Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.Benjamin T Mayne, Shalem Y Leemaqz, Alicia K Smith, James Breen, Claire T Roberts, Tina Bianco-Miott

ALTERNATIVE DESIGN AND ECONOMIC FEASIBILITY OF AN EXPERIMENTAL WHR FOR INTAKE AIR CONDITIONING OF A LARGE INTERNAL COMBUSTION ENGINE

This work presents an alternative design for an experimental waste heat recovery thermal system to be coupled to a large turbocharged internal combustion engine for combustion air conditioning. The goal is to carry out a design of a new thermal system under restricted economic requirements for one of the generators set of Luiz Oscar Rodrigues de Melo Thermoelectric Power Plant. Thereby, a comparison with the original proposal from previous works is also developed in order to demonstrate the differences in terms of thermo-economic design parameters. The waste recovery thermal system produces sufficient chilled water through a single-effect absorption chiller, powered by hot water which is produced by recovering the exhaust gases residual heat to supply cooling applications on the combustion air. The results showed a significant reduction for the chiller capacity demand, from 550 to 185 RT, that would be enough to provide chilled water for 98.72% of the analyzed operation historical period. The economic feasibility indicators reveal the proposal for the alternative waste heat recovery system as the best financial option, presenting a lower investment cost (US$316,793.27 of savings) and a time for capital recovery of 2.14 years, 1.61 years shorter when compared with the initial WHR system

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.Benjamin T. Mayne, Tina Bianco-Miotto, Sam Buckberry, James Breen, Vicki Clifton, Cheryl Shoubridge and Claire T. Robert

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

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

Acúmulo de fósforo em solos cultivados com videiras na região da Campanha Gaúcha.

O presente trabalho teve como objetivo avaliar o acúmulo de frações de P em solos cultivados com videiras e com histórico de aplicação de fertilizantes fosfatados na região da Campanha Gaúcha do RS.bitstream/item/73780/1/Comunicado-Tecnico-131.pd

PERFORMANCE ASSESSMENT OF A LARGE INTERNAL COMBUSTION ENGINE DUE TO INLET AIR COOLING AND DEHUMIDIFICATION: GT-POWER SOFTWARE SIMULATION

Large internal combustion engines (ICEs) performance is limited by knocking phenomenon due to harsh ambient conditions such as hot temperature and excessive humidity. The performance of these engines can be enhanced by cooling and dehumidifying the inlet air on turbocharger upstream under safe operation conditions through a cooling coil heat exchanger, hence, increasing the power output as well as reducing the brake specific fuel consumption and pollutant specific emissions. Analysis have been performed in the GT-POWER software through a 1-D thermodynamic modelling of the Wärtsilä W20V34SG engine, making it possible to verify the influence of cooled and dehumidified ambient air, considering a temperature range from 9.5°C (282.7 K) to 15.5°C (288.7 K), while keeping 1 bar for pressure and relative humidity of 100%. Furthermore, the brake mean effective pressure (BMEP) has been set from 20 to 23.45 bar with a step of 1.15 bar. Such simulations are aimed to find the maximum air temperature at the cooling coil outlet in which the average of maximum cylinder pressures does not exceed the safety limit pressure of 186 bar while maintaining control on the wastegate valve. As a result, it was possible to evaluate that the maximum temperature to be chosen, under the conditions already mentioned, should be lower than 13.8°C (287 K)

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

Soil phosphorus fractions in a sandy typic hapludaft as affected by phosphorus fertilization and grapevine cultivation period.

The purpose of this study was to quantify the phosphorus (P) fractions in phosphate-fertilized sandy soils under grapevines. Soil was sampled from a grassland site and two vineyards (13 and 31 years old) in the State Rio Grande do Sul, Brazil, from the layers 0-5, 5-10, 10-15, 15-20, and 20-40 cm deep. The samples were prepared and P fractions were assessed by chemical fractionation. Phosphate fertilization of the vineyard soils increased P contents to a depth of 40 cm, especially in the more recalcitrant fractions but detectable in the more labile fractions as well, which are plant available and may increase the risk of environmental contamination. Phosphate fertilizers and the period of grapevine cultivation had little effect on the levels of organic P forms, whereas cover crops in vineyards could be an appropriate strategy to increase or maintain the levels of soil organic matter and the levels of organic P over the years

Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis4991