Global identification of androgen response elements

Chromatin immunoprecipitation (ChIP) is an invaluable tool in the study of transcriptional regulation. ChIP methods require both a priori knowledge of the transcriptional regulators which are important for a given biological system and high-quality specific antibodies for these targets. The androgen receptor (AR) is known to play essential roles in male sexual development, in prostate cancer and in the function of many other AR-expressing cell types (e.g. neurons and myocytes). As a ligand-activated transcription factor the AR also represents an endogenous, inducible system to study transcriptional biology. Therefore, ChIP studies of the AR can make use of treatment contrast experiments to define its transcriptional targets. To date several studies have mapped AR binding sites using ChIP in combination with genome tiling microarrays (ChIP-chip) or direct sequencing (ChIP-seq), mainly in prostate cancer cell lines and with varying degrees of genomic coverage. These studies have provided new insights into the DNA sequences to which the AR can bind, identified AR cooperating transcription factors, mapped thousands of potential AR regulated genes and provided insights into the biological processes regulated by the AR. However, further ChIP studies will be required to fully characterise the dynamics of the AR-regulated transcriptional programme, to map the occupancy of different AR transcriptional complexes which result in different transcriptional output and to delineate the transcriptional networks downstream of the AR.

Improving composite damage modelling through automatic placement of cohesive elements

Numerous experimental studies of damage in composite laminates have shown that intralaminar (in-plane) matrix cracks lead to interlaminar delamination (out-of-plane) at ply interfaces. The smearing of in-plane cracks over a volume, as a consequence of the use of continuum damage mechanics, does not always effectively capture the full extent of the interaction between the two failure mechanisms. A more accurate representation is obtained by adopting a discrete crack approach via the use of cohesive elements, for both in-plane and out-of-plane damage. The difficulty with cohesive elements is that their location must be determined a priori in order to generate the model; while ideally the position of the crack migration, and more generally the propagation path, should be obtained as part of the problem’s solution. With the aim of enhancing current modelling capabilities with truly predictive capabilities, a concept of automatic insertion of interface elements is utilized. The consideration of a simple traction criterion in relation to material strength, evaluated at each node of the model (or of the regions of the model where it is estimated cracks might form), allows for the determination of initial crack location and subsequent propagation by the insertion of cohesive elements during the course of the analysis. Several experimental results are modelled using the commercial package ABAQUS/Standard with an automatic insertion subroutine developed in this work, and the results are presented to demonstrate the capabilities of this technique.

Streaming Elements for FPGA Signal and Image Processing Accelerators

Field programmable gate array devices boast abundant resources with which custom accelerator components for signal, image and data processing may be realised; however, realising high performance, low cost accelerators currently demands manual register transfer level design. Software-programmable ’soft’ processors have been proposed as a way to reduce this design burden but they are unable to support performance and cost comparable to custom circuits. This paper proposes a new soft processing approach for FPGA which promises to overcome this barrier. A high performance, fine-grained streaming processor, known as a Streaming Accelerator Element, is proposed which realises accelerators as large scale custom multicore networks. By adopting a streaming execution approach with advanced program control and memory addressing capabilities, typical program inefficiencies can be almost completely eliminated to enable performance and cost which are unprecedented amongst software-programmable solutions. When used to realise accelerators for fast fourier transform, motion estimation, matrix multiplication and sobel edge detection it is shown how the proposed architecture enables real-time performance and with performance and cost comparable with hand-crafted custom circuit accelerators and up to two orders of magnitude beyond existing soft processors.

Assessing elements of a family approach to reduce adolescent drinking frequency: parent-adolescent relationship, knowledge management, and keeping secrets

AIMS: To estimate 1) the associations between parent-adolescent relationship, parental knowledge and subsequent adolescent drinking frequency and 2) the influence of alcohol use on parental knowledge.

DESIGN: Path analysis of school based cohort study with annual surveys SETTING: Post primary schools from urban and intermediate/rural areas in Northern Ireland PARTICIPANTS: 4,937 post primary school students aged around 11 years in 2000 followed until around age 16 in 2005.

MEASUREMENTS: Pupil reported measures of: frequency of alcohol use; parental-child relationship quality; sub-dimensions of parental monitoring: parental control, parental solicitation, child disclosure and child secrecy.

FINDINGS: Higher levels of parental control (Ordinal logistic OR 0.86 95% CI 0.78, 0.95) and lower levels of child secrecy (OR 0.83 95% CI 0.75 0.92) were associated with less frequent alcohol use subsequently. Parental solicitation and parent-child relationship quality were not associated with drinking frequency. Weekly alcohol drinking was associated with higher subsequent secrecy (Beta -0.42 95% CI -0.53, -0.32) and lower parental control (Beta -0.15 95% CI -0.26, -0.04). Secrecy was more strongly predictive of alcohol use at younger compared with older ages (P=0.02), and alcohol use was less strongly associated with parental control among families with poorer relationships (P=0.04).

CONCLUSIONS: Adolescent alcohol use appears to increase as parental control decreases and child secrecy increases. Greater parental control is associated with less frequent adolescent drinking subsequently, while parent-child attachment and parental solicitation have little influence on alcohol use. 

Availability and transfer to grain of As, Cd, Cu, Ni, Pb and Zn in a barley agri-system: Impact of biochar, organic and mineral fertilizers

With biochar becoming an emerging soil amendment and a tool to mitigate climate change, there are only a few studies documenting its effects on trace element cycling in agriculture. Zn and Cu are deficient in many human diets, whilst exposures to As, Pb and Cd need to be decreased. Biochar has been shown to affect many of them mainly at a bench or greenhouse scale, but field research is not available. In our experiment we studied the impact of biochar, as well as its interactions with organic (compost and sewage sludge) and mineral fertilisers (NPK and nitrosulfate), on trace element mobility in a Mediterranean agricultural field (east of Madrid, Spain) cropped with barley. At harvesting time, we analysed the soluble fraction, the available fraction (assessed with the diffusive gradients in thin gels technique, DGT) and the concentration of trace elements in barley grain. No treatment was able to significantly increase Zn, Cu or Ni concentration in barley grain, limiting the application for cereal fortification. Biochar helped to reduce Cd and Pb in grain, whereas As concentration slightly increased. Overall biochar amendments demonstrated a potential to decrease Cd uptake in cereals, a substantial pathway of exposure in the Spanish population, whereas mineral fertilisation and sewage sludge increased grain Cd and Pb. In the soil, biochar helped to stabilise Pb and Cd, while marginally increasing As release/mobilisation. Some of the fertilisation practises or treatments increased toxic metals and As solubility in soil, but never to an extent high enough to be considered an environmental risk. Future research may try to fortify Zn, Cu and Ni using other combinations of organic amendments and different parent biomass to produce enriched biochars.

Generalized collisional radiative model for light elements: C: Data for the B isonuclear sequence

A first stage collision database is assembled which contains electron-impact excitation, ionization,\r and recombination rate coefficients for B, B + , B 2+ , B 3+ , and B 4+ . The first stage database\r is constructed using the R-matrix with pseudostates, time-dependent close-coupling, and perturbative\r distorted-wave methods. A second stage collision database is then assembled which contains\r generalized collisional-radiative ionization, recombination, and power loss rate coefficients as a\r function of both temperature and density. The second stage database is constructed by solution of\r the collisional-radiative equations in the quasi-static equilibrium approximation using the first\r stage database. Both collision database stages reside in electronic form at the IAEA Labeled Atomic\r Data Interface (ALADDIN) database and the Atomic Data Analysis Structure (ADAS) open database.

Generalized collisional radiative model for light elements. Part B: Data for the Be isonuclear sequence

A first-stage collision database is assembled which contains electron-impact excitation, ionization, and recombination rate coefficients for Be, Be+, Be2+, and Be3+. The first-stage database is constructed using the R-matrix with pseudo-states, time-dependent close-coupling, and perturbative, distorted-wave methods. A second-stage collision database is then assembled which contains generalized collisional-radiative and radiated power loss coefficients. The second-stage database is constructed by solution of collisional-radiative equations in the quasi-static equilibrium approximation using the first-stage database. Both collision database stages reside in electronic form at the ORNL Controlled Fusion Atomic Data Center and in the ADAS database, and are easily accessed over the worldwide internet. © 2007 Elsevier Inc. All rights reserved.

Generalised collisional-radiative model for light elements. A: Data for the Li isonuclear sequence

A first stage collision database is assembled which contains electron-impact effective collision strengths, and ionization and recombination rate coefficients for Li, Li+, and Li2+. The first stage database is constructed using the R-matrix with pseudo-states, time-dependent close-coupling, converged close-coupling, and perturbative distorted-wave methods. A second stage collision database is then assembled which contains generalized collisional-radiative and radiated power loss coefficients. The second stage database is constructed by solution of collisional-radiative equations in the quasi-static equilibrium approximation using the first stage database. Both collision database stages reside in electronic form at the ORNL Controlled Fusion Atomic Data Center and in the ADAS database, and are easily accessed over the worldwide internet. ?? 2006 Elsevier Inc. All rights reserved.

Cyclic behaviour of RC elements with plain reinforcing bars

O comportamento cíclico das estruturas de betão armado é fortemente condicionado pelo mecanismo de aderência entre o betão e o aço. O escorregamento relativo entre os dois materiais, resultante da degradação progressiva da aderência em elementos solicitados por ações cíclicas, é uma causa frequente de danos graves e até do colapso de estruturas devido à ocorrência de sismos. Entre as estruturas existentes de betão armado que foram dimensionadas e construídas antes da entrada em vigor dos regulamentos sísmicos atuais, muitas foram construídas com armadura lisa, e portanto, possuem fracas propriedades de aderência. A informação disponível na literatura sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa é reduzida e a influência das propriedades da aderência associadas a este tipo de armadura no comportamento cíclico das estruturas existentes não se encontra ainda devidamente estudada. O objectivo principal desta tese foi estudar a influência do escorregamento na resposta cíclica de elementos estruturais de betão armado com armadura lisa. Foram realizados ensaios cíclicos em elementos do tipo nó viga-pilar, construídos à escala real, representativos de ligações interiores em edifícios existentes sem pormenorização específica para resistir às ações sísmicas. Para comparação, foi realizado o ensaio de um nó construído com armadura nervurada. Foi ainda realizado o ensaio cíclico de uma viga de betão armado recolhida de uma estrutura antiga. Foram elaborados modelos numéricos não-lineares para simular a resposta dos elementos ensaiados, concentrando especial atenção no mecanismo do escorregamento. Os resultados obtidos no âmbito desta tese contribuem para o avanço do conhecimento sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa. As análises numéricas realizadas comprovam a necessidade de incluir os efeitos do escorregamento na modelação numérica deste tipo de estruturas de forma a representar com rigor a sua resposta às ações cíclicas.

Exposure modelling to traffic-related air toxic pollutants

Atualmente, a poluição atmosférica constitui uma das principais causas ambientais de mortalidade. Cerca de 30% da população europeia residente em áreas urbanas encontra-se exposta a níveis de poluição atmosférica superiores aos valores- limite de qualidade do ar legislados para proteção da saúde humana, representando o tráfego rodoviário uma das principais fontes de poluição urbana. Além dos poluentes tradicionais avaliados em áreas urbanas, os poluentes classificados como perigosos para a saúde (Hazard Air Pollutants - HAPs) têm particular relevância devido aos seus conhecidos efeitos tóxicos e cancerígenos. Neste sentido, a avaliação da exposição tornase primordial para a determinação da relação entre a poluição atmosférica urbana e efeitos na saúde. O presente estudo tem como principal objetivo o desenvolvimento e implementação de uma metodologia para avaliação da exposição individual à poluição atmosférica urbana relacionada com o tráfego rodoviário. De modo a atingir este objetivo, foram identificados os parâmetros relevantes para a quantificação de exposição e analisados os atuais e futuros potenciais impactos na saúde associados com a exposição à poluição urbana. Neste âmbito, o modelo ExPOSITION (EXPOSure model to traffIc-relaTed aIr pOllutioN) foi desenvolvido baseado numa abordagem inovadora que envolve a análise da trajetória dos indivíduos recolhidas por telemóveis com tecnologia GPS e processadas através da abordagem de data mining e análise geoespacial. O modelo ExPOSITION considera também uma abordagem probabilística para caracterizar a variabilidade dos parâmetros microambientais e a sua contribuição para exposição individual. Adicionalmente, de forma a atingir os objetivos do estudo foi desenvolvido um novo módulo de cálculo de emissões de HAPs provenientes do transporte rodoviário. Neste estudo, um sistema de modelação, incluindo os modelos de transporteemissões- dispersão-exposição, foi aplicado na área urbana de Leiria para quantificação de exposição individual a PM2.5 e benzeno. Os resultados de modelação foram validados com base em medições obtidas por monitorização pessoal e monitorização biológica verificando-se uma boa concordância entre os resultados do modelo e dados de medições. A metodologia desenvolvida e implementada no âmbito deste trabalho permite analisar e estimar a magnitude, frequência e inter e intra-variabilidade dos níveis de exposição individual, bem como a contribuição de diferentes microambientes, considerando claramente a sequência de eventos de exposição e relação fonte-recetor, que é fundamental para avaliação dos efeitos na saúde e estudos epidemiológicos. O presente trabalho contribui para uma melhor compreensão da exposição individual em áreas urbanas, proporcionando novas perspetivas sobre a exposição individual, essenciais na seleção de estratégias de redução da exposição à poluição atmosférica urbana, e consequentes efeitos na saúde.

Characterisation of the cyclic behaviour of reinforced concrete elements with plain bars

Sismos recentes comprovam a elevada vulnerabilidade dos edifícios existentes de betão armado. A resposta das estruturas aos sismos é fortemente condicionada pelas características da aderência aço-betão, que exibe degradação das propriedades iniciais quando sujeitas a carregamentos cíclicos e alternados. Este fenómeno é ainda mais gravoso para elementos com armadura lisa, predominantes na maioria das estruturas construídas até à década de 70 nos países do sul da Europa. A prática corrente de conceção, dimensionamento e pormenorização das estruturas antigas leva a que tenham características de comportamento e níveis de segurança associados não compatíveis com as exigências atuais. Os estudos realizados sobre o comportamento cíclico de elementos estruturais de betão armado com armadura lisa são ainda insuficientes para a completa caracterização deste tipo de elementos. Esta tese visou a caraterização da relação tensão de aderência versus escorregamento para elementos estruturais com armadura lisa e o estudo da resposta cíclica de pilares e nós viga-pilar de betão armado com armadura lisa. Foram realizados dez séries de ensaios de arrancamento (nove monotónicos e um cíclico) em provetes com varões lisos. Os resultados destes ensaios permitiram propor novas expressões empíricas para a estimativa dos parâmetros usados num modelo disponível na literatura para representação da relação tensão de aderência versus escorregamento. É ainda proposto um novo modelo monotónico para a relação tensão de aderência versus escorregamento que representa melhor a resposta após a resistência máxima de aderência. Uma campanha de ensaios unidirecionais em pilares e nós viga-pilar foi também realizada com o objetivo principal de caracterizar o comportamento cíclico deste tipo de elementos. No total foram realizados oito ensaios em pilares, sete ensaios em nós viga-pilar interiores e seis ensaios em nós viga-pilar exteriores representativos de estruturas antigas de betão armado com armadura lisa. Os resultados experimentais permitiram avaliar a influência do escorregamento e estudar o mecanismo de corte em nós e a evolução dos danos para elementos com armadura lisa. Com base nos resultados experimentais foi proposta uma adaptação na expressão do Eurocódigo 8-3 para o cálculo da capacidade última de rotação de elementos com armadura lisa. Foi também desenvolvido um estudo paramétrico, com diferentes estratégias de modelação não linear, para a simulação da resposta de pilares considerando o escorregamento da armadura lisa. Por último, foi proposto um novo modelo simplificado trilinear para o aço que contempla o efeito do escorregamento da armadura lisa.

Piñatex, the design development of a new sustainable material

This is a research project by practice, which firstly develops a new material invention derived from natural fibres extracted from waste pineapple leaves; secondly it articulates the contemporary designer’s role in facilitating sustainable solutions through: Insights from my own material invention, PiñatexTM, which integrates the materiality of design with the immateriality of concepts and values Developing a visual model of mapping I began with these questions: ‘What are the challenges in seeking to make a new and sustainable material from the waste products of pineapple agriculture in the Philippines?’ and ‘How can a design practice link elements of materiality (artifacts) with immaterial elements (value systems) in order to improve sustainable social and economic development?’ Significant influences have been the work of Papanek1 (2003), Hawken2 (1999) and Abouleish3 (2008) and in particular the ethical business model initiated by McDonough and Braungart in Cradle to Cradle®4 (2002). My own research project is inspired by the Cradle to Cradle® model. It proposes the development of a new material, PiñatexTM which is derived from natural fibres extracted from waste pineapple leaves and could be used in a wide variety of products that are currently fabricated in leather or petroleum-based materials. The methods have comprised: Contextual reviews; case studies (SEKEM, Cradle to Cradle® and Gawad Kalinga); practical experiments in the field of natural fibres, chemistry, product development, manufacturing and prototyping, leading to an invention and a theoretical model of mapping. In addition, collaboration has taken place across scientific, technological, social, ecological, academic and business fields. The outcome is a new material based on the synchronicity between the pineapple fibres, polymers, resins and coatings specially formulated. The invention of the new material that I developed as a central part of this research by practice has a patent in the national phase (PCT/GB 2011/000802) and is in the first stages of manufacturing, commercial testing and further design input (Summer 2014). The contribution to knowledge is firstly the material, PiñatexTM, which exhibits certain key qualities, namely environmentally non-toxic, biodegradable, income-generating potential and marketability. This is alongside its intrinsic qualities as a textile product: aesthetic potential, durability and stability, which will make it suitable for the accessories, interiors and furnishing markets. The theoretical mapping system Upstream and Downstream forms a secondary contribution.

Primary production in systems subject to natural and anthropogenic eutrophication

Tese dout., Química, Universidade do Algarve, 2005