Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Passive least-squares-type estimation algorithm for direct adaptive control

The standard least squares (LS) estimation algorithm is modified in such a way that it becomes passive. Therefore the scope of application of the LS algorithm is extended to those adaptive schemes whose convergence proof is based on passivity. The passive version of LS is presented in both continuous and discrete time.     

Chattering-Free Sliding Mode Altitude Control for a Quad-Rotor Aircraft: Real-Time Application

Nowadays, the chattering problem in sliding mode control is one of the most important points to consider in real-time applications. To address this problem, a real-time robust altitude control scheme is proposed for the efficient performance of a Quad-rotor aircraft system using a continuous sliding mode control. The sensing of altitude measurement sensing is performed by a pressure sensor in order to obtain a robust altitude control of the vehicle in hovering mode both indoor and outdoor. The altitude measurement has the advantage of introducing this state information directly in the closed loop control which should be very useful for achieving robust stabilization of the altitude control. Accordingly, we propose a sliding mode control strategy without chattering. The sliding mode control proposed removes the chattering phenomenon by replacing a sign function with a high-slope saturation function. The control algorithm is derived from the Lyapunov stability theorem. Moreover, we have assumed that the actuators are able to respond quickly and accurately and we have not enforced limits on the control signals for a real-time application. Finally, to verify the satisfactory performance of proposed nonlinear control law, several simulations and experimental results of the Chattering-free sliding mode control for the Quad-rotor aircraft in the presence of bounded disturbances are presented.     

Fault Estimation for a Quad-Rotor MAV Using a Polynomial Observer

This work addresses the problem of fault detection and diagnosis (FDD) for a quad-rotor mini air vehicle (MAV). Actuator faults are considered on this paper. The basic idea behind the proposed method is to estimate the faults signals using the extended state observers theory. To estimate the faults, a polynomial observer (Aguilar et al. 2011; Mata-Machuca et al., Commun Nonlinear Sci Numer Simul 15(12):4114–4130, 2010, BioSystems 100(1):65–69, 2010) is presented by using the available measurements and know inputs of the system. In order to investigate the diagnosability properties of the system, a differential algebra approach is proposed (Cruz-Victoria et al., J Frankl Inst 345(2):102–118, 2008; and Martinez-Guerra and Diop, IEE P-Contr Theor Ap 151(1):130–135, 2004). The effectiveness of the methodology is illustrated by means of numerical simulations.     

A color image watermarking framework for copyright protection of stereo images based on binocular just noticeable difference and LU decomposition

Multimedia Tools and Applications - The copyright protection of three-dimensional (3D) content is a matter of interest in artistic and creative works due to the rights of the holder for the...     

Stability conditions for integral delay systems

In this paper we consider a special class of integral delay systems arising in several stability problems of time‐delay systems. For these integral systems we derive stability and robust stability conditions in terms of Lyapunov–Krasovskii functionals. More explicitly, after providing the stability conditions we compute quadratic functionals and apply them to derive exponential estimates for solutions, and robust stability conditions for perturbed integral delay systems. Copyright © 2008 John Wiley & Sons, Ltd.     

Stabilization of the inverted pendulum around its homoclinic orbit

The inverted pendulum has been used as a benchmark for motivating the study of nonlinear control techniques. We propose a simple controller for balancing the inverted pendulum and raise it to its upper equilibrium position while the cart displacement is brought to zero. The control strategy is based on an energy approach of the cart and pendulum system.     

Stability Analysis of a Human Arm Interacting with a Force Augmenting Device

This paper presents a stability analysis of the interaction between a human and a linear moving Force Augmenting Device (FAD). The analysis employs a mathematical model of the human arm, the FAD and their interaction. As a depart from past works, this article presents a stability analysis considering time-delays in the human model. A key ingredient in the analysis is the use of the Rekasius substitution for replacing the time-delay terms. It is proved that the human machine interaction is stable when the human model has no delays. When delays are considered in the human model, the analysis provides an upper bound for the time-delays preserving a stable interaction. Numerical simulations allow to assess the human-FAD interaction. An experiment is performed with a laboratory prototype, where a human operator lifts a load. It is observed that the human machine interaction is stable and the human operator is able to move the load to a desired position by experiencing very little effort.     

High gain observer for a class of nonlinear systems with coupled structure and sampled output measurements: application to a quadrotor

This paper proposes a new high gain observer for a class of non-uniformly observable nonlinear systems with coupled structure driven by sampled outputs. The considered class of systems is particularly constituted by several subsystems where each subsystem is associated to a subset of the output variables. The observer design is carried out through two steps. First, a high-gain observer is proposed in the continuous-time output case under the assumption that an adequate persistent excitation condition is satisfied by each subsystem. Then, the proposed observer is redesigned to handle the case of sampled outputs leading thereby to a continuous-discrete time observer. The latter property is achieved thanks to the approach pursued along the convergence analysis. The effectiveness of the proposed observer is emphasised in a realistic simulation framework involving a mathematical model of a quadrotor which is diffeomorphic to the proposed class of considered systems.