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published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Angiogenesis is a fundamental driver of tumor biology and many other important aspect of human health. Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) has been shown to be a valuable biomarker for the indirect assessment of angiogenesis. However, DCE-MRI is very specialized technique that has limitations. In this dissertation new models and contrast agents to address some of these limitations are presented. Chapter 1 presents an introduction to DCE-MRI, the rationale to asses tumor biology with this technique, the MRI pulses sequences and the standard pharmacokinetic modeling used for the analysis of DCE- MRI data. Chapter 2 describes the application of DCE-MRI to asses the response to the hypoxia-activated drug TH-302. It is shown that DCE-MRI can detect a response after only 24 hours of initiating therapy. In Chapter 3, a new model for the analysis of DCE-MRI is presented, the so-called Linear Reference Region Model (LRRM). This new model improves upon existing models and it was demonstrated that it is ~620 faster than current algorithms and 5 times less sensitive to noise, and more importantly less sensitive to temporal resolution which enables the analysis of DCE-MRI data obtained in the clinical setting, which opens a new area of study in clinical MRI. Chapter 4 describes the extension of the LRRM to estimate the absolute permeability of two fluorinated contrast agents; we call this approach the Reference Agent Model (RAM). In order to make this new model an experimental reality, a novel pulse sequence and contrast agents (CA) for ¹⁹F MRI were developed. Two contributions to the field of DCE-MRI are presented in this chapter, the first simultaneous ¹⁹F-DCE-MRI detection of two fluorinated CA in a mouse model of breast cancer, and the estimation of their relative permeability. RAM eliminates some of the physiological variables that affect DCE-MRI, which may improve its sensitivity and specificity. Finally, new potential applications of LRRM and RAM are discussed in Chapter 5.

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This thesis deals with the nature and definition of phonological similarity and shows that, when similarity plays a role in the motivation of phonological processes, it is evaluated over abstract, phonological features and not purely phonetic properties. Empirical evidence for this position is drawn from the domain of consonant harmony. Typological studies of consonant harmony (Hansson 2001, Rose and Walker 2004) have argued that segments which interact in consonant harmony processes must be highly similar to one another. This thesis provides analyses of a range of consonant harmony processes and demonstrates that, in each case, the notion of similarity needed in order to determine participating segments is evaluated over contrastive feature specifications. Contrastive specifications are established according to language-specific feature hierarchies (Jackobson and Halle 1956, Dresher 2003, forthcoming) with some features taking scope over others. Languages analyzed in some detail include Bumo Izon, Kalabari Ijo, Hausa, Dholuo, Anywa, Tzutujil and Aymara. Two definitions of similarity are proposed in order to account for two sets of cases. In one set of consonant harmony processes, interacting segments are similar in the sense that they constitute the natural class of segments contrastively specified in the harmonic feature. In another set of cases, participating segments must be similar according to the following definition; they must differ in only a single marked and contrastive feature specification.

The world is full of extremes and I enjoy studying the contrasts of these extremes. I am influenced by the soft and subtle, as well as the rough and unrefined. From printing on the most delicate of papers, to constructing objects from scrap metal and reclaimed barn wood, the pieces I produce are studies in contrast. In these works, I place extremes of media next to one another in a way that makes the viewer feel that these opposites belong together. I struggle to make the improbable seem ordinary and the mundane seem amazing.

Contrastive research in English and Spanish passive based on the corpus The analysis that was accomplished in this thesis concerning a contrative comparison of the passive frequency in English and Spanish languages was supposed to confirm several hypotheses stated in the introduction. The hypotheses were about the agent of the passive constructions, its frequency and obligation of it being expressed according to the style of the text. Thanks to the analysis it was discovered that the agent is often unexpressed in neither of the styles - scientific or novelistic. If the agent is explicitly expressed it is often due to the practical reasons; otherwise the possibilty not to express it explicitly - one of the main advantages that the passive voice offers - is used abunadantly. Nevertheless, the texts representing the novelistic style are evidently using more instances of the reflexive type of the passive. Mainly, when the agent is not relevant or unknown. In the scientific texts, there is a great tendency towards using a personal pronoun or a general noun and the verb in active voice. The problem connected with this practice is the narrow number of possibilities and therefore lack of elegance in the text. The reasons for using the influence of the functional sentence perspective are also different according to...

Visual field testing, or perimetry, measures peripheral visual loss in eye diseases such as glaucoma. Rarebit Perimetry (RBP) is a new and novel perimetric method, introduced in 2002 by Lars Frisén (2002), with the aim of detecting low degrees of neural damage within the retina. / RBP is unlike conventional perimetric methods that measure levels of retinal sensitivity, but instead uses very bright (i.e. suprathreshold) and very small targets to detect tiny areas of absolute blindness within otherwise normal areas of vision. RBP thus claims to locate miniscule gaps in the receptive field matrix of neurons in the retina, with the assumption that dead neurons leave gaps in this matrix. The most useful application of this idea is to detect progressive eye disease in the earliest stages (Frisén, 2002). Current research shows that RBP correlates with other standard visual field tests (Brusini, Salvetat, et al., 2005; Frisén, 2003; Gedik, Akman, et al., 2007; Martin & Wanger, 2004), but may afford greater sensitivity by detecting very mild visual losses missed by other tests (Martin, Ley, et al., 2004; Martin & Nilsson, 2007; Nilsson, Wendt, et al., 2007). / To date, there are no studies that definitively test the theoretical basis of RBP, so in this thesis I aim to explore the proposed underlying mechanisms and assumptions of this test. In particular, the proposed mechanism of RBP leads to specific predictions as to how responses will alter when the luminances of the RBP targets are systematically decreased. I therefore compared RBP responses of mean hit rate as a function of target luminance and found results to be inconsistent with the proposed RBP mechanism. Mathematical simulations were performed to explore reasons for the differences between the two groups (Chapter Seven).