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Abstract: Psychostimulant abuse continues to present legal, socioeconomic and medical challenges as a primary psychiatric disorder, and represents a significant comorbid factor in major psychiatric and medical illnesses. To date, monotherapeutic drug treatments have not proven effective in promoting long-term abstinence in psychostimulant abusers. In contrast to clinical trials utilizing monotherapies, combinations of dopamine (DA) agonists and selective 5-HT3, 5HT2A/2C, or NK1 antagonists have shown robust efficacy in reversing behavioral and neurobiological alterations in animal models of psychostimulant abuse. One important temporal requirement for these treatments is that the 5-HT or NK1 receptor antagonist be given at a critical time window after DA agonist administration. This requirement may reflect a necessary dosing regimen towards normalizing underlying dysfunctional neural circuits and “addiction memory” states. Indeed, chronic psychostimulant abuse can be conceptualized as a consolidated form of dysfunctional memory maintained by repeated drug- or cue-induced reactivation of neural circuit and subsequent reconsolidation. According to this concept, the DA agonist given first may reactivate this memory circuit, thereby rendering it transiently labile. The subsequent antagonist is hypothesized to disrupt reconsolidation necessary for restabilization, thus leading progressively to a therapeutically-mediated abolishment of dysfunctional synaptic plasticity. We propose that long-term abstinence in psychostimulant abusers may be achieved not only by targeting putative mechanistic pathways, but also by optimizing drug treatment regimens designed to disrupt the neural processes underlying the addicted state. [Copyright &y& Elsevier]

Abstract: The reliable and instant transmission of vital signs is important for remote time-critical patient care through a telemedicine system. However, sometimes the reliability and instantaneity conditions cannot be satisfied simultaneously under a high-noise mobile network, because they are reciprocal to each other. In this paper, the vital sign transmission protocol (VSTP) running over a CDMA 1× EVDO (Code Division Multiple Access 1× Evolution Data Only) mobile network is proposed to comply with both the reliability and instantaneity requirements. The switching buffer management scheme is combined with a hybrid error control scheme, consisting of forward error correction (FEC) and automatic repeat request (ARQ). The CDMA 1× EVDO mobile network is modeled by two states using the Markov wireless channel model to test transmission performance under diverse network conditions. Throughout the noisy environment simulation, the performance of the VSTP is compared with the Transmission Control Protocol (TCP) and User Datagram Protocol (UDP) to demonstrate its efficacy over error-prone mobile network. [Copyright &y& Elsevier]

Abstract: We compared two different methamphetamine dosing regimens and found distinct long-term behavioral and neurochemical changes. Adult rats were treated with 1-day methamphetamine injection (3×5mg/kg s.c., 3h apart) or 7-day methamphetamine minipump (20mg/kg/day s.c.). The minipump regimen models the sustained methamphetamine plasma levels in some human bingers whereas the 1-day regimen models a naïve user overdose. On withdrawal days 7 and 28, rats were acutely challenged with cocaine to test for behavioral sensitization and subsequently sacrificed for caudate and accumbens dopamine tissue content. Other rats were analyzed on withdrawal days 3, 7 or 28 using voltammetry in caudate slices. On withdrawal days 7 and 28, the methamphetamine injection but not the minipump rats showed behavioral cross-sensitization to cocaine. There was no change in baseline dopamine release, reuptake or sensitivity to quinpirole in any treatment group on either withdrawal day. However, consistent with the behavioral sensitization, cocaine had a greater effect in potentiating dopamine release and in blocking dopamine reuptake in methamphetamine injection versus saline irrespective of withdrawal day. The minipump group showed tolerance to the dopamine releasing effect of cocaine on withdrawal day 28 and had lower dopamine tissue content in the caudate versus the methamphetamine injection group. Dopamine turnover as measured by the DOPAC/dopamine ratio tended to be higher in the minipump-treated rats. These data suggest that the behavioral cross-sensitization seen in the methamphetamine injection rats could be in part due to the increased potency of cocaine in blocking dopamine reuptake and in increasing dopamine release. The decreased potency of cocaine in the caudate slices from the minipump-treated group may be related to decreased dopamine tissue content. [Copyright &y& Elsevier]

We tested the tachykinin NK1 receptor antagonist WIN51708 (17βhydroxy17αethynyl5αandrostanol[3,2b]pyrimido[1,2-a]benzimidazole) in a behavioral sensitization model. Rats were given 7 days of cocaine then 7 days of withdrawal to induce sensitization. Thereafter, another 7 days of cocaine with WIN51708 (2 mg/kg i.p.) given 3.5 h after each cocaine injection was given. WIN51708 reversed sensitization but had no effect on controls. NK1 receptor antagonists may have use in stimulant abuse and schizophrenia treatment. [Copyright &y& Elsevier]

Abstract: We present in the paper the design of a hardware-in-the-loop simulation framework and its actual implementation on our custom constructed unmanned-aerial-vehicle (UAV) helicopter systems. Real-time hardware-in-the-loop simulation is one of the most effective methods for the verification of the overall control performance and safety of the UAVs before conducting actual flight tests. In our proposed framework, four modules, which include onboard hardware, flight control, ground station and software, are integrated together to realize the hardware-in-the-loop simulation. This design is successfully utilized for simulating several flight tests including basic flight motions, full-envelope flight and multiple UAV formation flight. Results obtained show that the constructed hardware-in-the-loop simulation system is highly effective and useful. [Copyright &y& Elsevier]

Abstract: In this study we established conditional silencing of integrin-linked kinase (ILK) expression in Sprague-Dawley rat brain by microinjection of rAAV-2-carrying, Tet-On-regulated siRNA expression cassette into nucleus accumbens (NAc) core and induction with doxycycline. We demonstrated that inhibition of ILK expression was effectively induced by administration of doxycycline for 2 weeks while ILK expression was restored after withdrawing doxycycline for 8 days. Increases in GFAP and OX42 expression were observed 5 weeks post virus injection. Importantly, inhibition of ILK expression in the NAc core had no significant effect on cell apoptosis and animal basal locomotion and stereotypical behaviors, but decreased dendritic density of medium spiny neurons. Our studies suggest that: (1) rAAV-delivered Tet-On-regulated siRNA expression can conditionally regulate gene expression in rat brain; (2) inhibition of ILK expression has no significant effect on cell apoptosis and basal locomotor and stereotypical behaviors, but decreases dendritic density; and (3) microinjection of rAAV-2 causes inflammatory response around the injection track. [Copyright &y& Elsevier]

We consider in this paper the design and implementation of a dual-stage actuated hard disk drive (HDD) servo system, in which an additional piezoelectric actuator is mounted on top of the conventional voice-coil-motor (VCM) actuator to provide a faster and finer response. More specifically, the dual-stage actuated HDD servo system consists of a primary VCM actuator and a secondary suspension piezoelectric microactuator. The VCM actuator is used to quickly move the read/write (R/W) head of the HDD servo system to a target track, whereas the microactuator is used to fine-tune the R/W head position when it is getting closer to the target. In our design, the primary actuator is controlled by a newly developed composite nonlinear feedback (CNF) control law, which has fast rise time and small overshoot, and the microactuator is controlled through a simple static gain together with a low-pass filter and a notch filter. Simulation and implementation results show that in track following, the dual-stage actuated HDD servo system has outperformed the single-stage actuated counterpart by more than 47% in settling time and by 39% in position error signal (PES) tests. [Copyright &y& Elsevier]

We have previously shown that ondansetron, given 3.5 h after intravenous cocaine self-administration, can attenuate self-administration the following day. Here we tested ondansetron given either before or after a 14-h oral cocaine session in rats. Ondansetron (0.2 mg/kg sc) given 30 min before the cocaine session had no effect. However, when given 3.5 h after, ondansetron attenuated cocaine intake the following day while having no effect on water intake. Taken with our previous data in intravenous cocaine self-administration, we suggest that the acute cocaine withdrawal period may be an important treatment window and that ondansetron may be an effective cocaine abuse therapy. [Copyright &y& Elsevier]

In a modern large-capacity magnetic hard disk drive (HDD), both fast track seeking and perfect positioning of the read/write head are required. Mode switching control (MSC) approaches are widely used to meet these requirements. This paper proposes a new approach in designing MSC with an application to HDD servo systems. The proposed scheme uses a proximate time-optimal servomechanism in the track seeking mode, and a robust perfect tracking (RPT) controller in the track following mode. Unlike the conventional MSC approaches, the new method does not require an initial value compensation during mode switching. This is because the RPT controller in the second stage is capable of rendering the Lp-norm (1&les;p<∞) of the resulting tracking error arbitrarily small in the presence of external disturbances and initial conditions. Simulation and experimental results show that the proposed method improves the seek and settling time by about 10% over the conventional approaches. [Copyright &y& Elsevier]

Highlights: [•] Changes in nicotinic neurotransmission may play a role in cocaine behavioral sensitization. [•] Locomotor stimulation by nicotine increases during early cocaine withdrawal in a time-dependent manner. [•] Daily mecamylamine during this period prevents subsequent maintenance of cocaine sensitization. [•] Nicotine receptors may be an effective target for treatment of chronic cocaine abuse. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a mode switching control (MSC) scheme in discrete-time domain for fast and precise set-point tracking in servo systems subject to control saturation and unknown disturbance. The basic idea is to combine the proximate time-optimal servomechanism (PTOS) and the composite nonlinear feedback (CNF) control, using the output position as the only measurable information for feedback. The PTOS is responsible for fast targeting in servo systems when the tracking error is large, and once the system trajectory enters into some specified region, the CNF will take over the control to ensure a smooth settling without compromising the fast transient performance. A reduced-order extended state observer is adopted to estimate the speed signal for feedback and the disturbance for compensation. The asymptotical stability of the proposed MSC scheme is analyzed and the switching conditions are provided. Simulation and experimental results on a permanent magnet synchronous motor (PMSM) servo system verify that the proposed control scheme is effective in improving the tracking performance for a wide range of target set-points. [Copyright &y& Elsevier]

Abstract: Psychostimulant abuse represents a psychiatric disorder and societal concern that has been largely unamenable to therapeutic interventions. We have previously demonstrated that the 5-HT3 antagonist ondansetron or non-selective 5-HT2A/2C antagonist ketanserin administered 3.5h following daily pergolide, a non-selective DA agonist, reverses previously established cocaine sensitization. The present study was conducted to evaluate whether the same treatments or delayed pairing of pergolide with the antidepressant mirtazapine can also reverse consolidated methamphetamine (METH) behavioral sensitization. Sprague-Dawley rats received METH infusion via osmotic minipumps (25mg/kg/day, s.c.) for 7 days, with accompanying daily injections of escalating METH doses (0–6mg/kg, s.c.). This regimen takes into account the faster elimination of METH in rats, and is designed to replicate plasma METH concentrations with superimposed peak drug levels as observed during METH binging episodes in humans. Following a 7-day METH withdrawal, ondansetron (0.2mg/kg, s.c.), ketanserin (1.0mg/kg, s.c.), or mirtazapine (10mg/kg, i.p.) was administered 3.5h after pergolide injections (0.1mg/kg, s.c., qd) for 7 days. Behavioral sensitization as a model of METH abuse was assessed 14 days after the combination treatment cessation (i.e., day 28 of METH withdrawal) through an acute challenge with METH (0.5mg/kg, i.p.). Pergolide combined with ondansetron or ketanserin reversed METH behavioral sensitization, but pergolide–mirtazapine combination was ineffective. The role of reactivation of addiction “circuit” by a non-selective DA agonist, and subsequent reconsolidation blockade through 5-HT3 or 5-HT2 antagonism in reversal of METH sensitization and treatment of METH addiction is discussed. [Copyright &y& Elsevier]

Abstract: In this work, we focus on the design and implementation of a robust flight control system for an unmanned helicopter. A comprehensive nonlinear model for an unmanned helicopter system, which is built by our research team at the National University of Singapore, is first presented. A three-layer control architecture is then adopted to construct an automatic flight control system for the aircraft, which includes (1) an inner-loop controller designed using the H ∞ control technique to internally stabilize the aircraft and at the same time yield good robustness properties with respect to external disturbances, (2) a nonlinear outer-loop controller to effectively control the helicopter position and yaw angle in the overall flight envelope, and lastly, (3) a flight-scheduling layer for coordinating flight missions. Design specifications for military rotorcraft set for the US army aviation are utilized throughout the whole process to guarantee a top level performance. The result of actual flight tests shows our design is very successful. The unmanned helicopter system is capable of achieving the desired performance in accordance with the military standard under examination. [Copyright &y& Elsevier]

Abstract: In this paper, we present the design and implementation of an autonomous flight control law for a small-scale unmanned aerial vehicle (UAV) helicopter. The approach is decentralized in nature by incorporating a newly developed nonlinear control technique, namely the composite nonlinear feedback control, together with dynamic inversion. The overall control law consists of three hierarchical layers, namely, the kernel control, command generator and flight scheduling, and is implemented and verified in flight tests on the actual UAV helicopter. The flight test results demonstrate that the UAV helicopter is capable of carrying out complicated flight missions autonomously. [Copyright &y& Elsevier]

Abstract: In traditional medicine, Panax ginseng has been used to treat various behavioral effects of psychostimulants (e.g., cocaine) and other drugs of abuse and to ameliorate withdrawal symptoms. The neurochemical bases for this efficacy, however, remain to be elucidated. We previously used the real-time fast-scan cyclic voltammetry in rat nucleus accumbens slices to demonstrate that cocaine not only enhances DA release evoked by single-pulse electrical stimulation and inhibits DA uptake during application but also further increases the release upon washout (termed a “rebound” release enhancement). In the present study, we determined whether co-application and washout of ginseng total saponin (GTS), the active ingredient of Panax ginseng, with cocaine attenuate cocaine-induced enhancement of evoked DA release, DA uptake inhibition and/or withdrawal-associated rebound enhancement. Cocaine rapidly potentiated the DA release within the first 10 min of application, and acute cocaine withdrawal caused a rebound increase. Co-application of GTS with cocaine inhibited the release enhancement and subsequently prevented the rebound increase during acute withdrawal. The effect of GTS was concentration-dependent. In contrast, GTS had no significant effects on the cocaine-mediated DA uptake inhibition. These results suggest that the attenuation of the cocaine-induced enhancement of impulse-dependent DA release, rather than uptake inhibition, might be one of the pharmacological bases for attenuation of behavioral effects of cocaine and amelioration of acute withdrawal symptoms by ginseng. [Copyright &y& Elsevier]

Abstract: In this paper, we present a comprehensive design methodology for constructing small-scale UAV helicopters. The systematic design procedure, which includes hardware component selection, design and integration, as well as experimental evaluation, is utilized to construct a fully functional UAV helicopter, named SheLion. Various ground and flight tests have been performed to verify the feasibility and reliability of SheLion. This simple, systematic and effective methodology can be easily followed and used for building small-scale UAV helicopters for general research purposes. [Copyright &y& Elsevier]

Abstract: Pivot bearing friction and flex cable nonlinearity are the two major torque nonlinearities which lead to performance degradation in hard disk drive (HDD) tracking tasks. Based on a comprehensive model of typical voice-coil-motor (VCM) actuator, which explicitly captures the characteristics of pivot bearing friction and flex cable nonlinearity, this paper presents the design of a parameterized controller for a microdrive using the robust and perfect tracking (RPT) technique combined with nonlinear torque compensation and integral enhancement. Simulation and experimental results show that the controller is capable of achieving fast settling and eliminating static bias. [Copyright &y& Elsevier]

Male Sprague–Dawley rats were given two separate sensitizing regimens of cocaine (7 days on, 7 days off, 7 days on at 40 mg/kg/day, s.c.) or saline injections. Half of the animals also received a drug with 5-hydroxytryptamine-2 (5-HT2) receptor antagonist properties (clozapine, 3 mg/kg; mianserin 6 mg/kg; ketanserin 1 mg/kg, all s.c.) or saline during the second cocaine dosing regimen in the acute withdrawal period, 3.5 h after each cocaine injection. On day 10 of withdrawal animals were challenged with cocaine (7.5 mg/kg, i.p.) and assessed by a behavioral rating scale and locomotor activity monitoring. The 5-HT2 receptor antagonists, but not saline, reversed behavioral sensitization and had little effect on behavior in the control animals. 5-HT2 receptor antagonists, therefore, may be a useful treatment for cocaine addicts that have undergone previous sensitization periods. The pharmacological profile of these antagonists suggests that the 5-HT2A receptor subtype may mediate this effect. [Copyright &y& Elsevier]