O antígeno B (AgB) de Echinococcus granulosus é um dos principais componentes do líquido hidático. O AgB é um proteína oligomérica de 120-160 kDa composta de subunidades de 8 kDa, que em SDS-PAGE dissocia-se em componentes de 8, 16, 24 e 32 kDa. Embora diferentes subunidades do AgB tenham sido isoladas, pouco se sabe sobre a estrutura da proteína e do seu mecanismo de oligomerização. Neste trabalho foi realizada a caracterização estrutural de homo-oligômeros de três subunidades recombinantes do AgB, AgB8/1, AgB8/2 e AgB8/3, expressadas a partir de seqüências previamente clonadas Essas subunidades associam-se em homo-oligômeros com características semelhantes às da proteína purificada de líquido hidático, como massa molecular, conteúdo de estrutura secundária, tendência agregativa e termoestabilidade, fazendo deles ferramentas importantes para o estudo da estrutura do AgB. Diferentes graus de estabilidade e compactação foram verificados entre os oligômeros recombinantes, com o oligômero de AgB8/3 apresentando-se mais estável e compacto. Através da modelagem molecular das subunidades do AgB, foi possível calcular a superfície de potencial eletrostático das moléculas e propor um mecanismo de oligomerização envolvendo interações eletrostáticas e hidrofóbicas. Foram também realizadas tentativas de cristalização de oligômeros de AgB8/3 para ensaios de difração de raios X, e cristais foram obtidos em três condições do screening inicial. Estes cristais difrataram à resoluções máximas de 8 Å, não permitindo a coleta de dados estruturais da proteína. Entretanto, estas condições podem ser refinadas para a obtenção de cristais com melhor qualidade. / Echinococcus granulosus antigen B is one of the major components of the hydatid fluid. AgB is a oligomeric protein of 120-160 kDa composed by 8 kDa subunits, that in SDS-PAGE dissociates in components of 8, 16 , 24 and 32 kDa. Although different AgB subunits have been isolated, little is known about AgB structure and its oligomerization mechanism. In this work we have performed the homo-oligomers structural characterization of three AgB recombinant subunits, AgB8/1, AgB8/2 and AgB8/3, expressed from previously cloned genes. These subunits self-assemble in homo-oligomers with similar characteristics to that of hydatid fluid purified protein, such as molecular mass, secondary structure content, aggregative tendency and thermostability, making them valuable tools for AgB structure study. Different degrees of stability and compactness were verified between the recombinant oligomers, with the AgB8/3 one showing a more stable and compact structure. Using molecular modelling it was possible to calculate the surface electrostatic potencial of AgB subunits and to propose a mechanism of oligomerization involving electrostatic and hydrophobic interactions. Also crystallization attempts had been carried through with AgB8/3 oligomer to X-ray diffraction, and crystals have been obtained in three conditions of initial screening. These crystals difracted to maximum resolutions of 8 Å, and it was not possible to collect protein structural data. However, these crystallization conditions can be refined in order to obtain crystals of better quality.

The epistemic theory of causality maintains that causality is an epistemic relation, so that causality is taken to be a feature of the way an agent represents the world rather than an agent-independent or non-epistemological feature of the world. The objective of this essay is to cause problems for the epistemic theory of causality. This is not because I think that the epistemic theory is incorrect. In fact, I spend some time arguing in favour of the epistemic theory of causality. Instead, this essay should be regarded as something like an exercise in stress testing. The hope is that by causing problems for a particular version of the epistemic theory, the result will be a more robust version of that theory. My gripe is with a particular version of the epistemic theory of causality, a version that is articulated with the help of objective Bayesianism. At first sight, objective Bayesianism looks like a plausible theory of rational belief. However, I argue that it is committed to a certain theory of evidence, a theory of evidence that recent work in epistemology has shown to be incorrect. In particular, objective Bayesianism maintains that evidence is perfectly accessible in a certain sense. But evidence just is not so perfectly accessible, according to recent developments in epistemology. However, this is not the end of the line for the epistemic theory of causality. Instead, I propose an epistemic theory of causality that dispenses with the assumption that evidence is perfectly accessible in the relevant sense.

This thesis will address the question of whether there are any situated cognition concepts of memory functioning as investigative kinds in the sciences of memory. Situated cognition is an umbrella term, subsuming extended, embedded, embodied, enacted and distributed cognition. I will be looking closely at case studies of investigations into memory where such concepts seem prima facie most likely to be found in order to establish a) whether the researchers in question are in fact employing such concepts, and b) whether the concepts are functioning well – functioning as investigative kinds – and should therefore continue to be employed, or whether something has gone wrong in the practice of the science and they should employ a different kind of concept. An historically situated approach to the case studies will allow me to answer part b) here. Along the way, I will argue for a way of construing scientific research that I call the dynamic framework account, an account of (im)maturity for science, a variety of conceptual role semantics with respect to scientific concepts, and the historically situated case study-based method I will employ in answering the central question. My conclusions, and the way I reach them, constitute contributions to debates about situated cognition particularly, and to philosophy of science more generally, as well as recommendations for scientific practice.

The central subject of this thesis is the nature of the self. I argue against an atomistic conception which takes the human self to exist self-sufficiently and prior to social relations, and in favour of a holistic conception which takes the self to be constitutively dependent on social relations. I defend this view against criticisms that a holistic account undermines the need for what I call 'critical distance' between subjects and their communities. This involves answering the charges that such constitutive dependence: 1) removes the possibility for individuals to determine themselves freely apart from the communities in which they engage; and 2) deprives us of an external standard with which to engage critically with those constitutive communities. I argue that the above criticisms are encouraged by reliance on a certain epistemological picture. This picture involves a foundationalist construal of knowledge that ultimately depends on a notion of an immediately given epistemic content that can serve to give us an absolute conception of an objective reality with which we can do away with partial or relative conceptions of ourselves and the world we inhabit. It is this that leads the critic to demand a standard external to communities, which in turn encourages a notion of the self and freedom that can ultimately be grounded apart from the "distortions" of social practice. I directly attack the notion of an immediately given epistemic content through a series of transcendental arguments, showing that the condition of possibility for our forming any conception of ourselves or the world is participation in social forms of life. I further argue that properly human identities are essentially shaped by the self-conceptions these forms of life make available to us. Since freedom can no longer depend on radical detachment, I offer a new account of freedom as a social achievement, based on a notion of rational progress which allows us to develop ourselves and our social world critically, drawing only on those standards available within our practices. With the notion of an immediately given epistemic content undermined, I have shown not only that freedom and rational progress are consistent with a holistic account, but that in fact they depend on such a holistic account.

Traditional approaches in access control rely on immutable criteria in which to decide and award access. These approaches are limited, notably when handling changes in an organisation’s protected resources, resulting in the inability to accommodate the dynamic aspects of risk at runtime. An example of such risk is a user abusing their privileged access to perform insider attacks. This thesis proposes self-adaptive authorisation, an approach that enables dynamic access control. A framework for developing self-adaptive authorisation is defined, where autonomic controllers are deployed within legacy based authorisation infrastructures to enable the runtime management of access control. Essential to the approach is the use of models and model driven engineering (MDE). Models enable a controller to abstract from the authorisation infrastructure it seeks to control, reason about state, and provide assurances over change to access. For example, a modelled state of access may represent an active access control policy. Given the diverse nature in implementations of authorisation infrastructures, MDE enables the creation and transformation of such models, whereby assets (e.g., policies) can be automatically generated and deployed at runtime. A prototype of the framework was developed, whereby management of access control is focused on the mitigation of abuse of access rights. The prototype implements a feedback loop to monitor an authorisation infrastructure in terms of modelling the state of access control and user behaviour, analyse potential solutions for handling malicious behaviour, and act upon the infrastructure to control future access control decisions. The framework was evaluated against mitigation of simulated insider attacks, involving the abuse of access rights governed by access control methodologies. In addition, to investigate the framework’s approach in a diverse and unpredictable environment, a live experiment was conducted. This evaluated the mitigation of abuse performed by real users as well as demonstrating the consequence of self-adaptation through observation of user response.

Pain is unpleasant. Given that pain is the paradigmatic example of an unpleasant experience, I aim to shed light on what pain and unpleasantness are by trying to understand what it means for a pain to be unpleasant, what the structure of unpleasantness is, and by tackling several problematic aspects of the relation between pain and unpleasantness. By doing this, I will also provide a general account of what it means for an experience that might not be a pain to be unpleasant. The thesis is organised into seven chapters and divided by three main themes: i) what the unpleasantness of pain consists in, ii) how we can account for the great phenomenal diversity among experiences of unpleasantness, and iii) which cases suggest that there could be pains that are not unpleasant. Broadly, the first two chapters deal with the first theme, the third and fourth chapter with the second theme, and the fifth and sixth chapter focus on the third theme. In the final chapter I offer a conclusion of the three main themes by providing my own view on the unpleasantness of pain. According to this account, an unpleasant experience is something felt, it is a phenomenal property of mental states, and this property should be understood using the determinable determinate distinction. By doing all of this, this thesis will provide a detailed understanding of the nature of pain and unpleasantness.

What kind of thing do you believe when you believe that you are in a certain place, that it is a certain time, and that you are a certain individual? What happens if you get lost, or lose track of the time? Can you ever be unsure of your own identity? These are the kind of questions considered in my thesis. Beliefs about where, when and who you are are what are called in the literature 'de se', or self-locating beliefs. This thesis examines how we can represent de se beliefs, and how we can reason about de se uncertainty. In the first part of the thesis, I present and motivate a specific account of the content of de se belief, based on the one given by David Lewis. On this account, the content of de se beliefs are centred propositions. I defend this view against a rival account, put forward by Robert Stalnaker, according to whom the content of de se beliefs are ordinary (non-centred) propositions. In the second part of the thesis, I explore how we can reason probabilistically about de se uncertainty. I start by defining probabilities over centred propositions, and investigate what probabilities mean in this context. As it turns out, all the main interpretations of probability can be extended to centred propositions. The only trouble seems to arise for the Bayesian principle of updating via conditionalization. After giving a diagnosis of the problem, I offer a solution by formulating a natural extension of conditionalization, which I argue preserves the essential features of Bayesian reasoning. In the final chapter, I apply my view and show that it leads to a natural resolution of a puzzle (known as the Sleeping Beauty problem) that is generally taken to be a test case for any account of centred updating.

The aim of this research is to provide a path to understand the phenomenal, intentional and physical nature of mind. Essential to the discussion of this thesis is the fundamental role that the phenomenal character of experience plays in the theory of intentionality. It is argued that both aspects must be understood physically as realized by a relevant brain state. I present an internalist view of the mind, in contrast with a more popular view in philosophy, representationalism, that is typically externalist. However, this thesis will argue in favour of a new exploration of the relation between consciousness and intentionality. Having gained some understanding of this connection at a conceptual level, and having explored the relevant empirical findings that support my view, a new understanding of the hard problem of consciousness will here be presented. The arguments will show that it is required to start with our phenomenology, and since our phenomenology will shape our representation, such phenomenology will be the basis of our intentionality and our understanding of the world. As a consequence, the explanatory gap, or consciousness’ hard problem, needs to be understood in another sense: the problem, as it has been formulated, is a misconceived problem.

This research explores the extent of the shift in the Turkish state’s discourse towards the Kurds’ language rights and the sources of resistance to their recognition under the successive AKP governments between 2003 and 2015. Examining this issue, I explore 1) the true nature of the Kurds’ language-related rights in lights of the relevant key points in the political theories of language rights; 2) the extent of the shift in the AKP’s Kurdish policy towards the Kurds’ language rights; 3) the sources of resistance to the Kurds’ language rights in the state discourse in view of the competing rationales behind language rights from both the state’s and minority groups’ perspectives; 4) whether the AKP’s Kurdish policy aims to contain the Kurds’ language rights or accord it greater recognition. The thesis concludes that the Turkish state discourse towards the Kurds’ language rights under the successive AKP governments between 2003-2015 primarily aimed to contain potentially far-reaching consequences of the Kurds’ language rights.

The aim of this thesis will be to give an elucidation of Nietzsche’s ideal of the post-moral autonomous individual: to give a picture of what Nietzsche takes such an individual to look like, and to show how this picture relates to some of Nietzsche’s most fundamental philosophical concerns. Overall, my argument will be that autonomy, or rather the degree of autonomy that a person possesses, is a function of the power of that person in relation to the other people and forces, and of their ability to extend their will over long periods of time. Moreover, the achievement of the highest degrees of autonomy, and by extension the achievement of the greatest levels of power, requires imposing (whether intentionally or not) an ethic upon one’s actions and one’s self. There are several features that this ethic must have if it is adequately to perform its function: it must be self-chosen rather than simply picked up from one’s surroundings, it must act to give unity to the most diverse collection of collection of drives and affects possible for the person who holds it, and it must be well tailored to fit their specific natural constitution. In order to establish this I will focus on four main issues: the significance of the sovereign individual of GM II: 2, the role of ethics/values in Nietzsche’s ideal of autonomy, the relation between Nietzsche’s deflationary account of consciousness and his views of freedom, and the notion of unity at play in Nietzsche’s writings. I will also offer some thoughts on the coherence of Nietzsche’s ideal of autonomy with his thoughts on life-affirmation.