Islamic reformism in India between 1857 and 1947: the conception of state in Chiragh ‘Ali, Muhammad Iqbal and Sayyid Abu’l ‘Ala Mawdudi

Tese apresentada para cumprimento dos requisitos necessários à obtenção do grau de Doutor em Ciência Política, especialidade de Teoria e Análise Política.

An approach to teach Calculus/Mathematical Analysis (for engineering students) using computers and active learning – its conception, development of materials and evaluation

Dissertação para obtenção do Grau de Doutor em Ciências da Educação

Conception and first results of a cross-sectional national study on the demography, disease characteristics and socioeconomics status of the Portuguese patients with multiple sclerosis : the PORT-MS study

RESUMO: Introdução e objetivos: Não existia um estudo multicêntrico que descrevesse as características dos doentes com EM, da doença em si, ou do seu tratamento, em Portugal.Métodos: Doentes McDonald 2010 positivos foram sequencialmente recrutados em 7 centros entre Maio e Novembro 2014. Aplicou-se um Caderno de Recolha de Dados incidindo na demografia, doença, educação e emprego (estudo PORT-MS). Resultados: 561 doentes incluídos. Primeiros sintomas aos 30,2±10,5 anos (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnóstico 3,2±5,3 anos depois (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); tempo de doença após diagnóstico 9,4±7,2 anos (semelhante RRMS no diagnóstico e PPMS); idade atual 42,9±12,4 anos (grupo RRMS no diagnóstico 42,0±12,1, PPMS 52,5±11,3, p<0,001); EDSS atual 2,5 (RRMS 2.0, PPMS 6.0); proporção feminino:masculino é 2,5:1 (RRMS semelhante, PPMS 1,1:1, p<0,05); no diagnóstico RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% dos RRMS encontravam-se em SP na inclusão (nomeadamente os com mais idade no diagnóstico e/ou atualidade ou tempo de doença mais prolongado). PPMS mais frequente em doentes diagnosticados mais tardiamente (p<0,001), onde aumenta também ligeiramente a proporção de mulheres na PPMS. Nas últimas décadas: novos casos mostram estabilidade na proporção de géneros e tipos de doença; idade nos primeiros sintomas e no diagnóstico aumentou ligeiramente, tempo entre eles diminuiu ligeiramente. Proporção sob DMT (Maio 2014): global 84,5%; atualmente RRMS 90,4%; SPMS 70,8%; PPMS 36,8%; progressivas agregadas 48%. Tipo de DMT, amostra global: interferões 56,5%, GA 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Global: economicamente ativos 61,5%, desemprego 13,5%, 74,1% dos não activos estão reformados por doença. Gravidezes após diagnóstico em 15% mulheres. Casos com história familiar positiva 7,8%. Discussão e conclusões: Incluída cerca de 10% da população portuguesa. Resultados congruentes com dados internacionais. Elevada proporção sob DMT, mesmo EDSS alto e formas progressivas. Terapêuticas de segunda linha sub representadas. Doentes jovens e com doença ligeira com vida económica ativa; restantes essencialmente reformados por doença.---------------- ABSTRACT : Background/aims: In Portugal, there wasn’t a multicentric study on the general characteristics (demography, disease milestones, DMT, socioeconomic status) of Multiple Sclerosis patients. Methods: Patients fulfilling McDonald 2010 criteria were sequentially recruited from May to November 2014 in 7 centers and data was systematically collected. Results: 561 patients included. First symptoms occurred at 30,2±10,5 years-old (RRMS 29,2±10, PPMS 39,4±11,7, p<0,001); diagnosis 3,2±5,3 years later (RRMS 3,0±5,1, PPMS 4,9±2,5, p=0,002); 9,4±7,2 years elapsed since diagnosis (similar for those is RRMS at diagnosis and PPMS); current age 42,9±12,4 years-old (group RRMS at diagnosis 42,0±12,1, PPMS 52,5±11,3, p<0,001); current EDSS 2,5 (RRMS 2.0, PPMS 6.0); females to males 2,5:1 (RRMS similar, PPMS 1,1:1, p<0,05); at diagnosis RRMS 90,6%, SPMS 0,9%, PPMS 8,6%; 9,5% of RRMS reached SP at inclusion (those older at diagnosis, in actuality, or with longer follow-up). PPMS more frequente in patients diagnosed at older ages (p<0,001), also slight increase in females. Along the last decades: new cases have showed stable proportions of gender and disease types; age at first symptoms and diagnosis slightly increased, time between them slightly decreased. Proportion on DMT (May 2014): 84,5% of all; 90,4% of currently in RRMS; 70,8% of SPMS; 36,8% of PPMS; 48% of progressive forms together. Type of DMT, all patients: interferons 56,5%, Glatiramer Acetate 18,4%, Natalizumab 11,6%, Fingolimod 9,7%. Economically active 61,5% of all, unemployment 13,5%, 74,1% of non-active are retired due to disease. Females pregnant after diagnosis 15%. Positive family cases in 7,8%. Discussion/Conclusions: 10% of the national MS population collected. Data generally consistente with international reports. Proportion under DMT relatively high in all disease types, but second line therapies underrepresented. Young patients with mild disease have an active economic life. Those not active are essentially retired due to disease.

Construção e utilização de equipamentos de baixo custo para ensino de Física

Experimental work has been taking a great importance in Science curricula in several countries. This fact is now changing the conception of the role of the laboratory in the classroom. This role no longer seen as an instrument to illustrate or confirm some concepts but became the essential place of the learning process in Science. However, the implementation of several experimental procedures frequently faces equipment limitations, whether because those indicated in textbooks do not exist in schools due to prohibitive costs for most school budgets, or because their use is far too complex to be done by students. In this dissertation, a few examples of experimental equipment, made with day-today supplies is analyzed, as well as those that can be acquired at low prices and might have high positive effect in the Science learning process. We also discuss some relevant equipment in the teaching of Physics that can be created by teachers and students in schools, as part of curricular or non curricular subject areas such as “Área de Projecto” in the twelfth grade. These equipments, easy to conceive and produce with reasonable costs resources, when compared to the commercial equipment, which are much more expensive, presents very good experimental results.

The globalisation in the clothing sector and its implications for work organisation: a view from the Portuguese case

The clothing sector in Portugal is still seen, in many aspects as a traditional sector with some average characteristics, such as: low level of qualifications, less flexible labour legislation and stronger unionisation, very low salaries and low capability of investment in innovation and new technology. Is, nevertheless, a very important sector in terms of labour market, with increased weight in the exporting structure. Globalisation and delocalisation are having a strong impact in the organisation of work and in occupational careers in the sector. With the pressure of global competitiveness in what concerns time and prices, very few companies are able to keep a position in the market without changes in organisation of work and workers. And those that can perform good responses to such challenges are achieving a better economical stability. The companies have found different ways to face this reality according to size, capital and position. We could find two main paths: one where companies outsource a part or the entire production to another territory (for example, several manufacturing tasks), close and/or dismissal the workers. Other path, where companies up skilled their capacities investing, for example, in design, workers training, conception and introduction of new or original products. This paper will present some results from the European project WORKS – Work organisation and restructuring in the knowledge society (6th Framework Programme), focusing the Portuguese case studies in several clothing companies in what concern implications of global context for the companies in general and for the workers in particular, in a comparative analysis with some other European countries.

Children, space, and the urban street: an ethnomathematics posture

Dissertation presented for the PhD Degree in Education Science – Curricular Theory and Science Teaching, by Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Characterization of the glycosylation of human tumor cells

Ovarian cancer is within the most lethal gynecological malignancies in woman. Therefore, many investigators study its biological aspects with the purpose of discovering more rapid diagnostic methods and efficient treatment. Resembling many other tumors, in ovarian cancer, aberrant glycosylation occurs with the appearance of novel or altered carbohydrate structures. These can be terminal motifs, such as the Lewis determinants, or entire carbohydrate sequences, which have been related to tumorigenesis and its outcome.(...)

Paleontologia e evolução a problemática da espécie em Paleozoologia

The concept of species in Paleontology is of paramount importance since the correct taxonomic determinations are essential to establish the age of the beds where fossils are collected. Particularly since 1940, the concept of species from a biological context, corresponding to the variability of a set of interpopulation compatibility, led us to a new approach, in which a typological conception has been replaced by a populationist one. If the notion of species is not necessarily identical for all living organisms, the greater the difficulties of interpretation in the private world of cephalopod fossils. The latter, lend themselves well to population systematics, and where this concept of species rests primarily on the morphological similarities. Thus, the introduction of general ideas analyse "typological species", "biological species", the problem of the definition of a "population" in Paleontology, and also the importance of the biometric analysis of fossil associations. The classic examples of polymorphism amd polytypism, in existing or extinct organisms, show that the concept of fossil species, observed in a well-defined period of its lifetime, is no different from that of biological species. The study of the evolution of fossil organisms allow us to understand the modelities of evolution and the mechanisms of speciation here synthesized and fully documented, namely the anagenesis or sequential evolution and the cladogenesis or divergent evoltuion; these mechanisms are the basis of the synthetic or gradualist theory of evolution developed by Dobzhansky, Mayr, Huxley, Rensch and impson. This summary ends with a reference to the theory of punctuated (or intermittent) equilibria proposed by Gould and Eldredge, who presented a more objective interpretation of morphological gaps, considered as elements of evolution itself. The interdisciplinary collaboration between zoologists, geneticists and paleontologists, is compulsory in this domain. Paleozoology has a key role since it conveys the dynamism and depth to the dimension of space-time duality.

Terapêuticas antigénio-especificas no tratamento das doenças desmielinizantes: estudos sobre a vacinação com ADN e a descoberta de um novo alvo antigénico

RESUMO A Esclerose Múltipla (EM) é uma doença desmielinizante crónica do Sistema Nervoso Central (SNC), provocada, em grande parte, por um ataque imuno-mediado contra diversos elementos da bainha de mielina. Dentro dos alvos antigénicos desta resposta autoimune, vários componentes proteicos e lipídicos da mielina têm vindo a ser identificados ao longo dos anos, entre os quais se destacam a proteína básica de mielina(MBP), glicoproteína ligodendrocitária da mielina (MOG), proteína proteolipídica (PLP) e glicoproteína associada à mielina (MAG). Com o desenvolvimento do modelo animal de Encefalomielite Autoimune Experimental (EAE), diversas terapias antigénio-específicas foram desenhadas, baseadas na modificação benéfica da resposta autoimune contra a mielina, tais como a administração de mielina ou seus componentes, os copolímeros terapêuticos, os ligandos peptídeos alterados e, recentemente, a vacinação com ácido desoxirribonucleico (ADN) codificador de proteínas de mielina, integrado em plasmídeos e purificado para administração parentérica. Neste trabalho, apresentamos os resultados de um extenso conjunto de experiências, subordinadas a dois temas fundamentais: 1) avaliação do potencial terapêutico, e dos mecanismos de acção, da vacinação tolerizadora com ADN codificador de proteínas de mielina (MBP, MOG, PLP, MAG) na EAE, e da associação desta vacinação com a administração de ADN de citocinas Th2, ou de oligonucleótidos imunomoduladores; 2) identificação e caracterização da resposta imune contra um novo componente da mielina com potencial antigénico, a proteína inibidora do recrescimento axonal, Nogo-A. No que respeita à vacinação com ADN, os nossos resultados comprovam a eficácia desta terapêutica antigénio-específica na prevenção e tratamento da EAE. Os seus mecanismos de acção incluem, entre outros, a supressão anérgica da proliferação antigénioespecífica dos linfócitos T anti-mielina (no modo de prevenção da doença), o enviesamento Th2 da resposta imune (quando co-administrada com a vacina de ADN codificadora da citocina IL-4, funcionando como terapia génica local), e a redução da diversificação de epítopos da resposta humoral anti-mielina, avaliada através de myelin spotted arrays. A associação das vacinas de ADN com oligonucleótidos imunomoduladores GpG, desenvolvidos para contrariar as sequências CpG imunoestimuladoras presentes no vector de vacinação, levou à melhoria da sua eficácia terapêutica, devida, provavelmente, ao efeito estimulador preferencial dos oligonucleótidos GpG sobre linfócitos Th2 e sobre células reguladoras NK-T. Com base nestes resultados a vacinação com ADN foi desenvolvida para o tratamento da EM em humanos, com ensaios clínicos a decorrerem neste momento. Em relação à proteína Nogo-A, estudos de estrutura primária e de previsão de antigenicidade identificaram a região Nogo-66 como alvo antigénico potencial para a EAE. Nas estirpes de ratinho SJL/J e C57BL/6, fomos capazes de induzir sinais clínicos e histológicos de EAE após imunização com os epítopos encefalitogénicos Nogo1-22, Nogo23- 44 e Nogo45-66, utilizando protocolos de quebra de tolerância imune. Ao mesmo tempo, identificámos e caracterizámos uma resposta linfocitária T específica contra os antigénios contidos na região Nogo-66, e uma resposta linfocitária B com diversificação intra e intermolecular a vários determinantes presentes noutras proteínas da mielina. A transferência adoptiva de linhas celulares Th2 anti-Nogo45-66, levou à melhoria clínica e histológica da EAE em animais recipientes induzidos com outros antigénios de mielina, após migração destas células para o SNC. Estes dados comprovam a importância da Nogo-66 como antigénio na EAE, e a eficácia de terapias antigénio-específicas nela baseadas. No seu conjunto, os nossos resultados confirmam o potencial terapêutico das vacinas de ADN codificadoras de proteínas de mielina, bem como a importância dos encefalitogénios contidos na proteína Nogo-A para a fisiopatologia da EAE e da EM, com eventual relevância para o desenvolvimento de novas terapias antigénio-específicas. O aperfeiçoamento futuro destas terapias poderá levar, eventualmente, a uma capacidade de manipulação da resposta imune que permita o tratamento eficaz das doenças inflamatórias desmielinizantes, como a Esclerose Múltipla. ABSTRACT Multiple Sclerosis (MS) is a chronic demyelinating disease of the Central Nervous System (CNS), caused, mainly, by an immune-mediated attack against several elements of the myelin sheath. Among the antigenic targets for this autoimmune response, several proteic and lipidic myelin components have been identified throughout the years, of which myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), proteolipidic protein (PLP), and myelin associated glycoprotein (MAG) are the best characterized. With the development of the animal model for MS, Experimental Autoimmune Encephalomyelitis (EAE), several antigen-specific therapies have been designed, based on beneficial modifications of the autoimmune response against myelin. These have included myelin and myelin component administration, therapeutic copolymers, altered peptide ligands and, more recently, vaccination with myelin-protein encoding deoxyribonucleic acid (DNA), integrated into plasmids and purified for parenteral administration. In this work we present the results of an extensive series of experiments, subordinate to two fundamental areas: 1) evaluating the therapeutic potential, and mechanisms of action, of tolerizing myelin protein (MBP, MOG, PLP, MAG) DNA vaccination in EAE, alone and in association with Th2 cytokine DNA administration, or immunomodulatory oligonucleotides; 2) identifying and characterizing the immuneresponse against a new myelin component with antigenic potential, the axonal regrowth inhibitor Nogo-A. Regarding DNA vaccination, our results prove the efficacy of this antigen-specific therapy for the prevention and treatment of EAE. Its mechanisms of action include, among others, anergic suppression of antigen-specific T-cell proliferation against myelin (in prevention mode), Th2 biasing of the immune response (when co-administered with the IL- 4 codifying DNA vaccine, acting as local gene therapy), and reduction of epitope spreading of the anti-myelin antibody response, assessed by myelin spotted arrays. The combination of myelin DNA vaccination with the administration of GpG immunomodulatory oligonucleotides, designed to counteract immunostimulatory CpG motifs present in the vaccination vector, led to an improvement in therapeutic efficacy, probably due to the preferential stimulatory effect of GpG oligonucleotides on Th2 lymphocytes and on regulatory NK-T cells. Based on these results, tolerizing DNA vaccination is being developed for human use, with ongoing clinical trials. As concerns the Nogo-A protein, based on studies of primary structure and prediction of antigenicity, we identified the Nogo-66 region (responsible for the most of the inhibitory capacity of this protein) as a potential antigenic target for EAE. In the SJL/Jand C57BL/6 mouse strains, we were able to induce clinical and histological signs of EAE,after immunization with the encefalitogenic epitopes Nogo1-22, Nogo23-44 and Nogo45-66,using a tolerance breakdown protocol. Concomitantly, we identified and characterized a specific T cell response against these antigens, together with a B cell response which showed extensive intra and intermolecular epitope spread to several determinants present in other myelin proteins. Adoptive transfer of nti-Nogo45-66 Th2 cell lines resulted in clinical and histological improvement of EAE in recipient animals induced with other myelin antigens, after intraparenchymal CNS migration of anti-Nogo cells. These data confirm the relevance of Nogo-66 as an antigen in EAE, as well as the efficacy of antigenspecific therapies based on the response against this protein.In conclusion, our results substantiate the therapeutic potential of myelin-encoding DNA vaccination, as well as the importance of encefalitogenic epitopes present in the Nogo-A protein for the pathophysiology of EAE and MS, with potential relevance for the creation of new antigen specific-therapies. The future development of these therapies may eventually lead to a degree of manipulation of the immune response that allows the effective treatment of autoimmune, inflammatory, demyelinating diseases, such as Multiple Sclerosis.

Natural and amyloid self-assembly of S100 proteins: structural basis of functional diversity

The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca2+ binding through EF-hand motifs and binding of Zn2+ and Cu2+ at additional sites, usually at the homodimer interfaces. Ca2+ binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.

Traços da medicina na azulejaria de Lisboa

RESUMO: A presente abordagem procura estabelecer uma relação entre a Medicina e a Azulejaria. Um conjunto de composições produzidas entre o século XVII e a década de 90 do século XX, localizado na área de Lisboa e seus arredores, organiza-se em torno de oito vectores que ilustram a presença de alusões à Medicina na Azulejaria da referida área. São estes, aspectos relacionados com a higiene, marcos da história da assistência, ciclos temáticos relacionados com os quatro elementos primordiais e com os cinco sentidos, representações ligadas à ideia de morte, episódios bíblicos, referências hagiográficas e elementos ligados à acção médica, como objectos, patologias, instituições ou acontecimentos, associados à Medicina, que atestam esta relação entre Arte e Ciência, de forma geral, e entre a Azulejaria e a Medicina, de forma particular. À análise destes vectores, antecede uma resenha histórica relativa à ligação entre Arte e Ciência e um apontamento histórico acerca da história da Azulejaria. Pretende-se demonstrar esta conexão interdisciplinar e reforçar a importância da vertente humanista da Medicina, na sua história, na sua aprendizagem e na sua prática.-------------------------------------ABSTRACT: The present approach aims at establishing a relation between Medicine and Tile Art. A group of compositions produced between the 17th century and the 1990s, located in the Lisbon area and its surroundings, is organized around eight vectors that illustrate the presence of allusions to Medicine in the Tile Art in the mentioned areas. These are related with hygiene aspects, landmarks in the history of assistance, thematic cycles related with the four main elements and with the five senses, representations connected to the idea of death, biblical episodes, hagiographic references and elements connected to the medical intervention, such as objects, pathologies, institutions or events related to Medicine that testify this relation between Art and Science in a broad context, and between Tile Art and Medicine in a strict sense. Prior to the analysis of these vectors there is a historic contextualization concerning the relationship between Art and Science and a historical note about the history of Tile Art. The aim is to demonstrate the interdisciplinary relation and reinforce the importance of the humanistic side of Medicine, in its history, its learning and its practice.------------------------------------RÉSUMÉ: Cet étude vise établir une relation entre la Médecine et l’Art de l’ « Azulejaria ». Un ensemble de compositions produites entre le XVII ème siècle et le dernier quart du XX ème siècle, dans la région de Lisbonne, s’organise autour de huit axes qui illustrent des références à la médecine. Nous avons récupéré des motifs allusifs à l’hygiène, à l’histoire de l’assistance, aux cycles thématiques des quatre éléments primordiaux et des cinq sens, à la mort, aux épisodes bibliques ou hagiographiques mais aussi aux motifs qui reproduisent des objets, des pathologies, des institutions ou des évènements médicaux. Tous ces exemples mettent à jour la relation entre l’Art et la Science, en général, et entre l’ « Azulejaria» et la Médecine, en particulier. Avant d’analyser ces huit axes, nous établirons un parcours historique pour expliquer la relation entre Art et Science, ainsi qu’une brève histoire de l’ «azulejaria». Nous prétendons démontrer cette relation interdisciplinaire et renforcer l’importance de la vertu humaniste des Sciences Médicales dans son histoire, son apprentissage et sa pratique.

Computational design with flexible backbone sampling for protein remodeling and scaffolding of complex binding sites

Dissertation presented to obtain the Doutoramento (Ph.D.) degree in Biochemistry at the Instituto de Tecnologia Qu mica e Biol ogica da Universidade Nova de Lisboa

Novel Secretion Apparatus Maintains Spore Integrity and Developmental Gene Expression in Bacillus subtilis

Plos Genetics, 5(7): ARTe1000566

Entretien avec François Bayle

La réalisation de cet entretien avec François Bayle a eu comme objectif premier d'approfondir la compréhension de sa conception du sonore. Le concept d’image de son (i-son) est évidemment l’élément central de sa pensée à propos du sonore. Nous l’avons approché en tant qu’élément présent dans l’espace et perçu par l’oreille. François Bayle nous présente le son en tant que présence porteuse de dimensions spatiales multiples. Il nous montre également que l’intentionnalité de l’écoute est un des éléments déterminants dans la perception des sons dans l’espace. Le compositeur rappelle enfin que les représentations mentales sont construites et que les images sonores de la musique sont composées.

Providing energy efficiency location-based strategies for buildings using linked open data

Dissertation submitted in partial fulfillment of the requirements for the Degree of Master of Science in Geospatial Technologies.