HLA-DR in Cytotoxic T lymphocytes predicts breast cancer patients' response to neoadjuvant chemotherapy

Prediction of breast cancer response to Neoadjuvant Chemotherapy (NACT) is an urgent need to promptly direct non-responder patients to alternative therapies. Infiltrating T lymphocytes, namely cytotoxic T lymphocytes (CTLs) have been appointed as predictors of response. However, cancer cells have the ability to dampen CTLs' activity and thus, the prognostic value of the CTLs, per se, is debatable. Here, we disclose that more than the occurrence of CTLs, it is their activation state, revealed by HLA-DR expression, that can accurately predict response to NACT. Flow cytometry analysis of breast cancer biopsies showed that the frequency of CTLs and other lymphocytes were similar regardless disease stage and between NACT responders and non-responders. However, only breast cancer patients without axillary lymph node metastasis and NACT responders have HLA-DRhi CTLs. Interestingly, HLA-DR levels in tumor CTLs is correlated with HLA-DR levels in systemic CTLs. These HLA-DR+ CTLs produce IFN-γ and Granzyme B, enlightening their effector and probable anti-tumor activity profile. Moreover, the level of HLA-DR in CTLs is negatively correlated with the level of HLA-DR in T regulatory lymphocytes and with immunosuppressive and pro-tumor molecules in the tumor microenvironment. Hence, HLA-DR levels in CTLs is a highly sensitive and specific potential predictive factor of NACT-response, which can be assessed in blood to guide therapeutic decisions.Fundacao para a Ciencia e Tecnologia: PD/BD/114023/2015; PTDC/BBB-BMD/4497/2014. Liga Portuguesa Contra o Cancroinfo:eu-repo/semantics/publishedVersio

THE DYNAMIC OF USING THE RIVERS ENERGY FROM REPUBLIC OF MOLDOVA TERRITORY

The dynamic of using the rivers energy from Republic of Moldova territory. One of the least explored and tapped energy sources in Moldova are the inland rivers. Considering the critical condition of the country regarding energy sources, it would be highly necessary to study the feasibility of hydraulic energy reserves. Although Moldova has no major rivers with a large flow of water, the network of small tributaries of its two large rivers, Dniester and Prut, could be used to a certain extent for partial power supply to villages situated along inland watercourses.The first scientific developments concerning the hydropower potential of the rivers in Bessarabia belong to professor D. Pavel. Around 1933 he was suggesting a series of hydro-technical facilities on Prut and Dniester rivers and their tributaries. Subsequently, in the ‘40s of the 20th century the first power plants were built on small rivers. After World War II some small hydropower plants, built during the interwar period, had been restored and some other put into operation. These include the plant at Dubăsari with a capacity of 48 MW that started operating in 1954 on Dniester River, and the hydroelectric complex at Costeşti -Stânca with a capacity of 16 MW, in 1978 on the River Prut. Nevertheless, the leverage of hydroelectric resources is not significant, only 23 being used nowadays, which is 7% of the hydropower potential - a rather modest number compared to other states

Comparação do cálculo de dose com os algoritmos Analytical Anisotropic Algorithm e Pencil Beam Convolution na patologia de pulmão

Mestrado em Radioterapia.O cancro do pulmão é o 4º com maior incidência e constitui a 2ª causa de morte por cancro em Portugal. Na Europa, é o 3º mais comum e a 1ª causa de morte por cancro. A radioterapia constitui uma terapêutica não invasiva que permite a destruição das células tumorais. Os movimentos respiratórios e do alvo, aliados à difícil simulação do comportamento do feixe na presença de interfaces tecidulares extremas elevam as dificuldades de irradiação destas lesões. O objetivo deste trabalho é a avaliação da diferença na dose calculada entre os algoritmos Pencil Beam Convolution (PBC) e Analytical Anisotropic Algorithm (AAA), disponíveis na versão 10.0 do Eclipse® da Varian Medical Systems®. Foi avaliada a diferença no cálculo de PBC para AAA, mantendo todas as características das distribuições iniciais e foi avaliada a diferença após otimização das distribuições AAA (AAAo). Em ambos os ramos foram estudados: a variação do número de unidades de monitor; a variação de dose no alvo; e a diferença de dose nos órgãos de risco. A dose nos órgãos de risco não excedeu as tolerâncias recomendadas e as diferenças encontradas não são clinicamente significantes. O PBC parece subestimar a dose no alvo com a sobrestimação da cobertura do PTV, na presença de heterogeneidades. O AAA apresenta-se mais preciso e rigoroso com as baixas densidades, embora a alteração do algoritmo provoque consequências significativas na cobertura do alvo, devendo sempre ser acompanhada de uma nova otimização, tendo em conta a melhoria substancial na cobertura do alvo.ABSTRACT - The Lung cancer is the 4th major incidence by cancer and the 2nd cause of death in Portugal. In Europe is the 3rd most common and the 1st cause of death by cancer. The radiotherapy constitutes a non invasive therapeutic that allows the elimination of tumor cells. The respiratory and target movements allied to the difficult simulation of the beam behavior in the presence of extreme tissue interfaces, increase the irradiation difficulties on this lesions. The aim of this work is the evaluation of the difference in the calculated dose between the Pencil Beam Convolution (PBC) and Analytical Anisotropic Algorithm (AAA), algorithms available in the version 10.0 of Eclipse® from Varian Medical Systems®. It was evaluated the differences between PBC and AAA calculations, keeping all the characteristics of the inicial distributions; and it was evaluated the differences after the optimization of the AAA versions (AAAo). In both arms were studied: the variation of the total monitor units; the dose variation within target; and the dose difference in the organs at risk. The dose within the organs at risk did not exceed the tabled tolerances recommended, and the differences found are not clinically relevant. The PBC seems to underestimate the target dose mainly by overestimating the target coverage, in the presence of heterogeneities. The AAA appears to be more precise and rigorous with lower densities, although the algorithm alteration creates significant consequences on the target coverage. Therefore, it is wise to re-optimize the distributions mostly by the substantial increase of the target coverage

Schutz von Holz- und TMP-Holzstoff-Oberflächen vor lichtinduzierter Vergilbung durch chemische Modifikation des Lignins

Ein neuer Reaktionsmechanismus der Chromophorenbildung im Lignin wurde bei der lichtinduzierten Vergilbung von Holz- und TMP-Holzstoff-Oberflächen identifiziert. Die Photolabilität der acetylierten Oberflächen wurde anhand von Untersuchungen mit Ligninmodellsubstanzen nachgewiesen. Basierend auf dieser Erkenntnis wurde eine neuartige Schutzmethode für Holz- und TMP-Holzstoff-Oberflächen vor lichtinduzierter Vergilbung entwickelt

Padrões de persistência da inovação de acordo com os tipos de inovação

The role of innovation in economic growth is widely explored, thus, in the last decades it has been understood that along with innovation per se, one must address the continuity of these behaviours over time. Analysing the details of innovation persistence helps in the understanding of firm dynamics, effectiveness of policy actions, raising productivity and prosperity generation. Persistence of innovation is empirically explored using technological innovation, and continuity of innovative behaviours in the same innovation type; non-technological innovation types are somehow neglected and, the existing literature may not apply to the innovation types in a generalised manner and iterative persistence of innovation has not been detailed so far. Understanding the specific characteristics of each innovation type will grant the design of fine tuning policy actions accommodating the array of particularities. Moreover, the effect of the absorptive capacity and the open innovation strategy has not been connected to the innovation types by the existing literature. The present thesis analyses persistence of innovation using a dynamic panel comprising 2147 firms operating in all economic sectors in Portugal, observed from 2008 to 2014, covering three editions of the Portuguese Community Innovation Survey (CIS). Using the random effects probit model, conventional hypothesis of persistence hypothesis is supported for interactive process innovation, reinforcing the specific characteristics of each innovation type. That fact that only a small number of firms are persistent in the technological types of innovation seems to prove that policy programs financing the same innovation type will fail to boost future innovation. The results point to intermittence in innovative behaviors in the different innovation types, however, process innovation presents a different pattern from all others. The open innovation strategy seems to reinforce intermittence and public funds are helpful only for technological innovations; there is a scale effect reinforcing persistence. Therefore, is seems rational to encourage differentiated public policies targeting the different innovation types avoiding the one size fits all approaches in use at present.O papel da inovação no crescimento económico está amplamente explorado, de tal forma que, nas últimas décadas aprofundou-se o tema da inovação e quais as suas interferências na sucessão de comportamentos inovadores ao longo do tempo. A análise dos detalhes da persistência da inovação ajuda a compreender a dinâmica das empresas, a eficácia das ações políticas, o aumento da produtividade e da prosperidade A persistência da inovação é analisada empiricamente com base na inovação tecnológica e na continuidade de comportamentos inovadores no mesmo tipo de inovação. Contudo, os tipos de inovação não tecnológica são, de certa forma, negligenciados e a literatura existente pode não aplicar os tipos de inovação de uma forma generalizada. Para além disso, a persistência iterativa da inovação ainda não foi estuda de forma detalhada. A compreensão das características específicas de cada tipo de inovação permitirá aos decisores de política ajustarem as suas decisões ao conjunto de particularidades. Além disso, o efeito da capacidade de absorção e da estratégia de inovação aberta não têm sido interligados com os tipos de inovação existentes na literatura. A presente dissertação analisa a persistência da inovação através de um painel dinâmico composto por 2147 empresas Portuguesas de todos os setores económicos, observadas entre 2008 e 2014, abrangendo três edições do Inquérito Comunitário à Inovação (CIS). Deste modo, utilizando o modelo probit de efeitos aleatórios, a hipótese convencional de persistência é apoiada para a inovação de processo iterativo, reforçando as características específicas de cada tipo de inovação. O facto de que apenas um pequeno número de empresas ser persistente nos tipos tecnológicos de inovação parece provar que os programas de políticas que financiam o mesmo tipo de inovação não conseguirão impulsionar a inovação futura. Os resultados apontam para intermitência de comportamentos inovadores nos diferentes tipos de inovação, no entanto, a inovação de processo apresenta um padrão diferente de todos os outros. A estratégia de inovação aberta parece reforçar a intermitência e os fundos públicos são úteis apenas para as inovações tecnológicas. Portanto, parece racional estimular políticas públicas diferenciadas visando os diferentes tipos de inovação, de forma a evitar uma visão única para todas as abordagens utilizadas atualmente.Mestrado em Economi

How many diseases is triple negative breast cancer; the protagonism of the immune microenvironment

Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, coupled with data coming from pathology and epidemiology, suggests that this negative definition is not capturing a single clinical entity, but several. We critically evaluate this evidence in this paper, reviewing clinical and epidemiological data and new studies that aim to subclassify TNBC. Moreover, evidence on the role of tumour infiltrating lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient outcome have been published. The heterogeneity, observed even at TILs level, highlights the idea that TNBC is much more than a single disease with a unique treatment. The exploration of the immune environment present at the tumour site could indeed help in answering the question 'How many diseases is TNBC' and will help to define prognosis and eventually develop new therapies, by stimulating the immune effector cells or by inhibiting immunological repressor molecules. In this review, we focus on the prospect of the patient's diverse immune signatures within the tumour as potential biomarkers and how they could be modulated to fight the disease.publishersversionpublishe

Abastecimento de água na zona norte da Figueira da Foz

Mestrado em Engenharia do AmbienteO abastecimento de água à população é fundamental para o desenvolvimento de uma sociedade saudável. Neste contexto, o abastecimento deve garantir o fornecimento de uma água de forma contínua, na pressão adequada, isenta de microrganismos e de substâncias químicas que possam constituir potencial perigo para a saúde humana. Como tal, o presente trabalho tem por objetivo central um diagnóstico geral do sistema de abastecimento de água, nomeadamente da zona norte do concelho da Figueira da Foz. Pretende-se essencialmente tomar contacto com os processos de tratamento e distribuição de água potável ao consumidor final. Para isso, recorreu-se à caracterização da água bruta, caracterização do sistema de tratamento da Estação de Tratamento de Água das Braças, caracterização das infraestruturas de adução e reserva de água, modelação matemática da rede de adução e análise da qualidade da água tratada.The water supply to the population is essential to the development of a healthy society. In such context, the company must ensure the provision of continuous and clear water with suitable pressure, free from microorganism and chemical substances that might be potentially dangerous to human health, so that the water should be well accepted by the consumers. As such, the main purpose of this paper is to make a general diagnosis of the water supply system in the north area of Figueira da Foz. It’s essential to understand the process of treatment and distribution of the drinking water to the final consumer. For this, we used the characterization of Raw Water, characterization of the treatment system in the water treatment station of Braças, characterization of the adduction infrastructures and water reserve, mathematical modellation of the adduction network and the analysis of the quality of the treated water