Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Psychiatric morbidity and quality of life of primary care attenders in two cities in Brazil

Objective: To identify the associations among quality of life (QoL), social determinants and psychological distress in primary care in two cities in Brazil. Methods: A cross-sectional study with 1,466 patients from 2009 to 2010. The statistical analysis used the t-test to compare the variables of interest to the study. Results: The prevalence of Common Mental Disorders (CMD3), severe forms of Common Mental Disorders (CMD5), anxiety and depression were 20.5%, 32%, 37% and 25.1% respectively. Thes presence of psychological distress is associated with worse QoL among the patients studied, especially those older than 40 years of age. In cases of CMD3, those with higher income and educational levels presented higher QoL in the psychical and psychological domains. For the cases of probable anxiety, those with higher educational levels presented lower scores on the physical and social relationship scores. Conclusion: Psychological distress can be associated with a worse QoL among those studied and can be influenced by socioeconomic conditions. Therefore, it is important to structure patient-centered help, which should also include patients’ social contexts.

Pharmacological evaluation of plant extracts from Chapada Diamantina (Bahia, Brazil): Focus on antioxidant and cytotoxic properties

Tese de Doutoramento em Biologia de Plantas MAP - Bioplant

Comparative genomics reveals adaptations of a halotolerant thaumarchaeon in the interfaces of brine pools in the Red Sea

The bottom of the Red Sea harbors over 25 deep hypersaline anoxic basins that are geochemically distinct and characterized by vertical gradients of extreme physicochemical conditions. Because of strong changes in density, particulate and microbial debris get entrapped in the brine-seawater interface (BSI), resulting in increased dissolved organic carbon, reduced dissolved oxygen toward the brines and enhanced microbial activities in the BSI. These features coupled with the deep-sea prevalence of ammonia-oxidizing archaea (AOA) in the global ocean make the BSI a suitable environment for studying the osmotic adaptations and ecology of these important players in the marine nitrogen cycle. Using phylogenomic-based approaches, we show that the local archaeal community of five different BSI habitats (with up to 18.2% salinity) is composed mostly of a single, highly abundant Nitrosopumilus-like phylotype that is phylogenetically distinct from the bathypelagic thaumarchaea; ammonia-oxidizing bacteria were absent. The composite genome of this novel Nitrosopumilus-like subpopulation (RSA3) co-assembled from multiple single-cell amplified genomes (SAGs) from one such BSI habitat further revealed that it shares [sim]54% of its predicted genomic inventory with sequenced Nitrosopumilus species. RSA3 also carries several, albeit variable gene sets that further illuminate the phylogenetic diversity and metabolic plasticity of this genus. Specifically, it encodes for a putative proline-glutamate 'switch' with a potential role in osmotolerance and indirect impact on carbon and energy flows. Metagenomic fragment recruitment analyses against the composite RSA3 genome, Nitrosopumilus maritimus, and SAGs of mesopelagic thaumarchaea also reiterate the divergence of the BSI genotypes from other AOA.

Estimation of statistical cure from cancer using population-based data

Dissertação de mestrado em Estatística

Desenvolvimento e validação de um método para a caracterização de vinhos por HPLC-DAD

Dissertação de mestrado em Técnicas de Caracterização e Análise Química

Some predictors of cardiovascular mortality among the elderly population of Botucatu (SP)

OBJECTIVE: To detect factors associated with cardiovascular mortality in the elderly of Botucatu. METHODS: We evaluated 29 variables of interest in a cohort of patients aged ³60 using data from a survey conducted between 1983/84. The elderly cohort was analyzed in 1992 to detect the occurrence of cardiovascular deaths. Survival analysis was performed using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. Three models were adapted for each group of variables, and a final model was chosen from those variables selected from each group. RESULTS: We identified predictor for cardiovascular death according to age for elderly males not supporting the family, not possessing a vehicle, and previous cardiovascular disease. In elderly females, the predictor variables were previous cardiovascular disease and diabetes mellitus. CONCLUSION: Socioeconomic indicators (family heading and vehicle ownerrship) may be added to well stabilished medical factors (diabete mellitus and hypertension to select target groups for programs intended to reduce deaths due to cardiovascular diseases in elderly people.

Predictive factors of in-hospital mortality and of severe perioperative complications in myocardial revascularization surgery

OBJECTIVE: To investigate preoperative predictive factors of severe perioperative intercurrent events and in-hospital mortality in coronary artery bypass graft (CABG) surgery and to develop specific models of risk prediction for these events, mainly those that can undergo changes in the preoperative period. METHODS: We prospectively studied 453 patients who had undergone CABG. Factors independently associated with the events of interest were determined with multiple logistic regression and Cox proportional hazards regression model. RESULTS: The mortality rate was 11.3% (51/453), and 21.2% of the patients had 1 or more perioperative intercurrent events. In the final model, the following variables remained associated with the risk of intercurrent events: age ³ 70 years, female sex, hospitalization via SUS (Sistema Único de Saúde - the Brazilian public health system), cardiogenic shock, ischemia, and dependence on dialysis. Using multiple logistic regression for in-hospital mortality, the following variables participated in the model of risk prediction: age ³ 70 years, female sex, hospitalization via SUS, diabetes, renal dysfunction, and cardiogenic shock. According to the Cox regression model for death within the 7 days following surgery, the following variables remained associated with mortality: age ³ 70 years, female sex, cardiogenic shock, and hospitalization via SUS. CONCLUSION: The aspects linked to the structure of the Brazilian health system, such as factors of great impact on the results obtained, indicate that the events investigated also depend on factors that do not relate to the patient's intrinsic condition.

Optimisation of a surface mount technology process using a SnAgCu lead-free alloy

The impending introduction of lead-free solder in the manufacture of electrical and electronic products has presented the electronics industry with many challenges. European manufacturers must transfer from a tin-lead process to a lead-free process by July 2006 as a result of the publication of two directives from the European Parliament. Tin-lead solders have been used for mechanical and electrical connections on printed circuit boards for over fifty years and considerable process knowledge has been accumulated. Extensive literature reviews were conducted on the topic and as a result it was found there are many implications to be considered with the introduction of lead-free solder. One particular question that requires answering is; can lead-free solder be used in existing manufacturing processes? The purpose of this research is to conduct a comparative study of a tin-lead solder and a lead-free solder in two key surface mount technology (SMT) processes. The two SMT processes in question were the stencil printing process and the reflow soldering process. Unreplicated fractional factorial experimental designs were used to carry out the studies. The quality of paste deposition in terms of height and volume were the characteristics of interest in the stencil printing process. The quality of solder joints produced in the reflow soldering experiment was assessed using x-ray and cross sectional analysis. This provided qualitative data that was then uniquely scored and weighted using a method developed during the research. Nested experimental design techniques were then used to analyse the resulting quantitative data. Predictive models were developed that allowed for the optimisation of both processes. Results from both experiments show that solder joints of comparable quality to those produced using tin-lead solder can be produced using lead-free solder in current SMT processes.

Proceedings of the 1st International Conference on Applied Innovations in IT

This volume contains publications of the 1st International Conference on Applied Innovations in IT (ICAIIT), which took place in Koethen March 25th 2013. The conference is devoted to problems of applied research in the fields of mechanical and economical engineering, auotmation and communications as well as of data mining. The research results can be of interest for researchers and development engineers, who deal with theoretical base and the application of the knowledge in the respective areas.

Proceedings of the 2nd International Conference on Applied Innovations in IT

This volume contains publications of the 2nd International Conference on Applied Innovations in IT (ICAIIT), which took place in Koethen March 27th 2014. The conference is devoted to problems of applied research in the fields of automation and communications. The research results can be of interest for researchers and development engineers, who deal with theoretical base and the application of the knowledge in the respective areas.

Proceedings of the 3rd International Conference on Applied Innovations in IT

This volume contains publications of the 3rd International Conference on Applied Innovations in IT (ICAIIT), which took place in Koethen March 19th 2015. The conference is devoted to problems of applied research in the fields of automation and communications. The research results can be of interest for researchers and development engineers, who deal with theoretical base and the application of the knowledge in the respective areas.

Population fluctuations of calliphorid species (Diptera, Calliphoridae) in the Biological Reserve of Tinguá, state of Rio de Janeiro, Brazil

The purpose of this work was to determine the diversity and population fluctuations of calliphorid flies in the Biological Reserve of Tinguá (ReBio-Tinguá), Nova Iguaçu, state of Rio de Janeiro, Brazil and to correlate their occurrence with the environmental variables of temperature, rainfall and relative air humidity. Specimens of Diptera were collected monthly between June 2002 and January 2005 using four traps placed at four points along a trail and exposed for 48 hours. The traps were baited with sardines and the trapped insects were stored in 70% alcohol. It was collected 8,528 calliphorids, thirteen species were identified among the blowflies including Laneela nigripes Guimarães 1977, Chrysomya megacephala (Fabricius, 1794), C. albiceps (Wiedemann, 1819), C. putoria (Wiedemann, 1830), Chloroprocta idioidea (Robineau-Devoidy, 1830), Cochliomyia macellaria (Fabricius, 1775), Hemilucilia semidiaphana (Rondani, 1850), H. segmentaria (Fabricius, 1805), Lucilia eximia (Wiedemann,1819), L. cuprina (Wiedemann, 1830), Paralucilia pseudolyrcea (Mello, 1969), Mesembrinella sp. and Eumesembrinella pauciseta (Aldrich, 1922). No significant correlation was found between the abundance of blowflies and the temperature and relative air humidity. Only C. megacephala and C. albiceps showed a positive and significant correlation with rainfall. An analysis of grouping by month (UPGMA) revealed no seasonal difference in the composition of the community, indicating that the community of calliphorid flies is probably more influenced by the ecological niches occupied by each species than by the seasons of the year.

Diet of Cnesterodon decemmaculatus (Poeciliidae) and Jenynsia multidentata (Anablepidae) in a hypertrophic shallow lake of Uruguay

Diet of Cnesterodon decemmaculatus (Jenyns, 1842) and Jenynsia multidentata (Jenyns, 1842) were analysed in Lake Rodó, an urban hypertrophic lake from Montevideo, Uruguay. Both species displayed omnivory. The most consumed items for C. decemmaculatus were zooplankton, periphyton, phytoplankton and detritus; the diet of J. multidentata included zooplankton, insects, crustaceans and juvenile fish. Our results suggest that both species could be acting as facultative planktivores. The fish community of this lake is characterised by the dominance of C. decemmaculatus and J. multidentata. Under this condition, predation on large-bodied zooplankton could indirectly be contributing to maintain a high phytoplankton abundance and a low water transparency.

Bird community in an Araucaria forest fragment in relation to changes in the surrounding landscape in Southern Brazil

The dynamics of the bird community in a small forest fragment was evaluated along seven years in relation to changes in the surrounding landscape. The study area is an Araucaria forest fragment in Southern Brazil (state of Paraná). The sampling period covered the years 1988 through 1994 and the mark-release-recapture method was utilized. The landscape analysis was based on Landsat TM images, and changes in exotic tree plantations, native forest, open areas (agriculture, pasture, bare soil, and abandoned field), and "capoeira"(native vegetation < 2 m) were quantified. The relationship between landscape changes and changes in abundance diversity of forest birds, open-area birds, forest-edge birds, and bamboo specialists was evaluated. Richness estimates were run for each year studied. The richness recorded in the study area comprised 96 species. The richness estimates were 114, 118 and 110 species for Chao 1, Jackknife 1 and Bootstrap, respectively. The bird community varied in species richness, abundance and diversity from year to year. As for species diversity, 1991, 1993 and 1994 were significantly different from the other years. Changes in the landscape contributed to the increase in abundance and richness for the groups of forest, open-area and bamboo-specialist species. An important factor discussed was the effect of the flowering of "taquara" (Poaceae), which contributed significantly to increasing richness of bamboo seed eaters, mainly in 1992 and 1993. In general, the results showed that landscape changes affected the dynamics and structure of the bird community of this forest fragment over time, and proved to have an important role in conservation of the avian community in areas of intensive forestry and agricultural activities.