Regulation of the pollen-specific actin-depolymerizing factor LIADF1

Pollen tube growth is dependent on a dynamic actin cytoskeleton, suggesting that actin-regulating proteins are involved. We have examined the regulation of the lily pollen-specific actin-depolymerizing factor (ADF) LIADF1. Its actin binding and depolymerizing activity is pH sensitive, inhibited by certain phosphoinositides, but not controlled by phosphorylation. Compared with its F-actin binding properties, its low activity in depolymerization assays has been used to explain why pollen ADF decorates F-actin in pollen grains. This low activity is incompatible with a role in increasing actin dynamics necessary to promote pollen tube growth. We have identified a plant homolog of actin-interacting protein, AIP1, which enhances the depolymerization of F-actin in the presence of LIADF1 by similar to60%. Both pollen ADF and pollen AIP1 bind F-actin in pollen grains but are mainly cytoplasmic in pollen tubes. Our results suggest that together these proteins remodel actin filaments as pollen grains enter and exit dormancy.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms:a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

A highly potent and specific MET therapeutic protein antagonist with both ligand-dependent and ligand-independent activity

Activation of the MET oncogenic pathway has been implicated in the development of aggressive cancers that are difficult to treat with current chemotherapies. This has led to an increased interest in developing novel therapies that target the MET pathway. However, most existing drug modalities are confounded by their inability to specifically target and/or antagonize this pathway. Anticalins, a novel class of monovalent small biologics, are hypothesized to be "fit for purpose" for developing highly specific and potent antagonists of cancer pathways. Here, we describe a monovalent full MET antagonist, PRS-110, displaying efficacy in both ligand-dependent and ligand-independent cancer models. PRS-110 specifically binds to MET with high affinity and blocks hepatocyte growth factor (HGF) interaction. Phosphorylation assays show that PRS-110 efficiently inhibits HGF-mediated signaling of MET receptor and has no agonistic activity. Confocal microscopy shows that PRS-110 results in the trafficking of MET to late endosomal/lysosomal compartments in the absence of HGF. In vivo administration of PRS-110 resulted in significant, dose-dependent tumor growth inhibition in ligand-dependent (U87-MG) and ligand-independent (Caki-1) xenograft models. Analysis of MET protein levels on xenograft biopsy samples show a significant reduction in total MET following therapy with PRS-110 supporting its ligand-independent mechanism of action. Taken together, these data indicate that the MET inhibitor PRS-110 has potentially broad anticancer activity that warrants evaluation in patients.

Mobilizing against neoliberalism? Global affirmative action in context

This article uses the example of Northern Ireland to illustrate how political mobilization may
be deployed to challenge structural forms of inequality. The experience suggests that regulatory
models can be designed for particular contexts to shape approaches that present challenges to
dominant economic and political orthodoxies. The intention is not to overstate the significance
of this specific transitional context but simply to highlight elements that might feature in any
attempt to mobilize successfully around human rights and equality, and against aspects of neoliberal
thinking.

Gender Equality under the Charter of Fundamental Rights - a new lease for positive action?

This paper, which was published as a chapter of a Festskrift for Professor Ruth Nielsen, analyses Article 23 CFREU, the new provision on gender equality. It argues that Article 23 adds to the notion of gender equality in EU law, and not only allows, but also demands positive action measures if necessary to ensure equality between women and men. The provision also demands that positive action measures are suitable to achieve their aim. This implies that the EU legislator has to adapt positive action measure to the specific needs of the sector. The paper offers a critique of the proposal to introduce women quotas in board rooms, as proposed by the EU Commission in late 2012. It argues that the Commission unimaginatively copied rules developed for the German public service into a different sector, although these rules have not proven particularly efficient even in the public service. Consequently, a proposal that is demanding, but adapted to the sector should be developed.

Proprioceptive acuity predicts muscle co-contraction of the tibalis anterior and gastrocnemius medialis in older adults’ dynamic postural control

Older adults use a different muscle strategy to cope with postural instability, in which they ‘co-contract’ the muscles around the ankle joint. It has been suggested that this is a compensatory response to age-related proprioceptive decline however this view has never been assessed directly. The current study investigated the association between proprioceptive acuity and muscle co-contraction in older adults. We compared muscle activity, by recording surface EMG from the bilateral tibalis anterior and gastrocnemius medialis muscles, in young (aged 18-34) and older adults (aged 65-82) during postural assessment on a fixed and sway-referenced surface at age-equivalent levels of sway. We performed correlations between muscle activity and proprioceptive acuity, which was assessed using an active contralateral matching task. Despite successfully inducing similar levels of sway in the two age groups, older adults still showed higher muscle co-contraction. A stepwise regression analysis showed that proprioceptive acuity measured using variable error was the best predictor of muscle co-contraction in older adults. However, despite suggestions from previous research, proprioceptive error and muscle co-contraction were negatively correlated in older adults, suggesting that better proprioceptive acuity predicts more co-contraction. Overall, these results suggest that although muscle co-contraction may be an age-specific strategy used by older adults, it is not to compensate for age-related proprioceptive deficits.

A comparison of gold nanoparticle surface co-functionalization approaches using Polyethylene Glycol (PEG) and the effect on stability, non-specific protein adsorption and internalization

To create clinically useful gold nanoparticle (AuNP) based cancer therapeutics it is necessary to co-functionalize the AuNP surface with a range of moieties; e.g. Polyethylene Glycol (PEG), peptides and drugs. AuNPs can be functionalized by creating either a mixed monolayer by attaching all the moieties directly to the surface using thiol chemistry, or by binding groups to the surface by means of a bifunctional polyethylene glycol (PEG) linker. The linker methodology has the potential to enhance bioavailability and the amount of functional agent that can be attached. While there is a large body of published work using both surface arrangements independently, the impact of attachment methodology on stability, non-specific protein adsorption and cellular uptake is not well understood, with no published studies directly comparing the two most frequently employed approaches. This paper compares the two methodologies by synthesizing and characterizing PEG and Receptor Mediated Endocytosis (RME) peptide co-functionalized AuNPs prepared using both the mixed monolayer and linker approaches. Successful attachment of both PEG and RME peptide using the two methods was confirmed using Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy and gel electrophoresis. It was observed that while the 'as synthesized' citrate capped AuNPs agglomerated under physiological salt conditions, all the mixed monolayer and PEG linker capped samples remained stable at 1M NaCl, and were stable in PBS over extended periods. While it was noted that both functionalization methods inhibited non-specific protein attachment, the mixed monolayer samples did show some changes in gel electrophoresis migration profile after incubation with fetal calf serum. PEG renders the AuNP stable in-vivo however, studies with MDA-MB-231 and MCF 10A cell lines indicated that functionalization with PEG, blocks cellular uptake. It was observed that co-functionalization with RME peptide using both the mixed monolayer and PEG linker methods greatly enhanced cellular internalization compared to PEG capped AuNPs.

Estratégia empresarial: contribuição para a análise estratégica das cooperativas vitivinícolas do Alentejo

O presente estudo tem como objetivos analisar a estratégia competitiva das adegas cooperativas do Alentejo, através da análise das ações que têm sido por elas desenvolvidas, propor linhas adicionais de ação estratégica e perspectivar as suas possibilidades de sucesso. A inovação e a flexibilidade das adegas cooperativas para se adaptarem ao crescente dinamismo dos contextos empresariais, conduziu a uma gestão mais profissional e a encarar a estratégia como necessária para uma maior competitividade. Nesse sentido, a cooperação entre as adegas cooperativas é vista como um meio de aumentar a competitividade no mercado internacional. A investigação permitiu constatar que o sector vitivinícola a nível mundial esta na fase de maturidade, com excesso de capacidade produtiva, procura global decrescente e queda de pregos, apresenta, no entanto, alterações significativas nos hábitos de consumo. As adegas cooperativas utilizam estratégias de diferenciação, apostam em produtos de qualidade e com elevados índices de notoriedade entre os consumidores. As principais diferenças competitivas entre elas estão relacionadas com a dimensão e a relação entre esta e a capacidade de recursos para investir ao nível do Marketing-Mix por forma a construir vantagens competitivas duradouras através da notoriedade dos seus vinhos. Para além disso, verifica-se também nas adegas de maior dimensão uma gestão estratégica mais orientada para a competitividade sustentável e maior visão estratégica. O método utilizado (estudo de caso comparativo, de natureza exploratória e, essencialmente qualitativo) não permite uma generalização extensiva dos seus resultados para além das cooperativas estudadas. Os resultados devem ser entendidos, de forma ponderada, no seu contexto específico e para os casos em concreto, pois, cada organização tem características únicas que influenciam o funcionamento da gestão. ABSTRACT - The present study has has been to analyse the competitive strategy of the Alentejo cooperative cellars, through the analysis of the shares that have been developed for the cooperative cellars, propose additional lines of strategic action and preview their possibility of success. The innovation and the flexibility of the cooperative cellars to the dynamic growth of the business contexts, accelerated shattering process of the enterprise contexts, lead to a more professional management and to face the strategy as necessary for a bigger competitiveness. In this direction, the cooperation between the cooperative cellars is seen as a way to increase the competitiveness in the international market. The inquiry allowed to evidence a world industry in maturity phase, with excess of productive capacity, presents a decreasing demand, alteration of the consumption habits and fall of the prices. The cooperative cellars use differentiation strategies, bet in products of quality and with raised indices of notoriety between the consumers. The main competitive differences between them are related with the dimension and the relation between this and the capacity of resources to invest to the level of Marketing-Mix for form to construct lasting competitive advantages through the notoriety of its wines. For moreover, a strategic management more guided for the sustainable competitiveness is also verified in the cellars of bigger dimension and bigger strategic vision. Due to the applied method (comparative case study, in searching manner and, essencialy qualitative) it cannot be purposed an extensive generalization of the results to another non-studied population. The results must be understood in a balanced way, in their Enterprise Strategy: Contribution for the Strategic Analysis of the Alentejo Wines Cooperatives specific context, and for real cases, since each company has its own features that influences the management work.

Novos saberes básicos dos alunos, novas competências dos professores : um estudo no âmbito da supervisão da formação de professores do 1º ciclo do ensino básico na Universidade de Aveiro

As mudanças sociais que, na actualidade, pressionam e desafiam a Escola, nomeadamente quanto aos papéis, funções e desempenho dos professores, implicam a necessidade de repensar a sua formação para que possam responder mais adequadamente aos desafios emergentes. Estes têm particularmente a ver com os novos saberes que essas condições exigem a todos os cidadãos e que são entendidos, do ponto de vista epistemológico, como saberes para agir responsavelmente. Assim, o principal objectivo deste estudo consiste em aprofundar o conhecimento acerca das ambiências e culturas de formação inicial de professores do 1. º Ciclo do Ensino Básico na Universidade de Aveiro, nomeadamente dos processos de supervisão ao nível da disciplina de Prática Pedagógica, tendo em consideração que as características de monodocência dos profissionais deste ciclo de ensino pressupõem um perfil de competência específico. A investigação, de natureza qualitativa, desenvolveu-se de acordo com as abordagens próprias da complexidade e da sistémica, das quais relevamos os princípios da totalidade em que os fenómenos são percebidos como sistemas globais e dinâmicos e da recursividade ao admitirmos a possibilidade de uma relação dialéctica entre os diversos subsistemas considerados. Do ponto de vista metodológico, no sentido de construir uma visão integrada do objecto em estudo, foi utilizado um conjunto de procedimentos específicos (mixed-methods), nomeadamente análise documental, inquirição por questionário e por entrevista semi-estruturada. O questionário foi aplicado à totalidade de licenciados em Ensino do 1.º Ciclo do Ensino Básico pela Universidade de Aveiro, compreendendo o período de 1998 até 2005. A entrevista foi realizada junto de supervisores (cooperantes e institucionais) que vêm acompanhando os núcleos de Prática Pedagógica, no decurso e ao longo do 4.º ano da referida Licenciatura. Quanto aos resultados do estudo, estes podem ser lidos em função de três eixos. Relativamente ao primeiro, que genericamente se refere à evolução dos saberes básicos dos alunos, os contributos parecem sugerir a necessidade de alicerçar os processos de ensino/aprendizagem não apenas nas literacias ler, escrever e contar, como também no desenvolvimento de saberes básicos de natureza geral e transversal, percebidos como competências, tais como aprender a pensar, aprender a aprender, aprender a comunicar e a resolver problemas, numa perspectiva de aprender a ser. O segundo eixo de leitura tem a ver com as competências requeridas aos professores para o desenvolvimento desses saberes estruturantes. De acordo com os dados recolhidos na fase extensiva do estudo, estes parecem coerentes com a revisão de literatura realizada, bem como com os normativos legais que, em Portugal, enquadram o perfil de desempenho dos professores do 1.º Ciclo. Porém, sugerem a necessidade de interligar as dimensões saber, saber-fazer e saber ser, com ênfase nesta última. À semelhança dos resultados referidos no ponto anterior, também o referencial de competências proposto para os professores integra as dimensões saber, saber fazer e saber ser, no qual são valorizadas as competências de reflexão crítica, de aprender a aprender e, de igual forma, o conhecimento profissional nas suas múltiplas dimensões. O terceiro eixo relaciona-se com a qualidade das ambiências e culturas de formação e supervisão. De forma geral, os dados apontam que ambientes que possibilitem uma dimensão de prática curricular alargada em contextos diversificados, que valorizem os princípios da pessoalidade e respeito pelo Outro e que estimulem a reflexão crítica, a auto-implicação dos formandos, o desenvolvimento de competências pessoais e de desenvolvimento profissional (destacando-se as competências para aprender a aprender, a comunicar, a investigar e reflectir), parecem adequar se melhor ao desenvolvimento pessoal e profissional destes professores, no contexto das sociedades contemporâneas. Assim, é possível verificar que os eixos considerados remetem para um conjunto recursivo de saberes e competências que, em diferentes níveis, implicam um compromisso com a acção, numa visão de mundo comprometida com as ideias de bem comum, ou seja, de cidadania universal.

A formação como actividade de aprendizagem docente

A partir dos pressupostos da teoria histórico-cultural, e em particular da Teoria da Actividade, desenvolvida por Leontiev, esta pesquisa estudou a aprendizagem docente num projecto de formação e investigação que privilegiou a atividade orientadora de ensino como metodologia de formação. Este desenvolveu-se em São João da Madeira e em Aveiro, com educadoras pertencentes a jardins de infância que mantinham um protocolo de colaboração com a disciplina de prática pedagógica da Licenciatura em Educação de Infância da Universidade de Aveiro. Para a dinâmica de formação, numa metodologia de pesquisa colaborativa, consideraram-se os encontros de formação como um espaço de discussão e reflexão dos pressupostos teóricos e da atividade orientadora de ensino, como desencadeadores de um movimento na aprendizagem docente. Dada a complexidade do objecto de estudo, investigar a aprendizagem docente, procurando compreender os sujeitos no seu próprio movimento de aprendizagem, assumimos o conceito de isolado (Caraça, 1998) como método de análise do fenómeno estudado. Identificamos três isolados que nos pareceram reunir factores determinantes, isto é, aqueles cuja acção de interdependência influiu sensivelmente no fenómeno estudado. O isolado contextual procurou analisar a aprendizagem num contexto próprio do desenvolvimento, considerando que as particularidades de cada contexto interferem no movimento de aprendizagem, definindo as acções e as operações de organização colectiva. A actividade reflexiva e crítica sobre a organização do ensino, sobre a prática e sobre o desenvolvimento docentes, constituiu o isolado reflexivo. Em estreita interdependência com os isolados anteriores, consideramos o isolado conceptual que mostra o movimento de apropriação, pelas educadoras, dos conceitos desenvolvidos ao longo do trabalho de investigação. A análise dos dados apresentou indicadores de mudança de qualidade na aprendizagem das educadoras, desencadeadas e sustentadas pela dinâmica de elaboração, de desenvolvimento e de reflexão de actividades de ensino, desenvolvidas colectivamente. Concluiu-se que a formação possibilitou a mudança nas concepções das educadoras sobre a aprendizagem, sobre a organização do ensino e sobre o seu próprio processo de aprendizagem. As contribuições teóricas da perspectiva histórico-cultural que fundamentam esse trabalho possibilitaram repensar a formação do professor, principalmente no que se refere aos processos de aprendizagem docente.

Isometrias: uma abordagem interdisciplinar no 8º ano de escolaridade

A sociedade atual requer indivíduos preparados para apresentar soluções inovadoras aos problemas encontrados nas mais variadas situações, sendo a criatividade considerada, na última década, uma competência essencial para o progresso. Neste contexto, emerge a necessidade da escola fomentar o seu desenvolvimento em qualquer área, e em particular, na Matemática. Por outro lado, não será alheio a este facto a promoção de um ensino, também ele, criativo. Tal ensino exige desde logo uma original, fluente e flexível gestão curricular envolvendo uma adequada seleção e ou (re) criação de tarefas relevantes, criteriosamente sequenciadas e autonomamente resolvidas pelos alunos, numa lógica de interdisciplinaridade e com recurso a tecnologia. No caso especifico das transformações geométricas isométricas, uma abordagem interdisciplinar reforçada com o recurso a ambientes de geometria dinâmica poderá constituir uma mais-valia nesse processo. Assim, desenvolveu-se este estudo, com o objetivo de avaliar o impacto de uma abordagem interdisciplinar, potenciada com o GeoGebra, no desenvolvimento de competências geométricas relacionadas com as isometrias, frisos e rosáceas, e em simultâneo, no desenvolvimento da criatividade e representações da mesma, de alunos do oitavo ano de escolaridade. Para isso desenvolveu-se um estudo de caso, centrado em três pares de alunos, que resolveram um conjunto de tarefas de natureza exploratória, com recurso ao GeoGebra e envolvendo a disciplina de Educação Visual. A análise dos dados recolhidos foi, essencialmente, de natureza qualitativa, tendo sido a observação, a inquirição e a análise documental,as principais técnicas de recolha de dados. A análise de conteúdo a que foram submetidos os dados, permitiu concluir que a implementação de uma abordagem interdisciplinar, centrada numa sequência de tarefas e aliada ao GeoGebra, potenciou a apropriação dos conhecimentos geométricos em causa e a sua aplicação. Contribuiu, também, para o desenvolvimento de atitudes favoráveis em relação à matemática e à geometria em particular. Por outro lado, os dados sugerem que tal abordagem permite obter indícios do desenvolvimento da criatividade nos alunos e de alterações a algumas das suas representações.

Role of insulin and insulin-like peptides in bone formation: identification of bone-specific target genes and regulatory mechanisms, and characterization of the insulin-mimetic effect of vanadium

Tese de Doutoramento em Biologia, Especialidade em Biologia Molecular, Universidade do Algarve, 2008

Discipline-specific writing for business students: Research, practice and pedagogy

In the past few years strong arguments have been made for locating academic writing in higher education within the students’ disciplinary contexts in the belief that a full understanding of the role and dynamic of writing can only be achieved if it is examined as a social practice in its context of production. This chapter reports on a study that examined the conceptualisations of writing for business by a group of undergraduate and postgraduate lecturers and students at the business school of a British university. Based on a critical analysis of the literature reviewed for the study, and the data collected, the chapter contributes to existing writing pedagogy with a number of research-informed transformative pedagogical applications for teaching discipline-specific writing for business. Such applications which combine context-oriented practices (e.g. raising awareness of the role of disciplinary values in shaping writing) and text-oriented activities (e.g. discipline-specific referencing) aim at influencing the pedagogic agenda for teaching writing in higher education. The chapter concludes with questions for reflection and discussion that provide an opportunity for readers to reflect upon their own teaching environment.

Adaptive learning in agents behaviour: a framework for electricity markets simulation

Electricity markets are complex environments with very particular characteristics. A critical issue regarding these specific characteristics concerns the constant changes they are subject to. This is a result of the electricity markets’ restructuring, which was performed so that the competitiveness could be increased, but it also had exponential implications in the increase of the complexity and unpredictability in those markets scope. The constant growth in markets unpredictability resulted in an amplified need for market intervenient entities in foreseeing market behaviour. The need for understanding the market mechanisms and how the involved players’ interaction affects the outcomes of the markets, contributed to the growth of usage of simulation tools. Multi-agent based software is particularly well fitted to analyze dynamic and adaptive systems with complex interactions among its constituents, such as electricity markets. This dissertation presents ALBidS – Adaptive Learning strategic Bidding System, a multiagent system created to provide decision support to market negotiating players. This system is integrated with the MASCEM electricity market simulator, so that its advantage in supporting a market player can be tested using cases based on real markets’ data. ALBidS considers several different methodologies based on very distinct approaches, to provide alternative suggestions of which are the best actions for the supported player to perform. The approach chosen as the players’ actual action is selected by the employment of reinforcement learning algorithms, which for each different situation, simulation circumstances and context, decides which proposed action is the one with higher possibility of achieving the most success. Some of the considered approaches are supported by a mechanism that creates profiles of competitor players. These profiles are built accordingly to their observed past actions and reactions when faced with specific situations, such as success and failure. The system’s context awareness and simulation circumstances analysis, both in terms of results performance and execution time adaptation, are complementary mechanisms, which endow ALBidS with further adaptation and learning capabilities.

Conceiving modern engineers within the framework of the sustainability action plan (PASUS) of ISEP: sustainability matters!

Engineering education practices have evolved not only due to the natural changes in the contents of the curricula and skills but also, and more recently, due to the requirements imposed by the Bologna revision process. In addition, industry is becoming more demanding, as society is becoming more and more aware of the global needs and consequences of industrial practices. Under this scope, higher education needs not only to follow but also to lead these trends. Therefore, the School of Engineering of the Polytechnic Institute of Porto (ISEP), a Global Reporting Initiative (GRI) training partner in Portugal, prepared and presented its Sustainability Action Plan (PASUS), with the main objective of creating a new kind of engineers, with Sustainable Development at the core of their graduation and MsC degrees. In this paper, the main strategies and activities of the referred plan along with the strategic approach, which guided its development and implementation, will be presented in detail. Additionally, a reflection about the above mentioned bridge between concept and application will be established and justified, in the framework of the action plan. Although in most of the situations, there was no prior discussion or specific request, many of the graduation and post-graduation programmes offered by ISEP already include courses that attend to PASUS philosophy. As a consequence, the number of Master thesis, Graduation projects and R&D projects that address sustainability problems has grown substantially, a proof that for ISEP community, sustainability really matters!