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The Global ETD Search service is a free service for researchers
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Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 381 to 382 of 382 (0.122 seconds)Spelling suggestions: "subject:"computational modeling,"" "subject:"eomputational modeling,""
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Investigating the porphyrias through analysis of biochemical pathways.Ruegg, Evonne Teresa Nicole January 2014 (has links)
ABSTRACT
The porphyrias are a diverse group of metabolic disorders arising from diminished
activity of enzymes in the heme biosynthetic pathway. They can present with acute
neurovisceral symptoms, cutaneous symptoms, or both. The complexity of these
disorders is demonstrated by the fact that some acute porphyria patients with the
underlying genetic defect(s) are latent and asymptomatic while others present with
severe symptoms. This indicates that there is at least one other risk factor required in
addition to the genetic defect for symptom manifestation. A systematic review of the
heme biosynthetic pathway highlighted the involvement of a number of micronutrient
cofactors. An exhaustive review of the medical literature uncovered numerous reports
of micronutrient deficiencies in the porphyrias as well as successful case reports of
treatments with micronutrients. Many micronutrient deficiencies present with
symptoms similar to those in porphyria, in particular vitamin B6. It is hypothesized
that a vitamin B6 deficiency and related micronutrient deficiencies may play a major
role in the pathogenesis of the acute porphyrias. In order to further investigate the
porphyrias, a computational model of the heme biosynthetic pathway was developed
based on kinetic parameters derived from a careful analysis of the literature. This
model demonstrated aspects of normal heme biosynthesis and illustrated some of the
disordered biochemistry of acute intermittent porphyria (AIP). The testing of this
model highlighted the modifications necessary to develop a more comprehensive
model with the potential to investigated hypotheses of the disordered biochemistry of
the porphyrias as well as the discovery of new methods of treatment and symptom
control. It is concluded that vitamin B6 deficiency might be the risk factor necessary
in conjunction with the genetic defect to trigger porphyria symptoms.
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| 382 |
F. A. Hayek's Critique of LegislationHolm, Cyril January 2014 (has links)
The dissertation concerns F. A. Hayek’s (1899–1992) critique of legislation. The purpose of the investigation is to clarify and assess that critique. I argue that there is in Hayek’s work a critique of legislation that is distinct from his well-known critique of social planning. Further that the main claim of this critique is what I refer to as Hayek’s legislation tenet, namely that legislation that aims to achieve specific aggregate results in complex orders of society will decrease the welfare level. The legislation tenet gains support; (i) from the welfare claim – according to which there is a positive correlation between the utilization of knowledge and the welfare level in society; (ii) from the dispersal of knowledge thesis – according to which the total knowledge of society is dispersed and not available to any one agency; and (iii) from the cultural evolution thesis – according to which evolutionary rules are more favorable to the utilization of knowledge in social cooperation than are legislative rules. More specifically, I argue that these form two lines of argument in support of the legislation tenet. One line of argument is based on the conjunction of the welfare claim and the dispersal of knowledge thesis. I argue that this line of argument is true. The other line of argument is based on the conjunction of the welfare claim and the cultural evolution thesis. I argue that this line of argument is false, mainly because the empirical work of political scientist Elinor Ostrom refutes it. Because the two lines of argument support the legislation tenet independently of each other, I argue that Hayek’s critique of legislation is true. In this dissertation, I further develop a legislative policy tool as based on the welfare claim and Hayek’s conception of coercion. I also consider Hayek’s idea that rules and law are instrumental in forging rational individual action and rational social orders, and turn to review this idea in light of the work of experimental economist Vernon Smith and economic historian Avner Greif. I find that Smith and Greif support this idea of Hayek’s, and I conjecture that it contributes to our understanding of Adam Smith’s notion of the invisible hand: It is rules – not an invisible hand – that prompt subjects to align individual and aggregate rationality in social interaction. Finally, I argue that Hayek’s critique is essentially utilitarian, as it is concerned with the negative welfare consequences of certain forms of legislation. And although it may appear that the dispersal of knowledge thesis will undermine the possibility of carrying out the utilitarian calculus, due to the lack of knowledge of the consequences of one’s actions – and therefore undermine the legislation tenet itself – I argue that the distinction between utilitarianism conceived as a method of deliberation and utilitarianism conceived as a criterion of correctness may be used to save Hayek’s critique from this objection.
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