Random-key genetic algorithms were introduced by Bean (ORSA J. Comput. 6:154–160,
1994
) for solving sequencing problems in combinatorial optimization. Since then, they have been extended to handle a ...wide class of combinatorial optimization problems. This paper presents a tutorial on the implementation and use of biased random-key genetic algorithms for solving combinatorial optimization problems. Biased random-key genetic algorithms are a variant of random-key genetic algorithms, where one of the parents used for mating is biased to be of higher fitness than the other parent. After introducing the basics of biased random-key genetic algorithms, the paper discusses in some detail implementation issues, illustrating the ease in which sequential and parallel heuristics based on biased random-key genetic algorithms can be developed. A survey of applications that have recently appeared in the literature is also given.
Abstract The nature of the toxic form of amyloid-beta peptide (Aβ) involved in early Alzheimer's disease (AD) pathology and whether it is the fibrillar or the oligomeric peptide that is the most ...deleterious to neurons remain controversial. This work aimed to compare the neurotoxicity of different amyloid-beta peptide 1-42 (Aβ1-42) assemblies, using fresh and aged samples enriched in oligomeric and fibrillar species, respectively, and also isolated oligomers and fibrils. The results obtained with fresh and aged Aβ1-42 preparations suggested that oligomeric species are more toxic to cortical neurons in culture than fibrillar forms, which was confirmed by using isolated oligomers and fibrils. In order to further elucidate the mechanisms involved in soluble Aβ toxicity, the involvement of endoplasmic reticulum (ER) calcium (Ca2+ ) release in oligomer-induced apoptosis was evaluated. We observed that oligomeric Aβ1-42 depletes ER Ca2+ levels leading to intracellular Ca2+ dyshomeostasis involving phospholipase C activation. Moreover, in the presence of dantrolene, an inhibitor of ER Ca2+ release through ryanodine receptors, the oligomer-induced apoptosis was prevented demonstrating the involvement of ER Ca2+ release.
We propose a novel, non-discriminatory classification of monkeypox virus diversity. Together with the World Health Organization, we named three clades (I, IIa and IIb) in order of detection. Within ...IIb, the cause of the current global outbreak, we identified multiple lineages (A.1, A.2, A.1.1 and B.1) to support real-time genomic surveillance.
The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its ...underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and ...metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.
Despite the importance of climate‐adjusted provenancing to mitigate the effects of environmental change, climatic considerations alone are insufficient when restoring highly degraded sites. Here we ...propose a comprehensive landscape genomic approach to assist the restoration of moderately disturbed and highly degraded sites. To illustrate it we employ genomic data sets comprising thousands of single nucleotide polymorphisms from two plant species suitable for the restoration of iron‐rich Amazonian Savannas. We first use a subset of neutral loci to assess genetic structure and determine the genetic neighbourhood size. We then identify genotype‐phenotype‐environment associations, map adaptive genetic variation, and predict adaptive genotypes for restoration sites. Whereas local provenances were found optimal to restore a moderately disturbed site, a mixture of genotypes seemed the most promising strategy to recover a highly degraded mining site. We discuss how our results can help define site‐adjusted provenancing strategies, and argue that our methods can be more broadly applied to assist other restoration initiatives.
see also the Perspective by Yessica Rico
The objective of this study was to compare the accuracies of double staining for p16/Ki-67 and the molecular test for high-risk HPV (hr-HPV) to identify high-grade cervical intraepithelial neoplasia ...(CIN2/CIN3) in women with cervical cytology of atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Data were collected from 201 women who underwent cervical cytology screening in the Barretos Cancer Hospital and their results were categorized as ASC-US (n=96) or LSIL (n=105). All patients underwent colposcopy with or without cervical biopsy for diagnosis of CIN2/CIN3. The hr-HPV test (Cobas 4800 test) and immunocytochemistry were performed to detect biomarkers p16/Ki-67 (CINtec PLUS test). Two samples (1 ASC-US/1 LSIL) were excluded from the analysis due to inconclusive results of the histologic examination. There were 8 cases of CIN2/CIN3 among 95 women with ASC-US (8.4%), and 23 cases of CIN2/CIN3 among 104 women with LSIL (22.1%). In the group of women with ASC-US, the sensitivity and specificity in diagnosing CIN2/CIN3 were 87.5% and 79.5% for the HPV test and 62.5% and 93.1% for p16/Ki-67. Among women with LSIL, the sensitivity and specificity in the diagnosis of CIN2/CIN3 were 87% and 34.7% for the HPV test and 69.6% and 75.3% for immunocytochemistry. Superior performance was observed for p16/Ki-67 double staining, especially among women under 30 for whom the test had an area under the ROC curve of 0.762 (p<0.001). Both p16/Ki-67 double staining and the hr-HPV DNA test had similar performance in predicting high-grade cervical intraepithelial neoplasia among women with ASC-US. The best performance was observed in women aged >30 years. In younger women (≤30 years) with LSIL, p16/Ki-67 had greater accuracy in identifying precursor lesions. Among women >30 years diagnosed with LSIL, the two methods showed similar performance.
Respiratory Syncytial Virus (RSV) is the main cause of pediatric morbidity and mortality. The complex evolution of RSV creates a need for worldwide surveillance, which may assist in the understanding ...of multiple viral aspects.
This study aimed to investigate RSV features under the Brazilian Influenza Surveillance Program, evaluating the role of viral load and genetic diversity in disease severity and the influence of climatic factors in viral seasonality.
We have investigated the prevalence of RSV in children up to 3 years of age with severe acute respiratory infection (SARI) in the state of Espirito Santo (ES), Brazil, from 2016 to 2018. RT-qPCR allowed for viral detection and viral load quantification, to evaluate association with clinical features and mapping of local viral seasonality. Gene G sequencing and phylogenetic reconstruction demonstrated local genetic diversity.
Of 632 evaluated cases, 56% were caused by RSV, with both subtypes A and B co-circulating throughout the years. A discrete inverse association between average temperature and viral circulation was observed. No correlation between viral load and disease severity was observed, but children infected with RSV-A presented a higher clinical severity score (CSS), stayed longer in the hospital, and required intensive care, and ventilatory support more frequently than those infected by RSV-B. Regarding RSV diversity, some local genetic groups were observed within the main genotypes circulation RSV-A ON1 and RSV-B BA, with strains showing modifications in the G gene amino acid chain.
Local RSV studies using the Brazilian Influenza Surveillance Program are relevant as they can bring useful information to the global RSV surveillance. Understanding seasonality, virulence, and genetic diversity can aid in the development and suitability of antiviral drugs, vaccines, and assist in the administration of prophylactic strategies.
This work presents new results about sporadic E-layers (Es layers) using
GPS (global positioning system) radio occultation (RO) measurements obtained
from the FORMOSAT-3/COSMIC satellites and ...digisonde data. The RO profiles are
used to study the Es layer occurrence as well as its intensity of the
signal-to-noise ratio (SNR) of the 50 Hz GPS L1 signal. The methodology was
applied to identify the Es layer on RO measurements over Cachoeira Paulista, a
low-latitude station in the Brazilian region, in which the Es layer
development is not driven tidal winds only as it is at middle latitudes. The
coincident events were analyzed using the RO technique and ionosonde observations during the
year 2014 to 2016. We used the electron density obtained using
the blanketing frequency parameter (fbEs) and the Es layer height
(h'Es) acquired from the ionograms to validate the satellite measurements.
The comparative results show that the Es layer characteristics extracted
from the RO measurements are in good agreement with the Es layer parameters
from the digisonde. Keywords. Ionosphere (ionosphere–atmosphere interactions)
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