Molecular markers in the treatment of metastatic colorectal cancer

Although significant progress has been made in colorectal cancer (CRC) treatment within the last decade with the approval of multiple new agents, the prognosis for patients with metastatic CRC remains poor with 5-year survival rates of approximately 8%. Resistance to chemotherapy remains a major obstacle in effective CRC treatment and many patients do not receive any clinical benefit from chemotherapy. In addition, other patients will experience adverse reactions to treatment resulting in dose modifications or treatment withdrawal, which can severely reduce treatment efficacy. Currently, significant research efforts are attempting to identify reliable and validated biomarkers with which will guide clinicians to make more informed treatment decisions. Specifically, the use of molecular profiling has the potential to assist the clinician in administering the correct drug, dose, or intervention for the patient before the onset of therapy thereby selecting a treatment strategy likely to have the greatest clinical outcome while minimizing adverse events. However, until recently, personalized medicine is a paradigm that has existed more in conceptual terms than in reality with very few validated biomarkers used routinely in metastatic CRC treatment. Rapid advances in genomic, transcriptomic and proteomic technologies continues to improve our understanding of tumor biology, but the search for reliable biomarkers has turned out to be more challenging than previously anticipated with significant disparity in published literature and limited translation into routine clinical practice. Recent progress with the identification and validation of biomarkers to the anti-epidermal growth factor receptor monoclonal antibodies including KRAS and possibly BRAF provide optimism that the goal of individualized treatment is within reach. This review will highlight and discuss current progress in the search for biomarkers, the challenges this emerging field presents, and the future role of biomarkers in advancing CRC treatment.

Molecular predictors of response to antiangiogenesis therapies

Angiogenesis is a crucial component of tumor growth and metastasis. Targeting the vascular endothelial growth factor pathway represents therapeutic potentials for treating cancer. To date, 3 Food and Drug Administration-approved agents targeting angiogenesis have been developed, bevacizumab, sunitinib, and sorafenib. However, no validated biomarkers are available to identify those patients who are likely to benefit from antiangiogenesis therapy. Molecular biomarker research in antiangiogenesis inhibition is an actively growing field. Although current data are extremely promising, it is still uncertain which biomarker(s) can reliably predict their efficacy. With increasing numbers of inhibitors being developed, the need for biomarkers is more critical than ever. This review will focus on translational research that strives to identify molecular biomarkers (tissue, circulating and genomic) for approved antiangiogenesis therapies that can indicate benefit, resistance, and toxicity.

Shape stabilised phase change materials based on a high melt viscosity HDPE and paraffin waxes

Shape stabilised phase change materials (SSPCMs) based on a high density poly(ethylene)(hv-HDPE) with high (H-PW, Tm = 56–58 °C) and low (L-PW, Tm = 18–23 °C) melting point paraffin waxes were readily prepared using twin-screw extrusion. The thermo-physical properties of these materials were assessed using a combination of techniques and their suitability for latent heat thermal energy storage (LHTES) assessed. The melt processing temperature (160 °C) of the HDPE used was well below the onset of thermal decomposition of H-PW (220 °C), but above that for L-PW (130 °C), although the decomposition process extended over a range of 120 °C and the residence time of L-PW in the extruder was <30 s. The SSPCMs prepared had latent heats up to 89 J/g and the enthalpy values for H-PW in the respective blends decreased with increasing H-PW loading, as a consequence of co-crystallisation of H-PW and hv-HDPE. Static and dynamic mechanical analysis confirmed both waxes have a plasticisation effect on this HDPE. Irrespective of the mode of deformation (tension, flexural, compression) modulus and stress decreased with increased wax loading in the blend, but the H-PW blends were mechanically superior to those with L-PW.

Biomass fly ash incorporation in cement based materials

In recent years, pressures on global environment and energy security have led to an increasing demand on renewable energy sources, and diversification of Europe’s energy supply. Among these resources the biomass could exert an important role, since it is considered a renewable and CO2 neutral energy resource once the consumption rate is lower than the growth rate, and can potentially provide energy for heat, power and transports from the same installation. Currently, most of the biomass ash produced in industrial plants is either disposed of in landfill or recycled on agricultural fields or forest, and most times this goes on without any form of control. However, considering that the disposal cost of biomass ashes are raising, and that biomass ash volumes are increasing worldwide, a sustainable ash management has to be established. The main objective of the present study is the effect of biomass fly ashes in cement mortars and concretes in order to be used as a supplementary cementitious material. The wastes analyzed in the study were collected from the fluidized bed boilers and grate boilers available in the thermal power plants and paper pulp plants situated in Portugal. The physical as well as chemical characterisations of the biomass fly ashes were investigated. The cement was replaced by the biomass fly ashes in 10, 20 and 30% (weight %) in order to investigate the fresh properties as well as the hardened properties of biomass fly ash incorporated cement mortar and concrete formulations. Expansion reactions such as alkali silica reaction (ASR), sulphate attack (external and internal) were conducted in order to check the durability of the biomass fly ash incorporated cement mortars and concretes. Alternative applications such as incorporation in lime mortars and alkali activation of the biomass fly ashes were also attempted. The biomass fly ash particles were irregular in shape and fine in nature. The chemical characterization revealed that the biomass fly ashes were similar to a class C fly ash. The mortar results showed a good scope for biomass fly ashes as supplementary cementitious materials in lower dosages (<20%). The poor workability, concerns about the organic content, alkalis, chlorides and sulphates stand as the reasons for preventing the use of biomass fly ash in high content in the cement mortars. The results obtained from the durability tests have shown a clear reduction in expansion for the biomass fly ash mortars/concretes and the binder blend made with biomass fly ash (20%) and metakaolin (10%) inhibited the ASR reaction effectively. The biomass fly ash incorporation in lime mortars did not improve the mortar properties significantly though the carbonation was enhanced in the 15-20% incorporation. The biomass fly ash metakaolin blend worked well in the alkali activated complex binder application also. Portland cement free binders (with 30-40 MPa compressive strength) were obtained on the alkali activation of biomass fly ashes (60-80%) blended with metakaolin (20-40%).

Biodiesel fuel formulation

O consumo de energia a nível mundial aumenta a cada dia, de forma inversa aos recursos fósseis que decrescem de dia para dia. O sector dos transportes é o maior consumidor deste recurso. Face ao actual cenário urge encontrar uma solução renovável e sustentável que permita não só, diminuir a nossa dependência de combustíveis fósseis mas fundamentalmente promover a sua substituição por energias de fontes renováveis. O biodiesel apresenta-se na vanguarda das alternativas aos combustiveis derivados do petróleo, para o sector dos transportes, sendo considerado uma importante opção a curto prazo, uma vez que o seu preço pode ser competitivo com o diesel convencional, e para a sua utilização o motor de combustão não necessita de alterações. O biodiesel é uma mistura líquida, não tóxica, biodegradável de ésteres de ácidos gordos, sem teor de enxofre ou compostos aromáticos, apresenta boa lubricidade, alto número de cetano, e origina emissões gasosas mais limpas. O presente trabalho contribui para um melhor conhecimento da dependência das propriedades termofisicas do biodiesel com a sua composição. A publicação de novos dados permitirá o desenvolvimento de modelos mais fiáveis na previsão do comportamento do biodiesel. As propriedades densidade e viscosidade são o espelho da composição do biodiesel, uma vez que dependem directamente da matéria prima que lhe deu origem, mais do que do processo de produção. Neste trabalho os dados medidos de densidade e viscosidade de biodiesel foram testados com vários modelos e inclusivamente foram propostos novos modelos ajustados para esta família de compostos. Os dados medidos abrangem uma ampla gama de temperaturas e no caso da densidade também foram medidos dados a alta pressão de biodiesel e de alguns ésteres metilico puros. Neste trabalho também são apresentados dados experimentais para o equilíbrio de fases sólido-liquído de biodiesel e equlibrio de fases líquidolíquido de alguns sistemas importantes para a produção de biodiesel. Ambos os tipos de equilíbrio foram descritos por modelos desenvolvidos no nosso laboratório. Uma importância especial é dado aqui a propriedades que dependem do perfil de ácidos gordos da matéria-prima além de densidade e viscosidade; o índice de iodo e temperature limite de filtrabalidade são aqui avaliados com base nas considerações das normas. Os ácidos gordos livres são um sub-produto de refinação de óleo alimentar, que são removidos na desodoração, no processo de purificação do óleo. A catálise enzimática é aqui abordada como alternativa para a conversão destes ácidos gordos livres em biodiesel. Estudou-se a capacidade da lipase da Candida antartica (Novozym 435) para promover a esterificação de ácidos gordos livres com metanol ou etanol, utilizando metodologia de superfície de resposta com planeamento experimental. Avaliou-se a influência de diversas variáveis no rendimento da reacção.

Using recycled aggregates in green roof substrates for plant diversity

Extensive green roofs are becoming a popular tool for restoring green infrastructure in urban areas, particularly biodiverse habitats such as post-industrial/brownfield sites. This study investigated the use of six recycled lightweight aggregates and combinations of them in green roof growing substrate, to determine their effectiveness for enhancing plant abundance and species diversity. In two separate experiments, we examined the roles of substrate type and depth on the establishment of a perennial wildflower mix over a 15-month period. We found that some of the alternative substrates are comparable to the widely used crushed red brick aggregate (predominantly found in commercial green roof growing substrate) for supporting plant establishment. For some materials such as clay pellets, there was increased plant coverage and a higher number of plant species than in any other substrate. Substrates that were produced from a blend of two or three aggregate types also supported higher plant abundance and diversity. Generally, increasing substrate depth improved plant establishment, however this effect was not consistent across substrates. We conclude that recycled materials may be viable constituents of growing substrate for green roofs and they may improve green roof resilience, through increased plant cover and diversity. The results could provide evidence to support the construction of mosaic habitat types on single roofs using various substrate blends.

Flourishing as a dialectical balance: emerging insights from second-wave positive psychology

Positive psychology, an emergent branch of scholarship concerned with wellbeing and flourishing, initially defined itself by a focus on “positive” emotions and qualities. However, critics soon pointed out that this binary logic—classifying phenomena as either positive or negative, and valorising the former while disparaging the latter—could be problematic. For example, apparently positive qualities can be harmful to wellbeing in certain circumstances, while ostensibly dysphoric emotional states may on occasion promote flourishing. Responding to these criticisms, over recent years a more nuanced “second wave” of positive psychology has been developing, in which wellbeing is recognized as involving a dialectical balance of light and dark aspects of life. This article introduces this emergent second wave, arguing that it is characterized by four dialectical principles. First, the principle of appraisal states that it is difficult to categorically identify phenomena as either positive or negative, since such appraisals are fundamentally contextually dependent. Second, the principle of co-valence holds that many states and qualities at the heart of flourishing, such as love, are actually a complex blend of light and dark elements. Third, the principle of complementarity posits that not only are such phenomena co-valenced, but that their dichotomous elements are in fact co-creating, two intertwined sides of the same coin. Finally, the principle of evolution allows us to understand second-wave positive psychology as itself being an example of a dialectical process. This article is published as part of a collection entitled “On balance: lifestyle, mental health and wellbeing”.

Acessibilidade e mobilidade no espaço público dos centros históricos: proposta de um percurso histórico-cultural acessível no núcleo histórico Vila Adentro de Faro

Dissertação de mestrado, Arquitetura Paisagista, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Innovative edible films to improve storage ability of fresh-cut apple cv. Bravo de Esmolfe

Dissertação de mestrado, Hortofruticultura, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Valorização de resíduos carbonosos de gasificação como precursores de materiais para adsorção de poluentes em fase aquosa

Tese de doutoramento, Energia e Ambiente (Energia e Desenvolvimento Sustentável), Universidade de Lisboa, Faculdade de Ciências, 2014

An Evaluative Case Study of a Career Coaching Approach to Improving Student Placement Success in a UK Business School

Describes the innovative approach adopted in a UK business school to improve the number of student placements. A module was designed to provide students with the skills to search, apply for and gain a year-long placement as part of a degree ‘sandwich’ course. A blend of workshops, recorded lectures, online formative feedback exercises and one-to-one career coaching created a tailored, practical approach to skill enhancement. This session provides the presentation of the adopted methodology the results of the evaluative research, a live demonstration of the coaching approach and a discussion with the audience of ideas for development of the approach.

Control of endosomal Toll-like receptor (TLR) signaling by nanoparticles and applications in cancer therapy

Thesis (Ph.D.)--University of Washington, 2014

Electrospun Contrast Agent-Loaded Fibers for Colon-Targeted MRI

Magnetic resonance imaging is a diagnostic tool used for detecting abnormal organs and tissues, often using Gd(III) complexes as contrast-enhancing agents. In this work, core–shell polymer fibers have been prepared using coaxial electrospinning, with the intent of delivering gadolinium (III) diethylenetriaminepentaacetate hydrate (Gd(DTPA)) selectively to the colon. The fibers comprise a poly(ethylene oxide) (PEO) core loaded with Gd(DTPA), and a Eudragit S100 shell. They are homogeneous, with distinct core–shell phases. The components in the fibers are dispersed in an amorphous fashion. The proton relaxivities of Gd(DTPA) are preserved after electrospinning. To permit easy visualization of the release of the active ingredient from the fibers, analogous materials are prepared loaded with the dye rhodamine B. Very little release is seen in a pH 1.0 buffer, while sustained release is seen at pH 7.4. The fibers thus have the potential to selectively deliver Gd(DTPA) to the colon. Mucoadhesion studies reveal there are strong adhesive forces between porcine colon mucosa and PEO from the core, and the dye-loaded fibers can be successfully used to image the porcine colon wall. The electrospun core–shell fibers prepared in this work can thus be developed as advanced functional materials for effective imaging of colonic abnormalities.

Segurança e sinalização na vizinhança de áreas escolares: estudos de casos em Santarém

A vizinhança viária dos estabelecimentos escolares constitui-se como um local de concentração de peões e de ciclistas, cuja movimentação conflitua com os veículos automóveis, quer sejam de natureza particular ou pública. O ambiente urbano em que se localiza o edifício escolar, a natureza da rede viária que lhe serve de acesso, a faixa etária e o número de alunos que a frequentam, são fatores que são determinantes no estudo de soluções que induzam e estimulem os comportamentos em segurança de todos os intervenientes, nomeadamente os escolares e os condutores. Com efeito, escolas em ambiente urbano requerem o estudo de composições viárias diferentes das localizadas em ambiente rural, da mesma forma que estabelecimentos do Ensino Básico ou Secundário apresentam comportamentos de utentes perfeitamente distintos. O planeamento inadequado e a dinâmica do crescimento e da transformação das cidades são alguns dos fatores que ao longo dos anos se traduziram em impactos muitas vezes negativos na segurança e fluidez do tráfego junto às escolas, resultados que deveriam representar a prioridade dos órgãos de trânsito nacionais e municipais. Alguns países do mundo e algumas cidades da Europa têm entretanto investido na implementação de várias medidas para mitigar os referidos impactes. Aproveitando-se como referência as melhores práticas sobre a temática segurança viária e os casos de sucesso desenvolvidos, pretendeu-se com este trabalho elaborar uma proposta de projeto para dois estabelecimentos de ensino da cidade de Santarém. Os resultados da análise prévia às condições particulares de segurança existentes e a comparação com outros estabelecimentos localizados na zona urbana da cidade, foram determinantes para esta escolha. Com base nos dados obtidos e nas características dos tráfegos pedonal e viário, são apresentadas duas soluções distintas que poderão ser genericamente aplicadas em situações similares, dada a impossibilidade de se estudarem soluções tipo que não resultariam, face à complexidade e diversidade das variáveis envolvidas.

Integração num plano municipal de segurança rodoviária: Cidade da Amadora: Freguesia da Venteira

Trabalho de Projeto para obtenção do grau de Mestre em Engenharia na Área de Especialização em Vias de Comunicação e Transportes