A machine learning approach for genome-wide prediction of morbid and druggable human genes based on systems-level data

Background: The genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.Results: In this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.Conclusions: We were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.

In vitro study of CD133 human stem cells labeled with superparamagnetic iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are applied in stem cell labeling because of their high magnetic susceptibility as compared with ordinary paramagnetic species, their low toxicity, and their ease of magnetic manipulation. The present work is the study of CD133(+) stem cell labeling by SPIONs coupled to a specific antibody (AC133), resulting in the antigenic labeling of the CD133+ stem cell, and a method was developed for the quantification of the SPION content per cell, necessary for molecular imaging optimization. Flow cytometry analysis established the efficiency of the selection process and helped determine that the CD133 cells selected by chromatographic affinity express the transmembrane glycoprotein CD133. The presence of antibodies coupled to the SPION, expressed in the cell membrane, was observed by transmission electron microscopy. Quantification of the SPION concentration in the marked cells using the ferromagnetic resonance technique resulted in a value of 1.70 x 10 (13) mol iron (9.5 pg) or 7.0 x 10 (6) nanoparticles per cell ( the measurement was carried out in a volume of 2 mu L containing about 6.16 x 10 5 pg iron, equivalent to 4.5 x 10 (11) SPIONs). (c) 2008 Elsevier B.V. All rights reserved.

Voltammetric determination of persulfate anions using an electrode modified with a Prussian blue film

Prussian blue [PB, iron(III) hexacyanoferrate(II)] films are effective for the electrocatalysis of the persulfate (peroxodisulfate)/sulfate redox system. This has been exploited in the voltammetric determination of persulfate anions using a PB-modified platinum disc electrode. A linear correlation between electrocatalytic current and persulfate concentration was found for the range 5 x 10(-5) to 3 x 10(-3) mol dm(-3), using 0.100 mol dm(-3) potassium chloride as supporting electrolyte at pH 4. This analytical method has the advantages of speed and ease of operation in relation to traditional titrimetric methods for persulfate determination. The applicability of the method to the determination of persulfate in a commercial hair bleaching 'booster' product is demonstrated. (C) 2000 Elsevier B.V. B.V. All rights reserved.

The characteristics of a test liquid formulation for use in evaluating the performance of handling and metering systems

Injection metering systems are an important option for the development of pesticide application equipment, with advantages relating to minimising the need for disposal of unused pesticide, improving the ease of cleaning and optimising the accuracy of chemical application. For all injection systems, characteristics such as the steady-state accuracy of delivered dose, dose stability and the time response for dose step changes are related to the ability of the system to operate with different chemical formulations. A system designed to inject liquids should be able to accommodate changes in viscosity and density. The aim of this study was to develop a methodology for testing chemical injection systems using liquids with different viscosities. The experimental arrangement simulating applications with injection metering systems used dye and salt solutions as tracers. Tests were conducted to analyse the influence of salt on the characteristics of the water and a viscous solution. Results showed that the salt interfered with the dye stability in the water solution. In tests with a viscous test liquid, the salt was introduced at different steps during the mixing process, providing four different liquids to be analysed in terms of viscosity, density and pH. Some differences in liquid characteristics were found which could influence the performance of the injection systems.

Influence of Environmental Conditioning on the Shear Behavior of Poly(phenylene sulfide)/Glass Fiber Composites

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Economic Survey of Latin America and the Caribbean 2004-2005

Includes bibliography

Analysis of quality in Brazilian e-commerce (B2C)

The business world has changed the way how people think and act on products and services. In this context, the most recent amendment of the scenarios of retail operations has been the use of technology in sales and distribution. The internet has revolutionized the way people communicate, and moreover as they purchase their goods and services. Thus, the e-commerce, specifically the relation business to customer, or simply B2C, has acted so convincingly in this change of paradigm, namely the purchases in the physical location for the virtual site. Quotes online, ease of payment, price, speed of delivery, have become real order winners of applications for companies that compete in this segment. With the focus on quality of services on e-commerce, the research examines the dimension related to the quality of services, and looks for what of these factors are winners of applications. © 2010 IFIP International Federation for Information Processing.

Development of an instrumentation system embedded on FPGA for real time measurement of mechanical vibrations in rotating machinery

The real-time monitoring of events in an industrial plant is vital, to monitor the actual conditions of operation of the machinery responsible for the manufacturing process. A predictive maintenance program includes condition monitoring of the rotating machinery, to anticipate possible conditions of failure. To increase the operational reliability it is thus necessary an efficient tool to analyze and monitor the equipments, in real-time, and enabling the detection of e.g. incipient faults in bearings. To fulfill these requirements some innovations have become frequent, namely the inclusion of vibration sensors or stator current sensors. These innovations enable the development of new design methodologies that take into account the ease of future modifications, upgrades, and replacement of the monitored machine, as well as expansion of the monitoring system. This paper presents the development, implementation and testing of an instrument for vibration monitoring, as a possible solution to embed in industrial environment. The digital control system is based on an FPGA, and its configuration with an open hardware design tool is described. Special focus is given to the area of fault detection in rolling bearings. © 2012 IEEE.

Effect of MTA-based sealer on the healing of periapical lesions

Some manufacturers have recently added specific components to improve the ease of handling and insertion material properties of MTA in order to create MTA-based sealers. Objective: The aim of this study was to evaluate the healing of periapical lesions in canine teeth after a single session of endodontic treatment with MTA Fillapex® compared with Sealapex® or Endo-CPM-Sealer®. Material and Methods: Sixty-two root canals were performed on two 1-year-old male dogs. After coronal access and pulp extirpation, the canals were exposed to the oral cavity for 6 months in order to induce periapical lesions. The root canals were prepared, irrigated with a solution of 2.5% sodium hypochlorite and filled with gutta-percha and different sealers, according to the following groups: 1) Sealapex®; 2) Endo-CPM-Sealer®; and 3) MTA Fillapex®. Some teeth with periapical lesions were left untreated for use as positive controls. Healthy teeth were used as negative controls. After 6 months, the animals were sacrificed and serial sections from the roots were prepared for histomorphologic analysis and stained with hematoxylin and eosin and the Brown and Brenn technique. The lesions were scored according to pre-established histomorphologic parameters and the scores statistically analyzed using the Kruskal-Wallis test. Results: All 3 materials produced similar patterns of healing (p>0.05); in particular, persistent inflammation and absence of complete periapical tissue healing were consistently noted. Conclusions: Preparation of the infected root canals followed by filling with the materials studied was insufficient to provide complete healing of the periapical tissues.

The Development of a Universal In Silico Predictor of Protein-Protein Interactions

Protein-protein interactions (PPIs) are essential for understanding the function of biological systems and have been characterized using a vast array of experimental techniques. These techniques detect only a small proportion of all PPIs and are labor intensive and time consuming. Therefore, the development of computational methods capable of predicting PPIs accelerates the pace of discovery of new interactions. This paper reports a machine learning-based prediction model, the Universal In Silico Predictor of Protein-Protein Interactions (UNISPPI), which is a decision tree model that can reliably predict PPIs for all species (including proteins from parasite-host associations) using only 20 combinations of amino acids frequencies from interacting and non-interacting proteins as learning features. UNISPPI was able to correctly classify 79.4% and 72.6% of experimentally supported interactions and non-interacting protein pairs, respectively, from an independent test set. Moreover, UNISPPI suggests that the frequencies of the amino acids asparagine, cysteine and isoleucine are important features for distinguishing between interacting and non-interacting protein pairs. We envisage that UNISPPI can be a useful tool for prioritizing interactions for experimental validation. © 2013 Valente et al.

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling - histomorphometrical, immunohistochemical, and molecular analysis

Background: Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling.Methods: One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5).Results: Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn't detect significant differences in expression of all the proteins and most of the genes tested.Conclusions: Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling. © 2013 Esteves et al.; licensee BioMed Central Ltd.

Cost-effective composite electrode for the fast voltammetric screening and determination of riboflavin (B2) and pyridoxine (B6) in pharmaceuticals

Different solid composites made by mechanical dispersions of graphite particles into heated paraffin (from 65 to 80% graphite, in mass) were prepared and assessed in order to optimize their use in electrochemical and electroanalytical procedures for bioanalysis. Besides these, composites were also evaluated by thermoanalytical techniques aiming to study their conservation and long-term stability (over eight months without special care), among others. Best results were found at 80% m/m graphite in paraffin. Such electrode combines low-cost, stability, sensitivity, ease of maintenance and clearance, besides the possibilities of manufacture in many different forms and shapes (with or without modifications) and applicability in a wide range of pH. Electrochemical studies by different voltammetric techniques involving vitamins from complex B (riboflavin and pyridoxine) leaded to a better understanding about their electrooxidative processes onto carbon-composite electrodes, specially regarding reversibility and pH-dependence. Data were also acquired and optimized with analytical purposes, being square-wave voltammetry in pH 4.2 chosen by its many advantages. Good linearity between peak responses as function of concentration were reached from 5 to 43 μmol L-1 for riboflavin (peak at -0.257 V) and up to 8.5 × 10-4 mol L -1 for pyridoxine (peak at +1.04 V), best studied conditions; limits of detection (at an S/N of 3) for both analites showed to be circa 1.0 mol L-1. Different commercial samples were analyzed for riboflavin (EMS® complex B syrup) and pyridoxine (Citoneurin 5000 Merck® ampoules) providing 96.6% and 98.7% recoveries, respectively.

Promoting economic links between the integration schemes of Latin America and the Caribbean

Includes bibliography

Saint Lucia: survey of living conditions and household budgets 2005/2006. User's manual.

This manual contains information on the dataset compiled from the Survey of Living Conditions and Household Budgets (SLC/HBS) conducted in Saint Lucia by the Kairi Consultants Limited and National Assessment Team between 2005 and 2006. The SLC/HBS is a sample survey which generates data on households and individuals in the country. This manual was developed by the Economic Commission for Latin America and the Caribbean (ECLAC) – Subregional Headquarters in the Caribbean as a supplementary document for the Caribbean Household Surveys Database (CHSD). It is sectioned out into two main parts- section one provides brief description of the survey and section two contains a concise data dictionary of variables generated from the survey as well as additional variables created by ECLAC. In addition, for ease of reference, an index of all variables in the database is included at the end of the document.

Effect of s/g ratio on kraft pulping and ecf bleaching of some poplars and eucalyptus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)