Rule-based knowledge aggregation for large-scale protein sequence analysis of influenza A viruses

Background: The explosive growth of biological data provides opportunities for new statistical and comparative analyses of large information sets, such as alignments comprising tens of thousands of sequences. In such studies, sequence annotations frequently play an essential role, and reliable results depend on metadata quality. However, the semantic heterogeneity and annotation inconsistencies in biological databases greatly increase the complexity of aggregating and cleaning metadata. Manual curation of datasets, traditionally favoured by life scientists, is impractical for studies involving thousands of records. In this study, we investigate quality issues that affect major public databases, and quantify the effectiveness of an automated metadata extraction approach that combines structural and semantic rules. We applied this approach to more than 90,000 influenza A records, to annotate sequences with protein name, virus subtype, isolate, host, geographic origin, and year of isolation. Results: Over 40,000 annotated Influenza A protein sequences were collected by combining information from more than 90,000 documents from NCBI public databases. Metadata values were automatically extracted, aggregated and reconciled from several document fields by applying user-defined structural rules. For each property, values were recovered from ≥88.8% of records, with accuracy exceeding 96% in most cases. Because of semantic heterogeneity, each property required up to six different structural rules to be combined. Significant quality differences between databases were found: GenBank documents yield values more reliably than documents extracted from GenPept. Using a simple set of semantic rules and a reasoner, we reconstructed relationships between sequences from the same isolate, thus identifying 7640 isolates. Validation of isolate metadata against a simple ontology highlighted more than 400 inconsistencies, leading to over 3,000 property value corrections. Conclusion: To overcome the quality issues inherent in public databases, automated knowledge aggregation with embedded intelligence is needed for large-scale analyses. Our results show that user-controlled intuitive approaches, based on combination of simple rules, can reliably automate various curation tasks, reducing the need for manual corrections to approximately 5% of the records. Emerging semantic technologies possess desirable features to support today's knowledge aggregation tasks, with a potential to bring immediate benefits to this field

miRNA Signatures in Sera of Patients with Active Pulmonary Tuberculosis.

Several studies showed that assessing levels of specific circulating microRNAs (miRNAs) is a non-invasive, rapid, and accurate method for diagnosing diseases or detecting alterations in physiological conditions. We aimed to identify a serum miRNA signature to be used for the diagnosis of tuberculosis (TB). To account for variations due to the genetic makeup, we enrolled adults from two study settings in Europe and Africa. The following categories of subjects were considered: healthy (H), active pulmonary TB (PTB), active pulmonary TB, HIV co-infected (PTB/HIV), latent TB infection (LTBI), other pulmonary infections (OPI), and active extra-pulmonary TB (EPTB). Sera from 10 subjects of the same category were pooled and, after total RNA extraction, screened for miRNA levels by TaqMan low-density arrays. After identification of "relevant miRNAs", we refined the serum miRNA signature discriminating between H and PTB on individual subjects. Signatures were analyzed for their diagnostic performances using a multivariate logistic model and a Relevance Vector Machine (RVM) model. A leave-one-out-cross-validation (LOOCV) approach was adopted for assessing how both models could perform in practice. The analysis on pooled specimens identified selected miRNAs as discriminatory for the categories analyzed. On individual serum samples, we showed that 15 miRNAs serve as signature for H and PTB categories with a diagnostic accuracy of 82% (CI 70.2-90.0), and 77% (CI 64.2-85.9) in a RVM and a logistic classification model, respectively. Considering the different ethnicity, by selecting the specific signature for the European group (10 miRNAs) the diagnostic accuracy increased up to 83% (CI 68.1-92.1), and 81% (65.0-90.3), respectively. The African-specific signature (12 miRNAs) increased the diagnostic accuracy up to 95% (CI 76.4-99.1), and 100% (83.9-100.0), respectively. Serum miRNA signatures represent an interesting source of biomarkers for TB disease with the potential to discriminate between PTB and LTBI, but also among the other categories

Identificação e análise de promotores de desidrinas no genoma da macieira.

Resumo

Treatment of Hepatitis C virus genotype 3 infection with direct-acting antiviral agents

Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of directacting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83-100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contra-indications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82-96% among patients without cirrhosis and 62-92% among those with cirrhosis. Finally, SOF plus DCV provides 94-97% SVR rates in non-cirrhotic patients, but 59-69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection491

Saberes lingüísticos e intervención normativa en el diario "La Nación" : Un análisis del "Diálogo semanal con los lectores"

Esta comunicación presenta un análisis del "Diálogo semanal con los lectores", una columna de divulgación publicada semanalmente por el diario La Nación, en la cual se brindan respuestas a consultas o comentarios de los lectores acerca de diversas cuestiones relativas a la lengua. Dada la naturaleza del corpus, el enfoque de análisis se filia, en primera instancia, en los estudios de Glotopolítica -que atienden a los modos de intervención sobre el lenguaje así como a los discursos que legitiman y/o intentan transformar determinados modos de regulación de la(s) lengua(s) y las prácticas lingüísticas en la sociedad (cf. Arnoux, 2000 y 2008; del Valle, 2007)- y, en segunda instancia, en los estudios de Historia de las Ideas Lingüísticas -que toman como objeto de investigación las diversas formas de teorización y de reflexión sistemática sobre el lenguaje que se produjeron en diferentes sociedades y en distintos momentos de la historia (cf. Auroux, 1989, 1992 y 1996). El trabajo se propone analizar el modo en que se articulan, en los textos que conforman el corpus, los saberes lingüísticos con el funcionamiento eminentemente normativo de la columna periodística, atendiendo tanto a las intervenciones de los lectores como a las respuestas que construye la periodista desde el lugar del saber especializado.Facultad de Humanidades y Ciencias de la Educació

First-principles prediction of structure, energetics, formation enthalpy, elastic constants, polarization, and piezoelectric constants of AlN, GaN, and InN: comparison of local and gradient-corrected density-functional theory

A number of diverse bulk properties of the zincblende and wurtzite III-V nitrides AlN, GaN, and InN, are predicted from first principles within density functional theory using the plane-wave ultrasoft pseudopotential method, within both the LDA (local density) and GGA (generalized gradient) approximations to the exchange-correlation functional. Besides structure and cohesion, we study formation enthalpies (a key ingredient in predicting defect solubilities and surface stability), spontaneous polarizations and piezoelectric constants (central parameters for nanostructure modeling), and elastic constants. Our study bears out the relative merits of the two density functional approaches in describing diverse properties of the III-V nitrides (and of the parent species N$_2$, Al, Ga, and In), and leads us to conclude that the GGA approximation, associated with high-accuracy techniques such as multiprojector ultrasoft pseudopotentials or modern all-electron methods, is to be preferred in the study of III-V nitrides.Comment: RevTeX 6 pages, 12 tables, 0 figure

Características da carcaça de Tourinhos Nelore x Limousin alimentados com dietas contendo gérmen de milho integral.

Foram avaliadas as características quantitativas das carcaças de 24 tourinhos Nelore X Limousin submetidos a dietas contendo 0%, 15% e 45% de gérmen de milho integral (GMI), terminados em confinamento, com peso e idade média inicial de 321,25 kg e vinte meses, respectivamente

Evolução da maturação da uva 'BRS Clara' sob cultivo protegido durante a safra fora de época.

A produção de uvas para mesa vem passando por alguns desafios que demandam alterações nas tecnologias de produção, devido, principalmente, à intensa necessidade de controle de doenças fúngicas. O objetivo deste trabalho foi avaliar o comportamento da evolução da maturação da uva 'BRS Clara' enxertada sobre o porta-enxerto IAC 766 'Campinas', sob cultivo protegido produzida em safra fora de época. Os experimentos foram realizados em Uraí e Marialva (PR). Foram avaliadas semanalmente as características químicas das bagas, como teor de sólidos solúveis, acidez titulável, índice de maturação e pH, a partir do início da maturação até a colheita, em dois sistemas de cultivo protegido: cobertura plástica e sombrite. O delineamento experimental adotado em ambas as áreas foi o inteiramente casualizado com sete repetições. A evolução da maturação nos dois sistemas de cultivo protegido foi comparada por meio da análise de regressão. Em ambas as áreas experimentais, a cobertura plástica possibilitou a antecipação da colheita das uvas em seis dias em relação ao sombrite, considerando o teor de sólidos solúveis. Não houve influência da cobertura plástica sobre o índice de maturação das uvas

Predictors Of Early Treatment Discontinuation And Severe Anemia In A Brazilian Cohort Of Hepatitis C Patients Treated With First-generation Protease Inhibitors

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin <= 8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.49