Glycosylation and Glycodiversification in Polyketide Antibiotics: Unraveling Biosynthetic Steps in Nogalamycin Formation

Soil-dwelling Streptomyces bacteria are known for their ability to produce biologically active compounds such as antimicrobial, immunosuppressant, antifungal and anticancer drugs. S. nogalater is the producer of nogalamycin, a potential anticancer drug exhibiting high cytotoxicity and activity against human topoisomerases I and II. Nogalamycin is an anthracycline polyketide comprising a four-ring aromatic backbone,a neutral deoxy sugar at C7, and an amino sugar attached via an O–C bond at C1 and a C–C bond between C2 and C5´´. This kind of attachment of the amino sugar is unusual thus making the structure of the compound highly interesting. The sugar is also associated with the biological activity of nogalamycin, as it facilitates binding to DNA. Furthermore, the sugar moieties of anthracyclines are often crucial for their biological activity. Together the interesting attachment of the amino sugar and the general reliance of polyketides on the sugar moieties for bioactivity have made the study of the biosynthesis of nogalamycin attractive. The sugar moieties are typically attached by glycosyltransferases, which use two substrates: the donor and the acceptor. The literature review of the thesis is focused on the glycosylation of polyketides and the possibilities to alter their glycosylation patterns. My own thesis work revolves around the biosynthesis of nogalamycin. We have elucidated the individual steps that lead to its rather unique structure. We reconstructed the whole biosynthetic pathway in the heterologous host S. albus using a cosmid and a plasmid. In the process, we were able to isolate new compounds when the cosmid, which contains the majority of the nogalamycin gene cluster, was expressed alone in the heterologous host. The new compounds included true intermediates of the pathway as well as metabolites, which were most likely altered by the endogenous enzymes of the host. The biological activity of the most interesting new products was tested against human topoisomerases I and II, and they were found to exhibit such activities. The heterologous expression system facilitated the generation of mutants with inactivated biosynthetic genes. In that process, we were able to identify the functions of the glycosyltransferases SnogE and SnogD, solve the structure of SnogD, discover a novel C1-hydroxylase system comprising SnoaW and SnoaL2, and establish that the two homologous non-heme α-ketoglutarate and Fe2+ dependent enzymes SnoK and SnoN catalyze atypical reactions on the pathway. We demonstrated that SnoK was responsible for the formation of the additional C–C bond, whereas SnoN is an epimerase. A combination of in vivo and in vitro techniques was utilized to unravel the details of these enzymes. Protein crystallography gave us an important means to understand the mechanisms. Furthermore, the solved structures serve as platforms for future rational design of the enzymes.

As questões de género nos materiais pedagógico-didáticos ao serviço do ensino de História e Geografia

Mestrado, Ensino de História e Geografia no 3.º Ciclo do Ensino Básico e Secundário, 7 de Julho de 2016, Universidade dos Açores (Relatório de Estágio).

Concepções de licenciandas em pedagogia sobre o ensino de ciências nos ciclos I e II da educação básica

O conteúdo de ciências no Ensino Fundamental dos ciclos I e II é ministrado por um professor polivalente com formação em Pedagogia. Sua formação deve possibilitar uma visão global do fenômeno educativo, o que implica a construção de conhecimentos múltiplos e contextualizados, porém com pouco aprofundamento. Este trabalho objetiva identificar as opiniões e dificuldades de licenciandos de Pedagogia a respeito dos conteúdos de Ciências nos dois primeiros ciclos do Ensino Fundamental, mediado por dois questionamentos: Com relação aos conteúdos de ciências ministrados no I e II ciclos, você os considera fácil ou difícil? Sendo solicitado que justificasse sua resposta; De acordo com seus conhecimentos sobre ciências, cite as principais dificuldades que você teria (tem/teve) em ensinar ciências nos ciclos I e II. Participaram do estudo 29 licenciandas da turma de Ensino das Ciências Naturais II do Curso de Pedagogia da Universidade Federal do Rio Grande do Norte. Com relação ao questionamento referente à consideração dos conteúdos de ciências, 52% das licenciandas consideraram fácil, 31% difícil e 17% não responderam a questão. Foram identificadas três categorias de respostas: processo de elaboração do planejamento (20,5% fácil e 20,5% difícil), nível de conhecimento dos alunos (7% fácil e 0% difícil) e natureza dos conteúdos abordados (14% fácil e 10,5% difícil). Foram classificadas três categorias distintas em relação às dificuldades em ensinar ciências: natureza dos conteúdos abordados (50%), aspectos metodológicos (25%), e conhecimento básico (25%). A análise dos resultados revelou que a principal dificuldade das licenciandas em Pedagogia quanto à aplicabilidade do ensino de ciências nos primeiros ciclos do Ensino Fundamental esta diretamente relacionada à falta de conhecimento básico destes conteúdos, que somente foram estudados por elas no Ensino Básico, indicando a necessidade de incorporação de abordagens de conteúdos de ciências no currículo do curso de Pedagogia.

Ontogeny and nutritional programming of the hepatic growth hormone-insulin-like growth factor-prolactin axis in the sheep

The liver is an important metabolic and endocrine organ in the fetus but the extent to which its hormone receptor (R) sensitivity is developmentally regulated in early life is not fully established. We, therefore, examined developmental changes in mRNA abundance for the growth hormone (GH) and prolactin (PRL) receptors (R) plus insulin-like growth factor (IGF)-I and –II and their receptors. Fetal and postnatal sheep were sampled at either 80, or 140 days gestation, 1, 30 days or six months of age. The effect of maternal nutrient restriction between early to mid (i.e. 28 to 80 days gestation, the time of early liver growth) gestation on gene expression was also examined in the fetus and juvenile offspring. Gene expression for the GHR, PRLR and IGF-IR increased through gestation peaking at birth, whereas IGF-I was maximal near to term. In contrast, IGF-II mRNA decreased between mid and late gestation to increase after birth whereas IGF-IIR remained unchanged. A substantial decline in mRNA abundance for GHR, PRLR and IGF-IR then occurred up to six months. Maternal nutrient restriction reduced GHR and IGF-IIR mRNA abundance in the fetus, but caused a precocious increase in the PRLR. Gene expression for IGF-I and –II were increased in juvenile offspring born to nutrient restricted mothers. In conclusion, there are marked differences in the developmental ontogeny and nutritional programming of specific hormones and their receptors involved in hepatic growth and development in the fetus. These could contribute to changes in liver function during adult life.

On the brink of madness: Leituras do tema da loucura na obra pré-heteronímica de Fernando Pessoa

O tema da loucura na obra pessoana tem sido objecto de várias aproximações interpretativas, decorrentes da multiplicidade de textos que fazem eco do fenómeno e da sua persistência enquanto topos ao longo de praticamente toda a sua produção. Na sua acepção literal, manteve constantes interferências com a dimensão empírica do autor sobretudo quando sustentadas na contingência de certos textos basilares, os quais têm vindo a ser questionados quanto ao seu valor estritamente testemunhal. Como fenómeno desde cedo relacionado com a criação artística, a loucura surge neste estudo não apenas na representatividade da condição distintiva do sujeito criador mas ainda como figuração da contingência que envolve qualquer acto criativo que tome a linguagem na sua dimensão essencialmente metafórica e ambígua. Neste sentido, o presente trabalho pretende a abertura de várias vias de leitura do fenómeno através da análise crítica dos vocabulários relativos a diferentes âmbitos e concepções de loucura e a sua relação com o génio (capítulos I e II), focando o seu interesse no que diz respeito a alguma produção pessoana pré-heteronímica, nomeadamente Charles Robert Anon, Alexander Search (capítulo III) e Jean Seul de Méluret (capítulo IV), a que acrescentaremos o Primeiro Fausto (capítulo IV), de modo a conseguirmos estabelecer uma possível relação entre as primeiras experiências de alterização e a descoberta simultânea da irredutibilidade do discurso literário face a tentativas de literalização e de racionalização da linguagem, defendidas por outros modelos (paradigma biologista). A identificação da ambiguidade e da ironia nas suas mais variadas acepções como componentes essenciais da aprendizagem do valor contingente do processo de criação contribuirá tanto para a definição da autonomização da literatura como para a redescrição moderna do sujeito criador, paradoxalmente investido do pathos criativo anunciado no Romantismo e confrontando-se com os seus limites, que corresponderão aos da própria linguagem, situação de crise de que a figuração do louco lúcido será um dos tópicos mais produtivos. ABSTRACT: The theme of madness in the Pessoa work has been the subject of several interpretive approaches, from the multiplicity of texts that echo the phenomenon and its persistence as a topos priority over virtually all its production. ln its physiological sense, remained constant interference with the empirical dimension of the author when sustained in the contingency of certain basic texts that have been questioned as to their strictly testimonial value. As early phenomenon associated with artistic creation, the madness in this study is not only representative in the distinctive condition of the subject creator but also as the contingency figuration involving any creative act to take the language mainly in its essential metaphorical and ambiguous dimension. Accordingly, this work intends to open several analysis manners of the phenomenon through critical analysis of vocabularies for different areas and concepts of madness and its special relationship with the genius (Chapters I and II), focusing its interest in respect to some of the previous-heteronomy Pessoa production, including Charles Robert Anon, Alexander Search (Chapter III) and Jean Seul de Méluret (Chapter IV), and the Primeiro Fausto (Chapter IV), among others, to establish a possible relationship between changing early experiences and the discovery simultaneous literary discourse of irreducibility in the face of the attempts of literacy and the rationalization of language defended by other models (biologist paradigm). The identification of the ambiguity and irony in its many different meanings as essential components of learning the contingent value of the creation process which will contribute to the definition of empowerment in the literature as to the redescription of the modem subject creator that paradoxically had the creative pathos announced in Romanticism and from the confrontation with its limits, which will correspond to the language itself, the crisis situation from which the mad-lucid figuration will be one of the most productive topics.

Seguridad social. Teoría crítica. Tomo I y II

Seguridad social teórica es, en esencia, un libro de derecho y como tal se ocupa en su parte central de ilustrar y esclarecer el estado en el que se halla la regulación de derechos y obligaciones que son propios; pero de la singularidad de esta materia se deriva una exigencia: un libro de seguridad social no puede limitarse a realizar dicha tarea. Son la ley y los reglamentos los que ponen en marcha un conjunto de instituciones para hacer cierto amparo social: a la jurisprudencia en los últimos lustros, le ha correspondido afinar los instrumentos y reelaborar la partitura; difícilmente se puede llegar a definir el contenido de la seguridad social que recibe hoy un ciudadano prescindiendo de lo que han hecho los jueces.

El derecho público en Iberoamérica. Libro homenaje al profesor Jaime Vidal Perdomo. Tomos I y II

La obra que se entrega hoy es un gran ejemplo de la riqueza académica con la que todos cuentan en Iberoamérica, motor de una nueva integración, que mueve y motiva por encima de intereses políticos y partidarios. Para una mejor lectura de las evoluciones y las expectativas en derecho público en Iberoamérica, así como del balance del derecho administrativo colombiano, en sus primeros cien años de justicia contencioso-administrativa, en este orden de ideas se ha dividido la publicación en dos tomos. El primero de ellos se divide en tres partes: derecho constitucional, teoría general del derecho administrativo, y acto y procedimiento administrativo. El segundo tomo viene distribuido en cinco partes: la primera parte se ha denominado contratos administrativos, la segunda parte régimen local, la tercera parte, denominada bienes del Estado, la cuarta parte, contencioso-administrativo y la última parte, se ha descrito como temas varios. En ella se encuentran reflexiones sobre la evolución de la teoría del daño especial en Colombia. Con lo anterior, se espera haber cumplido con un buen balance bicentenario del derecho público en Iberoamérica y del derecho administrativo colombiano en estos cien primeros años de justicia contencioso-administrativa, en homenaje al maestro Jaime Vidal Perdomo, eximio jurista colombiano consagrado al estudio y análisis del derecho público y exponente calificado y reconocido de la academia en Colombia y en los países iberoamericanos.

Historia de la Revolución de la República de Colombia en la América Meridional. Tomos I y II

Este es uno de los textos claves de la historiografía colombiana. Es una invitación a leer juiciosamente este libro, pues aunque no se compartan muchas de las ideas en él expuestas, ellas han tenido un peso decisivo en la conformación de la visión que se tiene hoy de la historia del país. Los personajes de la independencia en la obra del autor no son presentados en la forma idílica que una versión de la historia patria posterior ha difundido. Lejos de mostrar a estos héroes como prototipos de virtudes, amor por la patria, abnegación ante los infortunios, como modelos a seguir por las generaciones posteriores, en el, el autor señala las razones personales y de grupo que a su juicio los llevaron a actuar de una determinada manera. Así por ejemplo, la imagen que se da de la participación de Antonio Nariño en las luchas por el poder en el Estado de Cundinamarca en 1811 es la de un enemigo peligroso e insatisfecho por ocupar un cargo subalterno. La escritura de esta obra se enmarca dentro de la tradición de pensamiento racionalista del siglo XVIII.

Morphometric characteristics of Prochilodus lineatus (Valenciennes 1847), of the migratory and resident stocks of the river Mogí-Guaçu, São Paulo State, Brazil

A espécie Prochilodus lineatus é de grande importância comercial na região dos rios Grande, Pardo e Mogi-Guaçu e tem como característica a formação de grandes cardumes, apta a desenvolver amplos deslocamentos migratórios. O presente trabalho objetivou avaliar, por meio das características morfométricas e etária, se os curimbatás (P. lineatus) dos diferentes estoques migradores e residentes constituem uma única população, havendo interação entre as sub-populações no período de piracema (migração reprodutiva). Utilizou-se um delineamento inteiramente casualizado em esquema fatorial 4 x 2, com quatro tipos de estoques (um residente e três migradores) e dois sexos (macho e fêmea) com trinta repetições, considerando cada peixe como unidade experimental. Foi observada variação de 80,19% para o primeiro componente principal e 8,09% do segundo componente principal fornecida pelas dez variáveis morfométricas dos estoques residentes e migradores. O estoque residente correspondeu aos maiores valores para todas as variáveis morfométricas. Houve sobreposição dos escores individuais das mesmas características entre os estoques migradores. Observou-se predominância de machos entre os estoques residentes e migrador I e II. As semelhanças morfométricas verificadas entre os estoques migradores indicam tratar-se de uma única população, com pequenas variações interpopulacional.

A Livestock-Associated, Multidrug-Resistant, Methicillin-Resistant Staphylococcus aureus Clonal Complex 97 Lineage Spreading in Dairy Cattle and Pigs in Italy

Pandemic methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 97 (CC97) lineages originated from livestock-to-human host jumps. In recent years, CC97 has become one of the major MRSA lineages detected in Italian farmed animals. The aim of this study was to characterize and analyze differences in MRSA and methicillin-susceptible S. aureus (MSSA) mainly of swine and bovine origins. Forty-seven CC97 isolates, 35 MRSA isolates, and 6 MSSA isolates from different Italian pig and cattle holdings; 5 pig MRSA isolates from Germany; and 1 human MSSA isolate from Spain were characterized by macrorestriction pulsed-field gel electrophoresis (PFGE) analysis, multilocus sequence typing (MLST), spa typing, staphylococcal cassette chromosome mec (SCCmec) typing, and antimicrobial resistance pattern analysis. Virulence and resistance genes were investigated by PCR and microarray analysis. Most of the isolates were of SCCmec type V (SCCmec V), except for two German MRSA isolates (SCCmec III). Five main clusters were identified by PFGE, with the German isolates (clusters I and II) showing 60.5% similarity with the Italian isolates, most of which (68.1%) grouped into cluster V. All CC97 isolates were Panton-Valentine leukocidin (PVL) negative, and a few (n = 7) tested positive for sak or scn. All MRSA isolates were multidrug resistant (MDR), and the main features were erm(B)- or erm(C)-mediated (n = 18) macrolide-lincosamide-streptogramin B resistance, vga(A)-mediated (n = 37) pleuromutilin resistance, fluoroquinolone resistance (n = 33), tet(K) in 32/37 tet(M)-positive isolates, and blaZ in almost all MRSA isolates. Few host-associated differences were detected among CC97 MRSA isolates: their extensive MDR nature in both pigs and dairy cattle may be a consequence of a spillback from pigs of a MRSA lineage that originated in cattle as MSSA and needs further investigation. Measures should be implemented at the farm level to prevent spillover to humans in intensive farming areas.

Rättfärdigade prioriteringar - en kvalitativ analys av hur personal i äldreomsorgen hanterar motstridiga verksamhetslogiker

Tidigare forskning visar att äldreomsorgspersonal kämpar med två typer av logiker: en ekonomisk logik och en omsorgslogik. Även om båda logikerna behövs för att skapa god omsorg så utmanar de varandra. Dessa utmaningar kommer till uttryck i omsorgspraktiken där personalen ställs in för val och måste göra prioriteringar. Denna avhandling syftar till att förstå hur äldreomsorgspersonal beskriver att de arbetar för att finna balans mellan logikerna och hur de rättfärdigar sina prioriteringar i omsorgen om de äldre personerna. Frågeställningen för avhandlingen är att ta reda på hur personal och enhetschef vid ett kommunalt äldreboende förstår och hanterar interaktionen mellan de två logiker som styr omsorgsarbetet för att främja de äldre personernas välbefinnande. Syftet innehåller tre delsyften: 1) att analysera personalens erfarenheter av och meningsskapande kring de äldre personernas välbefinnande och deras reflektioner kring det omsorgsarbete de utför, 2) att belysa och problematiserade logiker som styr omsorgsarbetet samt 3) att analysera hur personalen rättfärdigar sina prioriteringar i rådande kontext och hur deras förklarbarhet påverkar deras professionella identiteter. Målet är att bidra med socialvetenskaplig kunskap om de överväganden personal gör när de ställs inför att göra prioriteringar i äldreomsorgens praktik. Material samlades in genom 12 individuella intervjuer med personal vid ett kommunalt äldreboende, en intervju med personalens enhetschef och en uppföljande gruppintervju med tre personer ur personalgruppen. Materialet analyserades med tre analysmetoder: fenomenologisk analys, reflexiv analys och positioneringsanalys. Resultatet visar att personalen definierar de äldre personernas välbefinnande som ett behov av att känna sig existentiellt berörd. Denna känsla av existentiell beröring delas in i tre delar: känsla av valfrihet, känsla av njutning och känsla av närhet till någon eller något. Arbetet för att uppnå detta välbefinnande beskrivs innebära ett balanserande av tre tvetydigheter: att vilja värna om de äldre personernas valfrihet och samtidigt hantera institutionella begränsningar, de äldre personernas behov av aktivering å ena sidan och att de inte behöver aktiveras å andra sidan samt att förstå de äldre personernas behov av rutiner samtidigt som det är svårt att veta vilka behov de har. Tvetydigheterna kontextualiserades och de två logikerna som styr omsorgsarbetet analyserades. Analysen visar att enhetschefen skapar en hybrid av den ekonomiska logiken och omsorgslogiken; ekonomi är omsorg och vice versa. Denna hybrid möter motstånd från personalen som skiljer på de båda logikerna genom att tala om ”vård och det där andra”. Personalen upplever att den ekonomiska logiken begränsar deras möjligheter att utföra omsorg i linje med omsorgslogiken. Motsättningar mellan de båda logikerna leder till prioriteringar som rättfärdigas av personalen i syfte att behålla de professionella identiteterna. Den teoretiska analysen bygger på teorier om institutionella logiker, förklarbarhet ochprofessionell identitet. Analyserna visar vikten av att väcka dialog mellan enhetschefer och personal där de diskuterar innebörder av olika värdeord som används på politisk nivå. Sådana diskussioner skulle kunna bidra till mindre motstånd och en högre överensstämmelse mellan verksamhetsmål och praktik. Avhandlingen visar även vikten av att förstå logiker som vertikala istället för horisontellt uppdelade. Alltså, att styrande verksamhetslogiker existerar uppifrån och ned i verksamheter (från politisk nivå till chefsnivå och till praktisk nivå) och att de inte kan delas in i exempelvis en professionslogik och en styrningslogik. Den senare synen kan bidra till potentiella missförstånd eftersom det gör att konflikter kan tolkas existera mellan personal och chef, medan de egentligen existerar mellan olika motstridiga värderingssystem. Slutsatsen är att de båda logikerna behövs för att stödja äldre personers välbefinnande. Ibland är logikerna samspelta och ibland är de i konflikt med varandra. När logikerna ställs mot varandra är det av vikt att komma ihåg att den ekonomiska logiken är lika förhandlingsbar som omsorgslogiken. De två logikerna existerar i samspel och om deras motstridigheter inte belyses finns risk att omsorgspraktiken inte stödjer de äldre personernas välbefinnande.

Carers in the welfare state : on informal care and support for carers in Sweden

  The general aim of this dissertation is to describe and analyse patterns of informal care and support for carers in Sweden. One specific aim is to study patterns of informal care from a broad population perspective in terms of types of care and types of carer. A typology of four different care categories based on what carers do revealed that women were much more likely than men to be involved at the ‘heavy end’ of caring, i.e. providing personal care in combination with a variety of other caring tasks. Men were more likely than women to provide some kind of practical help (Study I). Another aim is to investigate which support services are received by which types of informal caregiver. Relatively few informal caregivers in any care category were found to be receiving any kind of support from municipalities or voluntary organizations, for example training or financial assistance (Study II). The same study also examines which kinds of help care recipients receive in addition to that provided by informal carers. It appears that people in receipt of personal care from an informal caregiver quite often also receive help from the public care system, in this case mostly municipal services. However, the majority of those receiving personal, informal care did not receive any help from the public care system or from voluntary organizations or for-profit agencies (Study II). The empirical material in studies I and II comprises survey data from telephone interviews with a random sample of residents in the County of Stockholm aged between 18 and 84. In a number of countries there is a growing interest among social scientists and social policymakers in examining the types of support services that might be needed by people who provide informal care for older people and others. A further aim of the present dissertation is therefore to describe and analyse the carer support that is provided by municipalities and voluntary organizations in Sweden. The dissertation examines whether this support is aimed directly or indirectly at caregivers and discusses whether the Swedish government’s special financial investment in help for carers actually led to any changes in the support provided by municipalities and voluntary organisations. The main types of carer support offered by the municipalities were payment for care-giving, relief services and day care. The chief forms of carer support provided by the voluntary organizations were support groups, training groups, and a number of services aimed primarily at the elderly care recipients (Study III). Patterns of change in municipal carer support could be discerned fairly soon. The Swedish government’s special allocation to municipalities and voluntary organisations appears to have led to an increase in the number of municipalities providing direct support for carers, such as training, information material and professional caregiver consultants. On the other hand, only minor changes could be discerned in the pattern of carer support services provided by the voluntary organizations. This demonstrates stability and the relatively low impact that policy initiatives seem to have on voluntary organizations as providers (Study IV). In studies III and IV the empirical material consists of survey data from mail questionnaires sent to municipalities and voluntary organizations in the County of Stockholm. In the fields of social planning and social work there appears to be a need to clarify the aims of support services for informal carers. Should the support be direct or indirect? Should it be used to supplement or substitute caregivers? In this process of reappraisal it will be important to take the needs of both caregivers and care recipients into account when developing existing and new forms of support. How informal caregivers and care recipients interact with the care system as a whole is undeniably a fertile field for further research.

Correlacion entre hemoglobina glicosilada con hallazgos sintax score ii en pacientes con sospecha clínica de enfermedad coronaria, hospitalizados en la unidad coronaria del hospital San José centro en enero a septiembre del año 2015

Se realiza un estudio de corte transversal en el periodo de enero a septiembre del año 2016 en la unidad coronaria del Hospital San José Centro de la Ciudad de Bogotá; en pacientes con sospecha de enfermedad coronaria (Síndrome coronario agudo y angina estable) y antecedente de Diabetes Mellitus Tipo 2, se recolectaron 42 pacientes con los criterios de inclusión a quienes se realizó angiografía coronaria como parte del protocolo de estudio y manejo de la unidad, el objetivo primario fue demostrar la posible correlación entre niveles de hemoglobina glicosilada y la escala de severidad SYNTAX Score I y II de enfermedad coronaria, como objetivos secundarios; caracterizar las variables sociodemográficas, comorbilidades y posible relación con el tipo de presentación de enfermedad coronaria. Como hallazgos relevantes no se encontró correlación importante ni significativa entre niveles de hemoglobina glicosilada y la escala Syntax score II ni Syntax score I, a pesar de que la mayoría de pacientes mostraban mal control crónico de su diabetes mellitus tipo 2, con niveles mayores > 7%, como hallazgo positivo se encontro asociación estadísticamente significativa con niveles de LDL y las diferentes formas de presentación de enfermedad coronaria, a mayor niveles de LDL mayor probabilidad de IAM e IAM con elevación del segmento ST. Se considera que con estudios multicentricos en diferentes ciudades y unidades de cuidado cardiovascular con diferentes niveles de riesgo, se podría demostrar la posible correlación entre niveles de hemoglobina glicosilada y los grados de severidad de enfermedad coronaria representados por las escalas Syntax score I y II.

Do Espírito do Lugar - Música, Estética, Silêncio, Espaço, Luz I e II Residências Cistercienses de São Bento de Cástris (2013, 2014).

As Residências Cistercienses em S. Bento de Cástris que se vêm realizando desde 2013 têm como primeiro objectivo reinventar na contemporaneidade a densidade histórica do discurso cisterciense, integrando a realidade deste mosteiro tanto numa ampla geografia da Ordem de Cister em Portugal e na Europa, como na história da região e do país. Inspiradas nas questões da História, da Arte, da Arquitectura, da Música, do Património e da Paisagem, as Residências Cistercienses em Cástris vêm apostando no debate de questões actuais ligadas aos espaços monásticos e ao seu futuro, nomeadamente os cistercienses. Esta aposta concretiza-se também no presente trabalho, DO ESPÍRITO DO LUGAR. ESTÉTICA. SILÊNCIO, ESPAÇO, LUZ, resultado das I e II Residências Cistercienses (2013 e 2014), e integra estudos que se reportam especialmente ao Silêncio e às suas várias linguagens e significados e às dimensões da Estética monástico-religiosa, com algum privilégio para as temáticas da Música. A apropriação do mosteiro pelo silêncio e pela música e a apreciação do espólio musical e instrumental de S. Bento de Cástris permitem uma melhor percepção das diversidades conjunturais e dos seus ritmos, aliando-se às dimensões de valorização patrimonial, eacompanhando-as de sugestões estéticas na pintura, escultura, pintura mural, azulejaria…, no sentido da fruição plena dos espaços. A riqueza deste evento, a Residência Cisterciense no mosteiro de S. Bento de Cástris, permitirá que o futuro deste património, de tanta diversidade e espessura histórico-cultural, continue a ser debatido e a justificar edições futuras resultantes dos trabalhos de investigação aí apresentados e debatidos.

Integrated health prediction of bridge systems using dynamic object oriented Bayesian networks (DOOBNS)

The serviceability and safety of bridges are crucial to people’s daily lives and to the national economy. Every effort should be taken to make sure that bridges function safely and properly as any damage or fault during the service life can lead to transport paralysis, catastrophic loss of property or even casualties. Nonetheless, aggressive environmental conditions, ever-increasing and changing traffic loads and aging can all contribute to bridge deterioration. With often constrained budget, it is of significance to identify bridges and bridge elements that should be given higher priority for maintenance, rehabilitation or replacement, and to select optimal strategy. Bridge health prediction is an essential underpinning science to bridge maintenance optimization, since the effectiveness of optimal maintenance decision is largely dependent on the forecasting accuracy of bridge health performance. The current approaches for bridge health prediction can be categorised into two groups: condition ratings based and structural reliability based. A comprehensive literature review has revealed the following limitations of the current modelling approaches: (1) it is not evident in literature to date that any integrated approaches exist for modelling both serviceability and safety aspects so that both performance criteria can be evaluated coherently; (2) complex system modelling approaches have not been successfully applied to bridge deterioration modelling though a bridge is a complex system composed of many inter-related bridge elements; (3) multiple bridge deterioration factors, such as deterioration dependencies among different bridge elements, observed information, maintenance actions and environmental effects have not been considered jointly; (4) the existing approaches are lacking in Bayesian updating ability to incorporate a variety of event information; (5) the assumption of series and/or parallel relationship for bridge level reliability is always held in all structural reliability estimation of bridge systems. To address the deficiencies listed above, this research proposes three novel models based on the Dynamic Object Oriented Bayesian Networks (DOOBNs) approach. Model I aims to address bridge deterioration in serviceability using condition ratings as the health index. The bridge deterioration is represented in a hierarchical relationship, in accordance with the physical structure, so that the contribution of each bridge element to bridge deterioration can be tracked. A discrete-time Markov process is employed to model deterioration of bridge elements over time. In Model II, bridge deterioration in terms of safety is addressed. The structural reliability of bridge systems is estimated from bridge elements to the entire bridge. By means of conditional probability tables (CPTs), not only series-parallel relationship but also complex probabilistic relationship in bridge systems can be effectively modelled. The structural reliability of each bridge element is evaluated from its limit state functions, considering the probability distributions of resistance and applied load. Both Models I and II are designed in three steps: modelling consideration, DOOBN development and parameters estimation. Model III integrates Models I and II to address bridge health performance in both serviceability and safety aspects jointly. The modelling of bridge ratings is modified so that every basic modelling unit denotes one physical bridge element. According to the specific materials used, the integration of condition ratings and structural reliability is implemented through critical failure modes. Three case studies have been conducted to validate the proposed models, respectively. Carefully selected data and knowledge from bridge experts, the National Bridge Inventory (NBI) and existing literature were utilised for model validation. In addition, event information was generated using simulation to demonstrate the Bayesian updating ability of the proposed models. The prediction results of condition ratings and structural reliability were presented and interpreted for basic bridge elements and the whole bridge system. The results obtained from Model II were compared with the ones obtained from traditional structural reliability methods. Overall, the prediction results demonstrate the feasibility of the proposed modelling approach for bridge health prediction and underpin the assertion that the three models can be used separately or integrated and are more effective than the current bridge deterioration modelling approaches. The primary contribution of this work is to enhance the knowledge in the field of bridge health prediction, where more comprehensive health performance in both serviceability and safety aspects are addressed jointly. The proposed models, characterised by probabilistic representation of bridge deterioration in hierarchical ways, demonstrated the effectiveness and pledge of DOOBNs approach to bridge health management. Additionally, the proposed models have significant potential for bridge maintenance optimization. Working together with advanced monitoring and inspection techniques, and a comprehensive bridge inventory, the proposed models can be used by bridge practitioners to achieve increased serviceability and safety as well as maintenance cost effectiveness.