3,210 research outputs found
La filosofía del derecho de Alexandre Kojève
No full textThis article is a presentation of Alexandre Kojève’s philosophy of law, exposed in his Esquisse d’une phénoménologie du droit (1981). Little attention has been paid to this work. So there is a gap that has to be filled with a critical reflection of its strengths. Among them, undoubtedly, we count the fact that Kojève is introducing a conception of international justice that casts a singular light on current debates about cosmopolitanism and globalization. According to this author, citizenship is the key element of the process of global expansion of the juridical sphere. In sum, Kojève’s philosophy is useful to reflect upon the contrast between the juridical and the political, which is the basis for all philosophy of law, in order to achieve world peace and international justice.Este artículo es una presentación de la filosofía del derecho de Alexandre Kojève contenida en su Esquisse d’une phénoménologie du droit (1981). La poca atención que dicha obra ha recibido es un vacío que debiera llenarse con una reflexión crítica de sus puntos fuertes. Entre ellos destaca una concepción de la justicia internacional que proyecta una luz muy singular sobre los actuales debates en torno a la globalización y el cosmopolitismo. A ojos de este autor, la ciudadanía es el elemento clave para aquilatar la expansión global de lo jurídico. En suma, Kojève aparece como un valioso referente en la labor de pensar la contraposición entre lo jurídico y lo político que está en la base de toda filosofía del derecho, con la aspiración al logro de la justicia internacional y la paz mundial en el horizonte
Single-molecule detection and characterisation of alpha-synuclein aggregates
No full textAberrant protein aggregation is a predominant feature of many neurodegenerative disorders.
It has long been recognised that aggregates of alpha-synuclein (α-syn) drive pathogenesis in
Parkinson’s Disease (PD), and it is widely accepted that small α-syn oligomers are the key
cytotoxic species in PD. Notably, however, these oligomeric species are difficult to characterise
using traditional biochemical ensemble methods due to their high level of heterogeneity
and low abundance. Single-molecule fluorescence microscopy techniques have emerged
as a suitable approach to circumventing this problem, enabling the detection of individual
aggregates amongst monomeric protein and thus facilitating the identification, quantification,
and characterisation of rare oligomeric species. However, cellular mechanisms of α-syn aggregation
are poorly understood. Furthermore, there remains some limitations to the singlemolecule
techniques currently available. This thesis describes the work completed to address
some of these issues.
Chapter 1 provides the contextual background for the work presented in this thesis, detailing
the biological aspects of α-syn, its aggregation, and its implications in PD, as well as outlining
the single-molecule techniques used to investigate aggregate species. Chapter 2 describes
the methodologies undertaken in this thesis, and chapters 3 to 5 describe the findings made
using the single-molecule techniques which were utilised and developed in this work.
One primary approach for studying species in single-molecule experiments involves directly
labelling biomolecules of interest with a suitable fluorophore. Early steps in α-syn aggregation
have previously been identified using fluorescently tagged α-syn and single-molecule Förster
resonance energy transfer (smFRET) in vitro; however, the characterisation of early aggregate
formation in cells has thus far been difficult to achieve. Chapter 3 describes the use of duallabelled
α-syn to detect and characterise aggregates formed both intracellularly and in vitro
via smFRET, using both single-molecule confocal microscopy coupled with microfluidics and
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total internal reflection fluorescence microscopy (TIRFM) to determine both the sizes and
structures of the oligomers formed. This work reveals the presence of distinct oligomeric
species in vitro and in neurons resulting from structural conversion during early aggregate
formation.
The approach taken in Chapter 3 is highly suitable for investigating aggregate formation
resulting from the addition of exogenous α-syn to samples of interest. However, such an
approach is not ideal for the detection and characterisation of endogenous aggregates due to
issues with the covalent labelling of cellular protein. Extrinsic amyloid dyes are typically used
as an alternative approach to labelled protein; however, such dyes are non-protein-specific
and bind to the common amyloid beta-sheet motif. As an alternative, the work presented in
Chapter 4 describes a novel single-molecule method to specifically detect and characterise
α-syn aggregates with high sensitivity, making use of a high-affinity antibody labelled with
orthogonal fluorophores which is combined with fast-flow microfluidics and single-molecule
confocal microscopy. This enables the quantification and size approximation of α-syn aggregates
at picomolar concentrations, both in vitro and in biological samples.
Although the kinetics of α-syn aggregation have been studied extensively, much of our current
knowledge stems from ensemble averaging techniques which are associated with high levels
of variability and are not conducive to detecting the earliest steps in aggregate formation.
In addition, there remains uncertainty surrounding the effect of familial variants and posttranslational
modifications (PTM) on aggregation. Chapter 5 encompasses the study of the effects
of the ubiquitous N-terminal acetylation PTM, in addition to the familial, rapid-onset G51D
mutation, on α-syn aggregation, using the novel detection method developed in Chapter 4.
This is used in conjunction with single-molecule detection with thioflavin-T (ThT) to reveal new
insights into the aggregation of α-syn variants.
Overall, the work presented here provides new insights into the aggregation of α-syn via the
use and development of single-molecule techniques. The advancements made have added
to the current understanding of the molecular mechanisms of α-syn aggregation, both in
vitro and in neurons, and have also been used to develop a novel single-molecule detection
method for α-syn aggregates. The work presented in this thesis has resulted in two published
papers, ’Pathological structural conversion of alpha-synuclein at the mitochondria induces
neuronal toxicity’ in Nature Neuroscience, and ’Single-molecule two-color coincidence detection
of unlabeled alpha-synuclein aggregates’ in Angewandte Chemie International Edition.
Furthermore, the novel detection method presented here holds promise for measuring α-syn
oligomeric load in clinical samples due to its high sensitivity and specificity for α-syn aggregates.
This may therefore be used in future studies for identifying, detecting, and studying
potential biomarkers in PD, with potential use in disease diagnosis. It is therefore expected
that the work from this thesis will be used to aid researchers towards better understanding the
mechanisms of α-syn aggregation, both in vitro and in clinical samples
Reconfiguração do consensualismo contratual: as ações tituladas nominativas e os limites à transmissão
No full textPartimos da evolução histórica do consensualismo contratual salientando os
principais carateres que, nos diversos momentos históricos, se foram evidenciando.
Numa segunda etapa exploramos os fundamentos dogmáticos do modelo de
transmissão contratual assumido pelo legislador e a sua viabilidade no sistema
jurídico global, em particular, no direito dos valores mobiliários. Constatamos a
crescente necessidade na prática mercantil e inevitabilidade no sistema jurídico
global da admissibilidade da existência de contratos de compra e venda de natureza
meramente obrigacional. Num terceiro momento desenvolvemos os principais
aspetos do regime jurídico aplicável às ações tituladas nominativas fora do mercado
regulado, em particular, os principais limites à transmissão, enquanto instrumentos/barreiras ao consensualismo contratual.We start from the historical evolution of contractual consensualism emphasizing the
main aspects that, in different historical moments, were showing up. In a second
stage we explore the dogmatic foundations of the transmission model contractual
assumed by the legislator and its viability in the global legal system, in particular, in
securities law. We note the growing need in commercial practice and inevitability in
the global legal system the admissibility of the existence of contracts of sale purely
obligatory. In the third stage we develop the main aspects of the legal regime
applicable to nominative titled actions outside the regulated market, in particular,
the main limits to the transmission, as instruments / barriers to contractual
consensualism
“Era por Alexandre tod’esto demostrado”: ¿pruebas verídicas y pruebas engañosas en el Libro de Alexandre?
No full textEl Libro de Alexandre es un texto de s. XIII, que se escribió en la España medieval. En este escrito, el autor pretende demostrar que, en el Alexandre, algunas de las situaciones que se ponen a prueba son aceptadas, pero eso no significa que el macedonio gane la prueba. El articulo esta dividido en tres apartados. En el primero, el autor da cuenta de la historia textual de la obra y también dedica ciertas líneas al Estado de la cuestión del texto; mientras que, en la segunda parte, nos guía a conceptos etimológicos de los términos prueba, evidencia y demás. En el tercer apartado se centra en algunas pruebas expuestas en el Libro de Alexandre.The Libro de Alexandre is a literary work, written during the medieval Spain. In this paper, the author tries to demonstrate that, carefully reading the L.A, some of the situations that are set as proves are accepted, but it does not mean that Alexander can be a victor. This paper is divided in three sections: firstly, the author tells the textual history of the L.A and, then, tries to update the State of art: on the other hand, in the second part, the author offers meanings about terms as: prueba and evidencia. Finally, the author focuses on certain passages contained in the Libro de Alexandre that can be taken as failed proves
Mixing the Immiscible: Improvisation within Fixed-Media Composition
No full textThis paper will explore ways in which mastered improvisation practice, with the studio as an instrument, is a proposed avenue to bridge the historical dichotomy between what Ted Gioia describe as ‘the aesthetics of perfection’ and ‘the aesthetics of imperfection’. It is proposed as a way to re-embody fixed music, as experimented by the author through the composition of his last fixed-media work. This will be put in the context of a wider trend observed amongst the current emerging generation of composers interested in the aesthesics of the work, by opposition to the previous generations that placed the value of the work in its poietics. The vital and primal importance of practice outcome as practice-based research’s main document will also be advocated for, as these trends are happening in the laboratory of live music
Alexandre de Rhodes (1593?-1660)
No full textBiografia do jesuíta francês Alexandre de Rhodes (1593?-1660), missionário na Cochinchina (Vietname) e no Tonquim. Autor do Dicionário Anamita-Português-Latim (1651), Rhodes foi uma figura central no choque de interesses entre o Padroado Português e as ambições diplomáticas e políticas da França na Indochina e na China.Biography of the French Jesuit Alexandre de Rhodes (1593?-1660), missionary in Cochinchina (Vietnam) and Tonkin. Author of the Anamita-Portuguese-Latin Dictionary (1651), Rhodes was a central figure in the clash of interests between the Portuguese Padroado and France's diplomatic and political ambitions in Indochina and China.info:eu-repo/semantics/publishedVersio
La Clerecía de "Alexandre"
No full textEl artículo reflexiona sobre la educación que recibe Alexandre “El grande” a manos de su profesor Aristóteles, retratado en el “Libro de Alexandre”; a continuación analiza las disciplinas que compusieron dicho programa con el interés de proponer una interpretación de la lista de las siete artes liberales mencionadas. Este artículo ofrece una visión de las diferentes maneras en las que los textos reflejan la “clerecía” del protagonista así como de otros personajes, incluyendo el anónimo autor de los mismos. Cualquiera que se dedique a las mencionadas artes liberales será glorificado y Alexandre se presenta él mismo como modelo ideal de un príncipe en quien la nobleza y al inteligencia van unidas, una defensa clara de la “clerecía” como fuente fundamental de toda excelencia. This article deals with the education imparted on Alexander the Great by Aristotles, as portrayed in the “Libro de Alexandre”, analyzes the disciplines and proposes an interpretation of the list of the seven liberal arts mentioned therein. This article also offers an encompassing view of the different ways in which the text reflects the “clerecía2 of the protagonist as well as that of the other characters, including the anonymous author himself. Anyone who dedicates him or herself to the aforementioned liberal arts is thereby glorified, and Alexander presents himself as the ideal model of a prince in whom nobility and cleverness are joined, in a clear defense of the “clerecía” as the fundamental source of all excellence
The monarchy of Portugal in Alexandre Herculano's work
No full textA pesquisa A Monarquia Portuguesa na Obra de Alexandre Herculano analisa a construção do modelo ideal de monarca por Alexandre Herculano, com especial ênfase na produção histórica em que os monarcas portugueses foram retratados com maior riqueza de detalhes e analisados de forma mais criteriosa. A pesquisa se dá a partir da conjuntura histórica portuguesa marcada pelo estabelecimento do Estado Liberal e pelos debates entre os diferentes grupos políticos em que a participação dos intelectuais é um ponto relevante. No tocante a Alexandre Herculano, o envolvimento do autor em diversas polêmicas e articulações políticas é uma evidência da importância e da atuação da intelligentsia na sociedade portuguesa do século XIX. Ao lado da conjuntura histórica na qual a obra de Herculano foi produzida, o universo conceitual forjado pelo autor com fundamento nos pressupostos teóricos e políticos também foi contemplado, pois o modelo de monarca construído pelo autor foi elaborado a partir deste universo conceitual que, conforme os pressupostos teóricos empregados nesta pesquisa atuam e interferem nos debates contemporâneos à obra.The research The Portuguese Monarchy in Alexandre Herculanos work analyses the building of the monarchs ideal model (by Alexandre Herculano) especially focusing on the historical production on which the Portuguese monarchs were detailedly portrayed and discerningly analysed. Considering the Portuguese historical conjuncture marked not only by the establishment of the Liberal State but also by the debates among the different political groups in which the intellectuals partaking is relevant. Concerning Alexandre Herculano, the authors involvement in several debates and political articulations is an evidence of the intelligentsias outstanding role in the Portuguese society of the nineteenth century. Along with the historical context in which Herculanos work was produced, the conceptual universe created by the author reasoned on theoretical and political assumptions was also considered because the monarchs model built by the author was created from this universe of concepts that, according to the theoretical assumptions used in this research, act and expand their sphere of influence towards the contemporary debates to his work
A comparison of the images of women in selected works by Moliere and Alexandre Dumas, fils, 1978
No full textThe purpose of studying these two dramatists is to discover, to analyze and to compare the female characters in their respective plays. By so doing, the author wishes to discern their Ideas, attitudes and prejudices concerning women. The study is presented in four chapters. The introduction, which is Chapter I, presents the lives and works of Moliere and Alexandre Dumas, fils. Details of their personal life histories are given so that the reader can more fully understand the influence of the society in which they lived upon their work. Chapter II represents a study of the images of women in Moliere's theater. In this chapter one finds that females, in general, are presented as having intelligence, wit and high moral standards. In many instances women are shown to surpass men in these areas. The third chapter discusses the images of women as presented in selected plays by Alexandre Dumas, fils. It deals with Dumas's depiction of women as inferior to man in every aspect of their physical, mental and moral being. The fourth chapter is a comparison of both authors' ideas concerning the mental and moral status of women. Their ideas regarding a woman's place in marriage and society are presented. The conclusion is that Moliere, quite lenient and fair in his portrayals, fills the stage with delightful images of noble women of his era, while Dumas paints a very dismal and discouraging image of the woman of his day
Mathematics under the Microscope
No full textIt is an unusual book which casts new and paradoxical light on the nature of mathematics.
The book will be interesting -- perhaps for different reasons -- to school teachers of mathematics and maths majors at universities, to graduate students in mathematics and computer science, to research mathematicians and computer scientists, to philosophers and historians of mathematics, to psychologists and neurophysiologists.
The author attempts to start a dialogue between mathematicians and cognitive scientists. He discusses, from a working mathematician's point of view, the mystery of mathematical intuition: why are certain mathematical concepts are more intuitive than the others? To what extent the "small scale" structure of mathematical concepts and algorithms reflects the workings of the human brain? What are the "elementary particles'' of mathematics which build up the mathematical universe?
One of the principal points of the book is the essential vertical unity of mathematics, the natural integration of its simplest objects and concepts into the complex hierarchy of mathematics as a whole. The same ideas and patterns of thinking can be found in elementary school arithmetic and in the cutting edge mathematical theories. There are no boundaries between "recreational'', "elementary'', "undergraduate'' and "research'' mathematics; the book freely moves throughout the whole range. Nevertheless, the author takes great care of keeping the book as non-technical as possible.
The book is saturated with amusing examples from a wide range of disciplines -- from turbulence to error-correcting codes to logic -- as well as just puzzles and brainteasers. Despite the very serious subject matter, the author's approach is lighthearted and entertaining
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