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When planning planetary rover missions it is useful to develop intuition and skills driving in, quite literally, alien environments before incurring the cost of reaching said locales. Simulators make it possible to operate in environments that have the physical characteristics of target locations without the expense and overhead of extensive physical tests. To that end, NASA Ames and Open Robotics collaborated on a Lunar rover driving simulator based on the open source Gazebo simulation platform and leveraging ROS (Robotic Operating System)components. The simulator was integrated with research and mission software for rover driving, system monitoring, and science instrument simulation to constitute an end-to-end Lunar mission simulation capability. Although we expect our simulator to be applicable to arbitrary Lunar regions, we designed to a reference mission of prospecting in polar regions. The harsh lighting and low illumination angles at the Lunar poles combine with the unique reflectance properties of Lunar regolith to present a challenging visual environment for both human and computer perception. Our simulator placed an emphasis on high fidelity visual simulation in order to produce synthetic imagery suitable for evaluating human rover drivers with navigation tasks, as well as providing test data for computer vision software development. In this paper, we describe the software used to construct the simulated Lunar environment and the components of the driving simulation. Our synthetic terrain generation software artificially increases the resolution of Lunar digital elevation maps by fractal synthesis and inserts craters and rocks based on Lunar size-frequency distribution models. We describe the necessary enhancements to import large scale, high resolution terrains into Gazebo, as well as our approach to modeling the visual environment of the Lunar surface. An overview of the mission software system is provided, along with how ROS was used to emulate flight software components that had not been developed yet. Finally, we discuss the effect of using the high-fidelity synthetic Lunar images for visual odometry. We also characterize the wheel slip model, and find some inconsistencies in the produced wheel slip behavior.

This paper presents the software framework established to facilitate cloud-hosted robot simulation. The framework addresses the challenges associated with conducting a task-oriented and real-time robot competition, the Defense Advanced Research Projects Agency (DARPA) Virtual Robotics Challenge (VRC), designed to mimic reality. The core of the framework is the Gazebo simulator, a platform to simulate robots, objects, and environments, as well as the enhancements made for the VRC to maintain a high fidelity simulation using a high degree of freedom and multisensor robot. The other major component used is the CloudSim tool, designed to enhance the automation of robotics simulation using existing cloud technologies. The results from the VRC and a discussion are also detailed in this work.

A novel series of selective negative allosteric modulators (NAMs) for metabotropic glutamate receptor 5 (mGlu5) was discovered from an isothiazole scaffold. One compound of this series, (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide (24), demonstrated satisfactory pharmacokinetic properties and, following oral dosing in rats, produced dose-dependent and long-lasting mGlu5 receptor occupancy. Consistent with the hypothesis that blockade of mGlu5 receptors will produce analgesic effects in mammals, compound 24 produced a dose-dependent reduction in paw licking responses in the formalin model of persistent pain.

The disclosed 3-phenyl-5-isothiazole carboxamides are potent allosteric antagonists of mGluR1 with generally good selectivity relative to the related group 1 receptor mGluR5. Pharmacokinetic properties of a member of this series (1R,2R)-N-(3-(4-methoxyphenyl)-4-methylisothiazol-5-yl)-2-methylcyclopropanecarboxamide (14) are good, showing acceptable plasma and brain exposure after oral dosing. Oral administration of isothiazole 14 gave robust activity in the formalin model of persistent pain which correlated with CNS receptor occupancy.

Objectives The present study was undertaken to characterize whether the pharmacologic interaction between duloxetine, a balanced serotonergic and noradrenergic reuptake inhibitor, and the non-steroidal anti-inflammatory drug ibuprofen was simply additive, less than additive, or greater than additive (i.e., synergistic) in preclinical models of visceral and inflammatory pain, specifically acetic acid-induced writhing in mice and carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats. Methods In the writhing test, male CF-1 mice were injected intraperitoneally with 0.55% acetic acid and 5 min later the number of writhes was counted over a 5-min period. In the carrageenan models, male Sprague-Dawley rats were injected with a 1.5% carrageenan solution into the ventral surface of the hind paw; hypersensitivity to thermal and mechanical stimuli was subsequently evaluated 2 h post-carrageenan. Results Vehicle or a dose of duloxetine alone (1–100 mg/kg), ibuprofen alone (10–300 mg/kg), or duloxetine and ibuprofen in combination in a dose-ratio of 1:10 duloxetine:ibuprofen were orally administered 30 or 60 min before testing. Isobolographic analysis of the effects of duloxetine in combination with ibuprofen revealed a significant synergistic (greater than additive) interaction between duloxetine and ibuprofen both for reducing acetic acid-induced writhing and carrageenan-induced thermal hyperalgesia, but were additive for reversing mechanical allodynia. Conclusions Our data indicate that duloxetine and ibuprofen have synergistic efficacy in a visceral and an inflammatory pain model in rodents, and suggest that duloxetine and ibuprofen in combination may provide a useful approach to the clinical treatment of persistent pain, particularly inflammation-related pain.

The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. We have developed a SAR study around LY255582 by comparing the effect of the hydroxy group in the 2- and 4-position of the phenyl ring. Also, we have proved that the 3-position of the phenyl ring is optimal for opioid activity. Furthermore, we have successfully replaced the hydroxy group in LY255582 by carbamate and carboxamide groups. The new analogs have high affinity for the opioid receptors comparable to the corresponding phenol. Carboxamide analog 12 has an improved metabolism profile and proved to be efficacious in in vivo studies.

The purpose of the present studies was to compare anticonvulsant drugs with diverse mechanisms of action in a persistent pain model, the formalin test. In addition, the anticonvulsant effects of the compounds were determined in the threshold electroshock tonic seizure test and the 6-Hz limbic seizure test. The effects of the compounds were also determined on locomotor activity. Carbamazepine, oxcarbazepine, lamotrigine, gabapentin and ethosuximide all produced statistically significant analgesic effects in the formalin test whereas phenytoin, topiramate, zonisamide, phenobarbital, tiagabine, valproate and levetiracetam did not. All compounds were anticonvulsant. In addition, morphine and phenobarbital increased locomotor activity while ethosuximide had no effect and all other compounds decreased locomotor activity. For those compounds that were analgesic, the doses required to produce analgesia were larger in magnitude than the anticonvulsant ED50 values in the threshold electroshock and 6-Hz tests, as well as larger than doses that altered locomotor activity. The present results demonstrate that the anticonvulsant and analgesic effects of clinically used antiepileptic drugs do not necessarily correlate and therefore suggest that the anticonvulsant and analgesic efficacy of these drugs may be due to different pharmacologic mechanisms.

Glutamatergic ionotropic and metabotropic receptor modulators have been shown to produce anticonvulsant activity in a number of animal seizure models, e.g. maximal electroshock (MES) and DBA/2 sensory-induced seizures. The 6 Hz model of partial seizures is an alternative low frequency, long duration stimulation paradigm resulting in a seizure characterized by jaw and forelimb clonus, immobility, and an elevated tail (Straub-tail). A unique aspect of this model is that it is the only acute electrically-induced seizure model in which levetiracetam has displayed anticonvulsant activity, suggesting that the 6 Hz seizure model may be useful in identifying compounds with unique anticonvulsant profiles. The purpose of the present study was to examine the role of glutamate receptors in the MES and 6 Hz seizure models using a number of NMDA, AMPA/KA, and mGlu receptor modulators. The pharmacological profile of the 6 Hz seizure model was compared to that of the MES model using eight ionotropic glutamate receptor antagonists and eight mGlu receptor modulators. The ionotropic receptor antagonists MK-801, LY235959, NBQX, LY293558, GYKI 52466, LY300168, and LY377770 produced complete protection from tonic extension in the MES model. Furthermore, the noncompetitive mGlu1 (LY456236) and mGlu5 (MPEP) metabotropic receptor antagonists and the mGlu8 metabotropic receptor agonist (PPG) were also effective in the MES model whereas the competitive mGlu1 (LY367385) receptor antagonist, the mGlu2/3 (LY379268 and LY389795) and Group III (L-AP4) metabotropic receptor agonists were ineffective. In contrast, all of the compounds tested, produced dose-dependent protection in the 6 Hz model with an increase in potency as compared to the MES model. The largest protective indices (P.I.=TD50/ED50) observed were associated with the iGlu5 antagonist LY382884 and the mGlu2/3 receptor agonists LY379268 and LY389795 (P.I.=>14, 14, and 4.9, respectively) in the 6 Hz model. The results from the present study support the continued search for glutamate receptor modulators as potential antiepileptic agents. Furthermore these results illustrate the importance of using several different animal seizure models in the search for novel AEDs and the potential utility of the 6 Hz seizure model in identifying novel AEDs.

Pre-synaptic metabotropic glutamate (mGlu) receptors modulate neuronal excitability by controlling glutamate and gamma-aminobutyric acid (GABA) release. The mGlu8 receptor is predominantly found in pre-synaptic terminals and its expression is highly restricted. To study the role of this receptor, mGlu8 receptor-deficient mice were generated. Here we report that naïve mGlu8 receptor-deficient mice showed increased anxiety-related behavior in the elevated plus maze in low illumination conditions (red light). Open arm avoidance and risk assessment behavior were both significantly increased in mutant mice. Increased stressfulness of the testing conditions abolished this behavioral difference. Fluorescent light or prior restraint stress decreased the open arm activity of wild-type mice, while the open arm activity of mutant mice was essentially unaffected, leading to similar values in both strains. The total number of arm entries or closed arm entries was not significantly different between strains, indicating that the lack of mGlu8 receptor does not affect locomotor activity. No gross behavioral changes, or changes in the function of the autonomic nervous system or somatomotor systems were observed in mutant mice. Moreover, no significant differences in seizure susceptibility were detected between strains. Our results suggest that mGlu8 receptor may play a role in responses to novel stressful environment.

The DARPA Virtual Robotics Challenge (VRC) [1] was a cloud-based robotic simulation competition. Teams competed by writing control software for a humanoid robot to perform disaster response tasks in real-time simulation. Simulating the physics and sensors of a humanoid robot in real-time presented challenges related to the trade-off between simulation accuracy and computational time. The Projected Gauss-Seidel (PGS) iterative solver was chosen for its performance and robustness, but it lacks the accuracy and the fidelity required for reliable simulation of task-level behaviors. This paper presents the modeling decisions and algorithmic improvements made to the Open Dynamics Engine (ODE) physics solver that improved PGS accuracy and fidelity without sacrificing its real-time simulation performance in the VRC. These improvements allowed for stable simulation regardless of user input during the VRC, and supported reliable contact dynamics during VRC tasks without violating the near real-time requirement.

α-Benzoyloxy- and α-methoxy-substituted glycine derivatives undergo homolytic reactions with tributyltin hydride to give the reduction product. With allyltributyltin they afford the product of allyl group transfer and the corresponding dimeric glycine derivative, while their reactions with hexabutylditin and di-tert-butyl disulfide afford the dimer and the α-tert-butylthio-substituted glycine derivative. The free-radical nature of these reactions is most clearly demonstrated in the formation of the glycine dimer.

Activation of muscarinic m1 receptors which are coupled to the phosphoinositide (PI) second messenger transduction system is the initial objective of cholinergic replacement therapy in Alzheimer's disease. Thus, we evaluated the ability of the selective muscarinic receptor agonist (SMRA) xanomeline to stimulate in vivo phosphoinositide (PI) hydrolysis and compared it to a number of direct acting muscarinic agonists, two cholinesterase inhibitors and a putative m1 agonist/muscarinic m2 antagonist. Using a radiometric technique, it was determined that administration of xanomeline robustly stimulated in vivo PI hydrolysis and the effect was blocked by muscarinic antagonists, demonstrating mediation by muscarinic receptors. The non-selective muscarinic agonists pilocarpine, oxotremorine, RS-86, S-aceclidine, but not the less active isomer R-aceclidine, also effectively stimulated PI hydrolysis in mice. Amongst the putative m1 agonists, thiopilocarpine, hexylthio-TZTP as well as xanomeline effectively stimulated PI hydrolysis, but milameline, WAL 2014, SKB 202026 and PD 142505 did not significantly alter PI hydrolysis. Furthermore, WAL 2014 and SKB 202026 inhibited agonist-induced PI stimulation, suggesting that they act as antagonists at PI-coupled receptors in vivo. The cholinesterase inhibitors, tacrine and physostigmine, and the mixed muscarinic m1 agonist/m2 antagonist LU25-109 did not activate in vivo PI hydrolysis. Xanomeline, hexylthio-TZTP and thiopilocarpine were relatively free of cholinergic side effects, whereas milameline, WAL 2014 and SKB 202026 produced non-selective effects. Therefore, these data demonstrate that xanomeline selectively activates in vivo PI hydrolysis, consistent with activation of biochemical processes involved in memory and cognition and xanomeline's beneficial clinical effects on cognition in Alzheimers patients.

We discuss an implementation of the RRT* optimal motion planning algorithm for the half-car dynamical model to enable autonomous high-speed driving. To develop fast solutions of the associated local steering problem, we observe that the motion of a special point (namely, the front center of oscillation) can be modeled as a double integrator augmented with fictitious inputs. We first map the constraints on tire friction forces to constraints on these augmented inputs, which provides instantaneous, state-dependent bounds on the curvature of geometric paths feasibly traversable by the front center of oscillation. Next, we map the vehicle's actual inputs to the augmented inputs. The local steering problem for the half-car dynamical model can then be transformed to a simpler steering problem for the front center of oscillation, which we solve efficiently by first constructing a curvature-bounded geometric path and then imposing a suitable speed profile on this geometric path. Finally, we demonstrate the efficacy of the proposed motion planner via numerical simulation results., United States. Army Research Office. Multidisciplinary University Research Initiative (Award W911NF-11-1-0046)

This paper describes the design of an optimal-control-based active safety framework that performs trajectory planning, threat assessment, and semi-autonomous control of passenger vehicles in hazard avoidance scenarios. This framework allows for multiple actuation modes, diverse trajectory-planning objectives, and varying levels of autonomy. A model predictive controller iteratively plans a best-case vehicle trajectory through a navigable corridor as a constrained optimal control problem. The framework then uses this trajectory to assess the threat posed to the vehicle and intervenes in proportion to this threat. This approach minimizes controller intervention while ensuring that the vehicle does not depart from a navigable corridor of travel. Simulation and experimental results are presented here to demonstrate the framework’s ability to incorporate configurable intervention laws while sharing control with a human driver.

Carbamate derivatives of α-amino acids react by N-methylation, without racemization, on treatment with tert-butyl perbenzoate in the presence of copper(II) octanoate; the selective reaction of N-tert-butoxycarbonylglycine methyl ester, in preference to the corresponding alanine and valine derivatives, indicates that the relative reactivity of substrates is determined by the comparative ease of their complexation to the copper.

An analogy between the dynamics of a cart-pole system and vehicle rollover dynamics is used to derive a controller for tipping up and stabilizing a planar model of a passenger vehicle near rollover by controlling lateral tire friction forces. The controller is based on a previously published controller for stabilizing a cart-pole using partial feedback linearization and energy shaping. A necessary condition for tip-up is given based on the surface friction coefficient and the location of the vehicle center of gravity (c.g.). A multi-body vehicle model with suspension is presented in the form of the robotic manipulator equations. Simulation results are presented demonstrating the effect of friction and suspension properties on the tip-up problem.

This paper presents a method for semi-autonomous hazard avoidance in the presence of unknown moving obstacles and unpredictable driver inputs. This method iteratively predicts the motion and anticipated intersection of the host vehicle with both static and dynamic hazards and excludes projected collision states from a traversable corridor. A model predictive controller iteratively replans a stability-optimal trajectory through the navigable region of the environment while a threat assessor and semi-autonomous control law modulate driver and controller inputs to maintain stability, preserve controllability, and ensure safe hazard avoidance. The efficacy of this approach is demonstrated through both simulated and experimental results using a semi-autonomously controlled Jaguar S-Type.Copyright © 2010 by ASME

This paper describes the design of an optimal-control-based active safety framework that performs trajectory planning, threat assessment, and semiautonomous control of passenger vehicles in hazard avoidance scenarios. The vehicle navigation problem is formulated as a constrained optimal control problem with constraints bounding a navigable region of the road surface. A model predictive controller iteratively plans an optimal vehicle trajectory through the constrained corridor. Metrics from this “best-case” scenario establish the minimum threat posed to the vehicle given its current state. Based on this threat assessment, the level of controller intervention required to prevent departure from the navigable corridor is calculated and driver/controller inputs are scaled accordingly. This approach minimizes controller intervention while ensuring that the vehicle does not depart from a navigable corridor of travel. It also allows for multiple actuation modes, diverse trajectory-planning objectives, and varying levels of autonomy. Experimental results are presented here to demonstrate the framework’s semiautonomous performance in hazard avoidance scenarios.

α-Benzoyloxy- and α-methoxy-substituted glycine derivatives are more stable than the corresponding bromides, yet they undergo analogous reactions with stannanes. Their reactions with mixtures of hexabutylditin and dialkyl disulphides give α-alkylthio-substituted glycine derivatives, a procedure that is applicable to the synthesis of cross-linked amino acid derivatives.

The effects of orally administered pergolide mesylate on the flexor reflex were evaluated in chronic spinal rats. The mixed D1/D2 agonist pergolide (0.1 to 3.0 mg/kg) produced a dose-related decrease in the magnitude of the flexor reflex elicited by a tetanic stimulus. The effects of pergolide were blocked by haloperidol, demonstrating that the effects of pergolide were mediated through dopamine receptors. In contrast, the selective D2 agonist bromocriptine (3.0 to 30 mg/kg) had no effect on the flexor reflex. The present results are consistent with the interpretation that pergolide produces an antinociceptive action at the spinal cord level by stimulating both D1 and D2 dopamine receptors.

In this paper, a novel crawler mechanism for sideways motion is presented. The crawler mechanism is of circular cross-section and has active rolling axes at the center of the circles. Conventional crawler mechanisms can support massive loads, but cannot produce sideways motion. Additionally, previous crawler edges sink undesirably on soft ground, particularly when the vehicle body is subject to a sideways tilt. The proposed design solves these drawbacks by adopting a circular cross-section crawler. A prototype has been developed to illustrate the concept. Motion experiments confirm the novel properties of this mechanism: sideways motion and robustness against edge-sink. Motion experiments, with a test vehicle are also presented.

Mobile robots and passenger vehicles are frequently required to operate at high speeds, on terrain that is sloped or uneven. These systems can be susceptible to rollover, particularly during severe maneuvers. This paper presents an analysis of rollover stability measurement for mobile robots operating at high speeds. The analysis examines the accuracy of a commonly accepted rollover stability metric during operation on sloped and rough terrain. The effects of sensor placement, center-of-gravity position estimation error, and wheel dynamics are examined. It is shown that these effects can have a significant impact on stability measurement during high speed operation

Duloxetine, a selective but balanced serotonergic and noradrenergic reuptake inhibitor, was evaluated in the acute nociceptive pain models of tail flick and hot plate in mice and in the persistent and/or inflammatory pain models of acetic acid-induced writhing in mice, carrageenan-induced thermal hyperalgesia and mechanical allodynia in rats, and capsaicin-induced mechanical allodynia in rats. In acute pain models, duloxetine had no significant effect on response latency in the mouse tail-flick test but produced modest increases in response latencies in the mouse hot plate test. Morphine produced dose-related analgesic effects in both the mouse tail-flick and hot plate tests. In models of inflammatory and/or persistent pain, duloxetine, morphine, and ibuprofen produced dose-related decreases in acetic acid-induced writhing in mice. Duloxetine, ibuprofen, and gabapentin also produced dose-dependent reversals of both thermal hyperalgesia and mechanical allodynia produced by carrageenan in rats. In addition, both duloxetine and morphine produced a significant reduction of capsaicin-induced mechanical allodynia in rats. Duloxetine and gabapentin were without substantial effect on the Rotorod test in mice, whereas morphine and ibuprofen produced a significant impairment. Our data indicate that duloxetine may be efficacious in the treatment of persistent and/or inflammatory pain states at doses that have modest or no effect on acute nociception or motor performance.

It is well established that muscarinic cholinergic agonists produce antinociceptive effects in a number of acute pain models. However, relatively little is known about the effects of muscarinic receptor agonists in models which involve central sensitization in pain pathways. The purpose of the present studies was to evaluate the effects of vedaclidine, a muscarinic receptor mixed agonist/antagonist across receptor subtypes, in models involving central sensitization. Vedaclidine (0.3–10 mg/kg s.c.) produced dose-related antihyperalgesic effects in the formalin test as well as a dose-related reversal of capsaicin-induced mechanical hyperalgesia in rats. In the carrageenan test, vedaclidine (0.1–30 mg/kg) produced a dose-related reversal of both mechanical and thermal hyperalgesia that were antagonized by the muscarinic receptor antagonist scopolamine. In addition, the antihyperalgesic effects of vedaclidine in the carrageenan test were synergistic with the antihyperalgesic effects of the non-steroidal antiinflammatory drug ketoprofen, as demonstrated by isobolographic analysis. The present studies demonstrate that vedaclidine produces antihyperalgesic effects in models involving central sensitization, suggesting that vedaclidine, and potentially other muscarinic receptor agonists, may have clinical utility in the management of pain states involving central sensitization, such as neuropathic and inflammatory pain states.

Xanomeline is an M(1)/M(4) preferring muscarinic receptor agonist which decreased psychotic behaviors in patients with Alzheimer's disease, suggesting that xanomeline might be useful in the treatment of psychotic symptoms in patients with schizophrenia. The purpose of the present studies was, therefore, to compare the pharmacologic profile of xanomeline with that of known antipsychotic drugs. Electrophysiologically, xanomeline, after both acute and chronic administration in rats, inhibited A10 but not A9 dopamine cells in a manner which was blocked by the muscarinic receptor antagonist scopolamine. Behaviorally, xanomeline, like haloperidol, clozapine and olanzapine, blocked dopamine agonist-induced turning in unilateral 6-hydroxydopamine-lesioned rats, as well as apomorphine-induced climbing in mice. However, unlike the dopamine antagonist antipsychotic haloperidol, xanomeline did not produce catalepsy in rats. Moreover, xanomeline, like haloperidol, clozapine and olanzapine, inhibited conditioned avoidance responding in rats, an effect which also was blocked by scopolamine. The present results thus demonstrate that xanomeline has a pharmacologic profile which is similar to that of the atypical antipsychotics clozapine and olanzapine, thus indicating that xanomeline has the potential to be a novel approach in the treatment of psychotic symptoms in patients with schizophrenia.

Irritable bowel syndrome (IBS) is a pathopysiolocal condition characterized by abnormal bowel habits that are frequently accompanied by abdominal pain. Current therapy based on reducing high-amplitude GI contractions with nonselective muscarinic antagonists is limited in efficacy due to typical muscarinic side effects and provides no pain relief. We have previously found potent antinociceptive agents acting through muscarinic receptors. In the present work, new 1,2,5-thiadiazole-based structures with muscarinic activity have been evaluated both for activity as analgesics in the mouse withing assay and for activity in normalizing spontaneous cluster contractions in ferret jejunum as a model of IBS in humans. (5R,6R)-exo-6-[4-[(4,4,4-Trifluorobutyl)thio]-1,2,5-thiadiazol+ ++-3-yl] -1-azabicyclo[3.2.1]octane (35, LY316108/NNC11-2192) was found to offer an exceptional profile combining analgesic potency in mouse writhing (ED50 = 0.1 mg/kg) along with potency for normalization of GI motility (ED50 = 0.17 mg/kg). This combination of GI and analgesic potency suggests 35 as an excellent candidate for evaluation as a potential treatment of IBS.

In an attempt to improve upon the M1 agonist activity of the selective M1 agonist xanomeline and related compounds, the M1 muscarinic efficacies and potencies of 3- and 6-substituted pyrazinylazacycles were varied by changing both the 3- and 6-substituents as well as the azacycle. Significant improvements in efficacy and potency over the previously prepared [3-(hexyloxy)pyrazinyl]tetrahydropyridine 19 were obtained with the [3-(hexyloxy)pyrazinyl]-quinuclidine 5i. The M1 activity of 5i showed some enantioselectivity with (S)-5i being ca. 4-fold more potent than (R)-5i. Like 19 and xanomeline, 5i was a functionally selective M1 agonist that showed greater functional selectivity than widely studied pyrazinylquinuclidine 5n (L-689,660). The improved functional selectivity of 5i over 5n could be attributed to the additional binding interactions between the hexyloxy side chain of 5i and the M1 receptor that are not available to 5n. Although 5i may show M1 functional selectivity comparable to xanomeliine, 5i is a less efficacious and potent M1 agonist than xanomeline.

This paper formulates the vehicle navigation task as a constrained optimal control problem with constraints bounding a traversable region of the environment. A model predictive controller iteratively plans an optimal vehicle trajectory through the constrained corridor and uses this trajectory to establish the minimum threat posed to the vehicle given its current state and driver inputs. Based on this threat assessment, the level of controller intervention required to prevent departure from the traversable corridor is calculated and driver/controller inputs are scaled accordingly. Simulated and experimental results are presented to demonstrate multiple threat metrics and configurable intervention laws.

The potency and efficacy of the selective dopamine D2 receptor agonist quinpirole, the mixed D1/D2 agonist apomorphine, and the selective D1 receptor agonist SKF 38393 in producing hypothermia and changes in locomotor activity were evaluated in four strains of mice: CBA/J, C57BL/6J, ICR Swiss and CF1. CBA/J mice previously have been shown to be deficient in dopamine cell and receptor number relative to other strains such as C57BL/6J mice, whereas ICR Swiss and CF1 are commonly used strains of mice. Quinpirole (0.125 to 1.0 mg/kg) was equiefficacious and equipotent in producing hypothermia in all 4 strains. Apomorphine (0.125 to 16 mg/kg) was equiefficacious in producing hypothermia in all 4 strains, but was approximately four-fold less potent in CBA/J mice than in the other strains. SKF 38393 had little effect on body temperature in any of the 4 strains. Basal motor activity was lowest in CBA/J mice, and tended to be highest in ICR Swiss mice. Quinpirole (0.125 to 32 mg/kg) had no effect on motor activity in CBA/J mice, but decreased motor activity in the other 3 strains. Apomorphine (1 to 16 mg/kg) produced modest increases in motor activity in all 4 strains. The magnitude of the changes produced by apomorphine was comparable in all strains when expressed as change from mean control values. SKF 38393 (8 to 64 mg/kg) also increased motor activity in all 4 strains, with comparable increases when expressed as change from mean control values. The present results are consistent with the interpretation that inherited deficiencies in dopamine cell and receptor number in CBA/J mice produce functional decrements in D2, but not D1, dopamine receptor function.

Carbamate derivatives of α-amino acids react by N-methylation, without racemization, on treatment with tert-butyl perbenzoate in the presence of copper(II) octanoate; the selective reaction of N-tert-butoxycarbonylglycine methyl ester, in preference to the corresponding alanine and valine derivatives, indicates that the relative reactivity of substrates is determined by the comparative ease of their complexation to the copper.

Thermal or silver-ion induced electrocyclic ring-opening of Cyclohexannulated [5.3.1]propellanes such as 7 and 8 provides ABC ring analogues of paclitaxel (taxol) including compounds 10, 11 and 14.

Obtention des produits d'oxydation sur les carbones endo- et exocycliques adjacents a l'azote du lactame