Membrane domains are an important structure in plasamatic membrane. They concentrate various signaling molecules. Their main structural component is cholesterol and by its removal the membrane domains are disrupted. The aim of our work was to examine the effect of cholesterol depeletion on signaling initiated thyreothropin releasing hormone (TRH). Although its signaling cascade is located within membrane domains the receptor itself is not. We showed that cholesterol depletion by -cyclodextrin caused release of Gq/11 proteins and caveolin 2 from membrane domains. We also discovered that cholesterol depletion decreases potency of TRH to activate G proteins as well as induction of release of intracellular Ca2+ In the last part we investigated the effect of disruption of the cell membrane integrity by cholesterol depletion on thyrotropin-releasing hormone receptor (TRH-R) surface mobility and internalization in HEK293 cells stably expressing TRH-R-eGFP fusion protein. CLSM studies indicated that the internalization of receptor molecules initiated by TRH stimulation was significantly attenuated. The detailed analysis of recovery of TRH-R-eGFP fluorescence in bleached spots of different sizes indicated that cholesterol depletion results in an increase of overall receptor mobility. We suggest that migration of...

Anyone who has ever had the opportunity to observe small children when playing or learning something new or telling something and anyone who has ever had the op- portunity to talk to them must have noticed the children sometimes treat the reality around them in a strange way. These are the funny moments when one is surprised what children think and how they treat logic. As though small children lived in an odd world where the rules of logic are completely different. The famous Swiss psy- chologist noticed this peculiar children's thinking and described the intellectual egocentrism in children of preschool and early school age. Egocentrism does not affect only the children's logical thinking but also other aspects of children's think- ing and experience. This special "setting" of children's minds can be observed when the children are playing, in children's communication, in their drawings or in chil- dren's moral judgement. In the field of children's morals Piaget spoke of the moral realism. Under the influence of moral realism children when morally judging the moral situations presented to them do not concentrate on the essential elements of the story but rather on irrelevant circumstances such as material results of an action and other outside matters. According to Piaget it is essential for...

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At the time of writing this thesis, the complete genomes of more than 180 organisms have been sequenced and more than 80000 biological macromolecular structures are available in the Protein Data Bank (PDB). While the number of sequenced genomes and solved three-dimensional structures are rapidly increasing, the functional annotation of protein sequences and structures is a much slower process, mostly because the experimental de-termination of protein function is expensive and time-consuming. A major class of in silico methods used for protein function prediction aim to transfer annotations between proteins based on sequence or structural similarities. These approaches rely on the assumption that homologous proteins of similar primary sequences and three-dimensional structures also have similar functions. While in most cases this assumption appears to be valid, an increasing number of examples show that proteins of highly similar sequences and/or structures can have different biochemical functions. Thus the relationship between the divergence of protein sequence, structure and function is more complex than previously anticipated. On the other hand, there is mounting evidence suggesting that minor changes of the sequences and structures of proteins can cause large differences in their conformational dynamics. As the intrinsic fluctuations of many proteins are key to their biochemical functions, the fact that very similar (almost identical) sequences or structures can have entirely different dynamics might be important for understanding the link between sequence, structure and function. In other words, the dynamic similarity of proteins could often serve as a better indicator of functional similarity than the similarity of their sequences or structures alone. Currently, little is known about how proteins are distributed in the 'dynamics space' and how protein motions depend on structure and sequence. These problems are relevant in the field of protein design, studying protein evolution and to better understand the functional differences of proteins. To address these questions, one needs a precise definition of dynamic similarity, which is not trivial given the complexity of protein motions. This thesis is intended to explore the possibilities of describing the similarity of proteins in the 'dynamics space'. To this end, novel methods of characterizing and comparing protein motions based on molecular dynamics simulation data were introduced. The generally applicable approach was tested on the family of PDZ domains; these small protein-protein interaction domains play key roles in many signalling pathways. The methodology was successfully used to characterize the dynamic dissimilarities of PDZ domains and helped to explain differences of their functional properties (e.g. binding promiscuity) also relevant for drug design studies. The software tools developed to implement the analysis are also introduced in the thesis. Finally, a network analysis study is presented to reveal dynamics-mediated intramolecular signalling pathways in an allosteric PDZ domain.

Student Number: 0111229X. PhD Thesis. Faculty of Science. School of Education / This study is part of a larger national study, the Learners’ Perspectives Study. The main focus of this particular study is to explore, describe and explain learners’ perspectives regarding the incorporation of the everyday in mathematics. Two Grade 8 mathematics classrooms in two different schools, Umhlanga and Settlers are used as sites for empirical data. Learners’ perspectives are sought through a series of post-lesson interviews with different groups of learners for lessons in which the everyday was summoned for a mathematics lesson. During these interviews, learners whether 1. They welcomed or appreciated the use of the everyday in class or not and 2. The everyday inhibited or enabled easy access to mathematics content. In order to understand the background against which these perspectives are held, mathematics lessons wherein the everyday was incorporated were observed, recorded and transcribed. In addition, teachers’ views about these lessons were explored through interviews and activities which incorporated the everyday were analysed. I used Bernstein’s notions of classification and framing as a theoretical lens through which to account for my observations. It became necessary though, to supplement these through Dowling’s domains of text analysis (esoteric, expressive, public and descriptive). I also introduced the notion of authentic/inauthentic and close/far descriptions. It is a combination of these three broad theoretical frameworks which assisted in the provision of a comprehensive theoretical account. The significance of mathematics-everyday aspect in mathematics education is highlighted by the number of studies, as discussed in the study, and different orientations from which this aspect is engaged. What can be teased out of these studies is that mathematics education debates are seldom informed by the learners’ perspectives. The study suggests that most of the learners who participated in the interviews welcomed and appreciated the use of the everyday in mathematics. However, most learners (particularly from Umhlanga) viewed mathematics as a platform to raise genuine concerns about the everyday used. In contrast, some learners (particularly from Settlers) viewed the everyday as vehicles or see-throughs towards the mathematics content. What this study viii suggests is that, firstly, the everyday is multifaceted and the nature of the context summoned tends to influence views learners hold about the role of the everyday in mathematics. Secondly, the study suggests that learners’ perspectives about the everyday cannot be divorced from the classroom context in which they encounter these everyday contexts.

The present study aimed to research links between autistic traits and creativity in the average adult population. The sample consisted of 108 adults,​ 60 females, 48 males, age 18-66 (M=34,90; SD=10,85), from 20 different social media pages who participated in the study through self-report questionnaires about autistic traits and creativity. The result shows that the autistic traits of difficulties in imagination and difficulties in social skills has associations with difficulties in creativity, while the autistic trait of attention to detail has associations with benefits in creativity. The creativity domains, differences between men and women and the method of self-report are discussed.

Este trabalho trata da descrição e da análise do contorno entoacional total de sentenças interrogativas globais e parciais, neutras e não-neutras, da variedade paulista do português brasileiro (PB). Investigamos a relação entre a associação de eventos tonais ao contorno entoacional dessas sentenças e a formação de domínios prosódicos. Nosso objetivo é identificar padrões entoacionais que codifiquem prosodicamente o significado pragmático dos diferentes tipos de sentenças interrogativas do PB. Partimos da hipótese de que o contorno entoacional total tem papel fundamental na codificação de significados pragmáticos, além do contorno nuclear. Em nosso trabalho, utilizamo-nos de corpora de fala controlada obtida em tarefa de leitura de sentenças interrogativas antecedidas por contextos propícios à produção de diferentes tipos frásicos interrogativos e de fala semicontrolada obtida em tarefa de leitura de mapa em dupla. A descrição e a análise prosódica das sentenças interrogativas de nossos corpora foram feitas à luz da visão integrada entre a abordagem Autossegmental e Métrica da Fonologia Entoacional (Pierrehumbert 1980; Pierrehumbert & Beckman 1988; Ladd 1996, 2008; Jun 2005/2014; entre outros) e a Fonologia Prosódica (Selkirk 1984, 1986, 2000; Nespor & Vogel 1986, 2007). Levamos em conta, para o desenvolvimento das análises desta investigação, os trabalhos desenvolvidos nesse mesmo quadro teórico e aplicados ao português (Frota & Vigário 2000; Tenani 2002; Fernandes 2007a, 2007b, Serra 2009, Toneli 2014; e, mais especificamente para sentenças interrogativas, Moraes 2008, Truckenbrodt, Sandalo & Abaurre 2009, Castelo 2011, 2016 e Frota et. al. 2015a). Os resultados obtidos a partir de nossa investigação revelam que (i) de maneira geral, o contorno nuclear das sentenças interrogativas da variedade paulista do PB tem um padrão ascendente-descendente; (ii) o contorno entoacional total tem papel importante na codificação do significado pragmático da interrogação; (iii) há características prosódicas especiais associadas ao contorno entoacional total que correspondem a significados pragmáticos específicos, como, por exemplo: (a) a marcação prosódica de foco e ênfase que varia a depender do significado pragmático associado à marcação de foco e ênfase nos diferentes tipos frásicos; (b) a associação de downstep ao contorno nuclear de sentenças interrogativas neutras; (c) a associação de upstep marcando o elemento enfático em sentenças interrogativas antiexpectativa; (d) o rebaixamento da gama de variação tonal no trecho do contorno entoacional correspondente à primeira palavra prosódica e o contorno nuclear em sentenças interrogativas retóricas; (e) as diferenças quanto à densidade tonal em sentenças interrogativas neutras e não-neutras; entre outras características prosódicas especiais associadas a significados pragmáticos específicos. Tais resultados revelam o cumprimento dos objetivos da pesquisa e confirmam nossa hipótese inicial de trabalho. / This study aims to describe the intonational contour of global and partial, neutral and non-neutral interrogative sentences of the Paulista variety of Brazilian Portuguese (BP). We investigate the relation between tonal events assignment and the formation of prosodic domains. Our goal is to find intonational patterns that codigy pragmatic meaning of different clause types of BP interrogative sentences. Our hypothesis is that the total contour has a fundamental role in codifying pragmatic meaning, besides the nuclear contour. In our work, the corpora analyzed includes controlled speech data obtained in a reading task that exposed interrogative sentences along with context to elicit the production of interrogatives with different pragmatic meanings and semicontrolled speech data recorded in a map task. The description and the prosodic analysis of the intonational phrasing of the interrogative sentences of our corpora were developed according to an integrated view of the Autossegmental Metrical approach within the framework of Intonational Phonology (Pierrehumbert 1980; Pierrehumbert & Beckman 1988; Ladd 1996, 2008; Jun 2005/2014; entre outros) and the Prosodic Phonology framework (Selkirk 1984, 1986, 2000; Nespor & Vogel 1986, 2007). Our analysis take into account previous works developed in this same framework and applied to Portuguese (Frota & Vigário 2000; Tenani 2002; Fernandes 2007a, 2007b, Serra 2009, Toneli 2014; and, more specifically regarding interrogative sentences, Moraes 2008, Truckenbrodt, Sandalo & Abaurre 2009, Castelo 2011, 2016 e Frota et. al. 2015a). The results achieved through this investigation reveal that (i) in general, the nuclear contour of interrogative sentences of the Paulista variety of BP show a rising-falling pattern; (ii) the total contour plays an important role in conveying pragmatic meaning of questions; (iii) there are special prosodic characteristics assigned to the total contour that correspond to specific pragmatic meaning, such as: (a) focus and emphasis marking that varies depending on the pragmatic meaning associated with different phrase types; (b) downstep association to the nuclear contour in neutral interrogative sentences; (c) upstep association to the emphatic element in counter expectation sentences; (d) lower tessiture of the range of variation in the portion of the intonational contour corresponding to the first prosodic word and the nuclear contour in rhetoric questions; (e) differences in tonal density between neutral and non-neutral sentences; among other prosodic characteristics associated with specific pragmatic meaning. These results confirm lead us to achieve our objectives and confirm our main hypothesis.

Este trabalho trata da descrição e da análise do fraseamento entoacional do contorno de sentenças declarativas neutras do português falado na Guiné-Bissau (PGB), no que se refere, especificamente, à investigação da relação entre atribuição de eventos tonais ao contorno entoacional e formação de domínios prosódicos. Além disso, faz-se a comparação dos resultados obtidos para o fraseamento entoacional dos dados do PGB com os resultados obtidos para o fraseamento entoacional já descritos em trabalhos anteriores para o português brasileiro (PB) e para o português europeu (PE). Os corpora utilizados para o desenvolvimento deste estudo derivam de dois tipos de discurso (sentenças de leitura e de fala espontânea). A descrição e a análise do fraseamento entoacional das sentenças declarativas neutras contidas nesses corpora é desenvolvido à luz da abordagem Autossegmental e Métrica da fonologia entoacional (PIERREHUMBERT, 1980; BECKMAN; PIERREHUMBERT, 1986; LADD, 1996, 2008; entre outros) e da Fonologia Prosódica (SELKIRK, 1984, 1986, 2000; NESPOR; VOGEL, 1986, 2007; entre outros) e com base em estudos prévios desenvolvidos nesses mesmos quadros teóricos e aplicados ao PB (CUNHA 2000; FROTA; VIGÁRIO 2000; TENANI 2002; FERNANDES, 2007a, 2007b; SERRA 2009; entre outros) e ao PE (GRØNNUM; VIANA, 1999; FROTA, 2000, 2002a, 2002b, 2003; VIGÁRIO, 2003; VIGÁRIO; FROTA, 2003; CRUZ, 2013; entre outros). Os resultados alcançados nesta dissertação revelam características entoacionais do PGB que são similares às encontradas nas demais variedades de português: (i) a frequente atribuição de acentos tonais a palavras fonológicas do contorno entoacional (característica também encontrada no contorno entoacional do PB); (ii) a associação obrigatória de um acento tonal à palavra fonológica cabeça do último sintagma fonológico do sintagma entoacional, seguido por um tom de fronteira associado à fronteira direita desse sintagma (assim como no PB e no PE); (iii) a correspondência do padrão do contorno nuclear do sintagma entoacional das declarativas neutras do PGB com os padrões do contorno nuclear desse mesmo sintagma das sentenças declarativas neutras do PB e das variedades do PE; (iv) a possibilidade de associação de acentos frasais a fronteiras de sintagmas fonológicos (evento tonal que é encontrado associado a sintagmas fonológicos desse mesmo tipo de sentenças em uma das variedades centro-meridionais do PE); e (v) a ocorrência de eventos tonais adicionais H associados a sílabas pretônicas de palavras fonológicas longas do contorno entoacional (semelhante aos tons adicionais encontrados associados a palavras fonológicas também longas no PB). / In this study, we investigate the intonation of neutral declarative sentences of Portuguese of Guinea-Bissau (GBP), with regarding to the investigation of the relation between tonal events assignment and prosodic domains formation. In addition, we compare the results obtained for the analysis of GBP data with the intonational patterns of neutral sentences described on previous works for Brazilian Portuguese (BP) and European Portuguese (EP). For this research, a corpus of two different speech styles (read sentences and spontaneous speech sentences) was used. For the description and analysis of intonational of neutral declarative sentences in this corpus we followed the Autosegmental Metrical aproach within the intonational phonology framework (PIERREHUMBERT, 1980; BECKMAN; PIERREHUMBERT, 1986; LADD, 1996, 2008; among others), the Prosodic Phonology framework (SELKIRK, 1984, 1986, 2000; NESPOR; VOGEL 1986, 2007; among others) and previous studies conducted on those theoretical frameworks and applied to BP (CUNHA; 2000; FROTA; VIGÁRIO, 2000; TENANI 2002; FERNANDES, 2007a, 2007b; SERRA 2009; among others) and EP (GRØNNUM; VIANA, 1999; FROTA, 2000, 2002a, 2002b, 2003; VIGÁRIO, 2003; FROTA; VIGÁRIO, 2003; CRUZ, 2013; among others). The results achieved in this work show that the intonation properties of GBP are similar to those found in the other varieties of Portuguese already studied. These properties are as follow: (i) frequent association of pitch accents with Phonological Words of intonation contour (tonal characteristic also found in BP); (ii) a pitch accent is obligatorily associated with the Phonological Word head of the last Phonological Phrase of a Intonation Phrase, followed by a boundary tone associated with the right edge of that Intonation Phrase (as in BP and EP); (iii) there is a matching in the nuclear contour of GPB neutral declarative sentences with the nuclear contour of BP and varieties of EP neutral declarative sentences; (iv) the possibility of phrasal accents to be associated with phonological phrases boundaries (the same possibility is found for one of the center-southern varieties of EP); and (v) the possibility of H tones to be associated with pretonic syllables of long Prosodic Words (as in BP).

Chapas de aço elétrico (0,7% Si e 0,3% Al) foram laminadas a diferentes graus de deformação e recozidas (760º C, 2h) de modo a obter diferentes tamanhos de grão por recristalização. Um outro conjunto de chapas do mesmo material foi recozido a tempos e temperaturas diferentes de modo a obter tamanho de grão variado por crescimento de grão. Os tamanhos de grão foram medidos pelo método dos interceptos e os parâmetros da distribuições de tamanho de grão determinados por um método semi-analítico que se baseia na medição das áreas individuais de cada grão na micrografia. A partir do ensaio quase-estático de histerese magnética no quadro de Epstein obtiveram-se os campos coercivos de cada amostra, a diferentes induções máximas (0,6 0,8 1,0 1,2 1,4 e 1,5T). Notou-se que o conjunto dos dados se enquadra com menos de 4% de desvio médio absoluto uma lei fenomenológica do tipo: Hc aBmax^c /TG bBmax^d Na qual Hc é o campo coercivo, TG é o tamanho de grão, Bmax é a indução máxima do ensaio de histerese e a, b, c e d são os parâmetros de ajuste. A partir da inserção do efeito do campo desmagnetizante no contorno de grão no modelo físico de Mager obteve-se uma boa estimativa para os valores dos parâmetros independentes da indução a e b, além de propor um significado físico para os mesmos. Com a integração dos modelos Mager e Preisach, determinou-se uma equação diferente para o ajuste dos dados, a qual oferece um valor aproximado de c. Para que o modelo físico explique completamente a relação fenomenológica resta ainda elucidar o parâmetro d. / Electrical steel sheets (0,7% Si and 0,3% Al) were cold-rolled and annealed (760º C, 2h) in order to obtain different grain sizes through recrystallization. Another set of sheets from the same material were annealed at different temperatures and time-frames, so as to produce different grain sizes through grain growth. Grain size was measured through the intercept method and grain size distribution parameters were determined via a semi-analytical method based on measurement of individual grain areas upon micrographs. From quasistatic hysteresis measurements in an Epstein frame, the coercive field of each sample was determined at various maximum induction values (0,6 0,8 1,0 1,2 1,4 e 1,5T). The data set fits with less than 4% average deviation a phenomenological law of the type: Hc aBmax^c /TG bBmax^d In which Hc is the coercive field, TG is the grain size, Bmax is the maximum induction value and a, b, c and d are the fitting parameters. By introducing the grain boundary demagnetizing field effect on Magers physical model, a good estimate of the values of a and b was obtained, as well as a reasonable explanation to their physical meaning. Integrating Mager and Preisach models, a different equation for the data was obtained, which offered an approximate value of c. In order for physical models do fully explain the phenomenological equation, there is still need to understand the parameter d.

Hoje eu vou morrer para nascer de novo. E como escrever histórias que existem em voz alta e que nunca quiseram estar nesta dissertação? Escrevo aqui uma dramaturgia a partir da alteridade, transformo o texto de um outro pela minha autoria. Procuro, assim, problematizar os usos de um discurso alheio ao escritor, como fundamento para o teatro. Para tanto, apresento três ações artísticas que realizei, Consulta, Fim da Fila e Jogo do Gênero, que são o motor para se pensar como a apropriação do real pode culminar na construção de um texto, processo que chamo de rubricagem. A presença física do dramaturgo em diálogo com o outro possibilita a construção de uma dramaturgia situada em campos expandidos do teatro, evidencia a performatividade do gesto, tanto no processo quanto na obra, e permite pensar caminhos da dramaturgia a partir da aproximação a alguém desconhecido. / Today I will die in order to be reborn. How to write spoken-word stories that never wanted to appear in this thesis? I describe here a dramaturgy of alterity, transforming the text of another into my own words. I thus seek to problematize the uses of a discourse foreign to the author as a foundation for theater. Therefore, I present three performances I have realized-- Consulta, Fim da Fila, and Jogo do Gênero--which drive my consideration about how the appropriation of the real can culminate in the construction of a text, a process I term rubricagem-- rubrication. The physical presence of the playwright in dialogue with another enables the construction of a text set in expanded domains of theatre, demonstrating the gesture\'s performativity--both in the process and final piece--and allowing us to conceive a dramaturgy that emanates from the approximation of someone unknown.