IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD/

Construção de modelos de interação in silico e in vitro do inibidor do tipo Kunitz de Adenanthera pavonina L. para as enzimas cisteínicas e serínicas

Serines proteinases inhibitors (PIs) are widely distributed in nature and are able to inhibit both in vitro and in vivo enzymatic activites. Seed PIs in than leguminous are classified in seven families, Bowman-Birk and Kunitz type families that most studied representing an important role in the first line of defense toward insects pests. Some Kunitz type inhibitors possess activities serine and cysteine for proteinases named bifunctional inhibitor, as ApTKI the inhibitor isolate from seed of Adenanthera pavonina. The A. pavonina inhibitor presenting the uncommon property and was used for interaction studies between proteinases serine (trypsin) and cysteine (papain). In order to determinate the in vitro interaction of ApTKI against enzymes inhibitor purification was carried cut by using chromatographic techniques and inhibition assays. The 3D model of the bifunctional inhibitor ApTKI was constructed SWISS-MODEL program by homology modeling using soybean trypsin inhibitor (STI, pdb:1ba7), as template which presented 40% of identity to A. pavonina inhibitor. Model quality was evaluated by PROCHECK program. Moreover in silico analyzes of formed complex between the enzymes and ApTKI was evaluated by HEX 4.5 program. In vitro results confirmed the inhibitory assays, where the inhibitor presented the ability to simultaneously inhibit trypsin and papain. The residues encountered in the inhibitor model of folder structural three-dimensional that make contact to enzymes target coud explain the specificity pattern against serine and cysteine proteinases

Rapid Prototyping applied to surgical planning for correcting craniofacial malformations in wild animals. A case study of a brazilian fox

Veterinary surgery for treatment of wild animals is becoming an increasingly demanding task because it involves animals of different anatomy, many of them are already stressed and treatment must be performed to the highest standard in the minimum period of time. Craniofacial alterations may occur for three main reasons: genetic, functional or a combination of both. It is possible to modify the functional cause using intraoral devices like inclined plane. The treatment planning can be made based on virtual 3D models and rapid prototyping. An approximately 9 months old, 3.7 kg male Brazilian fox (Lycalopex vetulus) was referred to the Veterinary Hospital. Physical examination showed malocclusion with a deviation of the mandible to the right side. The virtual 3D model of the head was generated based on CT image data. The 3D models and rapid prototyping opened up new possibilities for the surgical planning and treatment of wild animals.

Study of a degenerate dipolar Fermi gas of Dy-161 atoms

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TRICUT: a program to clip triangle meshes using the rapid and triangle libraries and the visualization toolkit

An efficient technique to cut polygonal meshes as a step in the geometric modeling of topographic and geological data has been developed. In boundary represented models of outcropping strata and faulted horizons polygonal meshes often intersect each other. TRICUT determines the line of intersection and re-triangulates the area of contact. Along this line the mesh is split in two or more parts which can be selected for removal. The user interaction takes place in the 3D-model space. The intersection, selection and removal are under graphic control. The visualization of outcropping geological structures in digital terrain models is improved by determining intersections against a slightly shifted terrain model. Thus, the outcrop line becomes a surface which overlaps the terrain in its initial position. The area of this overlapping surface changes with respect to the strike and dip of the structure, the morphology and the offset. Some applications of TRICUT on different real datasets are shown. TRICUT is implemented in C+ + using the Visualization Toolkit in conjunction with the RAPID and TRIANGLE libraries. The program runs under LINUX and UNIX using the MESA OpenGL library. This work gives an example of solving a complex 3D geometric problem by integrating available robust public domain software. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Segmentação de imagens e reconstrução de modelos aplicada a estruturas ósseas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação de núcleo metálico fundido, núcleo com fibra de vidro e endocrown em cerâmica: análise comparativa pelo método dos elementos finitos

Pós-graduação em Ciências Odontológicas - FOAR

On the Study of Complex Impulsive Systems

The article investigates complex impulsive systems in which the so-called controlling systems jumps effect emerges. In particular, this research includes the correctness of the solution to the impulsive control system and approximation lemmas. A 3D model example is provided which illustrates the relevance of the considered approach to the study of complex impulsive systems.

Caracterização e aplicação da Blenda PEDOT : PSS/PVA na construção de eletrodos transparentes e dispositivos eletroluminescentes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação do software Autodesk Revit 2016 para quantificação por meio da modelagem da informação da construção

The building budgeting quickly and accurately is a challenge faced by the companies in the sector. The cost estimation process is performed from the quantity takeoff and this process of quantification, historically, through the analysis of the project, scope of work and project information contained in 2D design, text files and spreadsheets. This method, in many cases, present itself flawed, influencing the making management decisions, once it is closely coupled to time and cost management. In this scenario, this work intends to make a critical analysis of conventional process of quantity takeoff, from the quantification through 2D designs, and with the use of the software Autodesk Revit 2016, which uses the concepts of building information modeling for automated quantity takeoff of 3D model construction. It is noted that the 3D modeling process should be aligned with the goals of budgeting. The use of BIM technology programs provides several benefits compared to traditional quantity takeoff process, representing gains in productivity, transparency and assertiveness

Avaliação do software Autodesk Revit 2016 para quantificação por meio da modelagem da informação da construção

The building budgeting quickly and accurately is a challenge faced by the companies in the sector. The cost estimation process is performed from the quantity takeoff and this process of quantification, historically, through the analysis of the project, scope of work and project information contained in 2D design, text files and spreadsheets. This method, in many cases, present itself flawed, influencing the making management decisions, once it is closely coupled to time and cost management. In this scenario, this work intends to make a critical analysis of conventional process of quantity takeoff, from the quantification through 2D designs, and with the use of the software Autodesk Revit 2016, which uses the concepts of building information modeling for automated quantity takeoff of 3D model construction. It is noted that the 3D modeling process should be aligned with the goals of budgeting. The use of BIM technology programs provides several benefits compared to traditional quantity takeoff process, representing gains in productivity, transparency and assertiveness

A Comparative Wet Collapse Buckling Study for the Carcass Layer of Flexible Pipes

When there is a failure on the external sheath of a flexible pipe, a high value of hydrostatic pressure is transferred to its internal plastic layer and consequently to its interlocked carcass, leading to the possibility of collapse. The design of a flexible pipe must predict the maximum value of external pressure the carcass layer can be subjected to without collapse. This value depends on the initial ovalization due to manufacturing tolerances. To study that problem, two numerical finite element models were developed to simulate the behavior of the carcass subjected to external pressure, including the plastic behavior of the materials. The first one is a full 3D model and the second one is a 3D ring model, both composed by solid elements. An interesting conclusion is that both the models provide the same results. An analytical model using an equivalent thickness approach for the carcass layer was also constructed. A good correlation between analytical and numerical models was achieved for pre-collapse behavior but the collapse pressure value and post-collapse behavior were not well predicted by the analytical model. [DOI: 10.1115/1.4005185]

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.

Ruolo dell'Enantiomero (R)-9-HSA nel controllo della proliferazione in una linea di Adenocarcinoma del Colon umano

9-hydroxystearic acid (9-HSA) is an endogenous lipoperoxidation product and its administration to HT29, a colon adenocarcinoma cell line, induced a proliferative arrest in G0/G1 phase mediated by a direct activation of the p21WAF1 gene, bypassing p53. We have previously shown that 9-HSA controls cell growth and differentiation by inhibiting histone deacetylase 1 (HDAC1) activity, showing interesting features as a new anticancer drug. The interaction of 9-HSA with the catalytic site of the 3D model has been tested with a docking procedure: noticeably, when interacting with the site, the (R)-9-enantiomer is more stable than the (S) one. Thus, in this study, (R)- and (S)-9-HSA were synthesized and their biological activity tested in HT29 cells. At the concentration of 50 M (R)-9-HSA showed a stronger antiproliferative effect than the (S) isomer, as indicated by the growth arrest in G0/G1. The inhibitory effect of (S)-9-HSA on HDAC1, HDAC2 and HDAC3 activity was less effective than that of the (R)-9-HSA in vitro, and the inhibitory activity of both the (R)- and the (S)-9-HSA isomer, was higher on HDAC1 compared to HDAC2 and HDAC3, thus demonstrating the stereospecific and selective interaction of 9-HSA with HDAC1. In addition, histone hyperacetylation caused by 9-HSA treatment was examined by an innovative HPLC/ESI/MS method. Analysis on histones isolated from control and treated HT29 confirmed the higher potency of (R)-9-HSA compared to (S)-9-HSA, severely affecting H2A-2 and H4 acetylation. On the other side, it seemed of interest to determine whether the G0/G1 arrest of HT29 cell proliferation could be bypassed by the stimulation with the growth factor EGF. Our results showed that 9-HSA-treated cells were not only prevented from proliferating, but also showed a decreased [3H]thymidine incorporation after EGF stimulation. In this condition, HT29 cells expressed very low levels of cyclin D1, that didn’t colocalize with HDAC1. These results suggested that the cyclin D1/HDAC1 complex is required for proliferation. Furthermore, in the effort of understanding the possible mechanisms of this effect, we have analyzed the degree of internalization of the EGF/EGFR complex and its interactions with HDAC1. EGF/EGFR/HDAC1 complex quantitatively increases in 9-HSA-treated cells but not in serum starved cells after EGF stimulation. Our data suggested that 9-HSA interaction with the catalytic site of the HDAC1 disrupts the HDAC1/cyclin D1 complex and favors EGF/EGFR recruitment by HDAC1, thus enhancing 9-HSA antiproliferative effects. In conclusion 9-HSA is a promising HDAC inhibitor with high selectivity and specificity, capable of inducing cell cycle arrest and histone hyperacetylation, but also able to modulate HDAC1 protein interaction. All these aspects may contribute to the potency of this new antitumor agent.

Metodi di ottimizzazione morfologica nel progetto preliminare di propulsori aeronautici avanzati

The aim of this Doctoral Thesis is to develop a genetic algorithm based optimization methods to find the best conceptual design architecture of an aero-piston-engine, for given design specifications. Nowadays, the conceptual design of turbine airplanes starts with the aircraft specifications, then the most suited turbofan or turbo propeller for the specific application is chosen. In the aeronautical piston engines field, which has been dormant for several decades, as interest shifted towards turboaircraft, new materials with increased performance and properties have opened new possibilities for development. Moreover, the engine’s modularity given by the cylinder unit, makes it possible to design a specific engine for a given application. In many real engineering problems the amount of design variables may be very high, characterized by several non-linearities needed to describe the behaviour of the phenomena. In this case the objective function has many local extremes, but the designer is usually interested in the global one. The stochastic and the evolutionary optimization techniques, such as the genetic algorithms method, may offer reliable solutions to the design problems, within acceptable computational time. The optimization algorithm developed here can be employed in the first phase of the preliminary project of an aeronautical piston engine design. It’s a mono-objective genetic algorithm, which, starting from the given design specifications, finds the engine propulsive system configuration which possesses minimum mass while satisfying the geometrical, structural and performance constraints. The algorithm reads the project specifications as input data, namely the maximum values of crankshaft and propeller shaft speed and the maximal pressure value in the combustion chamber. The design variables bounds, that describe the solution domain from the geometrical point of view, are introduced too. In the Matlab® Optimization environment the objective function to be minimized is defined as the sum of the masses of the engine propulsive components. Each individual that is generated by the genetic algorithm is the assembly of the flywheel, the vibration damper and so many pistons, connecting rods, cranks, as the number of the cylinders. The fitness is evaluated for each individual of the population, then the rules of the genetic operators are applied, such as reproduction, mutation, selection, crossover. In the reproduction step the elitist method is applied, in order to save the fittest individuals from a contingent mutation and recombination disruption, making it undamaged survive until the next generation. Finally, as the best individual is found, the optimal dimensions values of the components are saved to an Excel® file, in order to build a CAD-automatic-3D-model for each component of the propulsive system, having a direct pre-visualization of the final product, still in the engine’s preliminary project design phase. With the purpose of showing the performance of the algorithm and validating this optimization method, an actual engine is taken, as a case study: it’s the 1900 JTD Fiat Avio, 4 cylinders, 4T, Diesel. Many verifications are made on the mechanical components of the engine, in order to test their feasibility and to decide their survival through generations. A system of inequalities is used to describe the non-linear relations between the design variables, and is used for components checking for static and dynamic loads configurations. The design variables geometrical boundaries are taken from actual engines data and similar design cases. Among the many simulations run for algorithm testing, twelve of them have been chosen as representative of the distribution of the individuals. Then, as an example, for each simulation, the corresponding 3D models of the crankshaft and the connecting rod, have been automatically built. In spite of morphological differences among the component the mass is almost the same. The results show a significant mass reduction (almost 20% for the crankshaft) in comparison to the original configuration, and an acceptable robustness of the method have been shown. The algorithm here developed is shown to be a valid method for an aeronautical-piston-engine preliminary project design optimization. In particular the procedure is able to analyze quite a wide range of design solutions, rejecting the ones that cannot fulfill the feasibility design specifications. This optimization algorithm could increase the aeronautical-piston-engine development, speeding up the production rate and joining modern computation performances and technological awareness to the long lasting traditional design experiences.