Дисертації з теми "868 b"

This study intends to examine a ninth century anti-Christian polemic work written by the great Muslim litterateur al-Jaḥiẓ. The historical background of the treatise is presented within the contexts of the early `Abbasid regime (750-900), the Christian communities of the time, the impact of the translation movement, the rise and development of polemic discourse between Muslims and Christians, and the life and works of al-Jaḥiẓ. The study provides the manuscript background of the letter along with a translation supplemented by the work of Joshua Finkel. The analysis of the work is limited to one section, which reflects al-Jaḥiẓ's most original contribution to antiChristian Muslim polemic. The actual analysis is focused thematically in order to better ascertain al-Jaḥiẓ's portrayal of Christians before his Muslim readers.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-10-29T13:42:36Z No. of bitstreams: 1 Maria Isabel Magalhães Santos Perfil das....pdf: 1133942 bytes, checksum: bcc264f7cc24ec022846c05825fd31cf (MD5)
Made available in DSpace on 2014-10-29T13:42:36Z (GMT). No. of bitstreams: 1 Maria Isabel Magalhães Santos Perfil das....pdf: 1133942 bytes, checksum: bcc264f7cc24ec022846c05825fd31cf (MD5) Previous issue date: 2014
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Introdução: A doença causada pelo vírus da hepatite B (HBV) é um problema de saúde pública mundial. No Brasil, o sistema único de saúde (SUS) tem disponibilizado drogas antivirais para o tratamento de hepatite B crônica há mais de 10 anos, mas um sistema para o monitoramento e avaliação de resistência a estas drogas ainda não está disponível. Objetivo: Este estudo teve como objetivo determinar o perfil de mutações do HBV associadas com a resistência aos análogos de nucleos(t)ídeos entre 81 pacientes com infecção crônica pelo HBV: virgens de tratamento para hepatite B e tratados com diferentes análogos de nucleosídeos e nucleotídeos, no Hospital Professor Edgar Santos (HUPES-UFBA)- Salvador-BA. Metodologia: O HBV-DNA foi isolado de amostras de soro, amplificado por nested-PCR, utilizando-se primers deduzidos da região flaqueadora da domínio rt do gene P e sequenciados (ABI Prism 3730, Applied Biosystems, EUA). Duas a seis sequências de cada isolado foram alinhados e os sítios conflitantes foram resolvidos usando o software CLC Main Workbench v. 5.0 por inspeção visual dos eletroferogramas. As sequências consenso tinham um tamanho de 1032 pb (compreendendo os aminoácido 1-344 da rt). Estas sequências foram submetidas ao banco de dados HBVrt DB (Stanford University, EUA) para a análise de cada mutação de acordo com o genótipo e tratamento. Resultado: O genótipo A1 foi o mais prevalente (85,2%) seguido pelo genótipo A2 (4,9%) F (6,2%) e C1, D2 e D4 (1,2% cada). Seis pacientes (7 %) apresentaram mutações de resistência para LAM, ETV, TDF: dois com o padrão L180M + M204V e quatro com padrões diversos (L80I + L180M + M204I ;L80V + L180M + M204V; M204I; A194T). Todas estas mutações foram associadas ao genótipo A (quatro A1 e dois A2). Além disso, foi encontrado um paciente com HBV genótipo C típico do leste da Ásia. Destes pacientes, dois foram virgens de tratamento e quatro tinham histórico de tratamento para HIV ou HBV. Foram detectadas quatro mutações no gene S (três casos com a mutação sI195M e um a mutação sW196L) associadas às mutações do domínio rt do gene P, correspondendo à uma taxa de 6% de mutações de escape vacinal. A prevalência das mutações de resistência às drogas antivirais variou de acordo com a duração do tratamento e com o nível da barreira genética da droga utilizada. Neste estudo, foi encontrada uma forte associação entre a ocorrência de mutações de resistência do HBV e positividade para o AgHBe, co-infecção com o HIV e histórico de tratamento para HBV e/ou HIV. Conclusão: Antes da terapia ser iniciada é extremamente importante o monitoramento da carga viral e a identificação destas mutações para suportar decisões clinicas sobre o manejo dos pacientes e prevenir a emergência de vírus multi- resistentes.
Introduction: Hepatitis B virus (HBV) infection is a public health issue. The Brazilian public health system (SUS) has provided antiviral drugs for chronic hepatitis B treatment for over 10 years, but a system for monitoring for drug-related resistance mutations is not available. Objective: This study aims to determine the presence of HBV mutations associated with resistance to nucleos(t)ide analogs among 81 patients with chronic HBV infection-naïve and treated from University Hospital Professor Edgard Santos, Salvador-BA (HUPES-UFBA). Methods: Briefly, HBV-DNA was PCR amplified with primers deduced from the flanking of the rt domain at the HBV P gene and sequenced using ABI Prism 3730 (Applied Biosystems, USA). From two to six forward and reverse sequences of each isolate were assembled and conflicting sites were resolved using software CLC Main Workbench v. 5.0 by visual inspection of the electropherograms. Consensus sequence extended 1032 bp and encompassed the entire rt domain (from amino acid 1 to 344). Those sequences were submitted to the HBV drug resistance database (HBVrt DB, Stanford University, USA) to retrieve each mutation according to genotype and treatment. Results: HBV genotype A1 (85.2%) was the most prevalent followed by genotype A2 (4.9%), F (6.2%), and C1, D2 and D4 (1.2% each). Six patients (7%) exhibited resistance mutations to LAM, ETV and TDF: two with patterns L180M + M204V and four with other different patterns: L80I + L180M + M204I; L80V + L180M + M204V; M204I; A194T. All of these mutations were present in patients with genotype A (four A1 and two A2). Furthermore, this study found one patient with genotype C, common in East Asian. Of these patients, two were naïve and four had a history of treatment for HIV or HBV. In addition, four mutations in gene S (sI195M three cases with the mutation and one with the mutations W196L) associated with mutations in the rt domain of the P gene were detected, corresponding to a rate of 6% of vaccine escape mutations. Prevalence of drug-related resistance mutations varied according to treatment duration and the level of genetic barrier for the drugs used. Conclusion: In this study a strong association was found between the occurrence of HBV resistance mutations and HBeAg positivity, co-infection with HIV and a history of treatment for HBV and / or HIV. Once the drug therapy is initiated it is extremely important to monitor viral load and identify those mutations in order to support clinical decisions about patient management and also to prevent the emergence of multidrug-resistant viruses.

Background: Our aim was to determine if changes in ubiquitin are correlated with proteins known to be affected directly or indirectly by the ubiquitin-proteasome pathway. For example, the intermediary kinase of the NFκβ pathway IKK is tagged directly by ubiquitin, aiding its degradation within the large, self-compartmentalised protease called the 26S proteasome. IKK degradation allows the release of NFκβ (an indirect consequence of ubiquitination) that then translocates into the nucleus to initiate the transcription of survival factors such as cIAP2, BCL-XL, BFL1, FLIP, IL-8, and TNF-α. Methods: Lyophilised baboon endometrial tissues from the University of Illinois at Chicago (UIC) and from women undergoing laparoscopy from the Sydney South West Area of Health Service (SSWAHS) were processed for RNA extraction and analysis. Immunohistochemical studies were also conducted on formalin fixed baboon and human endometrial tissues from UIC and from the Sydney West Area Health Service (SWAHS). Results: IKKα immunostaining were elevated in the cytoplasm of glands during late follicular phase and stromal cells during menses in the baboon, whilst proteasome was elevated in the nucleus of glands and stroma at menses, as well as within the glandular cytoplasm of endometriotic tissues. Comparable levels of Iκβα exists throughout the menstrual cycle of the eutopic endometrium, whilst a reduced glandular nuclear Iκβα was seen in endometriotic tissues of the animal model. TNF-α was increased within stromal cells at menses but was equivalent between the eutopic and ectopic endometrium. Ubiquitin was similar between LF and mid luteal phase of eutopic glands and stroma, as well as between eutopic and ectopic endometrium at mid luteal. IKKβ and NFκβ levels were alike within eutopic and ectopic tissues throughout the menstrual cycle. In women however, IKKα, IKKβ, Iκβα and NFκβ had comparable levels within all cell types and cycle phases, whilst a greater proteasome immunostaining was seen in the nucleus of eutopic stromal cells at secretory phase, as well as in the nucleus of ectopic stromal cells at proliferative phase. However, the nucleus of stromal cells and glandular cytoplasm of endometriotic tissues both had lower proteasome levels during the secretory phase. Conclusions: In this study, IKKα had a greater potential to activate the p65 subunit of NFκβ in ectopic stromal cells than IKKβ and TNF-α did not seem to be correlated with greater free ubiquitin expression in endometriosis in the baboon. This suggests that IKKα is a likely candidate for ectopic stromal cell survival in endometriosis in the animal model but this is unlikely to be mediated by the ubiquitin NFκβ pathway. Similarly, in women with endometriosis a different pathway to NFκβ is potentially responsible for a greater ectopic cell survival potential, however an increased patient cohort is required to definitively ascertain the involvement of IKKα in the future.

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma. Patients who fail conventional therapy (~50%) have a poor prognosis and few treatment options. It is essential to understand the underlying biological processes, the progression of the disease, and utilize this information to develop new therapeutics. DLBCL patients with high C-MYC expression have a poor prognosis and new therapeutics for these patients are needed. This thesis describes work testing the hypothesis that JQ1, which can indirectly inhibit C-MYC in some tumors, can be used as an effective treatment for DLBCL. Some tumors have an unknown mechanism causing high C-MYC expression, leading me to investigate the underlying mechanisms. YY1 is a transcriptional regulator of c- Myc and has been implicated in DLBCL and as a potential regulator of the germinal center (GC) reaction. DLBCL arises from GC cells or post-GC cells. I tested the hypothesis that YY1 regulates the GC reaction. SMURF2 is an E3-ubiquitin ligase for YY1 and a tumor suppressor for DLBCL. I was interested in examining the mechanism underlying the suppression of DLBCL by SMURF2 leading to the hypothesis that SMURF2 regulates the GC. This thesis shows JQ1 leads to cell death and cellular senescence in human DLBCL cells. I conclude that BRD4 inhibition by JQ1 or derivatives could provide a new therapeutic avenue for DLBCL patients. I also show loss of YY1 perturbs the GC by decreasing the dark zone and increasing apoptosis. Finally I show modulation of SMURF2 does not affect the GC, suggesting SMURF2 utilizes a different mechanism to act as a tumor suppressor and may not modulate YY1 in the context of the GC.

Studien är en litteraturstudie som jämför tre läroböcker i gymnasiekursen Svenska B och hur dessa behandlar skönlitteratur. Främst är det läroböckernas elevfrågor till skönlitteraturen som ligger till grund för undersökningen. Om man ser till elevfrågornas utformning behandlar de tre läroböckerna skönlitteratur på likartade sätt. Eleverna tränas i att koppla skönlitteraturen både till det samhälle de lever i och det samhälle texterna uppkom i. Det finns dock en skillnad i hur läroböckerna presenterar författarna till de utvalda texterna. Spannet löper mellan att behandla författarna som viktiga kulturpersoner med personliga och långa presentationer och att endast beskriva dem i termer som författare av tidstypiska texter.

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Carbapenemase-producing Klebsiella pneumoniae is an enterobacteria, commonly associated with resistance to multiple antibiotics. The presence of multidrug resistance phenotype is an important challenge in the epidemiological point of view, regarding the therapeutic management and infection control. A retrospective observational study was conducted in a tertiary-care hospital in Goiânia, Brazil, in the period of 2006 to 2011 to investigate the carbapenemases phenotypes, the in vitro activity of tigecycline and polymyxin B and determine the risk factors associated with infection or colonization by carbapenemase-producing K. pneumoniae. The serine-carbapenemase production was detected by modified Hodge test and combined disk test with boronic acid; metallo-β-lactamases - MβL by double-disk synergy test with imipenem and EDTA; extended spectrum β-lactamases - ESBL by combined disk with cefotaxime and ceftazidime with and without clavulanate, and plasmid AmpC type by combined disk with boronic acid and cefoxitin. The in vitro activity of tigecycline and polymyxin B against the enzyme-producing isolates was assessed using the broth microdilution method and for not β-lactam antimicrobials by disk diffusion and semi-automated system. The association between independent risk factors and colonization or infection by carbapenemase-producing K. pneumoniae was determined by logistic regression analysis. The carbapenem resistance was found in 8.06% of all isolates K. pneumoniae and 6.90% were carbapenemase producers. Among carbapenemases producers isolates, 77.78% were KPC type β-lactamase, 37.04% demonstrated the simultaneous production of plasmid AmpC β-lactamase and KPC, 29.63% associated with MβL or ESBL and KPC, 11.11% MβL/ESBL/KPC and 7.41% MβL/ESBL/KPC/plasmid AmpC. High percentages of not β-lactams antimicrobial resistance were observed, ranging from 61.10% - 74.70% to fluoroquinolones and 52.10% - 54.30% to aminoglycosides. Polymyxin B showed limited activity against the carbapenemase-producing K. pneumoniae (35.70%) and tigecycline was the only antimicrobial that inhibited 75.0% of these multidrug-resistant strains. The independent risk factors for K. pneumoniae carbapenemase producers were prolonged hospitalization (p = 0.031), previous use of carbapenems (p = 0.041) and exposure to more than three antimicrobials (p = 0.034). The detection of multidrug- resistant carbapenemase-producing isolates and the knowledge of different resistance mechanisms can result in significant impact on the treatment outcomes and strategies for infection control and prevention.
Klebsiella pneumoniae produtora de carbapenemase é uma enterobactéria, comumente associada à resistência aos múltiplos antimicrobianos. A presença deste fenótipo de multirresistência consiste em um importante desafio do ponto de vista epidemiológico, quanto ao manejo terapêutico e ao controle de infecção. Um estudo observacional retrospectivo foi conduzido em um hospital público terciário em Goiânia, Go, Brasil, no período entre 2006 e 2011, para investigar os fenótipos de carbapenemases, a atividade in vitro da tigeciclina e polimixina B e determinar os fatores de risco associados à infecção ou colonização por K. pneumoniae produtora de carbapenemase. A presença de serina carbapenemase foi detectada por meio do teste de Hodge modificado e disco combinado com ácido borônico; metalo-β-lactamases – MβL por sinergismo de disco duplo com imipenem e EDTA; β-lactamases de espectro estendido – ESBL, através do disco combinado com cefotaxima e ceftazidima com e sem ácido clavulânico e AmpC plasmidial por disco combinado com ácido borônico e cefoxitina. A atividade in vitro da tigeciclina e polimixina B foi avaliada através do método de microdiluição em caldo e dos antimicrobianos não β-lactâmicos por disco-difusão e sistema semiautomatizado. A associação entre fatores de risco independentes e colonização ou infecção foi determinada através de regressão logística. A resistência aos carbapenêmicos foi verificada em 8,06% do total de K. pneumoniae e a atividade de carbapenemase em 6,90%. Dentre os isolados produtores de carbapenemases, 77,78% foram considerados β-lactamase tipo KPC, 37,04% demonstraram a produção simultânea de AmpC plasmidial e KPC, 29,63% associação com MβL ou ESBL e KPC, 11,11% MβL/ESBL/KPC e 7,41% MβL/ESBL/KPC/AmpC plasmidial. Altas taxas de resistência aos antimicrobianos não β-lactâmicos foram observadas, variando de 61,10% - 74,70% para fluoroquinolonas e 52,10% - 54,30% para aminoglicosídeos. A polimixina B apresentou baixa atividade in vitro contra estes isolados (35,70%) e a tigeciclina foi o único antimicrobiano que inibiu 75,0% dos mesmos. Os fatores de risco independentes para K. pneumoniae produtora de carbapenemase foram a internação prévia prolongada (p = 0,031), uso prévio de carbapenêmicos (p = 0,041) e exposição a mais de três antimicrobianos (p = 0,034). A detecção de isolados produtores de carbapenemase multirresistentes e o conhecimento dos diferentes mecanismos de resistência podem resultar em significante impacto nos resultados terapêuticos e estratégias de controle de infecção e prevenção.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
The present study aimed to determine the prevalence of Babesia equi and B. caballi in horses from the northern region of the State of Rio Grande do Sul, examining the maintenance practices and identifying the principal factors involved in transmission and infection rates. There were collected 380 blood samples and tested with ELISA and Indirect immunofluorescence (RIFI) for B. equi and for B. caballi was used competitive ELISA. The sample number was statistically representative for the equine population of the state. Testing positive for B. equi by ELISA and RIFI were 31,6% and 35,8%, respectively, of the samples examined. The prevalence of B. caballi was 0,86%. The concordance between tests was considered high as shown by the Kappa index of 0,86%. There was not observed a statistically significant difference (p<0,05) between the sex, age and breed of the horses. According to the present study the northern region of the state of Rio Grande do Sul can be characterized as an area of enzootic instability for B. equi and B. caballi, offering risks of economic losses due to babesiosis outbreaks, especially in sensible animals introduced from indene areas, horse trade and participating in events (as rodeos, auction sales, and others) or even in animals born in the region. Analyzing the questionnaires, the maintaining systems and the purposes of the equine use were the factors that had influence on the prevalence of equine babesiosis.
O trabalho teve por objetivo determinar a preval?ncia da Babesia equi e B. caballi em eq?inos da regi?o Norte do Estado do Rio Grande do Sul bem como conhecer as pr?ticas de manejo adotadas e identificar os principais fatores que est?o envolvidos na sua transmiss?o e preval?ncia. Coletaram-se 380 amostras de sangue, n?mero estatisticamente representativo para a popula??o de eq?inos em estudo, as quais foram analisadas por meio do teste de ELISA e pela rea??o de imunofluoresc?ncia indireta (RIFI) e para a B. caballi foi utilizado o Elisa competitivo. Do total das amostras, 31,6% e 35,8% foram positivas para B. equi ao teste de ELISA e RIFI respectivamente, sendo que, a preval?ncia de B. caballi foi de apenas 0,86%. A concord?ncia entre os testes foi considerada ?tima, atrav?s do ?ndice Kappa de 0,87. N?o foi constatada nenhuma diferen?a significativa estatisticamente (p<0,05) entre o sexo, ra?as e faixas et?rias dos eq?inos. De acordo com o presente estudo a regi?o Norte do Estado do Rio Grande do Sul ?, portanto caracterizada como uma ?rea de instabilidade enzo?tica para B. equi e B. caballi oferecendo riscos reais de ocorr?ncia e perdas econ?micas causadas por surtos de babesiose causada por B. equi e B. caballi especialmente em animais sens?veis, procedentes de ?reas indenes, com?rcio de animais, participa??o em eventos (esportivos ou recreativos dentro ou fora da Regi?o ou Estado) ou mesmo entre animais nascidos naquela regi?o. Ap?s a an?lise dos question?rios, os sistemas e as finalidades da cria??o foram os ?nicos fatores que influenciaram na preval?ncia das babesioses equinas.

A key effect of human papillomavirus (HPV) infection is to disrupt the normal cell cycle in order to subvert the cellular DNA replication machinery. Morphologically, condylomata induced by high and low risk HPV types cannot be distinguished and many studies have shown that the pattern of viral gene expression is similar in condylomata caused by both high risk and low risk HPV types. Detailed morphological study of cell cycle protein expression has not previously been performed on condylomata infected with low risk HPV types. The findings presented suggest that the mechanisms employed by low risk HPV6 or HPV11 to subvert cellular functions in condylomata acuminata are similar to those employed by high risk HPVs, with the exception of cyclin D1 and p53 protein over-expression. The differences in p53 expression and cyclin D1 expression seen between high and low risk HPV infection, reflect the known differences between high and low risk types and are in agreement with the known differences between high risk and low risk E6 and E7 proteins. PHK transduction studies demonstrated HPV E6 and E7 induce changes in cell cycle protein expression and that there are differences in cell cycle abrogation between HPV6 and HPV16. Disruption of the p53-MDM2 interaction can lead to activation of the p53 pathway. HPV infected lesions almost always contain wild-type p53. The binding of HPV E6 to p53, and its subsequent targeting for degradation, prevents activation of the p53 pathway in HPV infected cells. Cells over expressing HPV genes were treated with Nutlin-3, a MDM2-small molecule antagonist. The findings presented suggest treatment with Nutlin-3 induces cell cycle arrest in cells expressing HPV16 E7 and HPV6 E6 and HPV6 E7. This suggests a potential role for Nutlin-3 in the treatment of HPV infected cells.

This thesis is a detailed examination of the logico-semantic system propounded by the English philosopher and theologian William of Ockham (c.1287 – c.1347). It provides a reinterpretation of Ockham's account of mental content and mental-language semantics, as well as of his theory of consequential goodness. It does so from the standpoint of an inferentialist theory of meaning, in rejection of previous attempts made from the standpoint of internalist and externalist theories of mental content. Chapter 1 ('The Scientic Status of Logic') provides an account of Ockham's understanding of logic as a rational, practical, ostensive science. Chapter 2 ('The Received Interpretation') presents and casts doubt upon the arguments put forward by the defenders of both externalist and internalist construals of Ockham's semantic theory. Chapter 3 ('An Inferentialist Construal') presents the central tenets of a inferentialist theory of meaning. In order to show how Ockham's system can be understood within such a semantic paradigm, we will have to set out at least three things. First, Chapter 4 ('Ockham's Propositionalism') argues that the mature Ockham actually embraced a propositionalist theory of meaning. Second, Chapter 5 ('Obligationes and the Normativity of Asserting') seeks to prove that such a theory of meaning can only be properly understood against the normative background provided by his theory of obligationes. Finally, Chapter 6 ('Consequences') argues that Ockham's theory of consequential goodness is materialist, not formalist. That is to say, that the goodness of a certain kind of consequence ultimately depends upon the meaning of its propositional parts, rather than upon its structure. It is then shown that all remaining kinds of consequences (syllogisms included) are to understood with respect to these material inferences. The main sources of this research are Ockham's Ordinatio, his Summa logicae, and his Quodlibeta septem. As regards the inferentialist theory of meaning, Robert Brandom's Making it Explicit (1994) and Wilfrid Sellars 'Inference and Meaning' (1953) were essential to this research.

Il s'agit, dans ce travail, d'une etude contrastive au niveau phonetico-phonologique entre le francais et le ding du zaire. Elle commence par quelques generalites sur le bilinguisme, sur les apports de la linguistique a l'enseignement des langues (notamment etrangeres) ainsi que sur la problematique linguistique en afrique noire en matiere de politiques linguistiques. L'essentiel du travail consiste en une comparaison des elements phonetiques, phonologiques et graphiques de ces deux langues dans le but de faire ressortir les differences susceptibles de provoquer des interferences chez les ding qui vont apprendre ou qui ont deja appris le francais, mais aussi les similitudes sur lesquelles on peut s'appuyer pour elaborer toute methode d'enseignement du francais aux ding ou toute methode de correction de ces interferences. Les resultats ainsi obtenus ayant ete confirmes d'une certaine maniere par l'analyse des erreurs commises par les eleves ding en francais, ont permis d'organiser vers la fin de l'etude quelques techniques de correction de ces interferences sur les plans phonique et graphique ; techniques que l'on peut, sous certaines conditions, etendre a l'ensemble du zaire
This work is a contrastive study of french and ding in a phonetico-phonological level. It starts with generalities on bilingualism, on the contribution of linguistics in language teaching (and mainly foreign languagues) and also on the linguistic problems in black africa in the field of linguistic politicies. The work consists essentially in a comparison of phonetic, phonologic and graphic elements of both languages aiming to make clear discrepancies capable to create interferences among ding speakers who are going to learn or have already learned french, as well as similarities from which we can drive teaching methods of french for ding speakers or methods of correction of interferences. The results have been confirmed at some extent by analysis of french errors made by ding pupils. Subsequently, by the end of this work, some correction techniques of the interferences on phonic and graphic levels have been elaborated, that is, techniques that we can apply to other zairean locutors under some precise conditions

Este trabalho analisa o desempenho jornalístico dos semanários portugueses Expresso e o Jornal e das revistas semanais brasileiras Istoé e Veja no período das Assembleias Constituintes, de 1975/76 e de 1987/88, em Portugal e no Brasil, respectivamente. A imprensa é concebida como integrante da cultura política e social dos países. Nesta perspectiva, é geradora de opiniões e visões do mundo, porém, ao mesmo tempo, reflete a dinâmica social e política. Portanto, é a síntese de um determinado tempo histórico, como também contribui para a formação desse mesmo momento histórico, ao criar referenciais de ideologias e de mentalidades na opinião pública. Tal estudo apresenta-se em perspectiva comparada entre os periódicos, analisados sob o ponto de vista das culturas políticas e históricas dos dois países. Por conseguinte, aborda as características dos processos de democratização em Portugal e no Brasil, nos ambientes em que floresceram os marcos constitucionais das democracias nos anos setenta e oitenta.

Obesidade é fator de risco para a hipertensão arterial e os mecanismos envolvidos nesta doença não são totalmente esclarecidos. Camundongos C57BL/6J e transgênicos com com deleção em neurônios e glia da via inflamatória do receptor toll-like-NFκB foram submetidos à dieta hiperlipídica (HL) por 8 e 15 semanas e avaliados parâmetros metabólicos, pressão arterial, frequência cardíaca, atividade do sistema nervoso autônomo, fatores inflamatórios e neuropeptídeos no hipotálamo e no tronco encefálico. Os camundongos expostos HL desenvolveram hipertensão arterial acompanhada de disfunção autonômica e aumento de CART no DMH. Os animais transgênicos quando submetidos à dieta HL desenvolveram um quadro de obesidade, porém não apresentaram hipertensão arterial e disfunção autonômica. Além disso, o grupo de animais HL aumentou o RNAm de CCL5 no hipotálamo e de CD86 no tronco-encefálico e a densidade de microglia no NTS caudal. Os resultados sugerem novos mecanismos para a hipertensão e disfunção autonômica secundárias à ingestão de dieta hiperlipídica mostrando o papel do CART o DMH e o envolvimento da via inflamatória do TLR-NFκB em neurônios e glia nos mecanismos desta patologia.
Obesity is a risk factor for high blood pressure and the mechanisms involved in this disease are not fully clarified. C57BL/6J and transgenic mice with toll-like-NFκB receptor inflammatory- pathway deletion in neurons and glia were fed with high-fat diet (HL) for 8 or 15 weeks and assessed metabolic parameters, blood pressure, heart rate, autonomic nervous system activity, inflammatory factors and neuropeptides in the hypothalamus and brainstem. The HL mice developed hypertension accompanied with autonomic dysfunction and increased CART in DMH. Transgenic animals when submitted to HL diet developed obesity, but not showed high blood pressure and autonomic dysfunction. In addition, HL animals had increased CCL5 mRNA in hypothalamus, CD86 mRNA in brainstem and micróglia density in caudal NTS. The results suggest new mechanisms for hypertension and autonomic dysfunction secondary to intake of high-fat diet by showing CART role in DMH and the involvement of the inflammatory pathway TLR-NFκB in neurons and glia.

Les protéines de chocs thermiques (HSP) sont des protéines très conservées au cours de l’évolution des espèces. Ce sont des chaperons moléculaires impliqués dans le repliement des protéines nouvellement synthétisée ou dénaturées. Les HSP sont fortement exprimées dans les cellules cancéreuses, où elles contribuent à la résistance à l’apoptose et aux chimiothérapies. Parmi les HSP, HSP110 est jusqu’à présent peu étudiée. Cependant, HSP110 a été récemment associée au lymphome diffus à grandes cellules B (DLBCL). Le DLBCL est le syndrome lympho-prolifératif agressif le plus fréquent chez l’adulte (30% des lymphomes non-Hodgkinien). Il existe trois principaux sous-type de DLBCL : le type B activé (ABC-DLBCL), le type centre germinatif (GC-DLBCL) et le type lymphome primaire du médiastin (PMBL). La forme activée est celle associée au plus mauvais pronostic clinique. Bien que les thérapies classiques de chimiothérapies associées aux anti-CD20 aient permis d’augmenter le pronostic de survie des patients souffrant de l’ABC-DLBCL, nombreux sont ceux qui développent des résistances ou qui ne répondent pas aux traitements. L’identification de nouvelles cibles thérapeutiques est donc nécessaire.Mes travaux présentent un rôle de HSP110 dans l’activité d’une voie oncogénique du lymphome ABC-DLBCL. En effet, ces travaux démontrent une forte expression d’HSP110 dans les échantillons patients ABC-DLBCL. De plus, ces travaux in vitro sur des lignées ABC-DLBCL montrent une interconnexion entre HSP110 et Myd88 L265P, protéine mutée responsable de l’activation de la voie NF-kB. HSP110 stabilise l’oncogène Myd88 L265P, et participe à l’amplification de la voie NFkB dans le lymphome ABC, voie responsable de la survie et de la prolifération des cellules ABC-DLBCL.Par le biais d’une collaboration, nous avons pu obtenir récemment des inhibiteurs de HSP110. Ainsi, mon travail à également consisté aux criblages in vitro de ces inhibiteurs pour évaluer leur capacité d’inhibition de HSP110. Deux composés ont alors été identifiés comme candidats inhibiteurs d’HSP110. Je me suis ensuite intéressé à l’utilisation de ces inhibiteurs in vitro dans l’ABC-DLBCL. Mes résultats tendent à montrer que ces inhibiteurs ont une action similaire à ceux observés lors de l’inhibition de HSP110 par siRNA ou shRNA.Mes travaux de thèse présente donc HSP110 comme une cible moléculaire potentielle de l’ABC DLBCL
Heat shock proteins (HSPs) are highly conserved protein across species, and are expressed in all cell type. HSPs are molecular chaperones involved in the folding of newly synthesized or denaturated proteins. HSPs are overexpressed in cancer cells, where they contribute to cancer resistance to chemotherapies. Among HSPs, roles and functions of HSP110 are less described. Interestingly, HSP110 was recently associated with lymphoma aggressiveness in Diffuse Large B Cell Lymphoma (DLBCL). DLBCL is the most lymphoproliferative disease diagnosed in adult (30% of Non-Hodgkin Lymphoma). Three main subtypes of DLBCL are described: Activated-B-Cell lymphoma (ABC-DLBCL), Germinal Center lymphoma (GC-DLBCL), and Primary Mediastinal B Lymphoma (PMBL). ABC-DLBCL is the most aggressive form associated with a poor prognosis. Even if R-CHOP therapies had improve patient’s survival over the last decades, most of patients experiences relapses or treatment resistances. New molecular target are now necessary to treat efficiently these subtypes.My PhD work has highlighted the role of HSP110 in the NFkB signaling pathway, which is an oncogenic pathway in ABC-DLBCL. First, we show that HSP110 is overexpressed in ABC-DLBCL patient sample. We also show an interaction between HSP110 and Myd88 L265P, that is an oncogenic protein responsible for NFkB pathway activation. Consequently, HSP110 stabilizes Myd88 L265P, leading to a sustain NFkB pathway activation in lymphoma cells, and promoting ABC-DLBCL cell survival and proliferation.Finally, our team recently characterized the first known HSP110 inhibitors. I took the opportunity to test these putative inhibitors in my study. My results suggest that these compounds have similar effects than siRNA or shRNA inhibition of HSP110 on ABC-DLBCL survival. This result provide a ground for future in vivo testing of chemical inhibitors of HSP110.In conclusion, my work highlight HSP110 as a potential therapeutic target in ABC-DLBCL

International Telemetering Conference Proceedings / October 26-29, 1992 / Town and Country Hotel and Convention Center, San Diego, California
Due to the vast amount of data required to be collected for design/performance analysis of operational and development systems, there has evolved a real requirement for a high-speed, large capacity, data collection/record system in a small Flight/Ruggedized package. This need is realized by several user communities and factors which include the evolution of small operational vehicles (airborne, land and UAV’s), the desire of weapons manufacturers/integrators to be independent from the vehicle during vehicle integration, and a general need for a field/airborne, reliable portable data collection system for intelligence gathering, operational performance verification and on-board data processing. In the Air Defence community, the need for a ruggedized record system was highlighted after Desert Storm, in which the operational performance of the Patriot Missile was questioned and data collection was not performed to support the performance. The Aydin Vector Division in conjunction with the prime contractor, has come up with a solution to this problem which utilizes a commercially available helical scan 8mm data storage unit. This solution provides a highly reliable record system, ruggedized for airborne and field environments and a low price in comparison with the more traditional approaches currently offered. This paper will describe the design implementation of this small ruggedized, flight worthy Data collection system deemed the ATD-800. It will also discuss the performance and limitations of implementing such a system, as well as provide several applications and solutions to different operational environments to be encountered. Additionally, the paper will conclude with several product enhancements which may benefit the flight test, operational and intelligence communities in the future.

Abstract The neutral B mesons B0 and B0s can under go flavor changing oscillations due to interactions by the weak force. Experiments which measure the frequency of these state transitions produce extremely noisy results that are difficult to analyse. A method for extracting the frequency of B mesons oscillations using the continuous wavelet transform is developed here. In this paper the physics of B meson mixing is related, leading to the derivation of a function describing the expected amount of mixing present in B0 and B0s meson decays. This result is then used to develop a new method for analysing the underlying frequency of oscillation in B mixing. An introduction to wavelet theory is provided in addition to details on interpreting daughter wavelet coefficient diagrams. Finally, the effectiveness of the analysis technique produced, referred to as the Template Fitting Method, is investigated through an application to data generated using Monte Carlo methods.

The current study revisits the causal link between finite cognitive capacity and infant perseveration originally put forth by Berger (2004) wherein perseverative errors resulted from a limited amount of cognitive resources. A dynamic systems perspective was used to test the interaction of a limited cognitive capacity and task difficulty by manipulating the contextual layout of Berger’s stair A-not-B paradigm (i.e. from 90-degrees to 180-degrees). Two groups of infants, differing in walking experience but not in biological age, were presented the task of descending A-side 5 consecutive times and to B-side on the 6th trial. Perseveration was not seen in either experience group; however, inexperienced walkers exhibited slower decision-making and stair descent on B-trial than their experienced counterparts. Results suggest that task difficulty alone is not enough to elicit perseveration but is a considerable factor when investigating the error.

PhD (Agric) (Food Science and Technology)
Department Food Science and Technology
In recent years, there has been a lot of interest in orange fleshed sweet potato (OFSP) [Ipomoea batatas (L.) Lam] cultivar, as a cheaper source of vitamin A. In Southern Africa, reports have shown that one in every three children has deficiency in vitamin A. This study investigated the variations in β-carotene (vitamin A precursor) content among selected OFSP cultivars grown in Limpopo Province, South Africa. In addition, the study investigated the effects of location on functional properties, total carotenoids and antioxidant profile of the sweet potato flour as well as their physicochemical, functional and nutritional properties. Four (4) sweet potato cultivars [Dagga, Bophelo, Impilo (orange fleshed) and Mvuvhelo (cream fleshed)] were obtained from two locations, namely, University of Venda (Univen) agricultural experimental farm and Tshiombo irrigation scheme (Tshiombo) and analysed for pasting, functional, physicochemical and nutritional properties. The sweet potato flours from these two locations were also analysed by computed tomographic (CT) scans for flour particle density. Mineral and microstructure of OFSP flours were analysed by scanning electron microscope (SEM). All measurements, except the tristimulus L* a* b* and other colour parameters from five replicates, were performed in triplicate. Statistical analysis was performed using a one-way analysis of variance and means were separated using Duncan’s multiple range test; P < 0.05 was considered to be statistically significant. Pearson’s correlation coefficients were used to determine the correlation among functional, physicochemical, nutritional and pasting properties of sweet potato flour. β-carotene content varied significantly between the two locations from 70.98 ± 0.8 μg/g (Tshiombo) to 86.09 ± 2.0 μg/g (Univen), among cultivars from 1.71 ± 0.0 μg/g (Mvuvhelo) to 201.50 ± 1.0 μg/g (Dagga) and among orange fleshed (Dagga, Bophelo and Impilo) flours from 28.38 ± 0.2 μg/g (Impilo) to 201.50 ± 1.0 μg/g (Dagga). There was a similar trend in the contents of α-carotene to that of β-carotene from the two locations, which ranged from 0.63 ± 0.0 mol/L (Tshiombo) to 1.01 ± 0.0 mol/L (Univen). Mvuvhelo had significantly the lowest α-carotene content (0.50 ± 0.0 mol/L) and Impilo the highest (1.28 ± 0.0 mol/L). The total carotenoids was highest for Impilo (7.56 μg/g) and lowest for Mvuvhelo (1.33 ± 0.1 μg/g) but did not vary significantly (P > 0.05) between ii the locations. The antioxidant activity, based on 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging activity, was significantly highest in Bophelo (63.37 ± 0.8 mMAAE ml-1) and lowest in Dagga (26.93 ± 1.4 mMAAE ml-1) flours. The ferric reducing antioxidant power (FRAP) varied significantly across the locations and among the cultivars and ranged from 14.45 ± 0.3 μMTE ml-1 (Tshiombo) to 17.40 ± 1.1 μMTE ml-1 (Univen). FRAP was significantly highest in Impilo (21.12 ± 2.1 μMTE ml-1) and lowest in Mvuvhelo (8.16 ± 2.0 μMTE ml-1). Total carotenoid content positively correlated with DPPH (0.486*), FRAP (0.830**), β-carotene (0.370*), and α-carotene (0.424*). The antioxidant content and the radical scavenging activity were significantly correlated (0.563**). Vitamin A content was significantly lowest (6.88 ± 0.38 μg/g retinol) in Dagga flour and highest (7.97 ± 0.25 μg/g) in Impilo flour. Protein content varied significantly across the two locations and ranged from 4.23% (Tshiombo) to 7.16% (Univen). Dagga had significantly the lowest (3.47%) protein content while Impilo had the highest (7.53%). The fat content of the flours varied significantly between the two locations ranging from 0.63% (Tshiombo) to 1.01% (Univen). The protein content was positively correlated 0.594** and 0.421* to vitamin A and fat contents respectively. The Bophelo colour luminosity was significantly lower (L* 76.2) than the other two OFSP, Dagga (L* 83.51) and Impilo (L* 82.07). Bophelo a* (14.09) also differed significantly across all sweet potato cultivars. All cultivars differed significantly in b* values. Colour intensity (ΔE*) ranged from 15.87 to 38.48 for Mvuvhelo and Bophelo, respectively. Chroma ranged from 87.52 to 84.95 for Dagga and Mvuvhelo respectively. Total starch content was significantly different in all sweet potato cultivars and ranged from 244.07 μg/100 g (Bophelo) to 325.04 mg/g (Dagga). Resistant starch differed significantly in all sweet potato cultivars ranging from 1.21 μg/100 g dwb (Bophelo) to 7.07 μg/100 g dwb (Impilo). Ash content was significantly different in all cultivars and ranged from 3.17% (Dagga) to 3.79% (Bophelo). Water holding capacity (WHC) varied significantly across the two locations and ranged from 1.44 g H2O/g DM (Tshiombo) to 1.72 g H2O/g DM (Univen). Bophelo had significantly the lowest (1.27 g H2O/g DM) WHC and Impilo the highest (1.99 g H2O/g DM). The ash content negatively correlated to total starch (-0.928**) but positively iii correlated to WHC (0.654**). Peak viscosity differed significantly across all cultivars under study and ranged from 126.54 RVU (Bophelo) to 302.36 RVU. (Dagga). There was significant difference in trough viscosity across all cultivars ranging from 55.97 RVU (Impilo) to 280.78 RVU (Dagga). There were significant differences in the final viscosity across all cultivars ranging from 78.99 RVU (Impilo) to 319.26 (Dagga). Peak time viscosity varied significantly across all cultivars ranging from 3.87 min (Impilo) to 8.47 min. (Bophelo). Dagga cultivar had significantly the highest pasting temperature (94.16oC) and Bophelo the lowest (77.75oC). The setback viscosity was significantly highest 51.10 RVU (Mvuvhelo) and lowest 23.01 RVU (Impilo). All cultivars from the two locations consistently showed high potassium content ranging from 0.46% (Impilo) to 1.38% (Dagga) as compared to other minerals such as magnesium, calcium and chlorine which ranged from 0.16% (Impilo) to 0.34%. (Dagga). The CT scans revealed that there was a possibility of evaluating the effect of location on the density of granules of sweet potato flour and also the inherent differences in granular distribution of various sweet potato cultivars. SEM revealed high amounts of potassium, magnesium and chlorine. A profile of physicochemical and functional properties of flour of some of the OFSP cultivars produced in Limpopo province, South Africa has been drawn. This study also highlights the nutritional quality of the flour from four sweet potato cultivars and provides a ranking of flour to help the producers in the selection process. Bophelo flour was ranked the highest in terms of β- and, α-carotenes, total carotenoids and antioxidant capacity while Impilo was ranked highest in terms of functional properties and ash content. This study has highlighted significant differences in a number of parameters measured among the sweet potato cultivars. Therefore, in order to derive the maximum benefit from aIn recent years, there has been a lot of interest in orange fleshed sweet potato (OFSP) [Ipomoea batatas (L.) Lam] cultivar, as a cheaper source of vitamin A. In Southern Africa, reports have shown that one in every three children has deficiency in vitamin A. This study investigated the variations in β-carotene (vitamin A precursor) content among selected OFSP cultivars grown in Limpopo Province, South Africa. In addition, the study investigated the effects of location on functional properties, total carotenoids and antioxidant profile of the sweet potato flour as well as their physicochemical, functional and nutritional properties. Four (4) sweet potato cultivars [Dagga, Bophelo, Impilo (orange fleshed) and Mvuvhelo (cream fleshed)] were obtained from two locations, namely, University of Venda (Univen) agricultural experimental farm and Tshiombo irrigation scheme (Tshiombo) and analysed for pasting, functional, physicochemical and nutritional properties. The sweet potato flours from these two locations were also analysed by computed tomographic (CT) scans for flour particle density. Mineral and microstructure of OFSP flours were analysed by scanning electron microscope (SEM). All measurements, except the tristimulus L* a* b* and other colour parameters from five replicates, were performed in triplicate. Statistical analysis was performed using a one-way analysis of variance and means were separated using Duncan’s multiple range test; P < 0.05 was considered to be statistically significant. Pearson’s correlation coefficients were used to determine the correlation among functional, physicochemical, nutritional and pasting properties of sweet potato flour. β-carotene content varied significantly between the two locations from 70.98 ± 0.8 μg/g (Tshiombo) to 86.09 ± 2.0 μg/g (Univen), among cultivars from 1.71 ± 0.0 μg/g (Mvuvhelo) to 201.50 ± 1.0 μg/g (Dagga) and among orange fleshed (Dagga, Bophelo and Impilo) flours from 28.38 ± 0.2 μg/g (Impilo) to 201.50 ± 1.0 μg/g (Dagga). There was a similar trend in the contents of α-carotene to that of β-carotene from the two locations, which ranged from 0.63 ± 0.0 mol/L (Tshiombo) to 1.01 ± 0.0 mol/L (Univen). Mvuvhelo had significantly the lowest α-carotene content (0.50 ± 0.0 mol/L) and Impilo the highest (1.28 ± 0.0 mol/L). The total carotenoids was highest for Impilo (7.56 μg/g) and lowest for Mvuvhelo (1.33 ± 0.1 μg/g) but did not vary significantly (P > 0.05) between ii the locations. The antioxidant activity, based on 2, 2-diphenyl-1picrylhydrazyl (DPPH) free radical scavenging activity, was significantly highest in Bophelo (63.37 ± 0.8 mMAAE ml-1) and lowest in Dagga (26.93 ± 1.4 mMAAE ml-1) flours. The ferric reducing antioxidant power (FRAP) varied significantly across the locations and among the cultivars and ranged from 14.45 ± 0.3 μMTE ml-1 (Tshiombo) to 17.40 ± 1.1 μMTE ml-1 (Univen). FRAP was significantly highest in Impilo (21.12 ± 2.1 μMTE ml-1) and lowest in Mvuvhelo (8.16 ± 2.0 μMTE ml-1). Total carotenoid content positively correlated with DPPH (0.486*), FRAP (0.830**), β-carotene (0.370*), and α-carotene (0.424*). The antioxidant content and the radical scavenging activity were significantly correlated (0.563**). Vitamin A content was significantly lowest (6.88 ± 0.38 μg/g retinol) in Dagga flour and highest (7.97 ± 0.25 μg/g) in Impilo flour. Protein content varied significantly across the two locations and ranged from 4.23% (Tshiombo) to 7.16% (Univen). Dagga had significantly the lowest (3.47%) protein content while Impilo had the highest (7.53%). The fat content of the flours varied significantly between the two locations ranging from 0.63% (Tshiombo) to 1.01% (Univen). The protein content was positively correlated 0.594** and 0.421* to vitamin A and fat contents respectively. The Bophelo colour luminosity was significantly lower (L* 76.2) than the other two OFSP, Dagga (L* 83.51) and Impilo (L* 82.07). Bophelo a* (14.09) also differed significantly across all sweet potato cultivars. All cultivars differed significantly in b* values. Colour intensity (ΔE*) ranged from 15.87 to 38.48 for Mvuvhelo and Bophelo, respectively. Chroma ranged from 87.52 to 84.95 for Dagga and Mvuvhelo respectively. Total starch content was significantly different in all sweet potato cultivars and ranged from 244.07 μg/100 g (Bophelo) to 325.04 mg/g (Dagga). Resistant starch differed significantly in all sweet potato cultivars ranging from 1.21 μg/100 g dwb (Bophelo) to 7.07 μg/100 g dwb (Impilo). Ash content was significantly different in all cultivars and ranged from 3.17% (Dagga) to 3.79% (Bophelo). Water holding capacity (WHC) varied significantly across the two locations and ranged from 1.44 g H2O/g DM (Tshiombo) to 1.72 g H2O/g DM (Univen). Bophelo had significantly the lowest (1.27 g H2O/g DM) WHC and Impilo the highest (1.99 g H2O/g DM). The ash content negatively correlated to total starch (-0.928**) but positively iii correlated to WHC (0.654**). Peak viscosity differed significantly across all cultivars under study and ranged from 126.54 RVU (Bophelo) to 302.36 RVU. (Dagga). There was significant difference in trough viscosity across all cultivars ranging from 55.97 RVU (Impilo) to 280.78 RVU (Dagga). There were significant differences in the final viscosity across all cultivars ranging from 78.99 RVU (Impilo) to 319.26 (Dagga). Peak time viscosity varied significantly across all cultivars ranging from 3.87 min (Impilo) to 8.47 min. (Bophelo). Dagga cultivar had significantly the highest pasting temperature (94.16oC) and Bophelo the lowest (77.75oC). The setback viscosity was significantly highest 51.10 RVU (Mvuvhelo) and lowest 23.01 RVU (Impilo). All cultivars from the two locations consistently showed high potassium content ranging from 0.46% (Impilo) to 1.38% (Dagga) as compared to other minerals such as magnesium, calcium and chlorine which ranged from 0.16% (Impilo) to 0.34%. (Dagga). The CT scans revealed that there was a possibility of evaluating the effect of location on the density of granules of sweet potato flour and also the inherent differences in granular distribution of various sweet potato cultivars. SEM revealed high amounts of potassium, magnesium and chlorine. A profile of physicochemical and functional properties of flour of some of the OFSP cultivars produced in Limpopo province, South Africa has been drawn. This study also highlights the nutritional quality of the flour from four sweet potato cultivars and provides a ranking of flour to help the producers in the selection process. Bophelo flour was ranked the highest in terms of β- and, α-carotenes, total carotenoids and antioxidant capacity while Impilo was ranked highest in terms of functional properties and ash content. This study has highlighted significant differences in a number of parameters measured among the sweet potato cultivars. Therefore, in order to derive the maximum benefit from a given cultivar careful selection of sweet potato cultivars would be necessary.

Das Mammakarzinom ist weltweit eine der häufigsten Malignomerkrankung der Frau. Im fortgeschrittenen Stadium der Erkrankung entwickeln bis zu 75 % der Patientinnen ossäre Metastasen. Basierend auf der Erkenntnis, dass GnRH-Analoga in vitro die Migration und Invasion von Mammakarzinomzellen während der Kokultur mit humanen Osteoblasten bzw. der Osteoblasten-ähnlichen Zellreihe MG-63 hemmen, sollten in dieser Arbeit die dem zugrundeliegenden molekularen Mechanismen näher betrachtet werden. Es ist bekannt, dass GnRH-Analoga in vielen verschiedenen GnRH-Rezeptor exprimierenden Tumorzelllinen die Wachstumsfaktor- und Wachstumsfaktorrezeptor-Expression beeinflussen und somit z.B. antiproliferative oder Apoptose-induzierende Effekte vermitteln. In dieser Arbeit wurde die humane Mammakarzinomzelllinie MCF-7 mit der osteoblasten-ähnlichen Zellreihe MG-63 kokultiviert. Zu bestimmten Zeitpunkten erfolgte die Behandlung der Mammakarzinomzellen mit drei verschiedenen GnRH-Analoga. Dem GnRH-I-Agonisten Triptorelin, dem GnRH-I-Antagonisten Cetrorelix und dem GnRH-II-Agonisten [D-Lysin]-GnRH-II. Neben einer nicht-kokultivierten Kontrolle jeder Zelllinie wurde eine nicht behandelte Kokulturkontrolle mitgeführt. Nach 48 h (bzw. nach 72 h od. 96 h) wurde der Versuch beendet und die mRNA-Expression von EGF, EGFR, TGF-beta und TGFBRI und -II in MCF-7 und MG-63 mittels PCR bestimmt. Zudem wurde die mRNA-Expression von EGF, EGFR und TGF-beta auch nach längerer Kokultur- und Behandlungszeit sowie unter Stressbedingungen beobachtet. Es hat sich gezeigt, dass es weder in MG-63 noch in MCF-7 signifikante Expressionsunterschiede von EGF, EGFR und TGF-beta im Vergleich zur Kokulturkontrolle gab. Dies hat sich auch weder im Zeitverlauf noch unter Stressbedingungen geändert. In MG-63 konnte man ebenfalls keine Expressionsunterschiede der TGFB-Rezeptoren beobachten. Dagegen konnte erstmals gezeigt werden, dass alle drei GnRH-Analoga die mRNA-Expression des TGFBR-I und -II während der Kokultur mit der osteoblasten-ähnlichen Zellreihe MG-63 signifikant hemmen. Während man in anderen Gewebetypen bereits eine verminderte Expression von TGFBR-I und -II nach Behandlung mit GnRH-Analoga nachweisen konnte, ist dies erstmals in einer Mammakarzinomzelllinie gelungen. Desweiteren kann man aus den vorliegenden Ergebnissen den Schluss ziehen, dass die verminderte Expression der TGFB-Rezeptoren eine Rolle in der bereits nachgewiesene GnRH-Analoga-vermittelten Migrations- und Invasionshemmung spielt.

abstract: The core element of this research paper is an analysis of the B-flat minor prelude and fugue BWV 867. The author’s analysis is then compared with the main contributors to Bach’s analytical studies. An understanding of the work’s structure, together with its motivic and harmonic details, help the performer develop an interpretive approach to the work. Significant Bach scholars, including David Ledbetter and Peter Williams, are used as the source for the additional works to be studied. These scholars also mention close associates of Bach who offer additional insight into his music: Kirnberger and Weiss. The paper includes a brief discussion of the opening chorus fugue BWV 64, instrumental prelude to the cantata BWV 106, chorale prelude BWV 721, and Tombeau sur la Mort de Mr Comte de Logy by Weiss, as they relate to the B-flat minor prelude and fugue. In addition, the analysis provides materials on how the elements of the work relate to the Doctrine of Affections. From the B-flat minor prelude and fugue, the harmonic progressions and figuration are examined from the point of view of the Doctrine. The research also examines the fugue subject, with its unusual leap of a minor 9th, to its structural connection to the opening chorus fugue of BWV 64, and its ties to the Doctrine. Through the analysis of the B-flat minor prelude and fugue and a comparison to works by Bach that are stylistically connected to this work, the author offers insights into the music and its relationship to works that have a sacred text association.
Dissertation/Thesis
Doctoral Dissertation Music 2020