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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
311

Ketogenic diet impacts Blood-Brain Barrier physiology : implications for Alzheimers's disease / Impact du régime cétogène sur la physiologie de la barrière hémato-encéphalique : importance pour la maladie d'Alzheimer

Corsi, Mariangela 22 February 2018 (has links)
Compte tenu de l'absence de traitement pharmacologique efficace contre la maladie d'Alzheimer (MA), le développement d'approches thérapeutiques alternatives telles que le régime cétogène (« ketogenic diet » : KD) pourrait être envisagé. Le KD est un régime riche en graisses, basé sur la production de corps cétoniques (« ketone nodies » : KB) dans le sang. En raison des effets bénéfiques du KD sur le système nerveux central et de l'absence de données publiées sur la barrière hémato-encéphalique (BHE), nous avons utilisé une approche in vivo / in vitro pour étudier l'effet du KD et des KB sur la BHE. Pour l'étude in vivo, le sang de souris 129Sv a été récolté afin d’effectuer le dosage du beta-hydroxybutyrate et du glucose. Les capillaires cérébraux ont été isolés de cortex des souris, et des RT-qPCR ont été effectuées pour évaluer l'expression de l'ARNm des transporteurs / récepteurs impliqués dans la synthèse et le transport de KB, de glucose et du peptide bêta amyloïde. Les analyses transcriptionnelles ont été réalisées également dans un modèle in vitro de BHE, composé de cellules endothéliales dérivées de cellules souches hématopoïétiques (BLECs) en état de cétose. Après confirmation de l'intégrité des jonctions cellulaires des BLECs, Enfin, des expériences de transport de peptides beta amyloïde fluorescents après traitement avec les KBs ont été réalisées in vitro. Nos résultats montrent que les KBs modulent la physiologie de la BBB et l'expression de certains transporteurs et récepteurs du peptide bêta amyloïde, renforcent ainsi notre motivation à décrypter les mécanismes moléculaires et cellulaires au niveau vasculaire et plus précisément au niveau de la BHE. / Given the current absence of an effective pharmacologic treatment for Alzheimer’s disease (AD), the development of alternative therapeutic approaches (such as the ketogenic diet, KD) might be considered. The KD is a low-carbohydrate, high-fat diet based on the production of ketone bodies (KBs) in the blood. In view of the KD’s beneficial effects on the central nervous system and the lack of published data on the blood brain barrier (BBB), we used an in vivo/in vitro approach to investigate the effect of the KD and KBs on the BBB. For the in vivo study, blood from 129Sv mice was assayed for beta-hydroxybutyrate and glucose dosage. Brain capillaries were isolated from mouse cortices, and RT-qPCR assays were used to evaluate the mRNA expression of transporters/receptors involved in the synthesis and transport of KBs, glucose and beta-amyloid peptide. The mRNA assays were also performed in an in vitro BBB model, based on brain-like endothelial cells (BLECs). After a ketotic state had been established and the BLECs’ integrity had been confirmed, we evaluated the mRNA expression of KB-, glucose- and amyloid-beta-related genes. Lastly, the transport of fluorescently labelled beta-amyloid peptide across the BBB was studied after treatment with KBs. Our results showed that KBs modulate the physiology of the BBB by regulating the expression of certain beta-amyloid peptide transporters/receptors and amyloid peptide-synthesizing enzymes. These data suggest that it is possible to modulate key molecular players in beta-amyloid peptide transport and synthesis at the BBB, and thus open up new perspectives for studying KB-related therapeutic approaches.
312

Modeling an internal hydraulic system which controls ball motions within a bounded fluid.

Chambers, Diane Idec January 1976 (has links)
Thesis. 1976. M.S.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering. / Microfiche copy available in Archives and Engineering. / Bibliography: p.163-164. / M.S.
313

The Australian Senate : an institutional study of a federal second chamber

Cadle, Don Duane January 1954 (has links)
No description available.
314

Development of a novel lentiviral vaccine vector and characterisation of in vitro immune responses

McLean, Rebecca Kathryn January 2018 (has links)
Vaccines are a highly effective means of preventing infectious disease. However, for many diseases of livestock the available vaccines are ineffective or sub-optimal. This is partly due to challenges surrounding the specific targeting of antigen presenting cells (APCs). In order to improve the delivery of protective antigens to host APCs, a novel lentiviral vector derived from visna / maedi virus (VMV) has been developed. Initial characterisation using an enhanced green fluorescent protein (eGFP) reporter transgene found that the novel VMV vector efficiently transduced a wide range of cell lines including cells of ovine, human, murine, bovine and caprine origin. In addition, the VMV vector was found to elicit sustained transgene expression for at least 4 weeks in rapidly dividing cell lines. One of the most important factors for acceptable vaccines is their safety. Therefore, in order to increase the bio-safety of the VMV vector, integration-defective and self-inactivating forms were produced. Integration-defective VMV lentiviral vectors (IDLVs) were found to produce 1-LTR circular episomes favourably over integrated provirus following the transduction of target feline and ovine cell lines. This led to a decrease in transgene expression over time in dividing cells. In contrast, in non-dividing cells transgene expression was maintained at a similar level to integration-competent VMV vectors. Self-inactivating (SIN) VMV vectors were constructed and found to have a significant decrease in LTR activity. Transgene expression was maintained by the insertion of an internal promoter derived from human cytomegalovirus (CMV) acting directly on the transgene. When self-inactivating and integration-defective modifications were incorporated into the same vector particle, a 4-fold decrease in transduction relative to the parent vector was observed. Ovine monocyte-derived dendritic cells (MDDCs) and macrophages (MDMs) were found to be efficiently transduced by the VMV vector, whereas lentiviral vectors derived from HIV-1 poorly transduced both of these primary cell populations. Following this work, the ability to deliver pathogen genes into APCs was studied using the Chlamydia abortus (C. abortus) major outer membrane protein (MOMP) as the transgene. C. abortus is the most common infectious cause of ovine abortion worldwide and MOMP has previously been shown to stimulate strong antibody responses after vaccination. Unexpectedly, the VMV vector encoding either eGFP or MOMP was found to induce apoptosis in MDDCs and MDMs using Annexin V staining. Apoptotic cells were detectable as early as 6 hours post-transduction of cells. Furthermore, release of the pro-inflammatory cytokine IL-1β was associated with the formation of late apoptotic cells. Apoptotic bodies produced post-transduction were able to be phagocytosed by immature MDDCs and the transgene efficiently cross-presented to T-cells. The ability of the novel VMV vector to induce a suitable recall immune responses was investigated using an in vitro model. Here, an autologous population of MDDCs were cultured with the apoptotic bodies produced post-transduction before the addition of autologous PBMC. Proteins from the apoptotic bodies were presented by the MDDCs to PBMC leading to a strong, antigen specific recall immune response against C. abortus MOMP. This was proven by the detection of cytokines IFNγ and IL-10 in the co-culture supernatant from PBMC activated by the MOMP transgene cross-presented by MDDCs. No release of IL-4 or IL-17A could be detected. These data presented in this thesis show the potential for improving delivery of antigens in livestock vaccines by the use of lentiviral vectors. In addition, this vector system provides a strong base for the study of other potential protective antigens in vitro.
315

Contribution à la parallélisation et au passage à l'échelle du code FLUSEPA / Contributions to the parallelization and the scalability of the FLUSEPA code

Couteyen Carpaye, Jean Marie 19 September 2016 (has links)
Les satellites sont mis en orbite en utilisant des lanceurs dont la conception est une des activités principales d’Airbus Defence and Space. Pour ce faire, se baser sur des expériences n’est pas facile : les souffleries ne permettent pas d’évaluer toutes les situations auxquelles un lanceur est confronté au cours de sa mission. La simulation numérique est donc essentielle pour l’industrie spatiale. Afin de disposer de simulations toujours plus fidèles, il est nécessaire d’utiliser des supercalculateurs de plus en plus puissants. Cependant, ces machines voient leur complexité augmenter et pour pouvoir exploiter leur plein potentiel, il est nécessaire d’adapter les codes existants. Désormais, il semble essentiel de passer par des couches d’abstraction afin d’assurer une bonne portabilité des performances. ADS a développé depuis plus de 20 ans le code FLUSEPA qui est utilisé pour le calcul de phénomènes instationnaires comme les calculs d’onde de souffle au décollage ou les séparations d’étages. Le solveur aérodynamique est basé sur une formulation volume fini et une technique d’intégration temporelle adaptative. Les corps en mouvement sont pris en compte via l’utilisation de plusieurs maillages qui sont combinés par intersections.Cette thèse porte sur la parallélisation du code FLUSEPA. Au début de la thèse, la seule version parallèle disponible était en mémoire partagée. Une première version parallèle en mémoire distribuée a d’abord été réalisée. Les gains en performance de cette version ont été évalués via l’utilisation de deux cas tests industriels. Un démonstrateur du solveur aérodynamique utilisant la programmation par tâche au dessus d’un runtime a aussi été réalisé. / There are different kinds of satellites that offer different services like communication, navigationor observation. They are put into orbit through the use of launchers whose design is oneof the main activities of Airbus Defence and Space. Relying on experiments is not easy : windtunnel cannot be used to evaluate every critical situation that a launcher will face during itsmission. Numerical simulation is therefore mandatory for spatial industry.In order to have more reliable simulations, more computational power is needed and supercomputersare used. Those supercomputers become more and more complex and this impliesto adapt existing codes to make them run efficiently. Nowadays, it seems important to rely onabstractions in order to ensure a good portability of performance. Airbus Defence and Spacedeveloped for more than 20 years the FLUSEPA code which is used to compute unsteady phenomenalike take-off blast wave or stage separation. The aerodynamic solver relies on a finitevolume formulation and an explicit temporal adaptive solver. Bodies in relative motion are takeninto account through the use of multiple meshes that are overlapped.This thesis is about the parallelization of the FLUSEPA code. At the start of the thesis,the only parallel version available was in shared memory through OpenMP. A first distributedmemory version was realized and relies on MPI and OpenMP. The performance improvementof this version was evaluated on two industrial test cases. A task-based demonstrator of theaerodynamic solver was also realized over a runtime system.
316

Um estudo sobre três problemas clássicos da geometria euclidiana / A study of three classic problems of euclidean geometry

Rafael Martins Gusmai 04 April 2016 (has links)
Este trabalho aborda os três problemas clássicos de geometria da Grécia antiga trazendo as principais histórias e conceitos necessários para compreensão dos mesmos. Construções geométricas com régua não graduada e compasso, números construtivos, corpos, números complexos e polinômios são alguns dos assuntos que antecedem o tratamento dos problemas. As construções são exibidas usando as relações existentes nas operações aritméticas, dá opções de como se representar geometricamente as quatro operações básicas e a extração de raízes quadradas, mostrando que todo problema modelado nessas condições pode ser solucionado através dos instrumentos euclidianos. Essa exibição vem ao encontro dos números construtivos, trazendo à tona quais os principais pensamentos sobre construções com régua e compasso, deixando claro a definição de construções geométricas para os gregos. São apresentados também propriedades da álgebra abstrata envolvendo conjuntos numéricos que possuem características de corpo, dentre eles os números complexos. Além disso, tratamos dos polinômios, os quais são fundamentais nas demonstração das impossibilidades clássicas. Por fim, esta pesquisa deixará claro a integração de todos os conteúdos citados acima e de que forma toda teoria pode ser organizada na realização das demonstrações da impossibilidade da duplicação do cubo, trissecção do ângulo e quadratura do círculo, frizando a mobilização dos matemáticos ao longo da história para tentar explicar tais problemas, acarretando um alto desenvolvimento da Matemática. / This work addresses the three classic problems ancient Greek geometry bringing the main stories and concepts needed to understand them. Geometric constructions with non-graded ruler and compass, building numbers, bodies, complex numbers and polynomials are some of the issues that precede the statements of problems. The buildings are displayed using the relationships in arithmetic operations, the options of how to represent geometrically the four basic operations and extraction of square roots, shows that every problem can be modeled in such conditions solucionas through Euclidean tools. This view comes against constructive rising numbers which the main thoughts of constructions with ruler and compass, making clear the definition of geometric constructions for the Greeks. It also present properties of abstract algebra involving numerical sets that have body characteristics, including complex numbers, also explains the importance of polynomials in the statement of classical impossibilities building the definition of degree of extension. Finally this research will clarify the integration of all the contents mentioned above and how every theory can be organized in the realization of doubling the cube demonstrations, angle trisection and squaring the circle, plus the mobilization of mathematicians throughout history for trying to explain such problems causing a high development of mathematics
317

Utilização de altas pressões hidrostáticas para o estudo e renaturação de proteínas com estrutura quaternária / Utilization of high hydrostatic pressure for the study and refolding of proteins with quaternary structure

Daniella Rodrigues 24 September 2012 (has links)
A produção de proteínas recombinantes é uma ferramenta essencial para a indústria biotecnológica e suporta a expansão da pesquisa biológica moderna. Uma variedade de hospedeiros pode ser utilizada para produzir estas proteínas e dentre eles, as bactérias E. coli são as hospedeiras mais utilizadas. No entanto, a expressão heteróloga de genes em E. coli frequentemente resulta em um processo de enovelamento incompleto que leva ao acúmulo de agregados insolúveis, conhecidos como corpos de inclusão (CI). Altas pressões hidrostáticas são capazes de desfavorecer interações intermoleculares hidrofóbicas e eletrostáticas, levando à dissociação dos agregados e por isso são úteis para solubilizar e renaturar proteínas agregadas em CI. O presente trabalho teve como objetivo o estudo do processo de desagregação dos CI e de renaturação das proteínas oligoméricas subunidade B da toxina colérica (CTB) e região globular da fibra adenoviral (RGFA) utilizando altas pressões hidrostáticas. A toxina colérica (CT) é composta por uma subunidade A e cinco subunidades B combinadas em uma holotoxina AB5. A CTB é a porção pentamérica não tóxica da CT, responsável pela ligação da holotoxina ao receptor gangliosídeo GM1. A fibra do adenovírus é uma proteína homotrimérica que forma parte do capsídeo viral, organizada em três regiões: a cauda N-terminal, a haste central e a região C-terminal (região globular). A RGFA se liga à proteína de membrana CAR nas células hospedeiras e promove a internalização do vírus. Os estudos apresentados neste trabalho demonstraram que a alta pressão hidrostática foi eficaz na desagregação dos CI da CTB e da RGFA. As condições de renaturação foram otimizadas utilizando-se diferentes proporções do par redox glutationa oxidada e reduzida, concentrações de agentes caotrópicos, presença de aditivos e esquemas diferenciados de compressão/descompressão daqueles previamente descritos na literatura. CTB solúvel e pentamérica foi obtida pela compressão da suspensão de CI a 2,4 kbar por 16 horas em tampão TrisHCl 50 mM pH 8,5, 1 mM de tween 20 e descompressão direta seguida de incubação em pressão atmosférica. O rendimento de renaturação da CTB solúvel e pentamérica foi de até 45 % e 288 mg de CTB/litro de cultura bacteriana. Esta proteína apresentou estrutura regular e atividade biológica. RGFA trimérica foi obtida pela compressão da suspensão de CI em tampão TrisHCl 50 mM pH 8,0 e 0,5 M de L-arginina a 2,4 kbar por 1,5 horas e 0,4 kbar por 16 horas antes da completa descompressão. O rendimento de proteína solúvel trimérica da RGFA foi de 4 %, porém não foi possível obter a atividade biológica desta proteína. / The production of recombinant proteins is an essential tool for the biotechnology industry and supports the expansion of modern biological research. Recombinant proteins can be produced by a variety of hosts and among them the bacteria E. coli is the most commonly used. However, the expression of heterologous genes in E. coli often results in an incomplete folding process that leads to the accumulation of insoluble aggregates known as inclusion bodies (IB). The application of high hydrostatic pressure impairs intermolecular hydrophobic and electrostatic interactions of proteins in solution, leading to dissociation of aggregates and is therefore useful tool to solubilize and refold aggregated proteins in IB. This work aimed to study the process of disaggregation of IB and refolding of oligomeric proteins the B subunit of cholera toxin (CTB) and the globular region of the adenoviral fiber (RGFA) using high hydrostatic pressure. The cholera toxin (CT) comprises one A subunit and five B subunits, combined in the AB5 holotoxin. The pentameric CTB is non-toxic moiety of CT which is responsible for binding to the receptor ganglioside GM1 holotoxin. The adenovirus fiber is a homotrimeric protein wich forms part of the viral capsid and it is organized into three regions: the N-terminal tail, the central rod and the C-terminal region (globular region). The RGFA binds to membrane protein CAR in host cells and promotes the internalization of virus. The studies presented here demonstrate that high hydrostatic pressure was effective in the disaggregation of the CTB and RGFA IB. The refolding conditions were optimized using different proportions of the redox couple oxidated and reduced glutathione, concentrations of chaotropic agents, presence of additives and pressure/decompression schemes distinguished from the previously described in the literature. Soluble pentameric CTB was obtained when the suspension of IB were compressed at 2.4 kbar for 16 hours in 50 mM of Tris-HCl buffer pH 8.5, 1 mM of tween 20, followed by direct decompression and incubation at atmospheric pressure. The yield of refolded soluble pentameric CTB was up to 45 % and 288 mg of CTB/ liter of bacterial culture. This protein was shown to presented regular structure and biological activity. Trimeric RGFA was obtained by compression of the suspension of IB in 50 mM of Tris-HCl buffer pH 8.0, 0.5M L-arginine at 2.4 kbar for 1.5 hours and at 0.4 kbar for 16 hours prior to the complete decompression. The yield of soluble trimeric RGFA was 4 %, however this protein did not present biological activity.
318

O CORPO SOB A PERSPECTIVA DE JOVENS SKATISTAS / The body under young skateboarders’s perspective.

Lima, Marco Antônio Oliveira 31 August 2017 (has links)
Submitted by admin tede (tede@pucgoias.edu.br) on 2017-11-10T11:18:05Z No. of bitstreams: 1 MARCO ANTÔNIO OLIVEIRA LIMA.pdf: 1903073 bytes, checksum: cc087ce08963501e122a04896c639936 (MD5) / Made available in DSpace on 2017-11-10T11:18:05Z (GMT). No. of bitstreams: 1 MARCO ANTÔNIO OLIVEIRA LIMA.pdf: 1903073 bytes, checksum: cc087ce08963501e122a04896c639936 (MD5) Previous issue date: 2017-08-31 / Schools hope that skateboarders follow the instituted rules. The skateboarders adopt a life style where the body is free to express/move under skating practice. Then comes this tense relationship between educational institutions and the young skateboarders. The educational rules may represent biopolitic estructures that act under the younger’s bodies. In this hard situation, we realise that schools and skateboarders influence each other dialectically. For the belief that schools need to rethink their pedagogical relationship about skateboarders, they went established as object of analysis. The adopted theme of this study – in the research area Education, Society and Culture, of the Stricto Sensu Postgraduate Program, in Pontifícia Universidade Católica de Goiás – is: The skateboarders’s relationship with his bodies at school. As a guiding question, it pretends to answer the following problem: How do young skateboarders give meaning to his bodies’s apropiation at school? In general, it was reflected about how young skateboarders give meaning to his bodies’s apropriation at school. And especifically 1) it checks how the young skateboarders’s bodies has been discuted in the academic space; 2) it analyzes the young skateboarders’s bodies while social dimension that’s historical built in streets, skate lanes and schools; and 3) it’s under study how the young skateboarders realise his own bodies at school. The target public of this study are skateboarders from 15 to 29 years old, high-school students. It was needed to understand how much they knew about this theme and make all the bibliographical search. Field research was needed to discover the target public, who was 7 young guys, being 3 from female sex and 4 from male sex. All the information was colected throught mixed questionaires and half structured interview. The information were interpreted throught qualitative reference. Among used authors, it’s needed to mencionate Adorno and Horkheimer (1985); Bourdieu (1998); Foucault (2004); Marcuse (1981a); and Marx and Engels (2001). It’s beliavable that throught this study it can find many other views that contributes for the school to reflect about young skateboarders bodies’s education in front of emancipation. / As escolas esperam que os skatistas obedeçam às regras instituídas. Os skatistas adotam forma de vida onde o corpo é livre para se expressar/movimentar mediante a prática do skate. Daí surge tensa relação entre as instituições de ensino e os jovens skatistas. As regras educacionais podem representar estruturas biopolíticas que incidem sobre os corpos da juventude. Nesta conflitante relação vê-se que escolas e skatistas se influenciam dialeticamente. Pelo fato de acreditar que as escolas precisam repensar sua relação pedagógica com os skatistas é que se estabeleceu o corpo destes como objeto de pesquisa. O tema adotado no estudo – inserido na linha de pesquisa Educação, Sociedade e Cultura, do Programa de Pós-Graduação Stricto Sensu, da Pontifícia Universidade Católica de Goiás – foi: A relação dos jovens skatistas com o corpo na escola. Como questão norteadora pretendeu-se responder ao seguinte problema: Como os jovens skatistas dão sentido a apropriação de seus corpos na escola? De forma geral refletiu-se a respeito de como os jovens skatistas dão sentido a apropriação de seus corpos na escola. E especificamente 1) verificou-se como o corpo dos jovens skatistas vem sendo discutido no cenário acadêmico; 2) analisou-se o corpo dos jovens skatistas enquanto dimensão social que se constrói historicamente na rua, pista de skate e escola; e 3) investigou-se como os jovens skatistas percebem os seus corpos na escola. O público do estudo foram skatistas, de 15 a 29 anos, estudantes do ensino médio. Realizou-se pesquisa bibliográfica e o estado do conhecimento do objeto. Recorreu-se à pesquisa de campo para descobrir o público do estudo, sendo 7 jovens das quais 3 foram do sexo feminino e 4 do masculino. Coletaram-se os dados através de questionários mistos e entrevista semiestruturada. Os dados foram interpretados pelo referencial qualitativo. Dentre os autores utilizados citam-se Adorno e Horkheimer (1985); Bourdieu (1998); Foucault (2004); Marcuse (1981a); e Marx e Engels (2001). Acreditase que pela pesquisa contemplam-se perspectivas que contribuam para que as escolas reflitam criticamente acerca da educação do corpo dos jovens skatistas rumo à emancipação.
319

Design and development of a novel bead-based assay for early stage alpha-synuclein aggregation

Pérez Pi, Irene January 2017 (has links)
α-synuclein is a small presynaptic protein whose misfolding and aggregation are considered drivers of the neurological disorders Parkinson’s disease, multiple system atrophy, dementia with Lewy bodies and related synucleopathies. α-synuclein exists in a dynamic state that changes from an α-helical conformation when bound to liposomes to natively unfolded in solution, the majority being in the latter state. The disease process by which native healthy α-synuclein undergoes a change in conformation to form β-sheet oligomers and fibrils is still unresolved. The fibrillation process has been widely studied by several different techniques and the structure of the fibrils has been determined by NMR, scanning transmission electron microscopy and X-ray diffraction. The early stages of aggregation into β-sheet rich oligomers, despite having been widely studied, has proven difficult to follow due to the heterogeneity of the species formed and the unpredictability of the process. The goal of the work reported here was to design and develop a novel, reproducible and quantitative assay to study the early stages of α-synuclein aggregation and to establish a platform for discovery of novel compounds that inhibit this process. These compounds could then be taken as a starting point for the development of new drugs for the treatment of synucleopathies. The assay developed herein has been designed, established and demonstrated to be suitable for the screening of α-synuclein aggregation inhibitors. The assay quantitatively measures aggregation using α- synuclein site-specifically labelled with green and red fluorescent dyes. Proteins labelled with the green dye are bound to microbeads. α-synuclein labelled with the red dye aggregates on the bead-linked green α-synuclein. The first part of the thesis describes the development of the tools required for the assay. α-synuclein single cysteine mutants were produced to introduce a specific attachment point to the protein. Single isomer carboxytetramethylrhodamine was synthesised in large scale for the label. Two different trifunctional tags that allow both the fluorescent labelling of the protein and the addition of a group for bead attachment in a single step were synthesised. Optimisation of the attachment of the functionalised proteins to beads of differing materials was accomplished enabling further development of the bead-based aggregation assay. With all tools established, the second part of the work comprised the development of the bead-based α-synuclein aggregation assay. Solid supports made of two different materials, TentaGel and Agarose, with two different types of bead surface attachment chemistry for α-synuclein were investigated, Ni-NTA on bead with His6-tag on the target or dibenzylcyclooctyne on bead and azide conjugation for the target. Only the combination of Ni-NTA agarose beads linking to His6-tag functionalised α-synuclein was found to be suitable for quantitative measurement of the aggregation process. Using 20 % EtOH, α-synuclein on-bead aggregation was reproducible within a 5 h time-frame with a linear dependence of aggregation rate as function of protein concentration on-bead. The third part of the thesis describes the research into novel starting points for the discovery of inhibitors of α-synuclein aggregation. In the peptides field, the most active peptides in the literature were selected and synthesised for study under the same conditions to find the most active ones. The most active peptide could be modified with non-natural amino acids to increase affinity and stability. While peptides and peptidomimetics would be applied in mechanistic studies, small molecular inhibitors of aggregation might represent lead compounds. One known inhibitor of α-synuclein aggregation was selected, NPT200-5, and an on-bead synthesis was developed so a diversity library could be generated around its four different building blocks. Finally the peptides, the NPT200-5 amide derivative and some known small molecule inhibitors of α-synuclein aggregation, such as curcumin, baicalein and EGCG amongst others, were screened on the bead-based α-synuclein aggregation assay. Strong inhibitory effects of curcumin and baicalein demonstrated the efficacy of the newly developed assay. In summary, the tools for the development of a novel micro-bead-based α-synuclein aggregation assay have been successfully produced. A novel bead-based α-synuclein early stage aggregation assay has been developed and optimised. Validation of this new technique was achieved with known small molecules inhibitors of α-synuclein aggregation.
320

Corpo(u)s de história e províncias de relações empáticas : uma etnografia de corpos de direitos recusados em Moçambique

Cossa, Segone Ndangalila January 2017 (has links)
As mulheres têm sido retratadas como inertes, sem vida e despojadas de seus lugares de sujeitos-históricos, dizem-nos isso os estudos sobre as relações de gênero em Moçambique. No entanto, os mesmos estudos ao construírem narrativas transversais dominantes sobre os gêneros, tendem a essencializar as mulheres como o único sujeito, oprimido pela cultura/tradição calcada pelo patriarcado. Com efeito, a mulher de que falam tais narrativas é sempre vitimizada, oprimida mesmo pelos estudos que têm a intenção de tornar sua voz audível. Sendo assim, nesta tese, objetivo traçar uma outra alternativa analítica que, a partir de uma corporalidade especifica – ubiquidade dos corpos – retrata-as de forma regenerada, como tendo agência feminina. / Women have been portrayed as inert, lifeless and deprived of their places as subjects of history, we are told about studies of gender relations in Mozambique. However, the same studies, when constructing dominant cross-narratives about gender, tend to essentialize women as the only subject, oppressed by the culture/tradition traced by patriarchy. Indeed, the woman of whom such narratives speak about always is victimized, oppressed even by the studies that are intended to make her voice audible. Thus, in this thesis, the objective is to outline another analytic alternative that, based on a specific corporality – the ubiquity of bodies – portrays them in a regenerated way, as having a female agency.

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