Between Modern and Postmodern: Nietzsche on Truth and Knowledge

This thesis examines Nietzsche’s epistemology. Its main interlocutors are two previously existing attempts to explain Nietzsche’s views on truth and knowledge. One of these interpretationsI dub the ‘postmodern’ reading, held most notably by Sarah Kofman, Jacques Derrida, and Paul de Man. The other is the ‘modern’ reading of Walter Kaufmann, John T. Wilcox, and most prominently Maudemarie Clark and Brian Leiter. Each of these readings emphasizes one aspect of Nietzsche’s thought. The postmodern reading focuses on Nietzsche’s more radical pronouncements, and promotes a type of scepticism and subjectivism. The modern reading, by contrast, emphasizes Nietzsche’s more traditional claims, and argues that he lauds science and preserves our ability to attain truth. However, neither reading is entirely satisfactory. In what follows, I first critically examine both of these readings in detail. The first chapter highlights the major points of these two readings, as well as some issues in each. After detailing these positions, I then turn to a largely chronological reading of Nietzsche’s works to establish an alternative account of his epistemology. Chapters two through four provide readings of Nietzsche’s epistemological claims in his major works from Human, All Too Human (1878) until Twilight of the Idols(1888). I combine this chronological reading withother informative aspects of Nietzsche’s thought. These other aspects include Nietzsche’s reading of Roger Boscovich (1711-1787) and his adoption of force-point ontology, his ontological commitment to nominalism, his views on evolution and its role in epistemology, and his similarities with Ernst Mach (1838-1916). Finally, I also connect Nietzsche’s epistemology with his critiques of morality and religion. I show that my reading is buttressed by the deep congruity between Nietzsche’s epistemology and his critiques, while the modern and postmodern readings are both unable to account for this congruity in a satisfactory manner.Doctor of Philosophy (PhD

A theoretical study of the response of vascular tumours to different types of chemotherapy

In this paper we formulate and explore a mathematical model to study continuous infusion of a vascular tumour with isolated and combined blood-borne chemotherapies. The mathematical model comprises a system of nonlinear partial differential equations that describe the evolution of the healthy (host) cells, the tumour cells and the tumour vasculature, coupled with distribution of a generic angiogenic stimulant (TAF) and blood-borne oxygen. A novel aspect of our model is the presence of blood-borne chemotherapeutic drugs which target different aspects of tumour growth (cf. proliferating cells, the angiogenic stimulant or the tumour vasculature). We run exhaustive numerical simulations in order to compare vascular tumour growth before and following therapy. Our results suggest that continuous exposure to anti-proliferative drug will result in the vascular tumour being cleared, becoming growth-arrested or growing at a reduced rate, the outcome depending on the drug’s potency and its rate of uptake. When the angiogenic stimulant or the tumour vasculature are targeted by the therapy, tumour elimination can not occur: at best vascular growth is retarded and the tumour reverts to an avascular form. Application of a combined treatment that destroys the vasculature and the TAF, yields results that resemble those achieved following successful treatment with anti-TAF or anti-vascular therapy. In contrast, combining anti-proliferative therapy with anti-TAF or antivascular therapy can eliminate the vascular tumour. In conclusion, our results suggest that tumour growth and the time of tumour clearance are highly sensitive to the specific combinations of anti-proliferative, anti-TAF and anti-vascular drugs

The metabolism of androstenone and other steroid hormone conjugates in relation to boar taint

Increased public interest in the welfare of pigs reared for pork production has led to an increased effort in finding new approaches for controlling the unpleasant odour and flavour from heated pork products known as boar taint. Therefore, this study investigated the metabolism of androstenone and the enzymes involved in its sulfoconjugation in order to further understand the pathways and genes involved in the development of this meat quality defect. Leydig cells that were incubated with androstenone produced 3-keto-sulfoxy-androstenone, providing direct evidence, for the first time, that sulfoconjugation of this steroid does occur in the boar. In addition, human embryonic kidney cells that were overexpressed with porcine sulfotransferase (SULT) enzymes showed that SULT2A1, but not SULT2B1, was responsible for sulfoconjugating androstenone. These findings emphasize the importance of conjugation in steroid metabolism and its relevance to boar taint is discussed

Petrography, geochemistry and petrogenesis of alkaline dyke rocks from the Coldwell Alkaline Complex, Northwestern Ontario

Dyke rocks occurring in the Coldwell alkaline instrusive complex, N. W. Ontario, were studied by various petrographic and geochemical means. The resulting observations indicate that 5 types of mafic alkaline lamprophyres, distinguished on the basis of chemistry and mineralogy according to the scheme of Rock (1977), and 1 type of felsic tinguaite occur in the complex (in approximate order of abundance): a) ocellar camptonites b) analcite tinguaites c) quartz-bearing camptonites e) amphibole camptonites f) monchiquites Lamprophyres are characterized mineralogically by phenocrysts of clinopyroxene and brown amphibole, and remnant phenocrysts of olivine...(see document for full abstract

Protein kinase C phosphorylates AMP-activated protein kinase α1 Ser487

The key metabolic regulator, AMP-activated protein kinase (AMPK) is reported to be downregulated in metabolic disorders, but the mechanisms are poorly characterised. Recent studies have identified phosphorylation of the AMPKα1/α2 catalytic subunit isoforms at Ser487/491 respectively as an inhibitory regulation mechanism. Vascular endothelial growth factor (VEGF) stimulates AMPK and protein kinase B (Akt) in cultured human endothelial cells. As Akt has been demonstrated to be an AMPKα1 Ser487 kinase, the effect of VEGF on inhibitory AMPK phosphorylation in cultured primary human endothelial cells was examined. Stimulation of endothelial cells with VEGF rapidly increased AMPKα1 Ser487 phosphorylation in an Akt-independent manner, without altering AMPKα2 Ser491 phosphorylation. In contrast, VEGF-stimulated AMPKα1 Ser487 phosphorylation was sensitive to inhibitors of protein kinase C (PKC) and PKC activation using phorbol esters or overexpression of PKC stimulated AMPKα1 Ser487 phosphorylation. Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle. These data indicate a novel regulatory role of PKC to inhibit AMPKα1 in human cells. As PKC activation is associated with insulin resistance and obesity, PKC may underlie the reduced AMPK activity reported in response to overnutrition in insulin-resistant metabolic and vascular tissues

Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation

yesInflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-inflammatory actions in adipose tissue, yet the mechanisms underlying this remain poorly characterised. The effect of AMPK activation on cytokine-stimulated proinflammatory signalling was therefore assessed in cultured adipocytes. AMPK activation inhibited IL-1β-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation and downregulated MKK4/JNK and IKK/IκB/NFκB signalling. AMPK activation inhibited TNF-α-stimulated IKK/IκB/NFκB signalling but had no effect on JNK phosphorylation. The JAK/STAT3 pathway was also suppressed by AMPK after IL-6 stimulation and during adipogenesis. Adipose tissue from AMPKα1−/− mice exhibited increased JNK and STAT3 phosphorylation, supporting suppression of these distinct proinflammatory pathways by AMPK in vivo. The inhibition of multiple pro-inflammatory signalling pathways by AMPK may underlie the reported beneficial effects of AMPK activation in adipose tissue.British Heart Foundatio

Xenotropic Murine Leukemia Virus-Related Virus as a Case Study: Using a Precautionary Risk Management Approach for Emerging Blood-Borne Pathogens in Canada

In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the United States, when tested, were infected with a novel gamma retrovirus, xenotropic murine leukemia virus-related virus (XMRV) (Lombardi et al., 2009). XMRV is a recently discovered human gammaretrovirus first described in prostate cancers that shares significant homology with murine leukemia virus (MLV) (Ursiman et al., 2006). It is known that XMRV can cause leukemias and sarcomas in several rodent, feline, and primate species but has not been shown to cause disease in humans. XMRV was detectable in the peripheral blood mononuclear cells (PBMCs) and plasma of individuals diagnosed with CFS (Lombardi et al., 2009). After this report was published there was a great deal of uncertainty surrounding this emergent virus and its involvement in the etiology of CFS. The uncertainty was, in part, due to CFS being a complex, poorly understood multi-system disorder with different disease criteria used for its diagnosis. CFS, also known as Myalgic Encephalomyelitis (ME), is a debilitating disease of unknown origin that is estimated to affect 17 million people worldwide. The initial report connecting XMRV to prostate cancers and CFS garnered significant media and scientific interest since it provided a potential Susie ElSaadany2**, Tamer Oraby1 * Daniel Krewski1, 4 and Peter R. Ganz5 1McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ontario, Canada 2Blood Safety Surveillance and Health Care Acquired Infections Division, Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada 3Aspinall and Associates, Cleveland House, High Street, and Earth Sciences, Bristol University, Bristol, United Kingdom 4Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada 5Health Canada, Director’s Office, Ottawa, Ontario, Canada ** Corresponding Author , Marian Laderoute2 , Jun Wu2 , Willy Aspinall3 , www.intechopen.com 32 The Continuum of Health Risk Assessments explanation for the disease but also an avenue for possible therapeutic treatments since XMRV is known to be susceptible to some anti-retroviral drugs (Cohen, 2011)