Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages

Cerebral malaria (CM) is associated with high mortality and morbidity as a certain percentage of survivors suffers from persistent neurological sequelae. The mechanisms leading to death and functional impairments are yet not fully understood. This study investigated biochemical and morphological markers of apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved caspase-3 was detected in the brains of animals with clinical signs of CM and immunoreactivity directly correlated with the clinical severity of the disease. Caudal parts of the brain showed more intense immunoreactivity for cleaved caspase-3. Double-labelling experiments revealed processing of caspase-3 primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic-like morphological profiles in ultrastructural analysis. Further, cleavage of caspase-3 was found in endothelial cells. In contrast to neurons and oligodendrocytes, apoptosis of endothelial cells already occurred in early stages of the disease. Our results are the first to demonstrate processing of caspase-3 in different central nervous system cells of animals with CM. Apoptosis of endothelial cells may represent a critical issue for the development of the disease in the mouse model. Neurological signs and symptoms might be attributable, at least in part, to apoptotic degeneration of neurons and glia in advanced stages of murine CM.

Design and synthesis of constrained azacyclic pyrrolidine analogues of FTY720 as anticancer agents & metal coordination-controlled and bifunctional catalysis toward tertiary β-Ketols

Cette thèse se compose en deux parties: Première Partie: La conception et la synthèse d’analogues pyrrolidiniques, utilisés comme agents anticancéreux, dérivés du FTY720. FTY720 est actuellement commercialisé comme médicament (GilenyaTM) pour le traitement de la sclérose en plaques rémittente-récurrente. Il agit comme immunosuppresseur en raison de son effet sur les récepteurs de la sphingosine-1-phosphate. A fortes doses, FTY720 présente un effet antinéoplasique. Cependant, à de telles doses, un des effets secondaires observé est la bradycardie dû à l’activation des récepteurs S1P1 et S1P3. Ceci limite son potentiel d’utilisation lors de chimiothérapie. Nos précédentes études ont montré que des analogues pyrrolidiniques dérivés du FTY720 présentaient une activité anticancéreuse mais aucune sur les récepteurs S1P1 et S1P3. Nous avons soumis l’idée qu’une étude relation structure-activité (SARs) pourrait nous conduire à la découverte de nouveaux agents anti tumoraux. Ainsi, deux séries de composés pyrrolidiniques (O-arylmethyl substitué et C-arylmethyl substitué) ont pu être envisagés et synthétisés (Chapitre 1). Ces analogues ont montré d’excellentes activités cytotoxiques contre diverses cellules cancéreuses humaines (prostate, colon, sein, pancréas et leucémie), plus particulièrement les analogues actifs qui ne peuvent pas être phosphorylés par SphK, présentent un plus grand potentiel pour le traitement du cancer sans effet secondaire comme la bradycardie. Les études mécanistiques suggèrent que ces analogues de déclencheurs de régulation négative sur les transporteurs de nutriments induisent une crise bioénergétique en affamant les cellules cancéreuses. Afin d’approfondir nos connaissances sur les récepteurs cibles, nous avons conçu et synthétisé des sondes diazirine basées sur le marquage d’affinité aux photons (méthode PAL: Photo-Affinity Labeling) (Chapitre 2). En s’appuyant sur la méthode PAL, il est possible de récolter des informations sur les récepteurs cibles à travers l’analyse LC/MS/MS de la protéine. Ces tests sont en cours et les résultats sont prometteurs. Deuxième partie: Coordination métallique et catalyse di fonctionnelle de dérivés β-hydroxy cétones tertiaires. Les réactions de Barbier et de Grignard sont des méthodes classiques pour former des liaisons carbone-carbone, et généralement utilisées pour la préparation d’alcools secondaires et tertiaires. En vue d’améliorer la réaction de Grignard avec le 1-iodobutane dans les conditions « one-pot » de Barbier, nous avons obtenu comme produit majoritaire la β-hydroxy cétone provenant de l’auto aldolisation de la 5-hexen-2-one, plutôt que le produit attendu d’addition de l’alcool (Chapitre 3). La formation inattendue de la β-hydroxy cétone a également été observée en utilisant d’autres dérivés méthyl cétone. Étonnement dans la réaction intramoléculaire d’une tricétone, connue pour former la cétone Hajos-Parrish, le produit majoritaire est rarement la β-hydroxy cétone présentant la fonction alcool en position axiale. Intrigué par ces résultats et après l’étude systématique des conditions de réaction, nous avons développé deux nouvelles méthodes à travers la synthèse sélective et catalytique de β-hydroxy cétones spécifiques par cyclisation intramoléculaire avec des rendements élevés (Chapitre 4). La réaction peut être catalysée soit par une base adaptée et du bromure de lithium comme additif en passant par un état de transition coordonné au lithium, ou bien soit à l’aide d’un catalyseur TBD di fonctionnel, via un état de transition médiée par une coordination bidenté au TBD. Les mécanismes proposés ont été corroborés par calcul DFT. Ces réactions catalytiques ont également été appliquées à d’autres substrats comme les tricétones et les dicétones. Bien que les efforts préliminaires afin d’obtenir une enantioselectivité se sont révélés sans succès, la synthèse et la recherche de nouveaux catalyseurs chiraux sont en cours.

Shakespeare's tragedy of King Lear;

Lear, the aging King of Britain, has chosen to lay aside the care of kingship and divide his kingdom between his three daughters. Their share is to be determined by their love for him. Two daughters speak with grandiose expressions of love while the third daughter finds nothing to say. The courts disinherit the third daughter, Cordelia. Much treachery, murder, and deceit ensued and Lear and Cordelia are captured and sentenced to death.

Disentangling the impact of seroconversion age and set-point viral load on ART-free HIV survival

Thesis (Master's)--University of Washington, 2016-06

Use of complementary and alternative medicine and quality of life: changes at the end of life

The purpose of this study was to compare the physical, psychological and social dimensions associated with quality-of-life outcomes over the last year of life, between advanced cancer users and nonusers of complementary and alternative medicine. One hundred and eleven patients were identified through Queensland Cancer Registry records, and followed up every four to six weeks until close to death using standardized protocols. Outcome measures were symptom burden, psychological distress, subjective wellbeing, satisfaction with conventional medicine and need for control over treatment decisions. At the initial interview, 36 (32%) participants had used complementary/ alternative medicine the previous week; mainly vitamins, minerals and tonics and herbal remedies. Among all participants, 53 (48%) used at least one form of complementary/ alternative medicine over the study period. Only six (11%) visited alternative practitioners on a regular basis. Overall, complementary/ alternative medicine users reported higher levels of anxiety and pain, less satisfaction with conventional medicine and lower need for control over treatment decisions compared with nonusers. These differences tend to change as death approaches. A more rigorous assessment of complementary/ alternative medicine use, psychological distress, pain and subjective wellbeing among patients with advanced cancer is needed in the clinical setting.

Economic Impact of E.coli 0111 Outbreak in 1995 in Australia

Increased incidence of food-borne illnesses is a matter of significant concern for the community and the government alike. An outbreak of E.coli O111 that occurred in Australia in 1995 affected 200 people of whom 22 developed HUS while one person died. This study analyses the economic costs of the outbreak. The total cost of the outbreak is estimated to be A$5.61 million. Productivity loss represented the highest percentage of outbreak costs (66%) due to death, disability and chronic illness. The direct medical costs contributed 33%. The estimated loss could be even higher if all costs could be quantified. Nevertheless, the findings provide an idea to the policy maker regarding the extent and nature of the damage that could result from an outbreak. The severity of the damage warrants allocation of necessary resources to prevent such occurrences.

Are interactions in Gray's Reinforcement Sensitivity Theory proximal or distal in the prediction of religiosity: a test of the joint subsystems hypothesis

Gray's Reinforcement Sensitivity Theory (RST) consists of the Behavioural Activation System (BAS) which is the basis of Impulsivity, and Behavioural Inhibition System (BIS) which is the basis of Anxiety. In this study, Impulsivity and Anxiety were used as distal predictors of attitudes to religion in the prediction of three religious dependent variables (Church attendance, Amount of prayer, and Importance of church). We hypothesised that Impulsivity would independently predict a Rewarding attitude to the Church and that Anxiety would independently predict an Anxious attitude to the church, and that these attitudes would be proximal predictors of our dependent variables. Moreover, we predicted that interactions between predictors would be proximal. Using structural equation modelling, data from 400 participants supported the hypotheses. We also tested Eysenck's personality scales of Extraversion and Neuroticism and found a key path of the structural equation model to be non-significant. (C) 2003 Elsevier Ltd. All rights reserved.

The nomenclature of style: Brutalism, Minimalism, art history and visual style in architecture journals

The naming of styles or movements is a basic mechanism of the architectural journals. The announcement of new tendencies, groups or philosophies, gives a journal its character as ‘news’, and if such terms are taken up in general discourse this demonstrates the prescience of the editor and enhances the repute of the journal. The announcement of phenomenon such as ‘critical regionalism’ or ‘deconstructivism’ referred architectural developments to a context in socio-politics or philosophy, and thus aimed to provide at least an initial resistance to their understanding as the formal styles which they quickly became. A different strategy, or occasion, which this paper will discuss, is where the name of an architectural moment is given in the traditional form of an art historical style. Here the nomenclature of style and a certain attitude to form is introduced as the starting point for a more open ended critical inquiry. Two examples of this strategy will be given. The first is Peter Reyner Banham and the Architecture Review’s promotion of ‘Brutalism’ as an anti-aesthetic which took its conceptual form from early twentieth century art movements, particularly Futurism. The second, identified with Architectural Design in the 1990’s is ‘Minimalism’, a term describing a strand of the visual arts of the 1960’s which can be understood as an attempt to nuance and add seriousness to the present rampant nostalgia for the style of the architecture of the 1960’s.

Organochlorine and heavy metal concentrations in blubber and liver tissue collected from Queensland (Australia) dugong (Dugong dugon)

Tissue samples of liver and blubber were salvaged from fifty-three dugong (Dugong dugon) carcasses stranded along the Queensland coast between 1996 and 2000. Liver tissue was analysed for a range of heavy metals and blubber samples were analysed for organochlorine compounds. Metal concentrations were similar in male and female animals and were generally highest in mature animals. Liver concentrations of arsenic, chromium, iron, lead, manganese, mercury and nickel in a number of individual animals were elevated in comparison to concentrations previously reported in Australian dugong. Dieldrin, DDT (and its breakdown products) and/or heptachlor epoxide were detected in 59% of dugong blubber samples. In general, concentrations of organochlorines were similar to those reported in dugong 20 years earlier, and were low in comparison to concentrations recorded from marine mammal tissue collected elsewhere in the world. With the exception of lead, the extent of carcass decomposition, the presence of disease or evidence of animal starvation prior to death did not significantly affect dugong tissue concentrations of metals or organochlorines. The results of the study suggest that bioaccumulation of metals and organochlorine compounds (other than dioxins) does not represent a significant risk to Great Barrier Reef dugong populations, particularly in the context of other pressures associated with coastal development and other anthropogenic activities. (c) 2004 Elsevier Ltd. All rights reserved.

FATORES ANTECEDENTES NA ATITUDE DE ALUNOS DE GRADUAÇÃO FRENTE AO PLÁGIO

A crescente preocupação com a desonestidade acadêmica e seus possíveis impactos para as organizações e sociedade tem requerido especial atenção. Diversos estudos indicam que a tecnologia e, em especial, a Internet, pode ocasionar o aumento da desonestidade acadêmica e, em especial, da prática de plágio. Tipos de desonestidade acadêmica são listados pela literatura como sendo a fraude, o plágio, o auxílio externo e a fraude eletrônica. Dentre estes tipos, o plágio está se tornando a maior preocupação entre as instituições de ensino superior em comparação com os demais (LOVETT-HOOPER et al., 2007). A existência da intencionalidade do indivíduo é uma característica central nos estudos sobre plágio, caracterizado como sendo a consequência de uma decisão individual. Do ponto de vista da Theory of Planned Behavior - TPB (Teoria do Comportamento Planejado), de Ajzen (1991), a ação do indivíduo é orientada por crenças (comportamentais, normativas e de controle) que influenciam sua atitude em relação a algo, que por sua vez leva à racionalização da intenção que influenciará o comportamento do indivíduo. Esta pesquisa tem como objetivo identificar os fatores antecedentes que influenciam a atitude em relação ao plágio dentre estudantes brasileiros do ensino superior, modalidade à distância. Um sistemático mapeamento da literatura sobre o tema identificou mais de 300 artigos e convergiu para um número de 74 artigos considerados fundamentais. Destes, foi gerado um modelo de análise que define como preditores da Atitude Positiva em relação ao Plágio (a partir de determinadas influências recebidas, o indivíduo considerará a prática do plágio), os seguintes construtos: Posicionamento Moral, Normas sociais e Aspectos situacionais. Para análise do modelo, utilizou-se uma pesquisa do tipo survey quando, nesta fase foram encaminhados, 1800 questionários, a alunos de diferentes períodos do curso de Administração, de uma Universidade particular. A taxa de retorno dos questionários foi de 28,95%, totalizando 353 questionários válidos. Para a análise dos dados utilizou-se a modelagem por equações estruturais com algoritmo Partial Least Squares (PLS), técnica adequada para um número reduzido de observações e quando não se pode assumir parâmetros para a distribuição. Os principais resultados encontrados nesta pesquisa foram: 41,8% da variablidade da Atitude explicada do modelo de Atitude Positiva frente ao plágio; e a identificação de seis construtos significantes associados ao modelo, sendo: Entendimento (-0,102, p<0,05), Expectativa de Valor (0,243, p<0,001), Facilidade (0,108, p<0,05), Situação de Pressão (0,126, p<0,01), Relativismo (0,272, p<0,001) e Severidade e Possibilidade de Punição (-0,255, p<0,001).

A ANÁLISE DAS CAPACIDADES DE SOBREVIVÊNCIA DE PEQUENOS NEGÓCIOS NAS CIDADES DE ITANHAÉM E MONGAGUÁ: ESTUDO MULTICASO DE PEQUENAS EMPRESAS

O presente trabalho traz uma análise das capacidades de sobrevivência de três micro e pequenas empresas (MPEs) do ramo alimentício de doces de banana, estabelecidas na Região Metropolitana da Baixada Santista, especificamente nas cidades de Itanhaém e Mongaguá. Essas capacidades se construíram fundamentadas em dois pressupostos: efeito do gestor e o efeito da localidade, que podem ser determinantes para a sobrevivência e o desempenho de MPEs. A pesquisa tem por objetivo geral identificar as características do gestor e os fatores da localidade que influenciam a sobrevivência das três MPEs estudadas. Para alcançar o objetivo geral foram traçados os seguintes objetivos específicos: identificar as características da gestão que foram propulsoras da sobrevivência das três MPEs estudadas; identificar os recursos da localidade que foram propulsores à sobrevivência das três MPEs; verificar a existência de outros fatores da gestão e da localidade que possam ter influenciado a sobrevivência das MPEs no longo prazo. O estudo teve como expectativa contribuir para o aprofundamento da reflexão sobre o tema concernente às capacidades de sobrevivência dos pequenos negócios. A pesquisa bibliográfica esteve centrada no encadeamento de tópicos teóricos de forma a construir fundamentos necessários sobre as influências do gestor e da localidade na sobrevivência das pequenas empresas, noções necessárias para se atingir o objetivo geral. Para alcançar os objetivos propostos, a investigação, de caráter descritivo e indutivo, foi desenvolvida por meio de estudo multicaso, compreendendo pesquisa documental, observações e entrevistas semi-estruturadas, preliminar e de profundidade, tendo como sujeitos os gestores, os funcionários, os fornecedores e os clientes das três MPEs. Os resultados indicam que há fatores importantes do efeito gestor e do efeito localidade influenciando a sobrevivência das empresas locus da pesquisa. Os resultados apontaram fatores como acesso ao amplo mercado, atitude frente à tecnologia, a presença de laço forte e laço fraco, entre outros considerados importantes influenciadores na sobrevivência das empresas estudadas. Os resultados abrem perspectivas de estudos mais aprofundados que possam proporcionar e criar alternativas e programas para melhorar o desempenho e a sobrevivência das MPEs.(AU)

O CONCÍLIO DOS DEUSES NO SALMO 82 E NA LITERATURA UGARÍTICA

O salmo 82, desde o início de seus versos, mostra o ambiente no qual se situa seu cântico: o concílio dos deuses. Nessa reunião celestial, um deus se levanta e acusa os outros deuses de negligenciar os mais fracos. Os deuses são condenados à morte e o deus que preside a assembleia dos deuses nomeia outro deus para governar todas as nações da terra. A cena do concílio dos deuses e os decretos promulgados nesses encontros no mundo celestial são recorrentes em outras literaturas do Antigo Oriente Próximo. Na literatura religiosa de Ugarit, antiga cidade cananeia, El, Baal, Asherah e outras deidades se reúnem para discutir assuntos pertinentes à ordem do cosmos. Nesse sentido, o Salmo 82 compartilha elementos da religiosidade e da cultura dos cananeus.

Corpos mortos e vivos: as cerimônias mortuárias e as representações da morte entre católicos brasileiros

Esta pesquisa procurou descrever, analisar e comparar as cerimônias mortuárias e as representações coletivas de católicos brasileiros da morte e do luto. Tivemos por objetivo estudar os sistemas simbólicos desenvolvidos em várias sociedades, começando com as culturas tribais, passando depois para o cristianismo dos primeiros séculos, antes da instauração do processo de institucionalização que originou o cristianismo católico e durante ele. Analisamos as práticas e representações católicas relacionadas com a morte e o morrer, na Idade Média, Idade Moderna e Contemporânea, tanto na Europa como no Brasil. O objetivo também foi apresentar os ritos mortuários como formas de dar sentido à vida, de reforçar e manter a coesão social, em que indivíduos vivem constantemente os desarranjos gerados pela presença da morte que arrebata um dos seus semelhantes provocando um desequilíbrio social. Ao realizar tal pesquisa sobre os rituais mortuários católicos, a meta consistiu em avançar um pouco mais no conhecimento sobre um fenômeno social religioso nem sempre abordado pelos pesquisadores: a morte do crente, as práticas mortuárias dos grupos católicos, seus hábitos e discurso quanto ao morto, dentro de um cenário brasileiro que se torna cada vez mais urbano e secularizado.(AU)

The genius of Erasmus Darwin

The Genius of Erasmus Darwin provides insight into the full extent of Erasmus Darwin's exceptional intellect. He is shown to be a major creative thinker and innovator, one of the minds behind the late eighteenth-century industrial revolution, and one of the first, if not the first, to perceive the living world (including humans) as part of a unified evolutionary scenario. The contributions here provide contextual understandings of Erasmus Darwin's thought, as well as studies of particular works and accounts of the later reception of his writings. In this way it is possible to see why the young Samuel Taylor Coleridge was moved to describe Darwin as 'the first literary character in Europe, and the most original-minded man'. Erasmus Darwin, Charles Darwin's grandfather, was one of the leading intellectuals of eighteenth-century England. He was a man with an extraordinary range of interests and activities: he was a doctor, biologist, inventor, poet, linguist, and botanist. He was also a founding member of the Lunar Society, an intellectual community that included such eminent men as James Watt and Josiah Wedgwood. Contents: Introduction; Setting the scene, Jonathan Powers; Prologue 'Catching up with Erasmus Darwin in the New Century', Desmond King-Hele. Section 1: Medicine: Physicians and physic in 17th and 18th century Lichfield, Dennis Gibbs; Dr Erasmus Darwin MD FRS (1731–1802): England's greatest physician?, Gordon Cook; William Pale (1743–1805) and James Parkinson (1755–1824): two peri-Erasmatic thinkers (and several others), Christopher Gardner-Thorpe; The vertiginous philosophers: Erasmus Darwin and William Charles Wells on vertigo, Nicholas Wade. Section 2: Biology: The Antipodes and Erasmus Darwin: the place of Erasmus Darwin in the heritage of Australian literature and biology, John Pearn; Erasmus Darwin on human reproductive generation: placing heredity within historical and Zoonomian contexts, Philip Wilson; All from fibres: Erasmus Darwin's evolutionary psychobiology, C.U.M. Smith; Two special doctors: Erasmus Darwin and Luigi Galvani, Rafaella Simili. Section 3: Education: But what about the women? The lunar society's attitude to women and science and to the education of girls, Jenny Uglow; The Derbyshire 'Darwinians': the persistence of Erasmus Darwin's influence on a British provincial literary and scientific community, c.1780–1850, Paul Elliot. Section 4: Technology: Designing better steering for carriages (and cars); with a glance at other inventions, Desmond King-Hele; Mama and papa: the ancestors of modern-day speech science, Philip Jackson; Negative and positive images: Erasmus Darwin, Tom Wedgwood and the origins of photography, Alan Barnes; Section 5: Environment: Erasmus Darwin's contributions to the geological sciences, Hugh Torrens; The air man, Desmond King-Hele; Erasmus Darwin, work and health, Tim Carter; Section 6: Literature: The progress of society: Darwin's early drafts for the temple of nature, Martin Priestman; The poet as pathologist: myth and medicine in Erasmus Darwin's epic poetry, Stuart Harris; 'Another and the same': nature and human beings in Erasmus Darwin's doctrines of love and imagination, Maurizio Valsania. Epilogue: 'One great slaughter-house the warring world': living in revolutionary times, David Knight; Coda: Midlands memorabilia, Nick Redman; Appendix: The Creation of the Erasmus Darwin Foundation and Erasmus Darwin House, Tony Barnard; Index.

The French Communist Party and the Algerian war : an ideological turning point?

The subject-matter of this thesis is the interaction between the Parti Communiste Français and the National Liberation struggle in Algeria , and the debate that ensued within the Party itself.For a detailed study of the Party ' s line on the war, PCF publications were contrasted with the texts produced by the opposition.Three main axes were identified crystallising discussion within the Party during the Algerian war: The relationship between France and Algeria and the Party ' s attitude to the French nation; The nature of the Algerian nation and its genesis; France's military engagement in Algeria.The dichotomy between the Party's national and internationalist responsibilities is shown to have resolved itself by the fundamental integration of the PCF into the political structure and value system of the French Republic. This study demonstrates the birth of a substantial internal opposition to the PCF during the Algerian war.