Variational Bayesian analysis of survival data using a log-logistic accelerated failure time model

The log-logistic regression model is one of the most commonly used accelerated failure time (AFT) models in survival analysis, for which statistical inference methods are mainly established under the frequentist framework. Recently, Bayesian inference for log-logistic AFT models using Markov chain Monte Carlo (MCMC) techniques has also been widely developed. In this work, we develop an alternative approach to MCMC methods and infer the parameters of the log-logistic AFT model via a mean-field variational Bayes (VB) algorithm. A piecewise approximation technique is embedded in deriving the VB algorithm to achieve conjugacy. The proposed VB algorithm is evaluated and compared with typical frequentist inferences and MCMC inference using simulated data under various scenarios. A publicly available dataset is employed for illustration. We demonstrate that the proposed VB algorithm can achieve good estimation accuracy and has a lower computational cost compared with MCMC methods

Production and characterization of new fibrinolytic protease from Mucor subtillissimus UCP 1262 in solid-state fermentation

Fibrinolytic enzymes have received attention regarding their medicinal potential for thrombolytic diseases, a leading cause of morbidity and mortality worldwide. Various natural enzymes purified from animal, plant and microbial sources have been extensively studied. The aim of this work was to produce fibrinolytic protease by solid state fermentation using agro industrial substrates. Rhizopus arrhizus var. arrhizus UCP 1295 and Mucor subtillissimus UCP 1262 filamentous fungi species isolated from soil of Caatinga-PE, Brasil, were used as producer microorganisms. Wheat bran was shown to be the best substrate for the production of the enzyme and by using a 23 full factorial design the main effects and interactions of the quantity of the substrate wheat bran, moisture and temperature on the fibrinolytic enzyme production and protease were evaluated. The best results for fibrinolytic and protease activities, 144.58 U/mL and 48.33 U/mL, respectively, were obtained with Mucor subtillissimus UCP 1262 using as culture medium 3 g wheat bran, 50% moisture at a temperature of 25˚C for 72 hours. The optimum temperature for the produced enzyme was 45˚C and most of its original activity was retained after being subjected to 80˚C for 120 min. The protease activity was enhanced by K+, Ca+ and Mn+; but with Cu+ there was an inhibition. The specificity to chromogenic substrate and the inhibition by PMSF indicates that it is a chymotrypsin-like serine protease. Presented results suggest that this enzyme produced by solid-state fermentation is an interesting alternative as a candidate for thrombolytic therapy

Improving the learning experience and learning environment of adults in Higher Education – Project LIHE: the Portuguese case

Project LIHE: the Portuguese Case. ESREA Fourth Access Network Conference – “Equity, Access and Participation: Research, Policy and Practice”. Edinburgh (Scotland), 11 – 13 December, 2003.The promotion of a knowledge-based society needs, on one hand, technological infrastructure and, on the other hand, a workforce with the necessary skills, knowledge and competences, supported by a well-structured initial education and by a continuous learning program. In the last years, Universities have opened their doors to all citizens, regardless of their status or origin, if they have the capacity to benefit from the educational services on offer. This strategy has allowed mature students to enter (or re-enter) the formal higher education system. Although these students may possess a richness of experience, they can also have difficulty in adapting to the pedagogical approaches of learning and teaching and their attitudes and problems are not necessarily the same as those of traditional students. It is in this context that the project LIHE – Learning in Higher Education emerges. In this paper, the background of the project and the most relevant literature for the subject are briefly described. It is followed by a presentation of the project aims, objectives and methodological approaches. The Portuguese case is introduced, together with the results of questionnaires and interviews. Some preliminary conclusions are outlined. Finally, avenues of future research are discusse

Evaluating steel fiber‐reinforced self‐consolidating concrete performance

The fiber‐reinforced self‐compacting concrete (FR‐SCC) is considered a high‐performance material, clustering characteristics of SCC combined with steel fibers. This paper assessed fresh and hardened state properties of a reference SCC and a FR‐SCC with fibers of three types and three quantities of reinforcement, totalizing 10 mixtures. Fresh state properties of the mixture were evaluated through the tests of slump‐flow, flow rate, filling ability, plastic viscosity by V‐funnel, passing ability by J‐ring and by L‐box; and hardened properties comprised compressive strength, flexural strength, and flexural toughness. Overall, it was observed that increasing the amount and length of fibers hindered the mixture workability. Also, the flexural strength and flexural toughness increased as the length and the amount of fibers increased. Regarding mechanical properties, it was not possible to identify an equivalence between the types of fibers evaluated and the compressive strength of mixtures. The flexural was proportional to the amount of fibers, with increases of up to 30% for concretes with fibers

High-resolution genetic map and QTL analysis of growth-related traits of Hevea brasiliensis cultivated under suboptimal temperature and humidity conditions

Rubber tree (Hevea brasiliensis) cultivation is the main source of natural rubber worldwide and has been extended to areas with suboptimal climates and lengthy drought periods; this transition affects growth and latex production. High-density genetic maps with reliable markers support precise mapping of quantitative trait loci (QTL), which can help reveal the complex genome of the species, provide tools to enhance molecular breeding, and shorten the breeding cycle. In this study, QTL mapping of the stem diameter, tree height, and number of whorls was performed for a full-sibling population derived from a GT1 and RRIM701 cross. A total of 225 simple sequence repeats (SSRs) and 186 single-nucleotide polymorphism (SNP) markers were used to construct a base map with 18 linkage groups and to anchor 671 SNPs from genotyping by sequencing (GBS) to produce a very dense linkage map with small intervals between loci. The final map was composed of 1,079 markers, spanned 3,779.7 cM with an average marker density of 3.5 cM, and showed collinearity between markers from previous studies. Significant variation in phenotypic characteristics was found over a 59-month evaluation period with a total of 38 QTLs being identified through a composite interval mapping method. Linkage group 4 showed the greatest number of QTLs (7), with phenotypic explained values varying from 7.67 to 14.07%. Additionally, we estimated segregation patterns, dominance, and additive effects for each QTL. A total of 53 significant effects for stem diameter were observed, and these effects were mostly related to additivity in the GT1 clone. Associating accurate genome assemblies and genetic maps represents a promising strategy for identifying the genetic basis of phenotypic traits in rubber trees. Then, further research can benefit from the QTLs identified herein, providing a better understanding of the key determinant genes associated with growth of Hevea brasiliensis under limiting water conditions

Hyperpigmentant activity of leaves and flowers extracts of Pyrostegia venusta on murine B16F10 melanoma

AbstractEthnopharmacological relevancePyrostegia venusta is a native Brazilian plant which has a variety of uses in traditional folk medicine including the treatment of vitiligo. However, its effectiveness on melanogenesis is not yet elucidated.Aim of the studyThis study aimed to investigate the melanogenic activity of hydroalcoholic extracts from the leaves and flowers of P. venusta on murine B16F10 melanoma cells.Materials and methodsDifferent concentrations of the hydroalcoholic extracts of flowers and leaves of P. venusta were evaluated in trials of spontaneous melanin content (4 days), and cell viability by the MTT assay in murine B16F10 cells, and in the mushroom tyrosinase activity in vitro.ResultsBoth extracts, leaves (0.1; 0.3; 1 and 3μg/mL) and flowers (0.03 and 0.1μg/mL) increased the melanin content in a concentration dependent manner after 4 days of incubation on melanoma cells. Leaves extract promoted enhancement of melanogenesis with maximum effect of 33.3±3% (3μg/mL), and the flower extract increased in 23.4±3% (0.1μg/mL). The cell viability test using MTT showed that in the same tested concentrations of both extracts no cell death was detected. Actually, either extract was not able to cause any change in the tyrosinase activity. HPLC analysis of P. venusta extracts found 0.09% and 1.08% of allantoin on leaves and flowers extracts, respectively.ConclusionsThe leaves and flowers extracts of P. venusta stimulates B16F10 melanogenesis at very low concentrations. These findings support the folk medicinal use of P. venusta on the treatment of hypopigmentation diseases, such as vitiligo

Evaluation and Validation of a Method for Determining Platelet Catecholamine in Patients with Obstructive Sleep Apnea and Arterial Hypertension

Background: Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions.Objective: in this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls.Methods: in the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension.Results: A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05).Conclusion: Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Associacao Fundo de Pesquisa a Psicobiologia (AFIP), BrazilConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiol, São Paulo, BrazilAssoc Fundo Incent & Pesquisa, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiol, São Paulo, BrazilWeb of Scienc

Linkage disequilibrium and population structure in wild and cultivated populations of rubber tree (Hevea brasiliensis).

Abstract: Among rubber tree species, which belong to the Hevea genus of the Euphorbiaceae family, Hevea brasiliensis (Willd. ex Adr.de Juss.) Muell. Arg. is the main commercial source of natural rubber production worldwide. Knowledge of the population structure and linkage disequilibrium (LD) of this species is essential for the efficient organization and exploitation of genetic resources. Here, we obtained single-nucleotide polymorphisms (SNPs) using a genotyping-by-sequencing (GBS) approach and then employed the SNPs for the following objectives: (i) to identify the positions of SNPs on a genetic map of a segregating mapping population, (ii) to evaluate the population structure of a germplasm collection, and (iii) to detect patterns of LD decay among chromosomes for future genetic association studies in rubber tree. A total of 626 genotypes, including both germplasm accessions (368) and individuals from a genetic mapping population (254), were genotyped. A total of 77,660 and 21,283 SNPs were detected by GBS in the germplasm and mapping populations, respectively. The mapping population, which was previously mapped, was constructed with 1,062 markers, among which only 576 SNPs came from GBS, reducing the average interval between two adjacent markers to 4.4 cM. SNPs from GBS genotyping were used for the analysis of genetic structure and LD estimation in the germplasm accessions. Two groups, which largely corresponded to the cultivated and wild populations, were detected using STRUCTURE and via principal coordinate analysis. LD analysis, also using the mapped SNPs, revealed that non-random associations varied along chromosomes, with regions of high LD interspersed with regions of low LD. Considering the length of the genetic map (4,693 cM) and the mean LD (0.49 for cultivated and 0.02 for wild populations), a large number of evenly spaced SNPs would be needed to perform genome-wide association studies in rubber tree, and the wilder the genotypes used, the more difficult the mapping saturation