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.     

Diagnostic focus on the child with myoclonic seizures in isolation or associated with other types of seizures

Myoclonus may be observed in children with mild or severe epileptic syndromes. Both types are seen at characteristic ages, together with other factors: aetiology, family history, hereditary pattern, effect on psychomotor development and EEG-EMG findings. In children with progressive or degenerative encephalopathies and myoclonus, better known as progressive myoclonic epilepsy, there are also specific clinical data, together with biological and genetic markers which permit identification. The most specific clinical characteristics of each of these clinical pictures are described, as are the complementary tests which permit confirmation of these diagnoses.     

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...     

A mixed integer programming approach to multi-skilled workforce scheduling

The potential benefits of using human resources efficiently in the service sector constitute an incentive for decision makers in this industry to intelligently manage the work shifts of their employees, especially those dealing directly with customers. In the long term, they should attempt to find the right balance between employing as few labor resources as possible and keeping a high level of service. In the short run (e.g., 1 week), however, contracted staff levels cannot be adjusted, and management efforts thus focus on the efficient assignment of shifts and activities to each employee. This article proposes a mixed integer program model that solves the short-term multi-skilled workforce tour scheduling problem, enabling decision makers to simultaneously design workers’ shifts and days off, assign activities to shifts and assign those to employees so as to maximize and balance coverage of a firm’s demand for on-duty staff across multiple activities. Our model is simple enough to be solved with a commercial MIP solver calibrated by default without recurring to complex methodologies, such as extended reformulations and exact and/or heuristic column generation subroutines. A wide computational testing over 1000 randomly generated instances suggests that the model’s solution times are compatible with daily use and that multi-skilling is a significant source of labor flexibility to improve coverage of labor requirements, in particular when such requirements are negatively correlated and part-time workers are a scarce resource.     

An optimization algorithm for multimodal functions inspired by collective animal behavior

Interest in multimodal function optimization is expanding rapidly as real-world optimization problems often demand locating multiple optima within a search space. This article presents a new multimodal optimization algorithm named as the collective animal behavior. Animal groups, such as schools of fish, flocks of birds, swarms of locusts, and herds of wildebeest, exhibit a variety of behaviors including swarming about a food source, milling around a central location, or migrating over large distances in aligned groups. These collective behaviors are often advantageous to groups, allowing them to increase their harvesting efficiency to follow better migration routes, to improve their aerodynamic, and to avoid predation. In the proposed algorithm, searcher agents are a group of animals which interact with each other based on the biologic laws of collective motion. Experimental results demonstrate that the proposed algorithm is capable of finding global and local optima of benchmark multimodal optimization problems with a higher efficiency in comparison with other methods reported in the literature.     

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.