enhanced hERG expression. My data indicate that Cav3 participates in hERG trafficking, and is an important regulator of hERG channel homeostasis in cardiac myocytes. This information provides a platform for future intervention of the hERG-induced type-2 long QT syndrome (LQTS).

Amorous Ex/Incursions: Love in Writings of Badiou, Weil, Fromm, and Barthes

My dissertation explores the enabling contributions of love to the practice of ethico-political and cultural critique. Engaging with the work of Alain Badiou, Simone Weil, Erich Fromm, and Roland Barthes, I examine love in terms of the following modalities: waiting, giving, and looking. I place the aforementioned thinkers in dialogue with selected literary and cinematic texts to explicate and interrogate the meaningful possibilities of their discourse on love. In my chapter on Alain Badiou, I discuss his ontology, which I draw upon heavily to set the theoretical parameters of my study. I also discuss the logic of love that he develops in his philosophy. Speaking to the problem of pre-Evental agency that critics of his work identify, I suggest that waiting as attention, as theorized by Simone Weil, might be the closest form of agency that a pre-Evental (amorous) being can experience. In my discussion of Erich Fromm, I reevaluate his “art of loving” within the constellation of late capitalism. Reading his work through a Lacanian lens, I explore the utility of his prescriptions by examining Chuck Palahniuk’s controversial novel Fight Club. In my chapter on Roland Barthes, I theorize the possibility of cinematic looking that does not depend on the antagonism inherent in the binaries masculine/ feminine and (Gazing) spectator/ (to-be-looked-at) image. Towards this objective, I propose the “amorous look,” a mode of viewing occasioned by cinematic punctual encounters, that I contend is beyond the domain of desire and perversion. I deploy the “amorous look” as I reflect on Aureus Solito’s film Ang Pagdadalaga ni Maximo Olivares (The Blossoming of Maximo Olivares) and its representations of love and waiting.

Calling for resistance: The political economy of Indian and Canadian call centre industries

Call centres have in the last three decades come to define the interaction between corporations, governments, and other institutions and their respective customers, citizens, and members. From telemarketing to tele-health services, to credit card assistance, and even emergency response systems, call centres function as a nexus mediating technologically enabled labour practices with the commodification of services. Because of the ubiquitous nature of the call centre in post-industrial capitalism, the banality of these interactions often overshadows the nature of work and labour in this now-global sector. Advances in telecommunication technologies and the globalization of management practices designed to oversee and maintain standardized labour processes have made call centre work an international phenomenon. Simultaneously, these developments have dislocated assumptions about the geographic and spatial seat of work in what is defined here as the new international division of knowledge labour. The offshoring and outsourcing of call centre employment, part of the larger information technology and information technology enabled services sectors, has become a growing practice amongst governments and corporations in their attempts at controlling costs. Leading offshore destinations for call centre work, such as Canada and India, emerged as prominent locations for call centre work for these reasons. While incredible advances in technology have permitted the use of distant and “offshore” labour forces, the grander reshaping of an international political economy of communications has allowed for the acceleration of these processes. New and established labour unions have responded to these changes in the global regimes of work by seeking to organize call centre workers. These efforts have been assisted by a range of forces, not least of which is the condition of work itself, but also attempts by global union federations to build a bridge between international unionism and local organizing campaigns in the Global South and Global North. Through an examination of trade union interventions in the call centre industries located in Canada and India, this dissertation contributes to research on post-industrial employment by using political economy as a juncture between development studies, critical communications, and labour studies.

IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.

Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.

The Influence of 1,25-Dihydroxyvitamin D3 on the Cross-Priming of Lymphocytic Choriomeningitis Virus Nucleoprotein

Biologically active 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) binds the vitamin D receptor (VDR) to exert its effect on target cells. VDR expression is found in a number of immune cells including professional antigen-presenting cells such as dendritic cells. It has been found that the actions of 1,25-(OH)2D3 on the immune system are mainly immunosuppressive. The cross-presentation pathway allows for exogenously derived antigens to be presented by pAPCs on MHC-I molecules to CD8+ T cells. CD8+ T cell activation results in the expansion of epitope-specific T cell populations that confer host protection. These epitopes can be organized into an immunodominance hierarchy. Previous work demonstrated that introducing LCMV-NP via the cross-priming pathway significantly alters the immunodominance hierarchy of a subsequent LCMV infection. Building upon these observations, our study assessed the effects of LCMV-NP cross priming in the presence of a single dose of 1,25-(OH)2D3. Treatment with 1,25-(OH)2D3 was found to have biological effects in our model system. In vitro pAPCs were demonstrated to up-regulate IL-10 and CYP24A1 mRNA, in addition to the transactivation of cellular VDR, as demonstrated by a relocalization to the nuclear region. Mice treated with 1,25-(OH)2D3 were found to produce up-regulated IL-10 and CYP24A1 transcripts. Expression of VDR was increased at both the transcript and protein level. Our results demonstrate that a single dose of 1,25-(OH)2D3 does not affect the cross-priming pathway in this system. Treatment with 1,25-(OH)2D3 did not influence the ability of differentiated pAPCs to phagocytose or cross-present exogenous antigen to epitope-specific CD8+ T cells. Furthermore, 1,25-(OH)2D3 did not alter cross-priming or the establishment of the LCMV immunodominance hierarchy in vivo. By confirming that 1,25-(OH)2D3 does not suppress cross-priming in our model, our study helps to expand the understanding of the immunomodulatory role of exogenous 1,25-(OH)2D3 on the outcome of virus infection. Collectively, our data supports the observation that the role of 1,25-(OH)2D3 in the immune system is not always associated with suppressive effects.

"The Black Imprint of Sandals in White Mosaic Floors": H.D.'s Mythomystical Poetics

My dissertation examines the traces of inverse (mytho)mysticism, more synchronous with mythical alchemy than transcendent mystery, in H.D.’s mature work (1946-1961). Whereas H.D.’s earliest works respond to a fin de siècle occultism and a collective psyche troubled by the eschatological distress that, as Susan Acheson writes, “was widespread amongst modernist writers grappling with …world events and with the implications of Nietzsche’s inaugural annunciation of modernity in terms of the death of God” (187), her later oeuvre is dedicated to the same work of soul undertaken by the “secret cult of Night” in Vale Ave. Here, her thematic scope faces two ways: backward to ancient Greek mystery cults and their palingenesic rites and forward to depth psychologists searching for the Soul of the World. Vale Ave plays a pronounced role in my study as symbolic guide; in its seventy-four sequences the layering of time in the “trilogy” of past, present, and future that H.D. had explored during the years of the Second World War in order to get behind the fallen walls of cause and effect collapses into two distinct phases of human origin—“meeting” (evolution) and “parting” (involution)—and the poem invites Lilith and Lucifer to be its archetypal guides. My method for the study is imaginal, entering such disciplines as history, philosophy, and theology and bringing psychological understanding to them. John Walsh’s introduction to Vale Ave notes H.D.’s theme “that the human psyche exists in a dimension outside of time and space as well as within them. In Vale Ave, H.D. presents the extremity of this dual-dimensionality: metempsychosis” (vii). However, the concept that H.D. investigates is more than a literary processus of characters who adopt different masks and appear at various junctures in a chronological unwinding of history. I explore H.D.'s works as part of a Modernist tradition of writing “books of the dead” designed not to guide the soul after death, but to draw the gaze upon “a nearer thing,” as H.D. writes in Erige Cor Tuum Ad Me In Caelum, the wisdom intrinsic in the spirit of life itself.

READING AND RESPONDING: FINDING AND MAKING MEANING IN THE LIFE WRITING OF DIASPORIC IRANIAN JEWISH WOMEN

This project investigates the English-language life writing of diasporic Iranian Jewish women. It examines how these women have differentially imagined their diasporic lives and travels, and how they have in turn been imagined and accepted or rejected by their audiences. In the first chapter, I use “home” as a lens for understanding three distinct life writing texts, showing how the authors write about what it means to have a home and to be at home in contrasting and even contradictory ways. I show how, despite potential hegemonic readings that perpetuate unequal relationships and a normative definition of the ideal home, the texts are open to multiple contestatory readings that create spaces for new formulations and understandings. In the second chapter, I look more closely at the intersections between trauma stories and the life writing of Iranian Jewish women, and I argue that readers use life writing texts about trauma to support an egocentric reconstruction of American democracy and dominance. I also show how a critical frame for understanding trauma can yield interpretations that highlight, rather than ignore, relationships of power and privilege. In the final chapter of the thesis, I present a case study of two online reading groups, and I show that communal reading environments, though they participate in dominant discourses, are also spaces where resistance and subversion can develop.

AUSTRALIA’S STRATEGIC CULTURE: An investigation of the concept of strategic culture and its application to the Australian case

The notion that each state in the international system approaches matters of war and peace somewhat differently because they each possess a unique strategic culture is not a new or obscure one – but it nevertheless remains controversial. While some scholars dismiss the utility or practicality of examining states’ cultures when seeking to explain or predict those states’ patterns of strategic decision-making, even amongst those who accept that we should pay attention to cultural differences between states when carrying out strategic analysis there remains a frustratingly eclectic range of offerings from scholars regarding how best to do so. In short, significant uncertainty remains regarding both whether strategic culture should be used as an analytical tool and, if it is so utilized, how one should go about doing so. This thesis therefore explores the concept of strategic culture in great detail, both theoretical and empirical. The opening three chapters examine why the more traditional rationalist/materialistic theories should not exclusively dominate strategic analysis, then the various existing strategic cultural offerings are considered and critiqued and, finally, a new conceptual model for strategic cultural analysis is proposed which draws from the hitherto largely neglected psychological and sociological literature. Both of these fields, it is submitted in Chapter 3, have spent more time and effort developing ways of understanding and analyzing culture than the field of IR has to date, and therefore the models and methods debated and developed in these fields should, it is argued, be ‘imported’ into IR to drive further strategic cultural research. The thesis then moves in the following six chapters to consider Australia’s strategic culture. The purpose of this part of the thesis is two-fold: first, it illustrates how the model offered in Chapter 3 works and, by implication, suggests how scholars may go about applying it to other cases. Second, and perhaps more importantly, the latter six chapters explore the twists and turns of Australia’s substantive strategic decision-making over the course of the last century or more, thereby explaining how Australia’s strategic history can be understood from a cultural perspective.

Livelihood Strategies of Dock Workers in Durban, c. 1900-1959

This dissertation examines the livelihood strategies of African dock workers in Durban, South Africa, between the Anglo-Boer War and the 1959 strikes. These labourers did not conform to common conceptions of radical dock workers or conservative African migrant workers. While Marxist scholars have been correct to stress the working class consciousness of Durban’s dock workers, this consciousness was also more ambiguous. These workers and their leaders displayed a peculiar mix of concern for workers’ issues and defences of the rights and interests of African traders. Many of Durban’s dock workers were not only wage labourers. In fact, only a minority had wages as their only source of income. The Reserve economy played a role in sustaining the consumption levels of their households and, more importantly, more than half of the former dock workers interviewed for this research engaged in some form of commercial enterprise, often based on the pilferage and sale of cargoes. Some also teamed up with township women who sold pilfered goods while the men were at work. This combination of commercial strategies and wage labour has often been overlooked in the literature. By looking at these livelihood strategies, this dissertation considers how rural and urban economies interacted in households’ strategies and reinterprets the reproduction of labour and the household in order to move beyond dichotomies of proletarian versus rural consciousness. The dock workers’ households were neither proletarian households that were forced to reside in the countryside because of apartheid, nor traditional rural homesteads with a missing migrant member. The households were reproduced in three geographically separate spheres of production and consumption, none of which could reproduce the household on its own. These spheres were dependent on each other, but also separate, as physical distance gave the different household members some autonomy. Such multi-nodal households not only bridged the rural and the urban, but equally straddled the formal/informal divide. For many, their employment on the docks made their commercial enterprises possible, which allowed them to retire early from urban wage labour. Consequently, the interests of wage labourers could not be divorced from those of African small-scale entrepreneurs.

Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor in Non-Hepatic Cells

Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme that, once activated, attenuates fibrinolysis. TAFIa also possesses anti-inflammatory properties. Although liver is the main source of plasma TAFI, platelet-derived TAFI has also been reported. An alternatively spliced TAFI variant resulted from the skipping of exon 6 and a 52-base deletion in exon 10 of CPB2 mRNA (∆6+10) was described to be brain specific. This TAFI variant is reputed to possess a secretase-like activity that cleaves β-amyloid precursor protein to form β-amyloid, a process involved in the onset of Alzheimer's disease. In this thesis, we report the identification of CPB2 mRNA and TAFI protein in various vascular and inflammatory cells. Specifically, we describe the expression of CPB2 mRNA in the megakaryocytic cell lines MEG-01 and Dami, the monocytic cell line THP-1, and peripheral blood mononuclear cells. TAFI protein was detected in differentiated Dami and THP-1 cells. We next describe the effect of external stimuli such as phorbol myristate acetate (PMA) on CPB2 expression in Dami and THP-1 cells. We found that PMA treatment increases both CPB2 mRNA abundance and promoter activity in Dami cells, and decreases both CPB2 mRNA abundance and promoter activity in THP-1 cells. Deletion analysis of the CPB2 promoter indicated cell-type specific regulation of CPB2 gene expression. Finally, we evaluated the expression of alternatively spliced CPB2 mRNA variants in hepatic and non hepatic cells. We found that exon 6 skipping variants are expressed in all cell types of interest. The variant previously reported to be brain specific was also found to be expressed in platelets. We found that the alternatively spliced TAFI variants accumulated inside the cells in a non-secretable, hypoglycosylated form and showed no carboxypeptidase activity. Taken together, this thesis provides further evidence supporting the hypothesis that platelet-derived TAFI is originated from CPB2 gene expression in megakaryocytes. Moreover, our data imply a potential for site-specific anti-inflammatory control provided by macrophage-derived TAFI. Alternative splicing of the CPB2 mRNA may give rise to variants with an intracellular role, perhaps as a peptidase chaperone, and may modulate the synthesis of secretable TAFI.

THE INFORMATION ERA THREATENS PRIVACY: A Comparative Study of Electronic Money’s Privacy Policies and Privacy Laws

This thesis consists of an analysis of electronic money (e-money), e-money’s privacy policies and relevant privacy laws. The value of information and the development of technology enhance the risk of privacy violations in the information era. Consumer privacy interests with respect to e-money are governed in part by the Personal Information Protection and Electronic Documents Act (PIPEDA) in Canada and by the European Union’s Data Protection Directive. The analysis is directed at whether the privacy policies of three kinds of e-money – Octopus Card, PayPal and MasterCard – comply with the spirit and letter of these laws. In light of technology change, the laws should be interpreted to apply broadly to protect privacy interests. Enhanced privacy protection may in fact lead to greater adoption of e-money by consumers.

Bystander Narratives: The Fiction of J.M. Coetzee and the Holocaust

J.M. Coetzee’s novels are suffused with a pervasive, though often oblique, Holocaust awareness. Direct references to the event and to the historical era to which it belongs, subtle stylistic and thematic echoes of Holocaust writing, and the recurrent mobilization of Holocaust imagery in Coetzee’s novels all contribute to suggest the significance of the event to the author’s work and thought. Providing Coetzee with a lens through which to view the contemporary situation, both local and global, the Holocaust offers Coetzee a means by which difficult and complex questions of ethics and historiographical truth may be approached. Above all, the Holocaust and its representation contribute to Coetzee’s exploration of the dilemmas of translating the traumatic lived experience of atrocity – including, but not limited to, life in apartheid South Africa – into narrative form. Taken as a whole, Coetzee’s oeuvre initially anticipates and later responds to, in characteristically oblique fashion, the narrative project(s) facing post-apartheid South Africa as the newly-democratic nation sought to make sense of its past through a variety of means, the most important of which was the country’s Truth and Reconciliation Commission. Implicitly challenging the TRC’s findings as well as its narrative assumptions, the Coetzean oeuvre accordingly invites being read as offering a continuous and evolving counter-narrative to the TRC and its construction of a narrative of the apartheid past for the post-apartheid nation. In utilizing the Holocaust, its representations, and the reception thereof to frame his response to apartheid, Coetzee implicates both in a critique of the Western model of modernity, suggesting, in the process, the importance of reconfiguring modernity in a more ethical shape.

Optical Characterization of Indium Gallium Nitride for Application in High-Efficiency Solar Photovoltaic Cells

The semiconductor alloy indium gallium nitride (InxGa1-xN) offers substantial potential in the development of high-efficiency multi-junction photovoltaic devices due to its wide range of direct band gaps, strong absorption and other optoelectronic properties. This work uses a variety of characterization techniques to examine the properties of InxGa1-xN thin films deposited in a range of compositions by a novel plasma-enhanced evaporation deposition system. Due to the high vapour pressure and low dissociation temperature of indium, the indium incorporation and, ultimately, control of the InxGa1-xN composition was found to be influenced to a greater degree by deposition temperature than variations in the In:Ga source rates in the investigated region of deposition condition space. Under specific deposition conditions, crystalline films were grown in an advantageous nano-columnar microstructure with deposition temperature influencing column size and density. The InxGa1-xN films were determined to have very strong absorption coefficients with band gaps indirectly related to indium content. However, the films also suffer from compositional inhomogeneity and In-related defect complexes with strong phonon coupling that dominates the emission mechanism. This, in addition to the presence of metal impurities, harms the alloy’s electronic properties as no significant photoresponse was observed. This research has demonstrated the material properties that make the InxGa1-xN alloy attractive for multi-junction solar cells and the benefits/drawbacks of the plasma-enhanced evaporation deposition system. Future work is needed to overcome significant challenges relating to crystalline quality, compositional homogeneity and the optoelectronic properties of In-rich InxGa1-xN films in order to develop high-performance photovoltaic devices.

Breaking New Ground: The First Generation of Women to Work as Professional Authors in English Canada (1880-1920)

In the later decades of the nineteenth century and the early decades of the twentieth, large numbers of Canadian women were stepping out of the shadows of private life and into the public world of work and political action. Among them, both a cause and an effect of these sweeping social changes, was the first generation of Canadian women to work as professional authors. Although these women were not unified by ideology, genre, or date of birth, they are studied here as a generation defined by their time and place in history, by their material circumstances, and by their collective accomplishment. Chapters which focus on E. Pauline Johnson (Tekahionwake), the Eaton sisters (Sui Sin Far and Onoto Watanna), Joanna E. Wood, and Sara Jeannette Duncan explore some of the many commonalities and interrelationships among the members of this generation as a whole. This project combines archival research with analytical bibliography in order to clarify and extend our knowledge of Johnson’s and Duncan’s professional lives and publishing histories, and to recover some of Wood’s “lost” stories. This research offers a preliminary sketch of the long tradition of the platform performance (both Native and non-Native) with which Johnson and others engaged. It explores the uniquely innovative ethnographic writings of Johnson, Duncan, and the Eaton sisters, among others, and it explores thematic concerns which relate directly to the experiences of working women. Whether or not I convince other scholars to treat these authors as a generation, with more in common than has previously been supposed, the strong parallels revealed in these pages will help to clarify and contextualize some of their most interesting work.

Interactions of Lipoprotein(a) with the Plasminogen System: Mechanisms and Pathophysiological Consequences

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are associated with increased risk of atherothrombotic disease. Lp(a) is a unique lipoprotein consisting of a low density lipoprotein-like moiety covalently linked to apolipoprotein(a) (apo(a)), a homologue of the fibrinolytic proenzyme plasminogen. Apo(a) is extremely heterogeneous in size with small isoforms being independently associated with increased cardiovascular risk. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue-type plasminogen activator (tPA)-mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin-dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin-mediated conversion of Glu1-plasminogen to Lys78-plasminogen. Additionally, abnormal fibrin clot structures have been associated with both an increased risk of cardiovascular disease and elevated Lp(a) levels. Similarly, oxidized phospholipids have been implicated in the development of cardiovascular disease, and are not only preferentially carried by Lp(a) in the plasma but have also been shown to covalently-modify both apo(a) and plasminogen. In this thesis, we built upon the understanding of the role of apo(a) in plasminogen activation on the fibrin/degraded fibrin surface by determining that: (i) apo(a) inhibits plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion and identifying the critical domains in apo(a) responsible for this effect, (ii) apo(a) isoform size does not affect either the inhibition of tPA-mediated plasminogen activation or the inhibition of plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion, (iii) apo(a) modifies fibrin clot structure to form more dense clots with thinner fibers and reduced permeability, modifications that enhance the ability of apo(a) to inhibit tPA-mediated plasminogen activation and (iv) the phosphorus content of apo(a) affects its ability to inhibit tPA-mediated plasminogen activation and the phosphorus content of plasminogen affects its ability to be activated by tPA. By understanding these individual reactions, each of which has the potential to affect the broader fibrin clot lysis process, we have expanded our understanding of the overall effect of Lp(a)/apo(a) in the inhibition of plasminogen activation on the fibrin/degraded fibrin surface and thus broadened our understanding of how Lp(a)/apo(a) may mediate the inhibition of thrombolysis in vivo.