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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.
31

Análise do gênero portuário NOR sob a ótica da linguística sistêmico-funcional / Analysis of the cargo shipping genre NOR from the perspective of systemic functional linguistics

Alessandra Cristina Bittencourt Alcântara 06 May 2013 (has links)
O ensino de inglês em uma escola técnica é voltado para atender às necessidades dos alunos e do curso. Atuando como professora de inglês para fins específicos no CEFET UnED Itaguaí, deparei-me com um curso novo no estado do Rio de Janeiro, o Curso Pós-Médio Técnico em Portos. Em vista disto, este estudo propõe-se a investigar como o documento portuário, NOR, Notice of Readiness, ou ainda, Aviso de Prontidão, fundamental em uma operação portuária e, consequentemente, material importante para o curso de Portos, se estrutura em estágios para transmitir significados. Objetivamente, este trabalho responde as seguintes questões: em que situação o gênero NOR se constitui? e que linguagem medeia a atividade social nessa situação?. Para tanto, no desenvolvimento da pesquisa, são utilizados os pressupostos da Linguística Sistêmico-funcional (HALLIDAY, 1985; HALLIDAY; HASAN, 1989), que tem a função e a semântica como base da linguagem e da atividade comunicativa, sendo a língua influenciada pelo contexto social. Dessa forma, adota-se uma concepção de gênero a partir de uma perspectiva funcionalista: o gênero é visto como uma atividade direcionada por objetivos e propósitos, realizada em estágios e na qual os falantes são engajados como membros da nossa cultura (MARTIN, 1992). Adota-se, ainda, a noção de configuração contextual (CC) de um gênero, que faz referência às variáveis de registro localizadas no contexto situacional: o campo, a relação e o modo, que possibilitam perceber os elementos obrigatórios e opcionais que compõem a estrutura potencial de um gênero (EPG), assim como verificar seus traços estruturais, lexicais, gramaticais e semânticos (HALLIDAY; HASAN, 1989). O corpus desta pesquisa é constituído de dez exemplares do documento NOR, coletados em duas empresas que possuem terminais portuários na região da Costa Verde, no Rio de Janeiro. A fim de analisar os exemplares do documento, fizemos uma pesquisa de base qualitativa para identificar os seus estágios obrigatórios e opcionais a partir das marcas léxico-gramaticais no texto, mapeando suas funções, conforme a proposta de Hasan (1989). Os resultados da análise dos dez documentos sugere que há quatro estágios obrigatórios nestes textos, ou seja, o documento NOR possui quatro estágios que cumprem certas funções importantes na atividade social em que se insere. Estes estágios ocorreram em todos os exemplares pesquisados e são portanto determinantes para caracterizar o gênero NOR. Nestes estágios, foram identificados padrões da léxico-gramática que sinalizam as respectivas funções dos segmentos textuais que compõem o NOR, mostrando a estreita relação entre texto (representado por suas características lexico-gramaticais) e contexto (representado pela configuração contextual postulada para o NOR). Assim, esta análise aponta vantagens para o contexto portuário uma vez que propõe um modelo para facilitar a leitura e escrita do documento NOR, levando o profissional da área a se tornar um participante mais competente. Além do aporte à área portuária, esta dissertação pode auxiliar na análise de outros gêneros, nos quais seus pesquisadores tenham como premissa um modelo que considera o meio social onde o texto é produzido / The teaching of English as a foreign language in a technical school is designed to meet students' and the courses needs. Acting as a teacher of English for Specific Purposes at CEFET Itaguaí, I came across a new course in Rio de Janeiro state, the Technical Course of Cargo shipping. Considering this, the present study aims to investigate how the cargo shipping document, NOR, or Notice of Readiness, which is a crucial cargo shipping operation and, consequently, an important material for the course at CEFET, is structured in stages to transmit meanings. Objectively, this paper answers the following research questions: "what is the situation in which the NOR is produced? " and "what are the main features of the language that mediates social activity in this situation?". To answer these questions the theoretical assumptions of Systemic functional linguistics (SFL) (HALLIDAY, 1985, HALLIDAY; HASAN, 1989) were drawn upon: SFL sees function and semantics as the basis of language and of communicative activity, and thus considers language to be influenced by social context. The concept of gender adopted comes from the same functionalist perspective: genre is here seen as an activity driven by goals and purposes, held in stages and in which speakers are engaged as members of a particular culture (MARTIN, 1992). The notion of a contextual configuration (CC) for a genre is also adopted, and it refers to the variables located in the situational context (field, tenor and mode) that enable one to realize the obligatory and optional elements that make up a genres structure potential (GSP), as well as investigate their structural features, lexical, grammatical and semantic (HASAN, 1989). The corpus for this study consists of ten exemplars of the document NOR, collected in two companies with cargo shipping terminals in the region of Costa Verde in Rio de Janeiro. In order to examine these documents, a qualitative research was carried out to identify their obligatory and optional stages on the basis of the identification of lexico-grammatical signals in the text, thus mapping their functions, as Hasan (1989) proposed. The results of the analysis of the ten documents suggest that there are four obligatory stages in these texts: the NOR document has four stages that fulfill certain important functions in the social activity in which it operates. These stages occurred in all samples studied and are therefore crucial to characterizing the genre. This research contributes to the pedagogy in the area of cargo shipping negotiations as it establishes a suggested model to facilitate the reading and writing of the document NOR, which might lead to professionals in the field becoming more competent participants in the social activity under discussion. Apart from its contribution to the area of cargo shipping , this research may help in the analysis of other genres, in which researchers adopt a model that considers the social environment in which the text is produced
32

Vad lär sig elever mer än att sätta på kondomer på bananer? : En studie av vilka delar av sex och samlevnad som bör behandlas inom naturkunskapsundervisningen baserat på vad elever anser att de fått lära sig på grundskolan

Johansson, Mathilda, Reveny, Emelie January 2017 (has links)
Syftet med detta arbete är att granska vilka områden som elever på gymnasienivå upplever att de inte behandlat inom ämnesområdet sex och samlevnad på grundskolenivå samt vad gymnasieelever upplever att de vill lära sig mer om på gymnasienivå för att sedan undersöka om en koppling kan göras mellan vad gymnasieeleverna vill veta mer om och det centrala innehållet i naturkunskap. Uppsatsen tar sin grund i att lärare upplever att eleverna inte tycker att undervisningen inom sex och samlevnad känns relevant samt att det har konstaterats att ungdomar upplever att de inte kan ta hand om sin sexuella hälsa. Metoden som använts i detta arbete är en kvantitativ enkätundersökning med fasta svarsalternativ. Resultatet av denna undersökning bygger på 120 enkätsvar och påvisar att en majoritet upplever att de inte har behandlat ämnesområdet sex och samlevnad tillräckligt för att kunna ta hand om sin sexuella hälsa. Elever har ofta när de kommer till gymnasieskolan tagit del av undervisning inom sex och samlevnad som syftar till de fysiska delarna av ämnet så som hur könet ser ut samt hur barn blir till, men saknar den sociala och psykologiska delen av ämnet som bör behandlas så som områdena lust och kärlek. Vårt arbete ger en indikation om att de som gymnasieleverna vill lära sig mer om går att koppla till det centrala innehållet. Genom att elever får en undervisning de känner är intressant kan detta leda till att ungdomar får mer kunskap för att göra ett välinformerat val om hur de ska ta hand om sin sexuella hälsa vilket kan leda till att ungdomar blir mindre risktagande.
33

On the Automorphism Groups of Almost All Circulant Graphs and Digraphs

Bhoumik, Soumya 17 August 2013 (has links)
We attempt to determine the structure of the automorphism group of a generic circulant graph. We first show that almost all circulant graphs have automorphism groups as small as possible. Dobson has conjectured that almost all of the remaining circulant (di)graphs (those whose automorphism groups are not as small as possible) are normal circulant (di)graphs. We show this conjecture is not true in general, but is true if we consider only those circulant (di)graphs whose orders are in a “large” subset of integers. We note that all non-normal circulant (di)graphs can be classified into two natural classes (generalized wreath products, and deleted wreath type), and show that neither of these classes contains almost every non-normal circulant digraph.
34

Validation of an animal model of cognitive dysfunction associated with schizophrenia. Development and validation of the novel object recognition task using behavioural manipulations and psychotomimetic dosing regimens to induce cognitive deficits of relevance to schizophrenia in hooded-Lister rats.

Grayson, Ben January 2012 (has links)
Phencyclidine (PCP) is a non-competitive NMDA receptor antagonist that has been shown to induce schizophrenia-like psychotic symptoms that are clinically indistinguishable from schizophrenia in patients. When administered to rodents, PCP produces an array of behaviours that are characteristic of schizophrenia. Schizophrenia is associated with continual and treatment resistant cognitive deficits which are now recognised as a core feature of the disease. The aim of the studies reported in chapter 3 were to establish a set of objects with equal preference in the NOR (novel object recognition) test. Furthermore, the inter-trial-interval (ITI) of the NOR test was investigated in an attempt to elucidate the effects of time and location of the rats during the ITI on the cognitive impairments following sub-chronic PCP treatment. The experiments in chapter 4 were designed to compare the performance of male and female rats in the NOR test following treatment with acute d-amphetamine (d-amph), PCP and sub-chronic PCP treatment. In chapter 5, validation of the cognitive deficits induced by sub-chronic PCP treatment was assessed using carefully selected pharmacological agents. The aim of the studies in chapter 6 was to determine the effects of isolation rearing on cognitive performance in the NOR test following increasing ITIs. Additionally, the sensitivity of isolation reared rats compared to social controls following acute administration of PCP and d-amph was assessed using the NOR test. Studies in chapter 8 utilised the 16-holeboard maze to determine the effects of acute treatment with d-amphetamine, PCP and scopolamine on working memory in the rat. NOR is a visual learning and memory test that measures recognition memory which is impaired in patients with schizophrenia. Studies presented in this thesis demonstrate the importance of careful pilot studies when selecting objects for use in the NOR test. Initial studies in sub-chronic PCP (2 mg/kg for 7 days followed by 7 days drug free) treated female hooded-Lister rats revealed a preference of the rats for the wooden cone object; subsequently this object was eliminated from further NOR experiments. Sub-chronic PCP treated rats were found to be highly susceptible to the disruptive influence of distraction during the short 1 min inter-trial-interval (ITI) in the NOR test. These results are consistent with clinical findings of the effects of distraction on cognition in schizophrenia patients. Following the initial validation experiments, a 1 min ITI in the home cage was selected for all subsequent NOR studies. Further experiments provided evidence to confirm that information presented in the acquisition trial is encoded but not retained in the retention trial of the NOR test by IV PCP-treated rats. Male rats were less sensitive to the recognition memory deficits induced by acute treatment with PCP and d-amphetamine compared with females. Following sub-chronic PCP treatment, both males and females showed object recognition deficits, however, the impairments were more robust in female rats. Female rats were therefore selected for all subsequent experiments. Pharmacological validation was carried out using carefully selected agents which were assessed for their ability to restore the sub-chronic PCP induced cognitive deficit in the object recognition test. It was found that the classical antipsychotic agents haloperidol and fluphenazine, the benzodiazepine anxiolytic chlordiazepoxide and the SSRI antidepressant fluoxetine were ineffective. Further studies showed that the atypical antipsychotic agents, clozapine and risperidone, the analeptic agent modafinil, the nAChR full agonist nicotine, and full agonist and positive allosteric modulator of the ¿7 nAChR (PNU-282987 and PNU120596 respectively) reversed the recognition memory deficit induced by sub-chronic PCP treatment in the NOR test. Isolation rearing of rats at weaning is an environmental stressor that has relevance for modelling the symptomatology and pathology of schizophrenia. Isolates had a significantly increased locomotor activity (LMA) response to a novel environment and enhanced sensitivity to time delay-induced recognition memory deficits, compared with their socially reared counterparts. Isolates were less sensitive to an acute PCP-induced recognition memory deficit but more sensitive to an acute d-amphetamine induced recognition memory deficit in the NOR test compared to social controls. Preliminary results from the 16-holeboard maze experiments reveal that acute administration of the mAChR antagonist scopolamine, d-amphetamine, PCP and sub-chronic PCP treatment reduced working memory scores compared to vehicle treated controls. Taken together, these findings suggest that sub-chronic treatment with PCP induces cognitive deficits in behavioural tests of relevance to cognition associated with schizophrenia. This may allow the detection of novel pharmacotherapies to alleviate these cognitive deficits and exploration of the nature of cognitive disturbances in these patients.
35

Fuzzy Bayesian estimation and consequence modeling of the domino effects of methanol storage tanks

Pouyakian, M., Laal, F., Jafari, M.J., Nourai, F., Kabir, Sohag 07 April 2022 (has links)
Yes / In this study, a Fuzzy Bayesian network (FBN) approach was proposed to analyze the domino effects of pool fire in storage tanks. Failure probabilities were calculated using triangular fuzzy numbers, the combined Center of area (CoA)/Sum-Product method, and the BN approach. Consequence modeling, probit equations, and Leaky-Noisy OR (L-NOR) gates were used to analyze the domino effects, and modify conditional probability tables (CPTs). Methanol storage tanks were selected to confirm the practical feasibility of the suggested method. Then the domino probability using bow-tie analysis (BTA), and FBN in the first and second levels was compared, and the Ratio of Variation (RoV) was used for sensitivity analysis. The probability of the domino effect in the first and second levels (FBN) was 0.0071472631 and 0.0090630640, respectively. The results confirm that this method is a suitable tool for analyzing the domino effects and using FBN and L-NOR gate is a good way for assessing the reliability of tanks. / National Petrochemical Company (NPC) of Iran
36

Dinâmica nucleolar e a herança epigenética dos genes ribossomais / Nucleolar dinamics and the epigenetic inheritance of ribosomal genes

Silva, Natalia de Sousa Teixeira e 25 June 2014 (has links)
O nucléolo é uma organela subnuclear formada pela atividade transcricional dos genes ribossomais 18S-5.8S-26S (rDNA 45S) e consequente biogênese dos ribossomos. A atividade destes genes resulta na região organizadora do nucléolo (NOR), na forma de uma constrição secundária em cromossomos metafásicos. As constrições secundárias se condensam progressivamente durante a mitose e se descondensam ao final da telófase quando a reestruturação do nucléolo se inicia. Genomas que apresentam mais de um locus de rDNA 45S deve apresentar, obrigatoriamente, pelo menos um par de NORs, enquanto os demais loci poderão ou não serem expressos. O controle da expressão dos genes ribossomais e a formação da cromatina nucleolar são modulados por eventos epigenéticos. Embora alguns pontos sobre o funcionamento dos genes ribossomais e a formação do nucléolo estejam bem estabelecidos, questões como o padrão de condensação da cromatina nucleolar durante a mitose, o padrão de funcionamento de sítios adicionais de genes ribossomais, o papel das modificações epigenéticas na dinâmica da cromatina nucleolar e na expressão do rDNA 45S e o mecanismo de herança dos genes ativos, permanecem abertas. A espécie Crotalaria juncea (Leguminosae-Papilionoideae), com 2n=2x=16 cromossomos, que possui um locus de rDNA 45S no braço curto do cromossomo 1, que sempre forma constrição secundária, e um sítio adicional com atividade facultativa no braço curto do cromossomo 4, é um excelente modelo para o estudo destas questões. No contexto apresentado, foram estudadas a dinâmica de condensação das NORs durante o ciclo celular e sua correlação com a atividade dos genes ribossomais, incluindo o locus adicional, e ainda o papel da metilação da citosina do DNA durante estes processos. Os resultados demonstram que a cromatina da região organizadora do nucléolo segrega em um estado descondensado durante a mitose, na forma de constrição secundária, ou seja, tal estrutura não se condensa durante a metáfase e não volta a se distender no início da telófase. Aparentemente, o que causa correlações equivocadas entre a atividade nucleolar e a observação morfológica da constrição secundária na metáfase é a contração forçada da cromatina da NOR causada por agentes antimitogênicos. Este modelo de segregação em um estado aberto pode ser explicado pela descrição de diversas proteínas que permanecem diretamente ligadas ou indiretamente associadas à região da NOR durante a mitose, funcionando como uma barreira física para a compactação. Ambos os sítios, principais e adicionais, do rDNA 45S presentes em Crotalaria juncea apresentam atividade transcricional, embora o locus do cromossomo 4 mostre atividade facultativa. Ao contrário do que foi anteriormente proposto, uma vez ativo, o locus adicional permanece descondensado durante todo o ciclo mitótico, seguindo o mesmo comportamento dos sítios principais. As constrições secundárias e a cromatina nucleolar são hipermetiladas em nível citológico, independentemente de sua atividade. A aparente hipometilação observada no rDNA 45S em cromossomos mitóticos e núcleos interfásicos se deve ao menor grau de compactação da região organizadora do nucléolo e, consequentemente, à baixa densidade de cromatina. / The nucleolus is a subnuclear organelle formed as a result of transcriptional activity of ribosomal RNA genes 18S-5.8S-26S (45S rDNA) and subsequent ribosome biogenesis. This activity forms the nucleolar organizing region (NOR) as a secondary constriction in metaphase chromosomes. The secondary constrictions progressively condense during mitosis and decondense at the end of telophase, when nucleoli start to reassemble. Genomes presenting more than one 45S rDNA locus must have at least one pair of NOR bearing chromosomes, while other loci may be expressed or not. Ribosomal gene expression and nucleolar chromatin assembly are modulated by specific epigenetic events. Although some topics related to rDNA gene activity and nucleolus formation are well understood, questions such as the behavior of nucleolar chromatin condensation during mitosis, standard functions associated with rDNA additional sites, role of epigenetic modifications in nucleolar chromatin and 45S rDNA expression processes, and inheritance mechanism of active genes, remain to be solved. Crotalaria juncea (Leguminosae - Papilionoideae) has 2n=2x=16 chromosomes and carries a 45S rDNA locus at the short arm of chromosome 1, always presenting a secondary constriction, and an additional site with facultative activity at the short arm of chromosome 4, being an excellent model to resolve these questions. Thus, this study aimed to study NOR condensation dynamics during the cell cycle and its correlation with ribosomal gene activity, including the additional locus, while analyzing the role of rDNA cytosine methylation during this process. The results show that NOR chromatin segregate in a decondensed way throughout mitosis, as a secondary constriction. In other words, this structure does not condense during metaphase and the NOR is not reassembled at the beginning of telophase. Misinterpretations relating nucleolar activity with morphological observations of secondary constrictions, appear to be induced by the artificial contraction of NOR chromatin caused by antimitotic drugs. This segregation model in an open state may be supported by strong diversity of proteins that are maintained attached to NORs during mitosis, serving as a physic barrier for condensation. Both principal and additional 45S rDNA sites of C. juncea are transcriptionally active, although the additional locus in chromosome 4 presented facultative activity depending upon ribosomal request. Unlike what was previously proposed, once the additional site is activated, it remains in an open configuration throughout the cell cycle, similarly to principal site behavior. Secondary constrictions and nucleolar chromatin are hypermethylated at cytological level, regardless of their activity. The seeming hipomethylated state of 45S rDNA in interphase nucleus and mitotic chromosomes is due to a lower compaction level of nucleolar organizing regions and subsequent low chromatin density.
37

Approche Générale et Efficace des Terpénoïdes Possédant le Squelette Bicyclo[5.3.0]décane : Synthèse de Sesquiterpènes (Aromadendranes, Guaianes et Tri-nor-guaianes) et Approche des Diterpènes.

Calancea, Mihaela 26 September 2008 (has links) (PDF)
La cycloaddition [2+2] du dichlorocétène sur des cycloheptatriènes monosubstitués conduit, après expansion de cycle au diazométhane et déshydrohalogénation, de façon régio- et stéréosélective, à des alpha-chlorotriénones. Ces intermédiaires se sont déjà avérés des synthons particulièrement attractifs pour la synthèse totale de produits naturels possédant le squelette bicyclo[5.3.0]décane. Une cyclopropanation régio- et diastéréosélective avec l'ylure de soufre sur l'alpha-chlorotriénone nous a permis d'élaborer une approche générale des aromadendranes ainsi que la synthèse totale de la (±)-cyclocolorénone. Une réaction d'hydrogénation sélective nous a menés à la synthèse de la (±)-guaia-4,6-diéne-3-one et la synthèse formelle de la (±)-clavukerin A. Grâce à une réaction de Diels-Alder chimio-, régio- et stéréosélective nous avons développé une méthodologie efficace d'accès au squelette tricyclique des daphnanes et tiglianes, en seulement 3 étapes à partir du cycloheptatriène.
38

Porting Linux on ARM-Based Micro-controllers

Tsai, Ju-Chin 30 July 2006 (has links)
More and more embedded systems choose ARM-based micro-controllers as CPU. If no embedded OS built with the system, the application scope will be restricted. Therefore, the need of embedded OS is vital. There are many embedded OS¡¦s in the market, but the embedded Linux has many advantages and is widely accepted. Commercial embedded Linux takes less refund than other embedded OS¡¦s. The kernel and most applications are distributed in GPL open source copyright, and is highly portable to many machine platforms. Presently, the hardware key-technology is highly skilled. The margin of 3C industrial has gone down rapidly. Therefore, people focus on adapting integrated technology to practicality and innovation to make cost down. Developers choose appropriate ARM micro-controllers according to demanding functionality of their products. The microcontroller is not necessary running with Linux distribution. Two approaches can be used to resolve the embedded OS issue. The first approach is porting Linux to the platform without any refund. The second approach is to pay for commercial Linux. Embedded system peripheral devices aim at powerful functionalities and economy. For instance, UART interface is cheap and low data transfer rate. The target board communicates with host via RS-232. RS-232 acts as serial console to play dumb terminal under Linux. Industrial applications often make use of RS-xxx for UART physical transmission layer. For instance, RS-485 applies modbus protocol to build cheap monitor systems. Network transmission is a necessary function, and it generally achieves high data transfer rate application through Ethernet. The UNIX-like network socket has served network application very well. Embedded systems are usually diskless systems. In order to keep permanent data, using flash memory as block disk system is a widely adapted strategy and which operates flash memory through MTD subsystems¡][28]¡^. An MTD subsystem contains two different modules, ¡§user¡¨and ¡§driver¡¨. In the driver module, CFI¡][40]¡^ is applied to probe flash chip, partition it and provide operating function. Flash translation layer and file-system are applied in the user module. MTD BLOCK is used to emulate the flash partitions as block devices which are then mounted into Linux virtual file system¡]VFS¡^with JFFS2 type, designed according to the feature of flash devices. In this thesis, we will describe in detail the procedure of porting Linux to ARM micro-controllers. The motivation of the work is introduced in chapter 1. In chapter 2, we introduce development tools and the main flow of the porting procedure. In chapter 3, we describe the LH79525 platform and the main perepherals on the target board, then introduce the ARM programmer model. In chapter 4, we examine the required knowledge and the important issues for porting ARM Linux. In chapter 5, we describe the details of porting Linux to run with Sharp LH79525, including modifying the key source codes and adjusting kernel configuration for embedding the UART, ethernet MAC, and MTD subsystem. In chapter 6, we do step-by-step validation and apply an integrated application with the LF-314CP temperature controller¡][46]¡^ by law-chain technology for the LH79525 target board running with the ported ARM Linux. In chapter 7, we present some issues for future work and improvement, then make a conclusion for the thesis.
39

Malignant glioma : experimental studies with an estrogen-linked cytostatic

Schoultz, Eva von January 1990 (has links)
Malignant gliomas are the most common primary brain tumors in adults. Patients with these highly malignant tumors have an extremely poor prognosis. The situation with a highly proliferative tumor in a non-proliferating tissue should favor cytostatic treatment but so far the role of conventional chemotherapy has been adjunctive. The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor samples. Some malignant gliomas had high tissue concentrations of estradiol. Low progesterone levels may suggest steroid consumption. Estramustine (EM), a conjugate of estradiol-17ß and nornitrogen mustard had a dose-dependent antiproliferative effect on several human malignant glioma cell lines. At equimolar concentrations the inhibitory effects of the EM complex were clearly more pronounced than those of estradiol and nornitrogen mustard given alone or in combination. A specific binding protein (EMBP) is important for the cytotoxic action of EM. Using a mouse monoclonal antibody and an indirect antibodyperoxidase technique, EMBP was demonstrated in human glioma cells. Significant amounts of EMBP were also detected in human brain tumor tissue by radioimmunoassay. The mean concentrations (ng/mg protein) in 16 astrocytomas (2.6) and 7 meningiomas (5.1) were higher (p&lt;0.001) than in 18 samples of normal brain (0.5). The presence of the specific binding protein may suggest a selective binding and effect of EM in human brain tumor tissue. Human glioma cells displayed significant uptake, retention and metabolism of estramustine phosphate (EMP). After incubation with ^H-EMP a progressive uptake of radioactivity was recorded during 24 hours. Metabolism of parent EMP into estramustine and estromustine, which is a well known part of the metabolic pathway in man, was also demonstrated. A dose- dependent increase in DNA strand breaks was recorded at EMP- concentrations ranging 10-40 yg/ml. The uptake of ®^Rb, used as a tracer for potassium to study ion transport and membrane permeability, was reduced after incubation with EMP. Scanning electron microscopy gave further evidence for membrane damage. According to flow cytometric analyses exponentially growing glioma cells were accumulated in the G2/M stage and the fraction of Gi/Gq was reduced. EM seems to attack malignant cells in a multifocal fashion on several vital functions including the microtubule, the nucleus, and the cell membrane. The intact EM complex may be important for effects related to microtubule function which add to the cytotoxic potential of its constituents. These experimental findings justify further investigations on the role of sex hormones in brain tumor growth and development and of hormone-linked cytostatics in clinical treatment. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1990, härtill 6 uppsatser.</p> / digitalisering@umu
40

Dinâmica nucleolar e a herança epigenética dos genes ribossomais / Nucleolar dinamics and the epigenetic inheritance of ribosomal genes

Natalia de Sousa Teixeira e Silva 25 June 2014 (has links)
O nucléolo é uma organela subnuclear formada pela atividade transcricional dos genes ribossomais 18S-5.8S-26S (rDNA 45S) e consequente biogênese dos ribossomos. A atividade destes genes resulta na região organizadora do nucléolo (NOR), na forma de uma constrição secundária em cromossomos metafásicos. As constrições secundárias se condensam progressivamente durante a mitose e se descondensam ao final da telófase quando a reestruturação do nucléolo se inicia. Genomas que apresentam mais de um locus de rDNA 45S deve apresentar, obrigatoriamente, pelo menos um par de NORs, enquanto os demais loci poderão ou não serem expressos. O controle da expressão dos genes ribossomais e a formação da cromatina nucleolar são modulados por eventos epigenéticos. Embora alguns pontos sobre o funcionamento dos genes ribossomais e a formação do nucléolo estejam bem estabelecidos, questões como o padrão de condensação da cromatina nucleolar durante a mitose, o padrão de funcionamento de sítios adicionais de genes ribossomais, o papel das modificações epigenéticas na dinâmica da cromatina nucleolar e na expressão do rDNA 45S e o mecanismo de herança dos genes ativos, permanecem abertas. A espécie Crotalaria juncea (Leguminosae-Papilionoideae), com 2n=2x=16 cromossomos, que possui um locus de rDNA 45S no braço curto do cromossomo 1, que sempre forma constrição secundária, e um sítio adicional com atividade facultativa no braço curto do cromossomo 4, é um excelente modelo para o estudo destas questões. No contexto apresentado, foram estudadas a dinâmica de condensação das NORs durante o ciclo celular e sua correlação com a atividade dos genes ribossomais, incluindo o locus adicional, e ainda o papel da metilação da citosina do DNA durante estes processos. Os resultados demonstram que a cromatina da região organizadora do nucléolo segrega em um estado descondensado durante a mitose, na forma de constrição secundária, ou seja, tal estrutura não se condensa durante a metáfase e não volta a se distender no início da telófase. Aparentemente, o que causa correlações equivocadas entre a atividade nucleolar e a observação morfológica da constrição secundária na metáfase é a contração forçada da cromatina da NOR causada por agentes antimitogênicos. Este modelo de segregação em um estado aberto pode ser explicado pela descrição de diversas proteínas que permanecem diretamente ligadas ou indiretamente associadas à região da NOR durante a mitose, funcionando como uma barreira física para a compactação. Ambos os sítios, principais e adicionais, do rDNA 45S presentes em Crotalaria juncea apresentam atividade transcricional, embora o locus do cromossomo 4 mostre atividade facultativa. Ao contrário do que foi anteriormente proposto, uma vez ativo, o locus adicional permanece descondensado durante todo o ciclo mitótico, seguindo o mesmo comportamento dos sítios principais. As constrições secundárias e a cromatina nucleolar são hipermetiladas em nível citológico, independentemente de sua atividade. A aparente hipometilação observada no rDNA 45S em cromossomos mitóticos e núcleos interfásicos se deve ao menor grau de compactação da região organizadora do nucléolo e, consequentemente, à baixa densidade de cromatina. / The nucleolus is a subnuclear organelle formed as a result of transcriptional activity of ribosomal RNA genes 18S-5.8S-26S (45S rDNA) and subsequent ribosome biogenesis. This activity forms the nucleolar organizing region (NOR) as a secondary constriction in metaphase chromosomes. The secondary constrictions progressively condense during mitosis and decondense at the end of telophase, when nucleoli start to reassemble. Genomes presenting more than one 45S rDNA locus must have at least one pair of NOR bearing chromosomes, while other loci may be expressed or not. Ribosomal gene expression and nucleolar chromatin assembly are modulated by specific epigenetic events. Although some topics related to rDNA gene activity and nucleolus formation are well understood, questions such as the behavior of nucleolar chromatin condensation during mitosis, standard functions associated with rDNA additional sites, role of epigenetic modifications in nucleolar chromatin and 45S rDNA expression processes, and inheritance mechanism of active genes, remain to be solved. Crotalaria juncea (Leguminosae - Papilionoideae) has 2n=2x=16 chromosomes and carries a 45S rDNA locus at the short arm of chromosome 1, always presenting a secondary constriction, and an additional site with facultative activity at the short arm of chromosome 4, being an excellent model to resolve these questions. Thus, this study aimed to study NOR condensation dynamics during the cell cycle and its correlation with ribosomal gene activity, including the additional locus, while analyzing the role of rDNA cytosine methylation during this process. The results show that NOR chromatin segregate in a decondensed way throughout mitosis, as a secondary constriction. In other words, this structure does not condense during metaphase and the NOR is not reassembled at the beginning of telophase. Misinterpretations relating nucleolar activity with morphological observations of secondary constrictions, appear to be induced by the artificial contraction of NOR chromatin caused by antimitotic drugs. This segregation model in an open state may be supported by strong diversity of proteins that are maintained attached to NORs during mitosis, serving as a physic barrier for condensation. Both principal and additional 45S rDNA sites of C. juncea are transcriptionally active, although the additional locus in chromosome 4 presented facultative activity depending upon ribosomal request. Unlike what was previously proposed, once the additional site is activated, it remains in an open configuration throughout the cell cycle, similarly to principal site behavior. Secondary constrictions and nucleolar chromatin are hypermethylated at cytological level, regardless of their activity. The seeming hipomethylated state of 45S rDNA in interphase nucleus and mitotic chromosomes is due to a lower compaction level of nucleolar organizing regions and subsequent low chromatin density.

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