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The Internet of Things (IoT) is an emerging technological paradigm, which is experiencing an exponential growth. It focus on distributed sensing to acquire knowledge about the real world, and distributed computing for its computational capabilities. An IoT node is composed of a microprocessor, a communication unit (RF radio), sensors or actuators and a power source. It tries to achieve extremely high battery life (years or decades), mainly through aggressive duty cycling. This way, the node spends most of its life in a sleep state (apart from some always-on components). The duty cycling comes with a disadvantage: all data must be stored in retentive memories (e.g. flash memory) or in always-on parts of the circuitry. Static Random Access Memory (SRAM) is a type of non-retentive memory that can hold its data indefinitely (while powered). It is used in small embedded devices and SoC, as well as in processors cache. By designing a SRAM module for the sensors data that focus on lowering the power consumption, the overall power consumption of the power node can be reduced. This work focus on designing a full-custom 180 nm CMOS SRAM for Ultra Low Power. The SRAM has 128 bytes (1024 bits) of storage, and works at 128 Hz clock frequency, while powered at 200 mV.

Background Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). Methods We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. Results Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14+CD56+ and a lower fraction of CD14+CD16+ monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. Conclusions Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients. Electronic supplementary material The online version of this article (10.1186/s12878-018-0101-8) contains supplementary material, which is available to authorized users.

Background Red cell distribution width (RDW), a classical parameter used in the differential diagnosis of anemia, has recently been recognized as a marker of chronic inflammation and high levels of oxidative stress (OS). Fanconi anemia (FA) is a genetic disorder associated to redox imbalance and dysfunctional response to OS. Clinically, it is characterized by progressive bone marrow failure, which remains the primary cause of morbidity and mortality. Macrocytosis and increased fetal hemoglobin, two indicators of bone marrow stress erythropoiesis, are generally the first hematological manifestations to appear in FA. However, the significance of RDW and its possible relation to stress erythropoiesis have never been explored in FA. In the present study we analyzed routine complete blood counts from 34 FA patients and evaluated RDW, correlating with the hematological parameters most consistently associated with the FA phenotype. Results We showed, for the first time, that RDW is significantly increased in FA. We also showed that increased RDW is correlated with thrombocytopenia, neutropenia and, most importantly, highly correlated with anemia. Analyzing sequential hemograms from 3 FA patients with different clinical outcomes, during 10 years follow-up, we confirmed a consistent association between increased RDW and decreased hemoglobin, which supports the postulated importance of RDW in the evaluation of hematological disease progression. Conclusions This study shows, for the first time, that RDW is significantly increased in FA, and this increment is correlated with neutropenia, thrombocytopenia, and highly correlated with anemia. According to the present results, it is suggested that increased RDW can be a novel marker of stress erythropoiesis in FA. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0485-0) contains supplementary material, which is available to authorized users.

Comparatively to open repair, endovascular aneurysm repair has reduced transfusion rates but thereâs no recommendation about number of red blood cells units to be crossmatched preoperatively. Our aim is contribute to the analysis of red blood cells units needs in endovascular and hybrid aortic aneurysm repair and developing a protocol for maximum surgical blood orders schedule.We retrospectively analyzed our prospective database of elective endovascular aneurysm repair from 2001 to 2012. We analyzed patients' age, gender, ASA classification, maximum surgical blood orders schedule, red blood cells units transfused and timings, types of endoprosthesis, red blood cells units consumption/endoprosthesis' type ratio, crossmatch to transfusion ratio, conversion to open repair, hemoglobin concentrations before surgery and discharge.We selected 187 patients, 90% men, mean age 73.1, ASA mode III. The endoprosthesis were aorto-bi-iliac in 71%, aorto-uni-iliac in 23% and thoracic in 6%. Of these, 72,6% of the patients did not require blood transfusion. We transfused 171 red blood cells units. Crossmatch to transfusion ratio was 10.1 until 2010 and 7.3 after. The ratio of red blood cells units consumption/endoprosthesis in the first 24 hours was 0.21 red blood cells units/aorto-bi-iliac, 0.46 red blood cells units/aorto-uni-iliac, 0.8 red blood cells units/thoracic, 1.3 red blood cells units/hybrid-thoracic and 2 red blood cells units/hybrid-aorto-bi-iliac. A statistical correlation was observed between red blood cells units transfused postoperatively and type of endoprosthesis (p0.001) and between ASA classification and red blood cells units transfused after 24 hours (p0.01).Guidelines from the British Society of Haematology are based on a crossmatch to transfusion ratio of 2:1. Our crossmatch to transfusion ratio was 10.1 until 2010 and 7.3 from 2011 to 2012.These results changed our policy of maximum surgical blood orders schedule for endovascular aneurysm repair. We now type and screen aorto-bi-iliac and aorto-uni-iliac. We crossmatch two red blood cells units for thoracic, three red blood cells units for hybrid thoracic and four red blood cells units for hybrid abdominal procedures. This may lead to financial savings, improved efficiency and reduce workload in hematology department.Introdução: O tratamento endovascular dos aneurismas da aorta reduziu as taxas de transfusão. Não existem recomendações relativamente às unidades de glóbulos vermelhos a serem tipadas por crossmatch pré-operatoriamente. O nosso objetivo é contribuir para a análise das unidades de glóbulos vermelhos necessárias no tratamento endovascular dos aneurismas da aorta e na cirurgia híbrida de aneurismas da aorta e definir um protocolo do Maximum Surgical Blood Orders Schedule. Material e Métodos: Analisámos retrospetivamente a base de dados prospectiva dos doentes tratados eletivamente por tratamento endovascular dos aneurismas da aorta, entre 2001 e 2012. Analisamos idade, género, classe ASA, Maximum Surgical Blood Orders Schedule, unidades de glóbulos vermelhos transfundidas e tempos, endoprótese, relação unidades de glóbulos vermelhos consumidas/endoprótese, relação unidades crossmatched/transfundidas, conversão para cirurgia convencional, hemoglobina pré-operatória e na alta. Resultados: Selecionamos para análise 187 doentes, 90% homens, idade média 73,1, classe ASA III mais frequente. Usamos próteses aorto-bi-iliaca em 71%, aorto-uni-iliaca 23% e torácica 6%. Não necessitaram transfusão 72,6%. Transfundimos 171 unidades de glóbulos vermelhos. A relação unidades crossmatched/transfundidas foi 10,1 até 2010 e 7,3 após. A relação unidades de glóbulos vermelhos consumidas/endoprótese nas primeiras 24 horas foi 0,21 unidades de glóbulos vermelhos/aorto-bi-iliaca, 0,46 unidades de glóbulos vermelhos/aorto-uni-iliaca, 0,8 unidades de glóbulos vermelhos/torácica, 1,3 unidades de glóbulos vermelhos/híbrida-torácica e duas unidades de glóbulos vermelhos/híbrida-aorto-bi-iliaca. Obtivemos relação estatisticamente significativa entre unidades de glóbulos vermelhos transfundidas/endoprótese (p0,001) e entre classificação ASA e unidades de glóbulos vermelhos transfundidas após 24 h (p0,01). Discussão: As recomendações da British Society of Haematology baseiam-se numa relação unidades crossmatched/transfundidas de 2:1. Na nossa instituição, a relação unidades crossmatched/transfundidas foi de 10,1 até 2010 e 7,3 de 2011 a 2012. Conclusões: Os resultados mudaram o nosso Maximum Surgical Blood Orders Schedule para o tratamento endovascular dosaneurismas da aorta. Atualmente procedemos ao teste 'type and screen' para próteses aorto-bi-iliaca e aorto-uni-iliaca e a testes de crossmatch de duas unidades de glóbulos vermelhos para torácica, três para híbrida-torácica e quatro para híbrida-abdominal. Isto pode levar a menos gastos, aumento de eficácia e reduzir a sobrecarga no departamento de hematologia.

Fanconi anaemia (FA) is an inherited disorder characterized by chromosomal instability. The phenotype is variable, which raises the possibility that it may be affected by other factors, such as epigenetic modifications. These play an important role in oncogenesis and may be pharmacologically manipulated. Our aim was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. We compared expression of epigenetic genes and DNA methylation profile of tumour suppressor genes between FA and normal samples. FA samples exhibited decreased expression levels of genes involved in epigenetic regulation and hypomethylation in the promoter regions of tumour suppressor genes. Treatment of FA cells with histone deacetylase inhibitor Vorinostat increased the expression of DNM3T beta and reduced the levels of CIITA and HDAC9, PAK1, USP16, all involved in different aspects of epigenetic and immune regulation. Given the ability of Vorinostat to modulate epigenetic genes in FA patients, we investigated its functional effects on the FA phenotype. This was assessed by incubating FA cells with Vorinostat and quantifying chromosomal breaks induced by DNA cross-linking agents. Treatment of FA cells with Vorinostat resulted in a significant reduction of aberrant cells (81\% on average). Our results suggest that epigenetic mechanisms may play a role in oncogenesis in FA. Epigenetic agents may be helpful in improving the phenotype of FA patients, potentially reducing tumour incidence in this population. publishersversion published

Tese de doutoramento. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 2007

Doutoramento em Química A Bairrada é uma das regiões vitivinícolas mais antigas de Portugal, apesar de a Região Demarcada da Bairrada só ter sido oficialmente criada em 1979. A casta Fernão-Pires (FP) Vitis vinifera L. é a principal casta branca cultivada nesta região, onde é conhecida pelo nome de Maria-Gomes. As castas Bical (Bic), Arinto (Ari) e Cerceal (Cer), são outras castas brancas relevantes igualmente cultivadas na Região Demarcada da Bairrada. Estas quatro castas representam, respectivamente, 70%, 10%, 10% e 5% do total do encepamento de castas brancas nesta região. O conhecimento da composição volátil destas quatro variedades pode oferecer um meio de avaliar o seu potencial de aroma e melhorar a qualidade do aroma dos seus vinhos. No entanto, a composição volátil destas variedades ainda não se encontra caracterizada. Neste trabalho, o estudo foi centrado na casta FP, devido à sua importância no contexto da Região Demarcada da Bairrada, mostrando que esta casta apresenta um perfil significativamente diferente das outras castas brancas mais representativas (Bic, Ari e Cer), contendo um maior número de compostos voláteis e em maior concentração. As potencialidades de aroma da casta FP foram avaliadas pela análise da composição volátil das uvas, mostos e vinho. Nas uvas, os compostos voláteis varietais encontram-se principalmente associados às películas (69,3%) e parte líquida da polpa (25,3%), e encontram-se distribuídos pelas formas livre (66,7%) e glicosidicamente ligada (33,3%). Esta variedade apresenta terpenóides, álcoois aromáticos, norisoprenóides em C13 e álcoois em C6. Ela é caracterizada principalmente pela presença de monoterpenóides, um deles presente numa concentração acima do seu limite de percepção sensorial (geraniol), e pela presença de um terpendiol odorante na forma glicosidicamente ligada (Z-2,6-dimetil-2,7-octadieno-1,6-diol). De forma semelhante, os mostos são caracterizados pela presença de monoterpenóides, alguns deles em concentrações acima do seu limite de percepção sensorial (hotrienol e linalol), e pela presença de terpendióis, odorantes ou não, na forma de potencial (Z-2,6-dimetil-2,7-octadieno-1,6-diol e 3,7-dimetil-1,5-octadieno-3,7-diol), que podem representar uma importante fonte de monoterpenóides. O potencial em terpenóides das uvas, que se encontra principalmente associado às formas glicosidicamente ligadas das películas, assim como a presença de álcoois em C6 nas películas na forma livre, sugerem que as alterações/melhoramentos tecnológicos, relacionados principalmente com as preparações enzimáticas usadas durante a vinificação para libertar os compostos ligados, e o tempo de contacto com as películas devem ser tidos em conta como estratégias para aumentar a qualidade do aroma da casta FP. De facto, o efeito da utilização de uma enzima libertadora de aroma no vinho Fernão-Pires foi testado neste trabalho e confirmou a melhoria do seu aroma, ao contrário do que se verificou com a Bic. Essa melhoria traduziu-se pelo aumento de 9% no total dos compostos voláteis desta casta devido principalmente ao aumento do geraniol (67%), dos terpendiois (96%), fenóis e álcoois aromáticos (26%) e ésteres (32%). Alguns deles foram identificados em concentrações acima do seu limite de percepção sensorial, podendo contribuir com notas florais e frutadas. O facto das quatro castas estudadas exibirem composições voláteis diferentes permite dizer que, para a melhoria da qualidade do seu vinho, devem ser desenvolvidas tecnologias de vinificação especificamente para cada uma. Uma vez que estas castas crescem todas na mesma região (Bairrada), o conhecimento da sua composição volátil pemitirá aos vinicultores planear o seu uso em vinhos monovarietais ou em misturas, juntando o potencial em ácidos orgânicos voláteis das castas Ari e Cer (não mostrado neste estudo) às características terpénicas da casta FP, e em alcoois aromáticos da casta Bic. A variabilidade da composição volátil dos mostos da casta FP ao longo dos anos, foi também avaliada pela análise dos mostos de 4 colheitas. Com base nos dados obtidos, usando cromatografia de gás-espectrometria de massa seguida da análise de componentes principais (GC-MS-PCA), foram estabelecidas relações entre a composição varietal volátil dos mostos e a classificação da qualidade do aroma dos vinhos brancos das referidas colheitas, fornecidas pela câmara de prova da Comissão Vitivinícola da Região da Bairrada (CVRB). Os resultados das análises mostraram-se consistentes com a classificação da qualidade dos vinhos dada pela CVRB, indicando que a qualidade do aroma do vinho está claramente ligada com a composição varietal volátil na forma livre. Por outro lado, a fracção potencialmente volátil permitiu distinguir os mostos de acordo com a sua composição em precursores de aroma na forma potencial. Este estudo fornece informação aos vinicultores sobre as metodologias de vinificação que podem ser implementadas para a melhoria da qualidade do aroma dos vinhos. O crescente aparecimento de técnicas para a rápida caracterização de produtos alimentares, nomeadamente com recurso à espectrometria de massa, levou ao desenvolvimento de uma metodologia para a distinção rápida de vinhos através da análise da sua fracção volátil. Esta técnica baseada na microextracção em fase sólida, em modo de espaço de cabeça acoplada à cromatografia de gás- espectrometria de massa seguida da análise de componentes principais (HS-SPME-GC-MS-PCA), permitiu avaliar a assinatura global volátil do espaço de cabeça do vinho (perfil cromatográfico e padrões de fragmentação m/z para cada varrimento) sem uma completa separação cromatográfica dos seus componentes. Aos dados resultantes da fracção volátil não resolvida foi aplicada uma PCA para poder extrair dos dados a maior informação química possível e para extrair os fragmentos m/z (marcas) para a caracterização e distinção das variedades de vinhos. Esta metolodologia foi testada em dois vinhos monovarietais diferentes (FP e Ari Vitis vinifera L. var). Associada à rapidez desta metodologia pelo tempo de extracção e à robustez, é ainda importante realçar a elevada sensibilidade e o baixo efeito da humidade das amostras na resposta do detector MS, quando comparado com os “narizes-electrónicos” convencionais. As interacções que os compostos voláteis podem estabelecer com as macromoléculas do vinho e a importância deste fenómeno para a qualidade sensorial dos vinhos levou ao devenvolvimento de uma metodologia de microextracção em fase sólida em modo espaço de cabeça, acoplada à cromatografia de gás (HS-SPME-GC) para o estudo, em vinhos modelo, das interacções de 3 ésteres (hexanoato, octanoato e decanoato de etilo) e diferentes quantidades de fracção polimérica extraída do vinho FP (1.0 g/L, 10.0 g/L e 30 g/L). Esta técnica permite calcular o índice de retenção (RI) para cada composto, que é definido como sendo a capacidade de retenção da fracção polimérica de cada vinho em relação aos três ésteres. A maior capacidade de retenção foi observada para o composto mais hidrofóbico, o decanoato de etilo, e para a concentração mais elevada de fracção polimérica. No entanto, o decanoato de etilo é também retido para a concentração de fracção polimérica do vinho de 1.0 g/L. Este estudo sugere que os compostos retidos podem ser doseados para o espaço de cabeça promovendo a percepção do seu aroma por um longo período de tempo. Bairrada is one of the ancient winemaking regions in Portugal, although Bairrada Appellation was only officially created in 1979. Vitis vinifera L. Fernão-Pires (FP) is the main white grape variety in Bairrada, where it is known as Maria-Gomes. Other varieties, such as Bical (Bic), Arinto (Ari) and Cerceal (Cer), are also relevant white varieties cultivated in Bairrada Appellation. They represent 70%, 10%, 10% and 5% of the white vineyard, respectively. The knowledge of the volatile composition of these four varieties may offer a means of evaluating their potential aroma and to improve the quality of wine aroma. Nevertheless, the volatile composition of these varieties is not yet characterized. In this work, particular attention is devoted to Fernão-Pires variety due to its importance in the Bairrada Appellation context, showing that this variety exhibits a volatile profile significantly different from those of the other most representative white varieties (Bic, Ari and Cer), with a higher number and concentration of volatile compounds. The aroma potentialities of Vitis vinifera L. FP were estimated by the analysis of the volatile composition of its grapes, musts and wine. In grapes, the varietal volatile content is mainly associated to the skin (69.3%) and liquid pulp (25.3%) and is distributed by free (66.7%) and glycosidically-linked (33.3%) forms. This grapes variety exhibited terpenoids, aromatic alcohols, C13 norisoprenoids and C6 alcohols. It is mainly characterized by the presence of monoterpenoids, one of them over their sensory perception limit (geraniol), as well as the presence of an odour terpendiol in the glycosidically-linked form (Z-2,6-dimethylocta-2,7- dien-1,6-diol). Similarly, the musts are characterized by the presence of monoterpenoids, some of them over their sensorial perception limits (hotrienol and linalool), as well as the presence of odour/odourless terpendiols in the potential form (Z-2,6-dimethylocta-2,7-dien-1,6-diol and 3,7-dimethylocta-1,5- dien-3,7-diol), which may also represent an important source of monoterpenoids. The terpenoid potential of grapes, which is mainly associated to the glycosidically-linked form of skin, as well as the presence of C6 alcohols in the free form of skin, suggests that both technological changes/improvements, related mainly to enzymatic preparations used during winemaking to release the linked compounds and skin contact time must be taken into consideration as strategies to increase the aroma quality of wine from FP variety. In fact, the effect of an aroma release enzyme in FP wine was tested in this work, demonstrating the real improvement of its aroma, contrarily to Bic. There was an increase of 9% in the total amount of volatile compounds, due mainly to the increase of geraniol (67%), terpendiols (96%), phenols and aromatic alcohols (26%) and esters (32%). Some of them were within their sensory perception limits and may have a contribution to the floral and fruity notes. As a consequence of the fact that the four varieties under study exhibit different volatile composition patterns, winemaking technologies should be specifically developed for each variety for the improvement of wine aroma quality. As these varieties are all grown in the same region (Bairrada Appellation), knowledge of their varietal composition will allow winemakers to plan their use in monovarietal wines or in blends, providing the potential of the high volatile organic acid composition of Ari and Cer (data not shown) together with the terpenic characteristics of FP and the aromatic alcohols of Bic. The harvest variability of the varietal composition of FP grape variety was also evaluated from the musts across four harvests. Based on the data obtained, using gas chromatography- mass spectrometry (GC-MS) tandem with principal component analysis (PCA), relationships were established between the varietal volatile composition of the musts and the white wine aroma quality classification conferred by the wine taster chamber of Comissão Vitivinícola da Região da Bairrada (CVRB). The results of the volatile analysis were consistent with the wine quality classification given by CVRB, indicating that the wine aroma quality is clearly linked with the musts free varietal volatile composition. On the other hand, the PVC fraction allowed the distinction of the musts according to their potential aroma precursor’s composition. The proposed approach provides information to winemakers concerning the winemaking methodologies that can be implemented to improve the wine aroma quality. The emergency of techniques for the rapid characterization of food products, with the use of mass spectrometry, leaded us to the development of a methodology for the rapid distinction of wines by volatile fraction analysis. This technique based on headspace solid-phase microextraction- gas chromatography- mass spectrometry- principal component analysis (HSSPME- GC-MS-PCA), allows one to evaluate the global volatile signature of the wine headspace (chromatographic profile and m/z pattern of fragmentation in each scan) without complete chromatographic separation of its components. In order to retrieve from the data as much chemical information as possible and to extract m/z fragments (markers) for the characterization and distinction of the wines varieties, a PCA was applied to the data resultant from the unresolved volatile fraction. Two different monovarietal white wines (Vitis vinifera L. var FP and Ari) were tested. Associated to the fast character of the proposed methodology and robustness taking into account the extraction time, it is also important to highlight the higher sensibility and lower effect of the sample moisture of the MS sensor response when compared to the conventional e-noses. The interactions that volatile compounds can establish with the wine macromolecules and the importance of this ocurrence for the sensory quality of wines leaded us to the development of a methodology (HS-SPME-GC) for the study in model wines of the interactions between three ethyl esteres (ethyl hexanoate, ethyl octanoate and ethyl decanoate) and diferent amounts of polymeric fraction extracted from the FP wine (1.0 g/L, 10.0 g/L and 30 g/L). This methodology allowed to calculate the retention index (RI) for each compound, which is the retention capacity of each wine polymeric fraction towards the three esters established. The higher retention indexes were observed for ethyl decanoate, the more hydrophobic compound, and for the wine polymeric material with higher concentration. Ethyl decanoate was found to be retained even for the wine polymeric fraction concentration of 1.0 g/L. Furthermore, this study also suggested that the retained compounds are dosed to the headspace, which may promote the perception of their aroma for a longer period of time.

ResumoA luxação congênita da patela é uma patologia rara, em que a patela se encontra permanentemente luxada e manualmente irredutível. A patela desenvolve‐se normalmente como um osso sesamoide do fêmur. A luxação congênita da patela resulta da falência da rotação interna do miótomo que forma o fêmur, músculo quadricípite e o aparelho extensor. Usualmente manifesta‐se imediatamente após o nascimento, embora em alguns casos raros o diagnóstico possa ser adiado até a adolescência/idade adulta. O diagnóstico precoce é importante, permite a correção cirúrgica, evita as sequelas tardias, notadamente alterações degenerativas precoces do joelho. É apresentado um caso de luxação permanente da patela, numa criança de sexo feminino, com sete anos.AbstractCongenital patellar dislocation is a rare condition in which the patella is permanently dislocated and cannot be reduced manually. The patella develops normally as a sesamoid bone of the femur. This congenital dislocation results from failure of the internal rotation of the myotome that forms the femur, quadriceps muscle and extensor apparatus. It usually manifests immediately after birth, although in some rare cases, the diagnosis may be delayed until adolescence or adulthood. Early diagnosis is important, thereby allowing surgical correction and avoiding late sequelae, including early degenerative changes in the knee. A case of permanent dislocation of the patella is presented here, in a female child aged seven years.