Active site labeling of cysteine cathepsins by a straightforward diazomethylketone probe derived from the N-terminus of human cystatin C

We designed a straightforward biotinylated probe using the N-terminal substrate-like region of the inhibitory site of human cystatin C as a scaffold, linked to the thiol-specific reagent diazomethylketone group as a covalent warhead (i.e. Biot-(PEG)2-Ahx-LeuValGly-DMK). The irreversible activity-based probe bound readily to cysteine cathepsins B, L, S and K. Moreover affinity labeling is sensitive since active cathepsins were detected in the nM range using an ExtrAvidin®-peroxidase conjugate for disclosure. Biot-(PEG)2-Ahx-LeuValGly-DMK allowed a slightly more pronounced labeling for cathepsin S with a compelling second-order rate constant for association (kass = 2,320,000 M−1 s−1). Labeling of the active site is dose-dependent as observed using 6-cyclohexylamine-4-piperazinyl-1,3,5-triazine-2-carbonitrile, as competitive inhibitor of cathepsins. Finally we showed that Biot-(PEG)2-Ahx-LeuValGly-DMK may be a simple and convenient tool to label secreted and intracellular active cathepsins using a myelomonocytic cell line (THP-1 cells) as model.

'When I Land in Islamabad I Feel Home and When I Land in Heathrow I Feel Home': Gendered Belonging and Diasporic Identities of South Asian British Citizens in London, in Leicester and in North England

According to Deleuze and Guattari (1987) ‘de-territorialization’ is followed by a moment of re-territorialization. This moment, however, has to be regarded as a continuing educational process that becomes a different spatial site of social practices. It is argued in this chapter that regional, local as well as global identification override national and mono-ethno cultural identities, while shaping particular notions of gendered belonging and creating specific diasporic practices. Based on a sample of interviews with professional and academic South Asian British citizens in London, in Leicester, and in a number of Northern English cities gendered and generational patterns in terms of local diasporic identities are explored. Apart from multiple cultural belonging, foremost, territorial bonds and notions of group loyalty collapse at a point where temporary migration and settlement alternate in individual biographies.

Stability in a Network Economy: The Role of Institutions

We consider an economy in which agents are embedded in a network of potential value-generating relationships. Agents are assumed to be able to participate in three types of economic interactions: Autarkic self-provision; bilateral interaction; and multilateral collaboration through endogenously provided platforms.
We introduce two stability concepts and provide sufficient and necessary conditions on the network structure that guarantee existence, in cases of the absence of externalities, link-based externalities and crowding externalities. We show that institutional arrangements based on socioeconomic roles and leadership guarantee stability. In particular, the stability of more complex economic outcomes requires more strict and complex institutional rules to govern economic interactions. We investigate strict social hierarchies, tiered leadership structures and global market places.

Socialized credit and the working-class family economy: a comparative history of Britain and France 1900-2000

This paper provides a comparative analysis of working class consumer credit in Britain and France from the early twentieth century through to the 1980s. It indicates a number of similarities between the two nations in the earlier part of the period: in particular, in the operation of doorstep credit systems. For the British case study, we explore consumer finance offered by credit drapers (sometimes known as tallymen) whilst in France the paper explores a similar system that functioned in the coalmining communities around the city of Lens. Both methods operated on highly socialised relationships that established the trust on which credit was offered and long-term creditor/borrower relationships established. In the second part of the paper, we analyse the different trajectories taken in post-war France and Britain in this area of working class credit. In France this form of socialized credit gradually dwindled due to factors such as ‘Bancarisation’, which saw the major banks emerge as modern bureaucratized providers of credit for workers and their families. In contrast, in Britain the tallymen (and other related forms of doorstep credit providers) were offered a new lease of life in the 1960s and 1970s. This was a period during which British credit providers utilised multiple methods to evade the hire purchase controls put in place by post-war governments. Thus, whilst the British experience was one of fragmented consumer loan types (including the continuation of doorstep credit), the French experience (like elsewhere in Europe) was one of greater consolidation. The paper concludes by reflecting on the role of these developments in the creation of differential experiences of credit inclusion/exclusion in the two nations and the impact of this on financial inequality.

Poeta, ou aquele que faz: a poética como inovação em design

Com o objectivo de cumprir com as normas legais em vigor na Universidade de Aveiro conducentes ao reconhecimento do grau de Doutor em Design por avaliação da obra realizada, o presente relatório descreve os objectivos e procedimentos metodológicos, demonstrando o argumento da inovação no conjunto compilado das 100 obras seleccionadas entre os projectos de design realizados no período dos últimos dez anos de actividade profissional do candidato. Para além do enunciado em conformidade com os pressupostos legais, e porque a obra desenvolvida decorre de um contínuo processo de reflexão sobre a própria prática, entende o candidato oportuna a apresentação de um conjunto de textos realizados no mesmo período e que conformarão assim, uma cosmologia teórica própria, sobre a história e teoria do design que contribuirá para o melhor esclarecimento em contexto, das intenções éticas e estéticas dessa obra. O conjunto de contributos de reflexão teórica, que aqui se encontram revelam uma continuidade (maculada pela experiência existencial), que atribui à prática um desempenho quase sempre contaminado pelo corpo de afectos do seu agente, que assim dá origem ao género criativo (poietico) autobiográfico, fundado na metodologia fenomenológica (revelando a ciência do design nos seus próprios procedimentos, “voltando às próprias coisas”). Ao reflectir sobre a prática de projecto enquanto definição disciplinar de Design, verificou-se urgente o esclarecimento ontológico da disciplina, assim procurando perscrutar a definição do que seja, para compreender melhor de que forma lhe pudesse servir os seus interesses bioculturais, numa perspectiva metaprojectual, social, política e estética. O Design, enquanto disciplina da con-formação (da atribuição de forma às coisas), é também o lugar da atribuição de sentido, elevando-as à condição de seres idealizados _ formas são ideias, ainda que imperfeitamente desenhadas (Platão). Neste pressuposto parece inevitável a aproximação da prática projectual do design ao exercício da filosofia, já que a filosofia serve, sobretudo, para inventar conceitos operativos, funcionalizando a mudança (Deleuze). No entanto, o que se encontra neste registo não é uma produção prática que ilustra a jusante uma intencionalidade teórica motivadora mas, bem pelo contrário, uma teorização que anda a zorro da prática da vida, procurando perceber o que parecia inconscientemente suspeitar, confirmando-o. O conjunto de temas teoricamente tratados, constituem aproximações naturalistas por tentativa e erro, que se repetem no tempo em torno de palavras chave como poética, criação, criatividade, tecnologia, artesanato, ontologia, disciplina, desenho, desejo-desenho-desígnio, engenharia-arte-gestão, design, projecto, humano, humanização, diferença, dispositivo, ética, estética, domínio, submissão, zen. Muitos destes temas foram apropriados recorrendo a um conjunto muito diverso e heterogéneo de autores. Aqui misturam-se os filósofos universalmente consagrados, com outros pensadores do Design (Adorno, Aristóteles, Badiou, Di Bártolo, Branco, Brusatin, Calvera, Deleuze, Descartes, Doberti, Espinosa, Flusser, Heidegger, Leiro, Maldonado, Munari, Platão, Pombo, Séneca, Simon, Zizek, e Zumthor), aos quais se associa uma terceira vaga de colegas menos conhecidos, estudantes e investigadores, respigados no grande acaso da web. Na sua assistemática forma de abordagem teórica (Flusser), a teoria não é aqui convocada como janela modernista, abrindo-se sem limites sobre a paisagem organizada, mas como múltiplas aberturas determinadas pela urgência da necessidade, conformando uma arquitectura orgânica e espontânea, do vernacular dirigido por pontos de vista pertinentes e dispersos, produzindo uma visão caleidoscópica, múltipla, cubista, mas sincronicamente orientada sobre o objecto que, tendo vida própria, não pára para posar.

Introduction: Mapping Gwen John: Lives, Lines and Images

Nomadic Narratives, Visual Forces explores issues, questions, and problems emerging in the analysis of epistolary and visual narratives. This book focuses in particular on Gwen John's letters and paintings. It offers an innovative theoretical approach to narrative analysis by drawing on Foucault's theory of power, Deleuze and Guattari's analytics of desire, and Cavarero's concept of the narratable self. Furthermore, it examines the use of letters as documents of life in narrative research and highlights the dynamics of spatiality in the constitution of the female self in art. This study brings together theoretical insights that emerge from the analysis of life documents - some of them previously unpublished - combining innovative research with specific methodological suggestions on doing narrative analysis.

Various Joyful Encounters with the Dystopias of Affective Capitalism

This article contends that what appear to be the dystopic conditions of affective capitalism are just as likely to be felt in various joyful encounters as they are in atmospheres of fear associated with post 9/11 securitization. Moreover, rather than grasping these joyful encounters with capitalism as an ideological trick working directly on cognitive systems of belief, they are approached here by way of a repressive affective relation a population establishes between politicized sensory environments and what Deleuze and Guattari (1994) call a brain-becoming-subject. This is a radical relationality (Protevi, 2010) understood in this context as a mostly nonconscious brain-somatic process of subjectification occurring in contagious sensory environments populations become politically situated in. The joyful encounter is not therefore merely an ideological manipulation of belief, but following Gabriel Tarde (as developed in Sampson, 2012), belief is always the object of desire. The discussion starts by comparing recent efforts by Facebook to manipulate mass emotional contagion to a Huxleyesque control through appeals to joy. Attention is then turned toward further manifestations of affective capitalism; beginning with the so-called emotional turn in the neurosciences, which has greatly influenced marketing strategies intended to unconsciously influence consumer mood (and choice), and ending with a further comparison between encounters with Nazi joy in the 1930s (Protevi, 2010) and the recent spreading of right wing populism similarly loaded with political affect. Indeed, the dystopian presence of a repressive political affect in all of these examples prompts an initial question concerning what can be done to a brain so that it involuntarily conforms to the joyful encounter. That is to say, what can affect theory say about an apparent brain-somatic vulnerability to affective suggestibility and a tendency toward mass repression? However, the paper goes on to frame a second (and perhaps more significant) question concerning what can a brain do. Through the work of John Protevi (in Hauptmann and Neidich (eds.), 2010: 168-183), Catherine Malabou (2009) and Christian Borch (2005), the article discusses how affect theory can conceive of a brain-somatic relation to sensory environments that might be freed from its coincidence with capitalism. This second question not only leads to a different kind of illusion to that understood as a product of an ideological trick, but also abnegates a model of the brain which limits subjectivity in the making to a phenomenological inner self or Being in the world.

Heterotopias of mental health care: The role of space in experiences of distress, madness and mental health service use.

The change from an institutional to community care model of mental health services can be seen as a fundamental spatial change in the lives of service users (Payne, 1999; Symonds & Kelly, 1998; Wolch & Philo, 2000). It has been argued that little attention has been paid to the experience of the specific sites of mental health care, due to a utopic (idealised and placeless) idea of ‘community’ present in ‘community care’ (Symonds, 1998). This project hence explored the role of space in service users’ experiences, both of mental health care, and community living. Seventeen ‘spatial interviews’ with service users, utilising participatory mapping techniques (Gould & White, 1974; Herlihy & Knapp, 2003; Pain & Francis, 2003), plus seven, already published first person narratives of distress (Hornstein, 2009), were analysed using thematic analysis (Braun & Clarke, 2006). Mental health service sites are argued to have been described as heterotopias (Foucault, 1986a) of a ‘control society’ (Deleuze, 1992), dominated by observation and the administration of risk (Rose, 1998a), which can in turn be seen to make visible (Hetherington, 2011) to service users a passive and stigmatised subject position (Scheff, 1974; 1999). Such visible positioning can be seen to ‘modulate’ (Deleuze, 1992) participants’ experiences in mainstream space. The management of space has hence been argued to be a central issue in the production and management of distress and madness in the community, both in terms of a differential experience of spaces as ‘concordant’ or ‘discordant’ with distress, and with movement through space being described as a key mediator of experiences of distress. It is argued that this consideration of space has profound implications for the ‘social inclusion’ agenda (Spandler, 2007; Wallcraft, 2001).

The world without outside

The world is all that there is. In the world, ontology and epistemology coincide. The thing and the perspective are part of it, scale is ingested in its multiplicity, communication stops at the world's edge. By reading together Deleuze and Guattari's plane of immanence and Niklas Luhmann's proto-global concept of Weltgesellschaft (“world society”), I suggest a conceptualisation of the world as the materiality of the multiple spaces of creation in an insular, all-inclusive immanence. Deprived of an outside, the world pushes its own understanding of circumference through, first, the expansion of its own limits through the process of worlding, and, second, the multiplication of modes of material (self-)production through its process of othering. Thus, the world swells up from the inside and expands on both the material and the semantic level, producing a multiplicity of fractal microcosms. Issues of responsibility and justice arise that are intricately linked to the materiality of the world and take place in and between the various bodies and spaces of the world but without an overarching hierarchy or principle. This approach is a way of counteracting the all-pervasive Hegelian understanding of synthesis, arguing instead for a plenitude that brims with positivity and that can never become fully complete. The world remains its own infinite process of worlding.

Panos sem fundo (coordenadas para uma estética teatral deleuziana)

Dissertação de Mestrado em Filosofia Estética

O conhecimento sobre o medicamento e a literacia em Saúde - Um estudo em adultos, utentes de farmácias do concelho de Lisboa

Estudos recentes realizados nas farmácias portuguesas evidenciaram elevadas percentagens de indivíduos que não aderem à terapêutica. Em consequência não controlam adequadamente o seu problema de saúde e geram desperdício do medicamento. A utilização do medicamento requer conhecimento, competências e motivação por parte do indivíduo-utilizador. A informação sobre o medicamento é disponibilizada de forma verbal e escrita, desconhecendo-se até hoje, na população portuguesa, em que medida as competências de literacia da saúde permitem a sua obtenção, o uso e a compreensão quando perante a necessidade de utilizar medicamentos. Foi objectivo do presente estudo medir o conhecimento sobre o medicamento numa amostra de utentes de farmácia com idades compreendidas entre os 45 e os 64 anos, analisando de que forma está associado a competências de literacia da saúde. Realizou-se um estudo analítico transversal com a colaboração voluntária de farmácias do concelho de Lisboa que recolheram os dados mediante inquérito por entrevista quando o utente se encontrava na farmácia a adquirir a sua terapêutica. A amostra estudada foi constituída por 233 utentes com uma idade média de 57 anos (dp=5,7), maioritariamente do género feminino, activos, com uma escolaridade igual ou inferior ao 9º ano e com hábitos gerais de leitura referindo ler frequentemente (26%) ou muito frequentemente (30%). Em média responderam correctamente a 10,48 perguntas num total de 13 (dp=1,779), sendo este conhecimento independente do sexo (p=0,791) e da idade (p=0,131). O número de respostas correctas é, no entanto, maior quanto maior grau de escolaridade (p=0,000), a categoria profissional exercida (p=0,000), os hábitos de leitura (p=0,000), o índice de compreensão de informação (p=0,003), intensidade de leitura de informação sobre saúde ou medicamento (p=0,005), facilidade de utilização do folheto informativo do medicamento (p=0,027), intensidade de cálculo (p=0,018) e tempo de utilização do medicamento (p=0,047). Do conjunto de indicadores de literacia analisados, o grau de escolaridade, o índice de compreensão da informação transmitida pelos profissionais de saúde e a intensidade de leitura de materiais escritos relacionados com o medicamento ou saúde, são os que mais contribuem para o conhecimento sobre o medicamento, embora se revelem fracamente preditivos do nível de conhecimento (R2=0,013). Evidencia-se neste estudo que o conhecimento que os indivíduos possuem sobre o medicamento é influenciado de forma positiva por competências de literacia em saúde. Em consequência, as intervenções que visam melhorar a utilização do medicamento e as estratégias de comunicação em saúde, tanto verbal como escrita, devem ter em consideração o nível de literacia em saúde da população.

A necessidade da arte

Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Filosofia, especialidade de Estética

Esquizofrenizar a morte

Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Filosofia (especialidade em Ontologia e Filosofia da Natureza)