Thesis (Ph. D.)--University of Wisconsin--Madison, 1967. / Typescript. Vita. Includes bibliographical references (leaves 239-243).

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Made available in DSpace on 2014-06-11T19:32:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-18Bitstream added on 2014-06-13T18:43:05Z : No. of bitstreams: 1 franzini_cm_dr_arafcf.pdf: 2677878 bytes, checksum: 26759573900040571415a3fa5cbf34b2 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Universidade Estadual Paulista (UNESP) / O tratamento das infecções fúngicas sistêmicas impõe grandes dificuldades devido ao fato da terapia endovenosa requerer administração do fármaco solubilizado ou disperso em partículas de diminutas dimensões, além da necessidade de hospitalização. A anfotericina B (AmB) continua sendo um dos antibióticos mais efetivos para tais tratamentos, apesar de sua baixa solubilidade e graves efeitos colaterais. Considerando que microemulsões permitem contornar esses problemas e proporcionar administração oral do fármaco, essas formulações lipídicas contendo AmB estão sendo cada vez mais estudadas. Adicionalmente, a formação de complexos de inclusão com ciclodextrinas (CDs) também tem sido promissora no desenvolvimento de novas formas farmacêuticas. Neste trabalho os parâmetros de formação de microemulsões (MEs) contendo fosfatidilcolina de soja (FS), Tween-20 (Tw) e oleato de sódio (OS) como tensoativos e colesterol (CHO) como fase oleosa e a formação de complexos de inclusão com diferentes derivados de CD e sua incorporação nas MEs foi estudado. Um diagrama de fases pseudoternário foi elaborado objetivando caracterizar MEs. O comportamento reológico e a estruturação interna foram empregadas para avaliação e ainda caracterização por espalhamento dinâmico de luz. Foi avaliado o efeito da proporção de tensoativo e óleo na determinação do diâmetro da fase interna nos sistemas com ou sem AmB, além da avaliação da contribuição da fase oleosa e do tensoativo na incorporação do fármaco nas MEs. Um diagrama de solubilidade de AmB em CDs foi desenvolvido e suas constantes de estabilidade determinadas. O preparo de ME contendo CDs em sua fase aquosa, parâmetros de incorporação de AmB e estudos de liberação foram realizados seguidos de análise termogravimétrica, difração de raios x (DRX) e ressonância magnética nuclear (RMN)... / The fungal infections treatment imposes many difficulties mainly because the intravenous therapy requires administration of solubilized or dispersed drug in particles of smaller dimension beyond the need for hospitalization. Despite its low solubility and serious adverse effects the amphotericin B (AmB) remains one of the most effective antibiotics to the treatment. Microemulsions allow circumvent these problems and provide oral administration. Therefore these lipid formulations containing AmB have been increasingly studied. Additionally, the formation of inclusion complexes with cyclodextrins (CDs) has also been promising in developing new dosage forms. In this work the formation parameters of microemulsions (MEs) containing soybean phosphatidylcholine (FS), Tween-20 (Tw) and sodium oleate (SO) as surfactant and cholesterol (CHO) as oil phase and the formation of inclusion complexes with different CDs derivatives and their incorporation into MEs were studied. The pseudo ternary phase diagram was built in order to characterize MEs. The rheological behavior and internal structure were evaluated and characterized by dynamic light scattering. The effect of the proportion of surfactant and oil phase in the diameter of the internal phase in systems with or without AmB was evaluated. Therefore the contribution of the oil phase and surfactant in the drug loading eficience was studied. The Solubility diagram of AmB in CDs was developed and its stability constants determined. The preparation of ME containing CDs in its aqueous phase, the incorporation AmB parameters and the release studies were performed followed by thermal analysis, x-ray (XRD) diffraction and nuclear magnetic resonance (NMR). The results reveal the MEs formation in regions containing up to 30% surfactant and about 11% of the oil phase. Under polarized light, the interest systems showed a dark background and lamellar structure... (Complete abstract click electronic access below)

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Orientador: Liliana Scorzoni / Banca: Luciane Dias de Oliveira / Banca: Haroldo Cesar de Oliveira / Resumo: Cryptococcus neoformans são leveduras que acometem principalmente indivíduos imunocomprometidos, podendo causar a meningoencefalite dependendo do estado imunológico do hospedeiro. Os tratamentos convencionais têm enfrentado grandes desafios. Dessa forma, o objetivo desse estudo foi avaliar os efeitos antifúngicos dos fármacos cloridrato de verapamil (CV), cloridrato de fluoxetina (CF) e cloridrato de paroxetina (CP) isolados e combinados com anfotericina B (AmB) contra C. neoformans. Foram determinados os valores de Concentração Inibitória Mínima (CIM) e Concentração Fungicida Mínima (CFM) de acordo com a técnica de microdiluição em caldo proposta pelo Comitê Europeu de Teste de Susceptibilidade Antimicrobiana (EUCAST). Posteriormente, foi avaliada a atividade sinérgica dos fármacos combinados com AmB (EUCAST). Os efeitos das CIMs e das concentrações sinérgicas selecionadas foram avaliados em biofilmes, quantificando a biomassa por cristal violeta e sua viabilidade por contagem de colônias (UFC/mL). Além disso, foram analisados os efeitos dos mesmos na cápsula induzida desta levedura. Os ensaios in vivo foram realizados em Galleria mellonella avaliando a toxicidade dos compostos e a eficácia por análise de curva de sobrevivência e também o efeito em concentração de hemócitos. Os fármacos CV, CF e CP apresentaram valores de CIM de 113, 9,6 e 41µg/mL, respectivamente, e quando combinados com AmB resultaram em vinte concentrações sinérgicas, e uma concentração de cada combinação... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Cryptococcus neoformans are yeasts that mainly affect immunocompromised individuals, and may cause meningoencephalitis depending on the immunological state of the host. Conventional treatments have faced major challenges. Verapamil hydrochloride (CV), fluoxetine hydrochloride (CF) and paroxetine hydrochloride (CP) were isolated and combined with amphotericin B (AmB) against C. neoformans. Minimum Inhibitory Concentration (MIC) and minimum Fungicidal Concentration (CFM) values were determined according to the broth microdilution technique proposed by the European Committee for Antimicrobial Susceptibility Testing (EUCAST). Subsequently, the synergistic activity of drugs combined with AmB (EUCAST) was evaluated. The effects of MICs and selected synergistic concentrations were evaluated in biofilms, quantifying the biomass by violet crystal and its viability by colony-forming unit analysis (CFU / mL). In addition, the effects of the same in the induced capsule of this yeast were evaluated. In vivo assays were performed in Galleria mellonella evaluating the toxicity of the compounds and the efficacy by analysis of survival curve and also the effect on hemocyte concentration. The CV, CF and CP drugs had MIC values of 113, 9.6 and 41 μg / mL, respectively, and when combined with AmB resulted in twenty synergistic concentrations, and a concentration of each combination was chosen for the following trials. CV reduced biofilm biomass to 38%, while CF and CP reduced biomass to 22-30% w... (Complete abstract click electronic access below) / Mestre

In this thesis I present a rights-based theory of exploitation. I argue that successful conceptions of exploitation should begin with the ordinary language claim that exploitation involves `taking unfair advantage'. Consequently, they must combine an account of what it means to take advantage of another with an account of when transactions are unfair. Existing conceptions of exploitation fail to provide adequate accounts of both aspects of exploitation. Hillel Steiner and John Roemer provide convincing accounts of the unfairness involved in exploitation, but because they fail to provide restrictive `advantage taking' conditions, their theories of exploitation include cases that we would not ordinarily describe as exploitations. Ruth Sample and Robert Goodin provide accounts that place a stronger emphasis on the attitudes involved in exploitation and the processes that bring it about. Unfortunately, these theories do not properly incorporate the unfairness aspect of exploitation. Consequently, they are either self-frustrating or incomplete. I provide a conception of exploitation that combines both aspects.

Whether there exist causal relations between guns firing and people dying, between pedals pressed and cars accelerating, or between carbon dioxide emissions and global warming, is typically taken to be a mind-independent, objective, matter of fact. However, recent contributions to the literature on causation, in particular theories of contrastive causation and causal modelling, have undermined this central causal platitude by relativising causal facts to models or to interests. This thesis flies against the prevailing wind by arguing that we must pay greater attention to which elements of our causal talk vary with context and which elements track genuine features of the world around us. I will argue that once these elements are teased apart we will be in a position to better understand some of the most persistent problems in the philosophy of causation: pre-emption cases, absence causation, failures of transitivity and overdetermination. The result is a naturalist account of causation, concordant with the contextual variability we find in our ordinary causal talk, and parsimonious with respect to the theoretical entities posited.

I offer a novel defence of radically externalist theories of perception, via a strikingly spare and broadly physicalist metaphysics. The core, motivating claim is what I call a natural view of perception, according to which perception involves direct awareness of our environment, such that the phenomenology of experience consists of the worldly things perceived, as they appear to the perspective of the subject. To underpin this natural view, I propose a simple metaphysical picture of perception, which identifies the perceptual experience with the relation of awareness holding between subject and object, a relation that can be described in familiar physical terms as a causal process involving the thing perceived and the perceiver. Distinctively, the simple metaphysical picture has no place for the notion of ‘experiences’ understood as distinctively ‘mental’ states or events internal or otherwise belonging to the subject. Although there is some limited precedent for the simple metaphysical picture of perception, I offer the first detailed argument for its role in underpinning the natural view. The thesis offers new and detailed arguments to show that the simple metaphysical picture can not only account for normal perceptual experiences, but can also accommodate and explain other forms of sensory experience that have widely been considered to undermine the natural view of perception. These ‘problem’ cases include perceptual illusion, hallucination, and the role of memory and beliefs in influencing how things appear perceptually. In all of these cases, the simple metaphysical picture accounts for the phenomenology of the experience purely in terms of awareness of worldly objects, albeit in some cases objects that are not currently present in the subject’s environment. The simple metaphysical picture thus promises to explain not just perceptual experience but phenomenal consciousness more generally. The natural view is explicitly a commitment of some varieties of naïve realism, but I argue that the two theses come apart. For one thing, the simple metaphysical picture offers a solution to hallucination and other ‘problem’ cases quite different to the (chiefly disjunctivist) solutions offered by naïve realists. However, the most striking and novel claim advanced here is that the natural view can be defended without a commitment to realism. In this regard, I cite evidence for the subject-relativity or experience-dependence of certain perceived qualities, notably colour, and show the simple metaphysical picture allows us to square this with the natural view that colours are ‘out there’ in the environment. I discuss the metaphysical implications of rejecting realism while adhering to the simple metaphysical picture, and outline a radical – and radically simple – metaphysics of the world in general that might preserve the natural view and accommodate the simple metaphysical picture of phenomenal consciousness more generally. This metaphysics takes the form of a process monism in which the governing metaphysical structuring principle is one of top-down determination, such that whole processes determine the nature of their constituent parts.

In this thesis, I argue that physicalism should be understood to be the view that mental properties are realized by physical properties. In doing this, I explore what the realization relation might be. Since realization is the relation that should help us formulate physicalism, I suggest that the theoretical role of realization consists in explaining some of the things that physicalists wish to explain. These are: (i) How are mental properties metaphysically necessitated by physical properties? (ii) How are mental properties causally efficacious? A theory of realization should provide resources for answering these questions. Having identified the theoretical role of realization, I discuss several theories of realization, but then focus on the subset view of realization. According to the subset view, a property P realizes a property Q if and only if the causal powers of Q are a proper subset of the causal powers of P. I argue that the realization relation as it is formulated by the subset view is a promising candidate to play the theoretical role that I want realization to play. I then investigate how this theoretical role is occupied. In doing so, I provide a general metaphysical framework that the defenders of the subset view can appeal to. This framework specifies in what ways properties are related to their causal powers. Discussing some problems that the subset view faces, I propose my own version of the subset view. I argue that a property P realizes a property Q if and only if (i) the causal powers of Q are a proper subset of the causal powers of P, and (ii) P is more fundamental than Q. Thanks to the requirement that a realized property is less fundamental than its realizers, two things that the original version of the subset view cannot explain are guaranteed: first, fundamental properties are not realized; second, arbitrary conjunctions of properties do not realize their conjuncts. By showing how a theory of realization can help us explain some of the things that physicalists typically wish to explain, I also show that a non-reductive variety of physicalism does not face the problems that it is commonly thought to face.

The field of experimental philosophy has received considerable attention, essentially for producing results that seem highly counter-intuitive and at the same time question some of the fundamental methods used in philosophy. A substantial part of this attention has focused on the role of intuitions in philosophical methodology. One of the major contributions of experimental philosophy on this topic has been concrete evidence in support of intuitional diversity; the idea that intuitions vary systematically depending on variables such as ethnicity, socioeconomic background, or gender. Because of the important implications, these findings have been the subject of extensive debate. Despite the seeming significance of the findings and despite all the debates that the experimental philosophy movement has prompted, what has not been examined systematically is the reproducibility of the results. Instead, the reported findings have been simply accepted as established facts. We set out to replicate a wide range of experiments and surprisingly failed to reproduce many of the reported findings, some of which are from the most cited and attention grabbing papers of the field. We draw two conclusions from our findings. The first is that the instability of intuitions has been exaggerated by experimental philosophers. Intuitions appear to be more uniform across different demographic groups. The argument that intuitions need to be discarded because they depend on arbitrary factors such as ethnicity, socioeconomic background, or gender does not seem tenable anymore. The second conclusion is that experimental philosophy needs a better system to ensure the reproducibility of published findings. The current research-publication system of various empirical fields, especially those employing statistical methods, leads to an overproduction of false-positive findings in the published literature. Unless changes are made to the current research-publication system, this overproduction is likely to continue, in experimental philosophy as well as other disciplines.