Neurite Outgrowth Mediated by Translation Elongation Factor eEF1A1: A Target for Antiplatelet Agent Cilostazol

Cilostazol, a type-3 phosphodiesterase (PDE3) inhibitor, has become widely used as an antiplatelet drug worldwide. A recent second Cilostazol Stroke Prevention Study demonstrated that cilostazol is superior to aspirin for prevention of stroke after an ischemic stroke. However, its precise mechanisms of action remain to be determined. Here, we report that cilostazol, but not the PDE3 inhibitors cilostamide and milrinone, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Furthermore, specific inhibitors for the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling pathways (PLC-γ, PI3K, Akt, p38 MAPK, and c-Jun N-terminal kinase (JNK), and the Ras/Raf/ERK/MAPK) significantly blocked the potentiation of NGF-induced neurite outgrowth by cilostazol. Using a proteomics analysis, we identified that levels of eukaryotic translation elongation factor eEF1A1 protein were significantly increased by treatment with cilostazol, but not cilostamide, in PC12 cells. Moreover, the potentiating effects of cilostazol on NGF-induced neurite outgrowth were significantly antagonized by treatment with eEF1A1 RNAi, but not the negative control of eEF1A1. These findings suggest that eEF1A1 and several common cellular signaling pathways might play a role in the mechanism of cilostazol-induced neurite outgrowth. Therefore, agents that can increase the eEF1A1 protein may have therapeutic relevance in diverse conditions with altered neurite outgrowth

State estimation of non-linear piezoelectric stack actuator, hysteresis model

The state estimation of a non-linear model of a piezoelectric stack actuator showing hysteresis is proposed. Model uncertainties related to hysteresis effect in piezoelectric stack actuators, most prominently in higher frequency zone; can make the closed-loop control system unstable. Furthermore it may lead to inaccurate open-loop control frequently causing harmonic distortions when the stack is driven with sinusoidal input signals. In order to solve the above issues, it is very important to determine an accurate non-linear model of the piezoelectric stack actuator. The Unscented Kalman Filter (UKF) algorithm is used to accurately estimate the states of the non-linear model of the piezo-electric stack actuator such that hysteresis effect can be accurately predicted. The states of the piezo-electric stack actuator model are assumed to be zero-mean Gaussian random variables (GRV). The UKF uses the Unscented Transformation (UT) method to choose the minimal number of samples points such that the true mean and covariance. of the GRV is completely captured. On propagation through the true non-linear model of the piezo-electric stack actuator, these sample points capture the posterior mean and covariance accurately to third order for Gaussian inputs. The accurately estimated model thereby assists studies aiming at a better understanding of the hysteresis effect as well as is useful in robust control system design. Preliminary results of this investigation are presented.Jayesh L. Minase, Tien-Fu Lu, and Frank Wornl

Trajectory following with a three-DOF micro-motion stage

This paper presents the position control of a three-DOF (degree-of-freedom) micro-motion stage. This stage provides micro scale planar motion along the x and y axis and rotational motion along the z axis. It uses a 3 RRR (three revolute-revolute-revolute) °exure hinge based compliant mechanism driven by three piezo- electric stack actuators to achieve the micro motion along x, y and z axis. The micro-motion stage with operating frequency up to 1Hz is controlled to follow a prescribed circular tra- jectory. An analytical Jacobian of the stage is derived to relate the input displacements of the piezo-actuators to the output displacements of the stage. Closed-loop positioning control is achieved using the standard PI controller. The errors related to the position control along the x and y axis are presented.Yuen Kuan Yong, Tien-Fu Lu and Jayesh Minas

A comparison between PI & identification based inverse control for precise operation of a piezoelectric actuator for use in micro positioning application

Jayesh L. Minase, Tien-Fu Lu, Ben Cazzolato, Steven Grainge

A review, supported by experimental results, of voltage, charge and capacitor insertion method for driving piezoelectric actuators

A piezoelectric actuator consists of ceramic material that expands or contracts when a positive or a negative potential voltage signal is applied. The displacement of a piezoelectric actuator is commonly controlled using a voltage input due to its ease of implementation. However, driving a piezoelectric actuator using a voltage input leads to the non-linear hysteresis and creep. Hysteresis and creep are undesirable characteristics which lead to large errors when a piezoelectric actuator is used in positioning applications. The amount of hysteresis and creep could be minimized to a large extent when a piezoelectric actuator is driven using a charge input. Another method which substantially reduces hysteresis and creep involves the insertion of a capacitor in series with a piezoelectric actuator which is driven using a voltage input. A review of voltage, charge and capacitor insertion methods for driving piezoelectric actuators is presented in this paper. Experimental results, for a piezoelectric actuator driven using the above three methods, are presented to validate the facts presented in this review.J. Minase, T.-F. Lu, B. Cazzolato and S. Grainge

Inverse control of a piezoelectric actuator for precise operation of a micro-motion stage

The inverse control of a piezoelectric actuator for precise tracking operation of a three degree of freedom (DOF) micro-motion stage is presented in this paper. This stage, which provides translational motion in X and Y directions and rotation about the Z-axis, is actuated using three stack type piezoelectric actuators. Although capable of resolution in micrometres to sub-nanometres, the actuators exhibit a significant amount of hysteresis and creep, which may lead to substantial errors if the stage was used in a tracking application. Thus, for the stage to provide precise operation, it is necessary to mitigate the effects due to hysteresis and creep. To minimize these effects, an inverse, feed-forward, control strategy is presented in this paper. Experimental results are presented to display the effectiveness of this control strategy in precise operation of the stage over a wide band of amplitudes and frequencies.Jayesh Minase, Tien-Fu Lu, Ben Cazzolato and Steven Grainge

The poly(A) polymerase beta gene may not be associated with azoospermia caused by Sertoli-cell-only syndrome in Japanese patients by comparing patients and normal controls

Approximately 15% of couples are infertile, with half of these cases being due to a male factor. Testis-specific cytoplasmic poly(A) polymerase beta (PAPOLB) is known to be critical for spermatogenesis. In mice, the loss of function of the Papolb gene results in the arrest of spermiogenesis and in male infertility. To analyse the role of the PAPOLB gene in human male infertility, this study investigated the relevance of this gene to human Sertoli-cell-only syndrome (SCOS) with azoospermia. Mutation analysis of the PAPOLB coding region was performed on 139 Japanese patients by PCR and direct sequence analysis. No critical mutations directly causing SCOS were detected, but three single-nucleotide polymorphisms (SNPs; SNP1 (c1101C > T), SNP2 (c1347T > C) and SNP3 (c1903C > A)) were found in the coding region. However, there were no significant associations in the allelic and genotypic distributions of these three SNPs between the SCOS and control groups (p>.05). This study suggests a lack of association of PAPOLB with azoospermia due to SCOS in humans