The VINEYARD Approach: Versatile, Integrated, Accelerator-Based, Heterogeneous Data Centres.

Emerging web applications like cloud computing, Big Data and social networks have created the need for powerful centres hosting hundreds of thousands of servers. Currently, the data centres are based on general purpose processors that provide high flexibility buts lack the energy efficiency of customized accelerators. VINEYARD aims to develop an integrated platform for energy-efficient data centres based on new servers with novel, coarse-grain and fine-grain, programmable hardware accelerators. It will, also, build a high-level programming framework for allowing end-users to seamlessly utilize these accelerators in heterogeneous computing systems by employing typical data-centre programming frameworks (e.g. MapReduce, Storm, Spark, etc.). This programming framework will, further, allow the hardware accelerators to be swapped in and out of the heterogeneous infrastructure so as to offer high flexibility and energy efficiency. VINEYARD will foster the expansion of the soft-IP core industry, currently limited in the embedded systems, to the data-centre market. VINEYARD plans to demonstrate the advantages of its approach in three real use-cases (a) a bio-informatics application for high-accuracy brain modeling, (b) two critical financial applications, and (c) a big-data analysis application.

Influence of testing on permeability of compacted fine soils

The British standard constant-head triaxial test for measuring the permeability of fine-grained soils takes a relatively long time. A quicker test could provide savings to the construction industry, particularly for checking the quality of landfill clay liners. An accelerated permeability test has been developed, but the method often underestimates the permeability values compared owing to structural changes in the soil sample. This paper reports on an investigation
into the accelerated test to discover if the changes can be limited by using a revised procedure. The accelerated test is assessed and compared with the standard test and a ramp-accelerated permeability test. Four different finegrained materials are compacted at various water contents to produce analogous samples for testing using the three different methods. Fabric analysis is carried out on specimens derived from post-test samples using mercury intrusion porosimetry and scanning electron microscopy to assess the effects of testing on soil structure. The results show that accelerated testing in general underestimates permeability compared with values derived from the standard test, owing to changes in soil structure caused by testing. The ramp-accelerated test is shown to provide an improvement in terms of these structural changes.

As indústrias da pesca e conservas de atum no Algarve do Século XX

Dissertação mest., Culturas Árabe e Islâmica e o Mediterrâneo, Universidade do Algarve, 2010

Seasonal Variation in Diurnal Atmospheric Grass Pollen Concentration Profiles

In this study, the diurnal atmospheric grass pollen concentration profile within the Danish city of Aarhus was shown to change in a systematic manner as the pollen season progressed. Although diurnal grass pollen profiles can differ greatly from day-to-day, it is common practice to establish the time of day when peak concentrations are most likely to occur using seasonally averaged diurnal profiles. Atmospheric pollen loads are highly dependent upon emissions, and different species of grass are known to flower and emit pollen at different times of the day and during different periods of the pollen season. Pollen concentrations are also influenced by meteorological factors – directly through those parameters that govern pollen dispersion and transport, and indirectly through the weather-driven flowering process. We found that three different profiles dominated the grass pollen season in Aarhus – a twin peak profile during the early season, a single evening profile during the middle of the season, and a single midday peak during the late season. Whilst this variation could not be explained by meteorological factors, no inconsistencies were found with the theory that it was driven by a succession of different grass species with different diurnal flowering patterns dominating atmospheric pollen loads as the season progressed. The potential for exposure was found to be significantly greater during the late-season period than during either the early- or mid-season periods.

Mercado, formação e sucesso: actores e bailarinos entre persistência e desilusão

A tríade arte, formação e mercado tem sido amplamente discutida por sociólogos e economistas (Towse 1993, 2006; Menger 1997, 2009; Throsby 1996, 2006; Benhamou 2000; Santos et al. 2003, Ferreira 2003), utilizada nos discursos de agentes e decisores políticos e ainda nos estudos que avaliam as iniciativas públicas e privadas desenhadas para o sector cultural e criativo, a nível nacional (Mateus 2010) e supranacional (Relatório da UNESCO 2010). O crescente interesse pela relação entre arte, formação e inserção dos indivíduos no mercado de trabalho artístico parece estar relacionado com uma questão central das sociedades contemporâneas para a qual ainda não houve a devida resposta: qual é o papel assumido pelos vários aspectos da formação que os indivíduos recebem ao longo da sua vida na ligação bem-sucedida com a sua profissão e o mercado de trabalho artístico?

Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Influência de diferentes sistemas alimentares nos atributos da carcaça e da carne de novilhos.

Objetivou-se avaliar as características da carcaça e da carne de novilhos submetidos a diferentes sistemas alimentares.

Cuidado de si e metanoia em Michel Foucault

Na perspetiva genealógica e hermenêutica de Michel Foucault aplicada à Antiguidade, a nossa tese relaciona cuidado de si e metanoia, discutindo o contraste entre o modelo helenístico-romano do cuidado como conversão a si e o modelo cristão da conversão através da renúncia a si. Com o olhar fixo neste horizonte temático pretendemos construir um percurso alinhado com o pensamento de Foucault, começando por sinalizar alguns dos seus textos mais importantes e delinear os traços mais marcantes do seu pensamento histórico-filosófico, mormente as suas investigações, não já sobre as tecnologias do poder e as tecnologias do saber, mas sobre as tecnologias do si na Antiguidade – técnicas culturais que deram origem à hermenêutica do sujeito, práticas complexas de subjetivação e objetivação dos sujeitos, cujas raízes remontam à cultura grega do séc. V a.C., mas que se consolidou apenas com os movimentos ascético-monásticos cristãos dos séculos IV e V. Excluída necessariamente a pretensão de redesenhar criticamente todo este longo desenvolvimento, propomos assinalar alguns dos mais importantes processos da cultura do cuidado de si na Antiguidade: - a análise filosófica do cuidado de si a partir do preceito délfico “Conhece-te a ti mesmo!”; - a cultura do si helenístico-romana; - as técnicas ou práticas do cuidado de si, em especial quatro: parrēsía, áskēsis, exomológēsis e exagóreusis. Neste contexto, afigura-se relevante que as duas primeiras sejam comuns à filosofia e ao cristianismo, mas com caraterísticas diferentes, sendo as duas últimas exclusivas desta religião, nas quais Foucault reconhece um impulso decisivo para a constituição da hermenêutica do sujeito – a prática sistemática da desvelação do si, algo que gregos e romanos não alcançaram, porque ainda não se tinha constituído culturalmente a noção de sujeito. Para esclarecermos este duplo movimento de conhecimento e modificação do si, procuramos mostrar o contraste cultural na Antiguidade entre dois modelos de subjetivação e de objetivação dos indivíduos, a ética como prática refletida da liberdade e a moral cristã da obediência. O primeiro modelo orbitou em torno do princípio geral do cuidado de si, assimilado pela cultura grega e repercutido na filosofia, o segundo foi marcado pela nova forma de domínio e submissão – o poder pastoral – justificado pela obediência e pela renúncia a si, que transformaram o cristianismo numa religião confessional. Para confirmarmos esta interpretação, convocamos à reflexão a noção de conversão. Começamos por valorizar o contributo dos termos gregos epistrophē e metanoia. De seguida, justificamos a relevância da conversão para a Cultura Ocidental. Concluímos com a análise de três modelos históricos: platónico, helenístico-romano e cristão. O arco temático termina com a análise do valor paradoxal da renúncia a si em Paulo de Tarso, cujos textos Foucault não analisou no âmbito da cultura do si, mas que nós valorizamos e nos levam a divergir deste filósofo, para quem a renúncia a si anula a eficácia do cuidado de si, propondo em alternativa a tese de que as várias formas de renúncia, mesmo enunciadas numa perspetiva escatológica, não só integraram como intensificaram essa cultura do cuidado.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

Polysomy 8 defines a clinico-cytogenetic entity representing a subset of myeloid hematologic malignancies associated with a poor prognosis: report on a cohort of 12 patients and review of 105 published cases.

Tetrasomy, pentasomy, and hexasomy 8 (polysomy 8) are relatively rare compared to trisomy 8. Here we report on a series of 12 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD) associated with polysomy 8 as detected by conventional cytogenetics and fluorescence in situ hybridization (FISH). In an attempt to better characterize the clinical and hematological profile of this cytogenetic entity, our data were combined with those of 105 published patients. Tetrasomy 8 was the most common presentation of polysomy 8. In 60.7% of patients, polysomy 8 occurred as part of complex changes (16.2% with 11q23 rearrangements). No cryptic MLL rearrangements were found in cases in which polysomy 8 was the only karyotypic change. Our study demonstrates the existence of a polysomy 8 syndrome, which represents a subtype of AML, MDS, and MPD characterized by a high incidence of secondary diseases, myelomonocytic or monocytic involvement in AML and poor overall survival (6 months). Age significantly reduced median survival, but associated cytogenetic abnormalities did not modify it. Cytogenetic results further demonstrate an in vitro preferential growth of the cells with a high level of aneuploidy suggesting a selective advantage for polysomy 8 cells.

Ataxia telangiectasia mutated (ATM) inhibition transforms human mammary gland epithelial cells.

Carriers of mutations in the cell cycle checkpoint protein kinase ataxia telangiectasia mutated (ATM), which represent 1-2% of the general population, have an increased risk of breast cancer. However, experimental evidence that ATM deficiency contributes to human breast carcinogenesis is lacking. We report here that in MCF-10A and MCF-12A cells, which are well established normal human mammary gland epithelial cell models, partial or almost complete stable ATM silencing or pharmacological inhibition resulted in cellular transformation, genomic instability, and formation of dysplastic lesions in NOD/SCID mice. These effects did not require the activity of exogenous DNA-damaging agents and were preceded by an unsuspected and striking increase in cell proliferation also observed in primary human mammary gland epithelial cells. Increased proliferation correlated with a dramatic, transient, and proteasome-dependent reduction of p21(WAF1/CIP1) and p27(KIP1) protein levels, whereas little or no effect was observed on p21(WAF1/CIP1) or p27(KIP1) mRNAs. p21(WAF1/CIP1) silencing also increased MCF-10A cell proliferation, thus identifying p21(WAF1/CIP1) down-regulation as a mediator of the proliferative effect of ATM inhibition. Our findings provide the first experimental evidence that ATM is a human breast tumor suppressor. In addition, they mirror the sensitivity of ATM tumor suppressor function and unveil a new mechanism by which ATM might prevent human breast tumorigenesis, namely a direct inhibitory effect on the basal proliferation of normal mammary epithelial cells.

Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study.

We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.