Flexibility and inhibitor binding in Cdc25 phosphatases

Cdc25 phosphatases involved in cell cycle checkpoints are now active targets for the development of anti-cancer therapies. Rational drug design would certainly benefit from detailed structural information for Cdc25s. However, only apo- or sulfate-bound crystal structures of the Cdc25 catalytic domain have been described so far. Together with previously available crystalographic data, results from molecular dynamics simulations, bioinformatic analysis, and computer-generated conformational ensembles shown here indicate that the last 30-40 residues in the C-terminus of Cdc25B are partially unfolded or disordered in solution. The effect of C-terminal flexibility upon binding of two potent small molecule inhibitors to Cdc25B is then analyzed by using three structural models with variable levels of flexibility, including an equilibrium distributed ensemble of Cdc25B backbone conformations. The three Cdc25B structural models are used in combination with flexible docking, clustering, and calculation of binding free energies by the linear interaction energy approximation to construct and validate Cdc25B-inhibitor complexes. Two binding sites are identified on top and beside the Cdc25B active site. The diversity of interaction modes found increases with receptor flexibility. Backbone flexibility allows the formation of transient cavities or compact hydrophobic units on the surface of the stable, folded protein core that are unexposed or unavailable for ligand binding in rigid and densely packed crystal structures. The present results may help to speculate on the mechanisms of small molecule complexation to partially unfolded or locally disordered proteins.

De touch: extending service channels in an airport through touch technologies

This project aimed to create a communication and interaction channel between Madeira Airport and its passengers. We used the pre-existent touch enabled screens at the terminal since their potential was not being utilised to their full capacity. To achieve our goal, we have followed an agile strategy to create a testable prototype and take advantages of its results. The developed prototype is based on a plugin architecture turning it into a maintainable and highly customisable system. The collected usage data suggests that we have achieved the initially defined goals. There is no doubt that this new interaction channel is an improvement regarding the provided services and, supported by the usage data, there is an opportunity to explore additional developments to the channel.

Morte como desafio afetivo para o profissional da saúde: ansiedade e sentimentos de quem lida com o paciente terminal com câncer

It is a Cross-sectional and multi-disciplinary study whose population selection was made by department of human resources (composed by a Manager, an Oncologist and a Psychologist) from the hospital where this research was realized. They also collaborated with important information about the work of that professionals in the hospital. We also counted on a Statistic who made study design calculating the sample and analyzing data. This research issued Evaluating health professionals anxiety levels who care for cancer terminally ill and their feelings about that work as well as identifying the factors which have influence on it. 100 health professionals from the Hospital which is a reference on cancer caring in Brazil situated in the city of Natal, state of Rio Grande do Norte, participated of this research. There was a sample loss of 21%. Data were collected through a questionnaire and State-Trait Anxiety Inventory (STAI). Results showed that 15% of the professionals have low State Anxiety levels, 70% Medium State Anxiety levels and 15% high State anxiety levels. The Number of Patients and Working in another Institution have interfered in the anxiety levels. Doctors and Nursing Assistants and Technicians have got the highest high State Anxiety percentage (25%). 73% of them declare to feel some sort of different behavior and/or feelings in caring for terminally ill. The most remarkable professionals feelings were Suffering and Sadness, and Terminally ill Children was the most difficult age group to care for. We conclude that work overload and having more than one job can interfere in professional stress levels and anxiety. Dealing with terminally ill, specially children one, can cause on the professionals psychological suffering. It s recommended the development of supporting and training strategies to reduce and/or to prevent Stress and Anxiety high levels

Notes on vibration control of a micro/macromanipulator mounted on a flexible structure

The objective of this study is to describe the design and the implementation of an experimental set-up used to study the dynamics, the experimental identification, and the active vibration control of a flexible structure mounted manipulator system. The system consists of a three-degree-of-freedom cylindrical manipulator system with a flexible link on its tip. A two-degree-of-freedom polar rigid manipulator is mounted on the flexible macromanipulator. The dynamic modelling and experimental modal analysis identification in the frequency domain are being applied to design active digital control strategies for the micro-manipulator system to damp the mechanical vibrations of the flexible structure on the tip of the macro-manipulator system.

A planar flexible robotic manipulator

Presents the dynamic modelling of a flexible robotic manipulator with two flexible links and two revolute joints, which rotates in the horizontal plane. The dynamic equations are derived using the Newton-Euler formulation and the finite element method, based on elementary beam theory, which is used to discretize the displacements such that the small motion is represented in terms of nodal displacements. Computer simulation results are presented to illustrate this study. The dynamic model becomes necessary for use in future design and control applications.

Optimal and robust modal control of a flexible structure using an active dynamic vibration absorber

This paper is concerned with feedback vibration control of a lightly damped flexible structure that has a large number of well-separated modes. A single active electrical dynamic absorber is used to reduce a particular single vibration mode selectively or multiple modes simultaneously. The absorber is realized electrically by feeding back the structural acceleration at one position to a collocated piezoceramic patch actuator via a controller consisting of one or several second order lowpass filters. A simple analytical method is presented to design a modal control filter that is optimal in that it maximally flattens the mobility frequency response of the target mode, as well as robust in that it works within a prescribed maximum control spillover of 2 dB at all frequencies. Experiments are conducted with a free-free beam to demonstrate its ability to control any single mode optimally and robustly. It is also shown that an active absorber with multiple such filters can effectively control multiple modes simultaneously.

Computer-aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand-binding domain contains the ligand-dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations, and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6-31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new-ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. (c) 2005 Wiley Periodicals, Inc.

Dynamic modeling and simulation of a flexible robotic manipulator

This work focuses on the dynamic modeling of a flexible robotic manipulator with two flexible links and two revolute joints, which rotates in the horizontal plane. The dynamic equations are derived using the Newton-Euler formulation and the finite element method, based on elementary beam theory. Computer simulation results are presented to illustrate this study. The dynamic model becomes necessary for use in future design and control applications.

Application of a model updating technique for health condition monitoring and damage detection of flexible structures

This paper discusses the application of a damage detection methodology to monitor the location and extent of partial structural damage. The methodology combines, in an iterative way, the model updating technique based on frequency response functions (FRF) with monitoring data aiming at identifying the damage area of the structure. After the updating procedure reaches a good correlation between the models, it compares the parameters of the damage structure with those of the undamaged one to find the deteriorated area. The influence of the FEM mesh size on the evaluation of the extent of the damage has also been discussed. The methodology is applied using real experimental data from a spatial frame structure.

Active control in flexible plates with piezoelectric actuators using linear matrix inequalities

The study of algorithms for active vibrations control in flexible structures became an area of enormous interest, mainly due to the countless demands of an optimal performance of mechanical systems as aircraft, aerospace and automotive structures. Smart structures, formed by a structure base, coupled with piezoelectric actuators and sensor are capable to guarantee the conditions demanded through the application of several types of controllers. The actuator/sensor materials are composed by piezoelectric ceramic (PZT - Lead Zirconate Titanate), commonly used as distributed actuators, and piezoelectric plastic films (PVDF-PolyVinyliDeno Floride), highly indicated for distributed sensors. The design process of such system encompasses three main phases: structural design; optimal placement of sensor/actuator (PVDF and PZT); and controller design. Consequently, for optimal design purposes, the structure, the sensor/actuator placement and the controller have to be considered simultaneously. This article addresses the optimal placement of actuators and sensors for design of controller for vibration attenuation in a flexible plate. Techniques involving linear matrix inequalities (LMI) to solve the Riccati's equation are used. The controller's gain is calculated using the linear quadratic regulator (LQR). The major advantage of LMI design is to enable specifications such as stability degree requirements, decay rate, input force limitation in the actuators and output peak bounder. It is also possible to assume that the model parameters involve uncertainties. LMI is a very useful tool for problems with constraints, where the parameters vary in a range of values. Once formulated in terms of LMI a problem can be solved efficiently by convex optimization algorithms.

Flexible labour markets, workers' protection and the security of the wings": a Danish flexicurity solution to the unemployment and social problems in globalized economies"

Includes bibliography

Design of a CMOS voltage reference using current-model approach

A voltage reference with low sensibility to temperature and power-supply that can generate flexible reference values (from milivolts to several volts) is proposed. Designed for AMS 0.35μm CMOS process, the circuit provides a stable output voltage working in the temperature range of -40-150°C. The proposed reference provides a nominal output voltage of 1.358V with a power-supply of 3.3V. © 2011 IEEE.

A model for computing vibration induced stresses of electronic components in a general flexible mounting

This paper develops a novel full analytic model for vibration analysis of solid-state electronic components. The model is just as accurate as finite element models and numerically light enough to permit for quick design trade-offs and statistical analysis. The paper shows the development of the model, comparison to finite elements and an application to a common engineering problem. A gull-wing flat pack component was selected as the benchmark test case, although the presented methodology is applicable to a wide range of component packages. Results showed very good agreement between the presented method and finite elements and demonstrated the usefulness of the method in how to use standard test data for a general application. © 2013 Elsevier Ltd.

Estudo da interface e aplicação dos materiais mimétricos ao design de produto e segurança do trabalho

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)