Evaluation of (4‐Arylpiperidin‐1‐yl)cyclopentanecarboxamides As High‐Affinity and Long‐Residence‐Time Antagonists for the CCR2 Receptor

Animal models suggest that the chemokine ligand 2/CC‐chemokine receptor 2 (CCL2/CCR2) axis plays an important role in the development of inflammatory diseases. However, CCR2 antagonists have failed in clinical trials because of a lack of efficacy. We previously described a new approach for the design of CCR2 antagonists by the use of structure–kinetics relationships (SKRs). Herein we report new findings on the structure–affinity relationships (SARs) and SKRs of the reference compound MK‐0483, its diastereomers, and its structural analogues as CCR2 antagonists. The SARs of the 4‐arylpiperidine group suggest that lipophilic hydrogen‐bond‐accepting substituents at the 3‐position are favorable. However, the SKRs suggest that a lipophilic group with a certain size is desired [e.g., 3‐Br: K_i=2.8 nM , residence time (t_res)=243 min; 3‐iPr: K_i=3.6 nM , t_res=266 min]. Alternatively, additional substituents and further optimization of the molecule, while keeping a carboxylic acid at the 3‐position, can also prolong t_res; this was most prominently observed in MK‐0483 (K_i=1.2 nM , t_res=724 min) and a close analogue (K_i=7.8 nM ) with a short residence time.     

Prediction of chaotic behavior

This paper considers the prediction of chaotic behavior using a master-slave synchronization scheme. Based on the stability theory for retarded systems using a Lyapunov-Krasovskii functional, we derive a sufficient condition for perfect state prediction of the master system via a time-delayed output signal of the slave system. The obtained result is based on the delay-dependent stability of time-delay systems. In addition, we derive an upper bound of the admissible time delay by using linear matrix inequality techniques. Finally, we show the effectiveness of the proposed predictor by two numerical examples.     

Performance-Improved Design of N-PID Controlled Motion Systems With Applications to Wafer Stages

A nonlinear filter design is proposed to improve nanopositioning servo performances in high-speed (and generally linear) motion systems. The design offers a means to adapt fundamental control design tradeoffs-like disturbance suppression versus noise sensitivity-which are otherwise fixed. Typically performance-limiting oscillations in the feedback system that benefit from extra control are temporarily upscaled and subjected to nonlinear weighting. For sufficiently large amplitudes, this nonlinear filter operation induces extra controller gain. Oscillations that do not benefit from this extra control (typically because they represent noise contributions that should not be amplified) remain unscaled and, as such, do not induce extra controller gain. The combined usage of linear weighting filters with their exact inverses renders this part of the nonlinear filter design strictly performance based. The effective means to improve servo performance is demonstrated on a short-stroke wafer stage of an industrial wafer scanner. Since the nonlinear filter design is largely based on Lyapunov arguments, stability is guaranteed along the different design steps.     

Tiamulin selectively inhibits oxidative hepatic steroid and drug metabolism in vitro in the pig

An enquiry among 50 successful, general dental practitioners working under a capitation payment system for the treatment of children, showed that they all thought that prevention on selected patients was of value to their practice. They said that prevention enhances the reputation of the practice, adds to the job satisfaction of the dentist and is part of modern dental philosophy. However, only when practised selectively would it be cost: beneficial. The most popular preventive treatments were fissure sealants, particularly when used on selected patients, oral hygiene demonstrations and, among a group of enthusiastic dentists, dietary counselling. Dentists who employed hygienists had a significantly higher 'mean preventive awareness score' than those who did not.     

Robust control of robots via linear estimated state feedback

In this note we propose a robust tracking controller for robots that requires only position measurements. The controller consists of two parts: a linear observer part that generates an estimated error state from the error on the joint position and a linear feedback part that utilizes this estimated state. It is shown that this computationally efficient controller yields semi-global uniform ultimate boundedness of the tracking error. An interesting feature of the controller is that it straightforwardly extends results on robust control of robots by linear state feedback to linear estimated-state feedback     

Synthesis and Properties of Lead Magnesium Niobate Zirconate Relaxor Materials

Two materials were prepared with composition PbMg_0.3-Nb_0.6Zr_0.1O₃ (PMNZ/10) and PbMg_0.32Nb_0.65Zr_0.03O₃ (PMNZ/3). Slight modifications in lead oxide content of these materials were made to study its influence on the sintering properties. The stoichiometric PMNZ/3 gave the best results. It has a sintering temperature as low as 900°C and a relative dielectric constant of 10 000 at room temperature.     

On self-synchronization and controlled synchronization

An attempt is made to give a general formalism for synchronization in dynamical systems encompassing most of the known definitions and applications. The proposed set-up describes synchronization of interconnected systems with respect to a set of functionals and captures peculiarities of both self-synchronization and controlled synchronization. Various illustrative examples are given.     

Convergent dynamics, a tribute to Boris Pavlovich Demidovich

We review and pay tribute to a result on convergent systems by the Russian mathematician Boris Pavlovich Demidovich. In a sense, Demidovich's approach forms a prelude to a field which is now called incremental stability of dynamical systems. Developments on incremental stability are reviewed from a historical perspective.