Development of computational and experimental methods for biomass composition and evaluation of its impact in genome-scale models prediction

The use of genome-scale metabolic models has been rapidly increasing in fields such as metabolic engineering. An important part of a metabolic model is the biomass equation since this reaction will ultimately determine the predictive capacity of the model in terms of essentiality and flux distributions. Thus, in order to obtain a reliable metabolic model the biomass precursors and their coefficients must be as precise as possible. Ideally, determination of the biomass composition would be performed experimentally, but when no experimental data are available this is established by approximation to closely related organisms. Computational methods however, can extract some information from the genome such as amino acid and nucleotide compositions. The main objectives of this study were to compare the biomass composition of several organisms and to evaluate how biomass precursor coefficients affected the predictability of several genome-scale metabolic models by comparing predictions with experimental data in literature. For that, the biomass macromolecular composition was experimentally determined and the amino acid composition was both experimentally and computationally estimated for several organisms. Sensitivity analysis studies were also performed with the Escherichia coli iAF1260 metabolic model concerning specific growth rates and flux distributions. The results obtained suggest that the macromolecular composition is conserved among related organisms. Contrasting, experimental data for amino acid composition seem to have no similarities for related organisms. It was also observed that the impact of macromolecular composition on specific growth rates and flux distributions is larger than the impact of amino acid composition, even when data from closely related organisms are used.

Methods to solve the equations of motion

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Integration methods in dynamic analysis

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

A critical evaluation of methods for the reconstruction of tissue-specific models

Under the framework of constraint based modeling, genome-scale metabolic models (GSMMs) have been used for several tasks, such as metabolic engineering and phenotype prediction. More recently, their application in health related research has spanned drug discovery, biomarker identification and host-pathogen interactions, targeting diseases such as cancer, Alzheimer, obesity or diabetes. In the last years, the development of novel techniques for genome sequencing and other high-throughput methods, together with advances in Bioinformatics, allowed the reconstruction of GSMMs for human cells. Considering the diversity of cell types and tissues present in the human body, it is imperative to develop tissue-specific metabolic models. Methods to automatically generate these models, based on generic human metabolic models and a plethora of omics data, have been proposed. However, their results have not yet been adequately and critically evaluated and compared. This work presents a survey of the most important tissue or cell type specific metabolic model reconstruction methods, which use literature, transcriptomics, proteomics and metabolomics data, together with a global template model. As a case study, we analyzed the consistency between several omics data sources and reconstructed distinct metabolic models of hepatocytes using different methods and data sources as inputs. The results show that omics data sources have a poor overlapping and, in some cases, are even contradictory. Additionally, the hepatocyte metabolic models generated are in many cases not able to perform metabolic functions known to be present in the liver tissue. We conclude that reliable methods for a priori omics data integration are required to support the reconstruction of complex models of human cells.

Automated network resilience optimization using computational intelligence methods

This paper presents an automated optimization framework able to provide network administrators with resilient routing configurations for link-state protocols, such as OSPF or IS-IS. In order to deal with the formulated NP-hard optimization problems, the devised framework is underpinned by the use of computational intelligence optimization engines, such as Multi-objective Evolutionary Algorithms (MOEAs). With the objective of demonstrating the framework capabilities, two illustrative Traffic Engineering methods are described, allowing to attain routing configurations robust to changes in the traffic demands and maintaining the network stable even in the presence of link failure events. The presented illustrative results clearly corroborate the usefulness of the proposed automated framework along with the devised optimization methods.

Microfluidic based on aqueous two-phase system for plasmidic DNA purification

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biotecnologia)

The bussola study. Final results, conclusions and proposals

OBJECTIVE: To evaluate the use of thrombolytic and acetylsalicylic acid therapies in acute myocardial infarct patients as well as the availability of technical and human resources for the care of these patients in the emergency units of the city of Rio de Janeiro. Additional objectives were the evaluation of the use of primary angioplasty and the level of acceptance of SBC /RJ as an entity responsible for programs of continued medical education. METHODS: Interviews with physicians at 46 emergency units in the city of Rio de Janeiro. RESULTS: Of the 46 emergency units inspected, a policy of encouragement to use thrombolytic therapy was only prescribed in 6.5%. In 1/3 of the public wards no thrombolytic agents were available, and in none of them was access to primary angioplasty regularly available; 45.9% did not offer the minimal conditions required for the handling of cases of acute myocardial infarction; 60% of the physicians on-call (at both public and private emergency units), appeared not to know the importance of the use of acetylsalicylic acid in acute myocardial infarct patients; all physicians interviewed would participate in programs of continued medical education organized by the SBC/RJ. CONCLUSION: The study suggests there was: 1) the low probability of the use of thrombolytic therapy in the majority of the emergency units in of the city of Rio de Janeiro due to the inadequate policy of waiting for the transfer of the patient to coronary or intensive care unit; 2) a low awareness to the importance of early use of acetylsalic acid in acute myocardial infarct; 3) half of the emergency units of the public net do not have the minimal conditions required for the handling of cases of acute myocardial infarction; 4) a high level of credibility exists that would enable the SBC/RJ to set up programs for continued medical education to change the mentality regarding the use of thrombolytic therapy and of acetylsalicylic acid.

Numerical methods in multibody system dynamics

"Series: Solid mechanics and its applications, vol. 226"

Couple's willingness to donate embryos for research: a longitudinal study

Introduction. Decision-making on embryo disposition is a source of distress and is subject to change over time. This paper analyses the willingness of couples undergoing in vitro fertilization to donate cryopreserved embryos for research from 15 days after embryo transfer to 12 months later, taking into account the influence of psychosocial, demographic, and reproductive factors. Materials and methods. Prospective longitudinal study, with 74 heterosexual couples undergoing in vitro fertilization in a public fertility centre in Portugal, recruited between 2011 and 2012. Participants were evaluated twice: 15 days after embryo transfer and 12 months later. Results. A significant decrease in patients’ willingness to donate embryos for research over time was observed [86.5% to 73.6%; relative risk (RR) = 0.85; 95% CI 0.76–0.95]. A higher education level (>12 years) [adjusted RR (RRadj) = 0.79; 95% CI 0.64–0.96], considering research on human embryos to be important (vs. very important) (RRadj = 0.59; 95% CI 0.39–0.85) and practicing a religion less than once a month (vs. at least once a month) (RRadj = 0.73; 95% CI 0.53–1.00) seemed associated with unwillingness to donate embryos for research over time. Change towards non-donation happened mainly among couples who first considered that it was better to donate than wasting the embryos. Change towards donation occurred mostly among those stating that their priority at time 1 was to have a baby and who became pregnant in the meantime. Conclusions. Quality of care guided by patients’ characteristics, values, preferences, and needs calls for considering the factors and reasons underlying couples’ willingness to donate embryos for research over time as a topic in psychosocial guidelines for infertility and medically assisted reproductive care.

Validation study of an automated wrist monitor, omron model HEM-608, compared with the standard methods for blood pressure measurement

OBJECTIVE - The aim of our study was to assess the profile of a wrist monitor, the Omron Model HEM-608, compared with the indirect method for blood pressure measurement. METHODS - Our study population consisted of 100 subjects, 29 being normotensive and 71 being hypertensive. Participants had their blood pressure checked 8 times with alternate techniques, 4 by the indirect method and 4 with the Omron wrist monitor. The validation criteria used to test this device were based on the internationally recognized protocols. RESULTS - Our data showed that the Omron HEM-608 reached a classification B for systolic and A for diastolic blood pressure, according to the one protocol. The mean differences between blood pressure values obtained with each of the methods were -2.3 +7.9mmHg for systolic and 0.97+5.5mmHg for diastolic blood pressure. Therefore, we considered this type of device approved according to the criteria selected. CONCLUSION - Our study leads us to conclude that this wrist monitor is not only easy to use, but also produces results very similar to those obtained by the standard indirect method.

Hierarchical modelling of timber reference properties using probabilistic methods: Maximum Likelihood Method, Bayesian Methods and Probability Networks

In recent decades, an increased interest has been evidenced in the research on multi-scale hierarchical modelling in the field of mechanics, and also in the field of wood products and timber engineering. One of the main motivations for hierar-chical modelling is to understand how properties, composition and structure at lower scale levels may influence and be used to predict the material properties on a macroscopic and structural engineering scale. This chapter presents the applicability of statistic and probabilistic methods, such as the Maximum Likelihood method and Bayesian methods, in the representation of timber’s mechanical properties and its inference accounting to prior information obtained in different importance scales. These methods allow to analyse distinct timber’s reference properties, such as density, bending stiffness and strength, and hierarchically consider information obtained through different non, semi or destructive tests. The basis and fundaments of the methods are described and also recommendations and limitations are discussed. The methods may be used in several contexts, however require an expert’s knowledge to assess the correct statistic fitting and define the correlation arrangement between properties.

Correlations Between the Collagen Content of the Human Left Ventricular Myocardium, Measured by Biochemical and Morphometric Methods

OBJECTIVE: To assess, in myocardium specimens obtained from necropsies, the correlation between the concentration of hydroxyproline, measured with the photocolorimetric method, and the intensity of fibrosis, determined with the morphometric method. METHODS: Left ventricle myocardium samples were obtained from 45 patients who had undergone necropsy, some of them with a variety of cardiopathies and others without any heart disease. The concentrations of hydroxyproline were determined with the photocolorimetric method. In the histologic sections from each heart, the myocardial fibrosis was quantified by using a light microscope with an integrating ocular lens. RESULTS: A median of, respectively, 4.5 and 4.3 mug of hydroxyproline/mg of dry weight was found in fixed and nonfixed left ventricle myocardium fragments. A positive correlation occurred between the hydroxyproline concentrations and the intensity of fibrosis, both in the fixed (Sr=+0.25; p=0.099) and in the nonfixed (Sr=+0.32; p=0.03) specimens. CONCLUSION: The biochemical methodology was proven to be adequate, and manual morphometry was shown to have limitations that may interfere with the statistical significance of correlations for the estimate of fibrosis intensity in the human myocardium.

Correlation between turbidimetric and nephelometric methods of measuring C-reactive protein in patients with unstable angina or non-ST elevation acute myocardial infarction

OBJECTIVE: To evaluate the performance of the turbidimetric method of C-reactive protein (CRP) as a measure of low-grade inflammation in patients admitted with non-ST elevation acute coronary syndromes (ACS). METHODS: Serum samples obtained at hospital arrival from 68 patients (66±11 years, 40 men), admitted with unstable angina or non-ST elevation acute myocardial infarction were used to measure CRP by the methods of nephelometry and turbidimetry. RESULTS: The medians of C-reactive protein by the turbidimetric and nephelometric methods were 0.5 mg/dL and 0.47 mg/dL, respectively. A strong linear association existed between the 2 methods, according to the regression coefficient (b=0.75; 95% C.I.=0.70-0.80) and correlation coefficient (r=0.96; P<0.001). The mean difference between the nephelometric and turbidimetric CRP was 0.02 ± 0.91 mg/dL, and 100% agreement between the methods in the detection of high CRP was observed. CONCLUSION: In patients with non-ST elevation ACS, CRP values obtained by turbidimetry show a strong linear association with the method of nephelometry and perfect agreement in the detection of high CRP.