Structure-Based Approach for the Study of Estrogen Receptor Binding Affinity and Subtype Selectivity

Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpa (hER alpha) and beta (hER beta). Because the levels and relative proportion of hER alpha and hER beta differ significantly in different target cells, selective hER ligands could target specific tissues or pathways regulated by one receptor subtype without affecting the other. To understand the structural and chemical basis by which small molecule modulators are able to discriminate between the two subtypes, we have applied three-dimensional target-based approaches employing a series of potent hER-ligands. Comparative molecular field analysis (CoMFA) studies were applied to a data set of 81 hER modulators, for which binding affinity values were collected for both hER alpha and hER beta. Significant statistical coefficients were obtained (hER alpha, q(2) = 0.76; hER beta, q(2) = 0.70), indicating the internal consistency of the models. The generated models were validated using external test sets, and the predicted values were in good agreement with the experimental results. Five hER crystal structures were used in GRID/PCA investigations to generate molecular interaction fields (MIF) maps. hER alpha and hER beta were separated using one factor. The resulting 3D information was integrated with the aim of revealing the most relevant structural features involved in hER subtype selectivity. The final QSAR and GRID/PCA models and the information gathered from 3D contour maps should be useful for the design or novel hER modulators with improved selectivity.

O forjamento de ligas de alumínio : um estudo para a liga ABNT 6061

Este trabalho pretende, na visão de novas tecnologias, discutir o processo de forjamento das ligas de alumínio (ABNT 6061), buscando propor uma metodologia baseada na ciência da engenharia. Deseja-se minimizar os procedimentos de tentativa e erro no desenvolvimento de processos de conformação. Para tanto, novas tecnologias disponíveis atualmente, tais como o Projeto Assistido por Computador (CAD), a Fabricação Assistida por Computador (CAM) e a Simulação do Processo (CAE) são empregadas. Resultados experimentais mostrando o comportamento da liga ABNT 6061 através das curvas de escoamento bem como o estabelecimento da condição do atrito no processo de conformação, avaliando dois lubrificantes comerciais disponíveis (Deltaforge 31 e Oildag) para aplicações nas ligas de alumínio, são reportados neste trabalho. A comparação dos resultados obtidos de um experimento prático de forjamento com a simulação pelo “Método dos Elementos Finitos” usando o código “QForm” é apresentada para uma peça de simetria axial em liga de alumínio. Finalmente, os resultados obtidos no forjamento de um componente automotivo em liga de alumínio (ABNT 6061), desenvolvido em parceria com a empresa Dana, são analisados e comparados com as simulações computacionais realizadas usando o código “Superforge”.

Simulation of needle-type corona electrodes by the finite element method

This paper describes a software tool, called LEVSOFT, suitable for the electric field simulations of corona electrodes by the Finite Element Method (FEM). Special attention was paid to the user friendly construction of geometries with corners and sharp points, and to the fast generation of highly refined triangular meshes and field maps. The execution of self-adaptive meshes was also implemented. These customized features make the code attractive for the simulation of needle-type corona electrodes. Some case examples involving needle type electrodes are presented.

A malware detection system inspired on the human immune system

Malicious programs (malware) can cause severe damage on computer systems and data. The mechanism that the human immune system uses to detect and protect from organisms that threaten the human body is efficient and can be adapted to detect malware attacks. In this paper we propose a system to perform malware distributed collection, analysis and detection, this last inspired by the human immune system. After collecting malware samples from Internet, they are dynamically analyzed so as to provide execution traces at the operating system level and network flows that are used to create a behavioral model and to generate a detection signature. Those signatures serve as input to a malware detector, acting as the antibodies in the antigen detection process. This allows us to understand the malware attack and aids in the infection removal procedures. © 2012 Springer-Verlag.

Elaborazione di un algoritmo di pianificazione di ricostruzioni del cavo orale, dell'orofaringe, della mandibola.

1.Ricostruzione mandibolare La ricostruzione mandibolare è comunemente eseguita utilizzando un lembo libero perone. Il metodo convenzionale (indiretto) di Computer Aided Design e Computer Aided Manifacturing prevede il modellamento manuale preoperatorio di una placca di osteosintesi standard su un modello stereolitografico della mandibola. Un metodo innovativo CAD CAM diretto comprende 3 fasi: 1) pianificazione virtuale 2) computer aided design della dima di taglio mandibolari, della dima di taglio del perone e della placca di osteosintesi e 3) Computer Aided Manufacturing dei 3 dispositivi chirurgici personalizzati. 7 ricostruzioni mandibolari sono state effettuate con il metodo diretto. I risultati raggiunti e le modalità di pianificazione sono descritte e discusse. La progettazione assistita da computer e la tecnica di fabbricazione assistita da computer facilita un'accurata ricostruzione mandibolare ed apporta un miglioramento statisticamente significativo rispetto al metodo convenzionale. 2. Cavità orale e orofaringe Un metodo ricostruttivo standard per la cavità orale e l'orofaringe viene descritto. 163 pazienti affetti da cancro della cavità orale e dell'orofaringe, sono stati trattati dal 1992 al 2012 eseguendo un totale di 175 lembi liberi. La strategia chirurgica è descritta in termini di scelta del lembo, modellamento ed insetting. I modelli bidimensionali sono utilizzati per pianificare una ricostruzione tridimensionale con il miglior risultato funzionale ed estetico. I modelli, la scelta del lembo e l' insetting sono descritti per ogni regione. Complicazioni e risultati funzionali sono stati valutati sistematicamente. I risultati hanno mostrato un buon recupero funzionale con le tecniche ricostruttive descritte. Viene proposto un algoritmo ricostruttivo basato su template standard.

Animazione di personaggi mediante cinematica inversa in Maya

Lo sviluppo di questa tesi è nato dalla mia volontà di intraprendere un cammino nel campo dell’animazione computerizzata e della grafica in generale. La tesi tratta in generale della nascita dell’animazione, del suo sviluppo, delle principali tecniche e ne applica i principi nella realizzazione di un’animazione. Il progetto consiste nella modellazione di un personaggio di un cartone animato attraverso il programma Autodesk Maya, e nella sua successiva animazione, ossia nel rendere il movimento del personaggio in una scena realizzata sempre con gli strumenti di Maya. Nel primo capitolo viene presentata una breve storia della computer grafica, come e dove è nata e i ricercatori che hanno contribuito a svilupparla. Si parla del suo sviluppo, di cortometraggi e film d’animazione che hanno reso possibile il suo sviluppo sia nel cinema, sia in altri settori. In breve vengono descritte anche alcune applicazioni e uno schema che racchiude i rami della grafica. Nel secondo capitolo viene messa in rilievo una differenza tra animazione tradizionale e animazione computerizzata. Inoltre vengono elencati i principi cardini dell’animazione, particolare rilievo viene dato alle figure articolate e alle principali articolazioni importanti per l’animazione. Viene trattata la cinematica che permette lo studio del moto del corpo e viene descritta la differenza tra cinematica diretta e inversa, i tre approcci per utilizzarla e un confronto finale tra le due. Infine viene fatta una breve descrizione dell’animazione interattiva, della dinamica dei corpi e dell’animazione automatizzata. Il terzo capitolo tratta del software utilizzato per la realizzazione del progetto Autodesk Maya. È stata inserita una breve guida base sugli strumenti di Maya. Nel quarto capitolo vengono esposti i passi seguiti per la realizzazione del progetto. Il personaggio che è stato modellato è Olaf, il pupazzo di neve del film d’animazione Frozen. In questo capitolo vengono presentati anche i passi per lo sviluppo della scena, e le tecniche utilizzate per animare il personaggio.

Tiled Projector Displays Correction for Dark Scenes in Railway Simulators

Tiled projector displays are a common choice for training simulators, where a high resolution output image is required. They are cheap for the resolution that they can reach and can be configured in many different ways. Nevertheless, such kinds of displays require geometric and color correction so that the composite image looks seamless. Display correction is an even bigger challenge when the projected images include dark scenes combined with brighter scenes. This is usually a problem for railway simulators when the train is positioned inside a tunnel and the black offset effect becomes noticeable. In this paper, a method for fast photometric and geometric correction of tiled display systems where dark and bright scenes are combined is presented. The image correction is carried out in two steps. First, geometric alignment and overlapping areas attenuation for brighter scenes is applied. Second, in the event of being inside a tunnel, the brightness of the scene is increased in certain areas using light sources in order to create the impression of darkness but minimizing the effect of the black offset

Simulation of a mechanical thrombectomy device based in the use of self-expandable stents for the blood clots extraction

Recently, we have presented some studies concerning the analysis, design and optimization of one experimental device developed in the UK - GPTAD - which has been designed to remove blood clots without the need to make contact with the clot itself, thereby potentially reducing the risk of problems such as downstream embolisation. Based on the idea of a modification of the previous device, in this work, we present a model based in the use of stents like the SolitaireTM FR, which is in contact with the clot itself. In the case of such devices, the stent is self-expandable and the extraction of the blood clot is faciliatated by the stent, which must be inside the clot. Such stents are generally inserted in position by using the guidewire inserted into the catheter. This type of modeling could potentially be useful in showing how the blood clot is moved by the various different forces involved. The modelling has been undertaken by analyzing the resistances, compliances and inertances effects. We model an artery and blood clot for range of forces for the guidewire. In each case we determine the interaction between blood clot, stent and artery.

Contribución a las nuevas tendencias en el diseño de tuberías en construcción naval

En la situación actual, tanto las posibilidades de contratar como los resultados económicos de un astillero, dependen de su capacidad para construir un buque en el plazo mas corto posible. Dentro de los trabajos de diseño y construcción de de un buque el trabajo de tuberías ha sido el que tradicionalmente ha condicionado los plazos de construcción. En este estudio se considerara que se han tenido en cuenta los criterios necesarios para que las instalaciones del buque funcionen correctamente y se verá como los sistemas de diseño influyen en el coste y plazo del buque y, por tanto, en la productividad del astillero. Se estudian los distintos procesos de diseño, fabricación y montaje de tuberías, la evolución de estos procesos a lo largo del tiempo, los módulos de armamento que se realizan en los astilleros, los modelos de cámara de máquinas, y los sistemas de ayuda al diseño por ordenador. El autor, en su puesto de Jefe de la Oficina Tecnológica de la Factoría de Sevilla de Astilleros Españoles en los últimos 12 años, ha tomado parte activa en esta evolución, formando parte de un equipo que ha situado a este astillero entre los mas avanzarlos de Europa. Todo lo anterior sirve de base para la segunda parte de este estudio, donde se abordan las que, en opinión del autor, son las nuevas tendencias en el diseño de tuberías en la construcción naval. V Integración del CAD/CAM o CIM : CAD = computer aided design o diseño asistido por ordenador, CAM = computer aided manufacturing o fabricación asistida por ordenador, CIM = computer integrated manufacturing o fabricación integrada por ordenador. Se estudia la integración de los procesos de diseño con el resto de los procesos de gestión y de producción de un astillero, proponiéndose un modelo de cómo el autor ve esta integración. Se comenta la actual tendencia a pasar de las automatizaciones duras con maquinas especializadas para cada proceso, a las automatizaciones blandas en las que un robot puede realizar distintos procesos modificando su programación. Se estudian las nuevas posibilidades de la normal i zacio'n, de los planos parametrizados y de la tecnología de grupos aportando algunos ejemplos. Se estudia también como los procesos anteriores conducirán a una optimización del producto en sí, es decir a conseguir mejores buques. En las conclusiones destacamos como el camino que tienen los países desarrollados, como el nuestro, para mantener una industria competitiva de construcción naval va por la mecanización de los procesos constructivos siguiendo las tendencias anteriores y obteniendo buques optimizados. vi SUMMARY Under the present situation the possibilities to contract and the economical results of a Shipyard depend on its capacity to build a ship within the shortest time. i Within the works of design and construction of a ship, piping work has traditionally conditioned the construction time. In this study it shall be considered that the necessary criteria for the ship installations to operate correctly have been taken into account and it shall be noticed how the design systems influence on the cost and time of a ship and therefore on the Shipyard's productivity. Studies are made of different design processes, manufacturing and installation of piping, evolution of these processes along the time, outfitting modules made in the Shipyard, engine room models and computerized design aid systems. The author, in his post of Chief of the Technological Office of Sevilla Shipyard of Astilleros Españoles for the last 12 years, has taken an active part in this evolution, making part of a team which has placed this Shipyard among the most advanced in Europe. All of the above is used for the second part of this study, whereby an approach is made to those who, in the author's opinion, are the new trends in the piping design of shipbuilding. vii Integration of CAD/CAM or CIM: CAD = computer aided design, CAM = computer aided manufacturing, CIM = computer integrated manufacturing. i A study is made of the integration of design processes with the remaining step and production Shipyard processes, proposing a model of how the author views this integration. Comments are made on the present trend to go from hard automations with specialized machines for each process to soft automations, in which a robot can carry out different processes modifying its programmes. Studies are made of: New possibility of standardization, parametrized drawings and group technology, bringing some examples. It is also studied how the above processes shall lead to optimize the product itself, that is, to obtain better ships. In the conclusions we stand out how the way of developed countries (as ours) to maintain a competitive shipbuilding industry is by computerizing constructive processes, following the above trends and obtaining better ships.

Modeling and Simulation of Upper Brachial Plexus Injury

This article presents the first musculoskeletal model and simulation of upper plexus brachial injury. From this model is possible to analyse forces and movement ranges in order to develop a robotic exoskeleton to improve rehabilitation. The software that currently exists for musculoskeletal modeling is varied and most have advanced features for proper analysis and study of motion simulations. Whilst more powerful computer packages are usually expensive, there are other free and open source packages available which offer different tools to perform animations and simulations and which obtain forces and moments of inertia. Among them, Musculoskeletal Modeling Software was selected to construct a model of the upper limb, which has 7 degrees of freedom and 10 muscles. These muscles are important for two of the movements simulated in this article that are part of the post-surgery rehabilitation protocol. We performed different movement animations which are made using the inertial measurement unit to capture real data from movements made by a human being. We also performed the simulation of forces produced in elbow flexion-extension and arm abduction-adduction of a healthy subject and one with upper brachial plexus injury in a postoperative state to compare the force that is capable of being produced in both cases.

The design and implementation of a repository for the management of spatial data integrity constraints

This paper reviews the key features of an environment to support domain users in spatial information system (SIS) development. It presents a full design and prototype implementation of a repository system for the storage and management of metadata, focusing on a subset of spatial data integrity constraint classes. The system is designed to support spatial system development and customization by users within the domain that the system will operate.

Prediction of subcellular localization using sequence-biased recurrent networks

Motivation: Targeting peptides direct nascent proteins to their specific subcellular compartment. Knowledge of targeting signals enables informed drug design and reliable annotation of gene products. However, due to the low similarity of such sequences and the dynamical nature of the sorting process, the computational prediction of subcellular localization of proteins is challenging. Results: We contrast the use of feed forward models as employed by the popular TargetP/SignalP predictors with a sequence-biased recurrent network model. The models are evaluated in terms of performance at the residue level and at the sequence level, and demonstrate that recurrent networks improve the overall prediction performance. Compared to the original results reported for TargetP, an ensemble of the tested models increases the accuracy by 6 and 5% on non-plant and plant data, respectively.